THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW

THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA... | F1000Research "use strict";function _typeof(t){return(_typeof="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(t){return typeof t}:function(t){return t&&"function"==typeof Symbol&&t.constructor===Symbol&&t!==Symbol.prototype?"symbol":typeof t})(t)}!function(){var t=function(){var t,e,o=[],n=window,r=n;for(;r;){try{if(r.frames.__tcfapiLocator){t=r;break}}catch(t){}if(r===n.top)break;r=r.parent}t||(!function t(){var e=n.document,o=!!n.frames.__tcfapiLocator;if(!o)if(e.body){var r=e.createElement("iframe");r.style.cssText="display:none",r.name="__tcfapiLocator",e.body.appendChild(r)}else setTimeout(t,5);return!o}(),n.__tcfapi=function(){for(var t=arguments.length,n=new Array(t),r=0;r 3&&2===parseInt(n[1],10)&&"boolean"==typeof n[3]&&(e=n[3],"function"==typeof n[2]&&n[2]("set",!0)):"ping"===n[0]?"function"==typeof n[2]&&n[2]({gdprApplies:e,cmpLoaded:!1,cmpStatus:"stub"}):o.push(n)},n.addEventListener("message",(function(t){var e="string"==typeof t.data,o={};if(e)try{o=JSON.parse(t.data)}catch(t){}else o=t.data;var n="object"===_typeof(o)&&null!==o?o.__tcfapiCall:null;n&&window.__tcfapi(n.command,n.version,(function(o,r){var a={__tcfapiReturn:{returnValue:o,success:r,callId:n.callId}};t&&t.source&&t.source.postMessage&&t.source.postMessage(e?JSON.stringify(a):a,"*")}),n.parameter)}),!1))};"undefined"!=typeof module?module.exports=t:t()}(); dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://f1000research.com/js/vendor/ckeditor/' window.reactTheme = 'research'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); (function(h,o,t,j,a,r){ h.hj=h.hj||function(){(h.hj.q=h.hj.q||[]).push(arguments)}; h._hjSettings={hjid:2318163,hjsv:6}; a=o.getElementsByTagName('head')[0]; r=o.createElement('script');r.async=1; r.src=t+h._hjSettings.hjid+j+h._hjSettings.hjsv; a.appendChild(r); })(window,document,'https://static.hotjar.com/c/hotjar-','.js?sv='); search file_upload Submit your research search menu close search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Open Data, Software and Code Guidelines (PSE) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Article Processing Charges Peer Review Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Newsroom Contact My Research Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://f1000research.com/articles/14-716" }, "headline": "THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW", "datePublished": "2025-07-21T16:04:32", "dateModified": "2025-07-21T16:04:32", "author": [ { "@type": "Person", "name": "Regan Mujinya" }, { "@type": "Person", "name": "Swase Dominic Terkimbi" }, { "@type": "Person", "name": "Victor Otu Oka" }, { "@type": "Person", "name": "Monday Etukudo Ekon" }, { "@type": "Person", "name": "Makena Wusa" }, { "@type": "Person", "name": "Elna Owembabazi" }, { "@type": "Person", "name": "Patrick Aja Maduabuchi" }, { "@type": "Person", "name": "Daniel Udofia Owu" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Background Amnesia, a debilitating memory disorder, often arises from neurodegenerative diseases, oxidative stress, and synaptic dysfunction. Current therapies offer limited efficacy and are associated with adverse effects, prompting exploration of safer neuroprotective agents. Flavonoids, abundant in fruits, vegetables, and medicinal plants, have emerged as promising candidates due to their antioxidant, anti-inflammatory, and neurotrophic properties. Objective This systematic review critically evaluated experimental evidence on the protective role of flavonoids in amnesia, highlighting their mechanisms of action, therapeutic outcomes, and translational potential. Methods A comprehensive literature search was conducted using structured search strategies across the Web of Science, Scopus, and PubMed databases. Studies published between 2010 and 2024 were screened according to PRISMA 2020 guidelines. Only original experimental research investigating flavonoid interventions in animal models of amnesia was included. Results Out of 593 retrieved articles, 25 studies met the inclusion criteria. Behavioral assessments predominantly employed the Morris Water Maze, Novel Object Recognition Test, and Y-Maze to evaluate cognitive performance. Flavonoid interventions consistently improved memory functions, reduced oxidative stress markers (MDA), enhanced antioxidant defenses (GSH, SOD, CAT), and modulated neuroprotective gene expressions (BDNF, CREB1, Nrf2). Both crude plant extracts and isolated flavonoids, administered primarily via oral routes, demonstrated robust efficacy. Animal models included Swiss albino mice, Wistar rats, and zebrafish. Conclusions Flavonoids exhibit multi-targeted neuroprotection against amnesia by enhancing synaptic plasticity, combating oxidative damage, and modulating apoptotic pathways. These findings support advancing flavonoids toward clinical applications for cognitive disorders, warranting further translational studies and optimized formulations. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-716/v1", "name": "THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW" } } ] } Home Browse THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Mujinya R, Dominic Terkimbi S, Otu Oka V et al. THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.12688/f1000research.164798.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Systematic Review THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] Regan Mujinya https://orcid.org/0000-0002-6673-6817 1,2 , Swase Dominic Terkimbi https://orcid.org/0000-0002-4205-1880 3 , Victor Otu Oka 1 , [...] Monday Etukudo Ekon 4 , Makena Wusa 4 , Elna Owembabazi 4 , Patrick Aja Maduabuchi https://orcid.org/0009-0006-2450-9460 3 , Daniel Udofia Owu https://orcid.org/0000-0002-8264-9131 1 Regan Mujinya https://orcid.org/0000-0002-6673-6817 1,2 , Swase Dominic Terkimbi https://orcid.org/0000-0002-4205-1880 3 , [...] Victor Otu Oka 1 , Monday Etukudo Ekon 4 , Makena Wusa 4 , Elna Owembabazi 4 , Patrick Aja Maduabuchi https://orcid.org/0009-0006-2450-9460 3 , Daniel Udofia Owu https://orcid.org/0000-0002-8264-9131 1 PUBLISHED 21 Jul 2025 Author details Author details 1 Department of Physiology, Faculty of Biomedical sciences, Kampala International University - Western Campus, Bushenyi, Western Region, P.O Box. 71, Uganda 2 Department of Physiological, Equator University of Science and Technology, Masaka, Masaka, B.O. `box 21, Uganda 3 Department of Biochemistry, Faculty of Biomedical Sciences, Kampala International University - Western Campus, Bushenyi, Western Region, B.O Box. 71, Uganda 4 Department of Human Anatomy, Faculty of Biomedical sciences, Kampala International University - Western Campus, Bushenyi, Western Region, P.O.Box 71, Uganda Regan Mujinya Roles: Conceptualization, Formal Analysis, Methodology, Resources, Software, Writing – Original Draft Preparation, Writing – Review & Editing Swase Dominic Terkimbi Roles: Conceptualization, Formal Analysis, Methodology, Visualization, Writing – Review & Editing Victor Otu Oka Roles: Conceptualization, Investigation, Methodology, Resources, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Monday Etukudo Ekon Roles: Conceptualization, Investigation, Resources, Software, Visualization, Writing – Original Draft Preparation Makena Wusa Roles: Formal Analysis, Investigation, Methodology, Software, Writing – Original Draft Preparation, Writing – Review & Editing Elna Owembabazi Roles: Conceptualization, Formal Analysis, Investigation, Project Administration, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Patrick Aja Maduabuchi Roles: Conceptualization, Investigation, Methodology, Software, Supervision, Validation, Writing – Original Draft Preparation Daniel Udofia Owu Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background Amnesia, a debilitating memory disorder, often arises from neurodegenerative diseases, oxidative stress, and synaptic dysfunction. Current therapies offer limited efficacy and are associated with adverse effects, prompting exploration of safer neuroprotective agents. Flavonoids, abundant in fruits, vegetables, and medicinal plants, have emerged as promising candidates due to their antioxidant, anti-inflammatory, and neurotrophic properties. Objective This systematic review critically evaluated experimental evidence on the protective role of flavonoids in amnesia, highlighting their mechanisms of action, therapeutic outcomes, and translational potential. Methods A comprehensive literature search was conducted using structured search strategies across the Web of Science, Scopus, and PubMed databases. Studies published between 2010 and 2024 were screened according to PRISMA 2020 guidelines. Only original experimental research investigating flavonoid interventions in animal models of amnesia was included. Results Out of 593 retrieved articles, 25 studies met the inclusion criteria. Behavioral assessments predominantly employed the Morris Water Maze, Novel Object Recognition Test, and Y-Maze to evaluate cognitive performance. Flavonoid interventions consistently improved memory functions, reduced oxidative stress markers (MDA), enhanced antioxidant defenses (GSH, SOD, CAT), and modulated neuroprotective gene expressions (BDNF, CREB1, Nrf2). Both crude plant extracts and isolated flavonoids, administered primarily via oral routes, demonstrated robust efficacy. Animal models included Swiss albino mice, Wistar rats, and zebrafish. Conclusions Flavonoids exhibit multi-targeted neuroprotection against amnesia by enhancing synaptic plasticity, combating oxidative damage, and modulating apoptotic pathways. These findings support advancing flavonoids toward clinical applications for cognitive disorders, warranting further translational studies and optimized formulations. READ ALL READ LESS Keywords Flavonoids, Amnesia, Cognitive Enhancement, Oxidative Stress, Neuroprotection, Corresponding Author(s) Regan Mujinya ( [email protected] ) Close Corresponding author: Regan Mujinya Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Mujinya R et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Mujinya R, Dominic Terkimbi S, Otu Oka V et al. THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.12688/f1000research.164798.1 ) First published: 21 Jul 2025, 14 :716 ( https://doi.org/10.12688/f1000research.164798.1 ) Latest published: 21 Jul 2025, 14 :716 ( https://doi.org/10.12688/f1000research.164798.1 ) Introduction Amnesia, broadly defined as the loss or disruption of memory function, represents a major clinical challenge with profound personal, social, and economic consequences. 1 It can arise from diverse etiologies, including neurodegenerative diseases such as Alzheimer’s disease, traumatic brain injury, cerebrovascular events, infections, and psychiatric conditions. Despite the underlying causes varying significantly, a common feature across many forms of amnesia is neuronal dysfunction or death within brain regions critical for memory processing, particularly the hippocampus and associated cortical structures. 2 Current pharmacological therapies, including cholinesterase inhibitors and NMDA receptor antagonists, offer limited efficacy and are often associated with undesirable side effects. This therapeutic gap has intensified interest in exploring safer, more effective neuroprotective agents, particularly those derived from natural sources. 3 Flavonoids, a large group of polyphenolic compounds naturally occurring in fruits, vegetables, teas, and medicinal plants, have gained considerable attention due to their diverse pharmacological activities. 4 Numerous experimental studies have demonstrated that flavonoids exert antioxidant, anti-inflammatory, anti-apoptotic, and neurotrophic effects, all of which are mechanisms critically implicated in memory preservation and cognitive enhancement. Flavonoids are known to modulate critical signaling pathways, including ERK/CREB/BDNF and PI3K/Akt, which are central to synaptic plasticity, neurogenesis, and long-term potentiation, the molecular substrates of memory formation and retrieval. 5 Additionally, flavonoids have been observed to attenuate oxidative stress-induced neuronal damage and inhibit neuroinflammation, both of which are prominent pathological features in various models of amnesia. 6 Despite the biological plausibility and encouraging preclinical findings, the evidence surrounding the protective effects of flavonoids in amnesia has yet to be systematically synthesized. The diversity of flavonoid subclasses, varying models of amnesia, and different outcome measures employed across studies make it necessary to critically appraise and integrate available data. Such a synthesis will help identify the most promising flavonoid compounds, clarify their mechanisms of action, and guide future research toward the development of flavonoid-based therapeutic interventions for memory disorders. 7 Therefore, the primary objective of this systematic review is to evaluate existing experimental evidence on the protective role of flavonoids in amnesia. Specifically, this review will focus on assessing the efficacy of different flavonoid compounds, elucidating their mechanisms of neuroprotection, and identifying key knowledge gaps that warrant further investigation. Materials and methods Study design This systematic review was designed to comprehensively investigate the protective role of flavonoids in amnesia. The review adhered strictly to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to ensure transparency, accuracy, and reproducibility throughout the process. Literature search strategy A comprehensive literature search of published articles investigating the protective role of flavonoids in amnesia was conducted across three major electronic databases: Web of Science (WoS), Scopus, and PubMed. The search was performed on the 10 th of December 2024. Search terms included the keywords “flavonoid” and “amnesia,” with the search fields restricted to “Title,” “Abstract,” and “Keywords” in WoS and Scopus databases to ensure a robust and targeted retrieval of relevant studies. Boolean operators (AND, OR, NOT), quotation marks, parentheses, wildcards, and asterisk (*) symbols were strategically employed to optimize the search results, following established search optimization techniques. The search strategy combined multiple related flavonoid terms and was structured as follows for WoS and Scopus: (“flavonoid” OR “flavonol” OR “flavanone” OR “flavone” OR “flavan-3-ol” OR “isoflavone” OR “daidzein” OR “genistein” OR “kaempferol” OR “apigenin” OR “catechin” OR “epicatechin” OR “epigallocatechin” OR “gallocatechin” OR “luteolin” OR “hesperetin” OR “quercetin” OR “biochanin” OR “theaflavin” OR “formononetin” OR “baicalein” OR “myricetin” OR “chrysin” OR “naringenin” OR “glycitein” OR “eriodictyol” OR “isorhamnetin” OR “thearubigin” OR “anthocyanin” OR “delphinidin” OR “peonidin” OR “malvidin” OR “anthocyanidin” OR “petunidin” OR “cyanidin” OR “pelargonidin”) AND (“amnesia”). For PubMed, the search was adapted to include MeSH terms and field tags, resulting in the following syntax: (“flavonoid” [Title/Abstract] OR “flavonol” [Title/Abstract] OR …) AND (“amnesia” [Title/Abstract]) NOT (review [Publication Type]). Screening and selection process All retrieved articles from the database searches were downloaded in CSV format and subsequently uploaded onto the Rayyan platform, a web-based tool designed to streamline systematic review processes. Rayyan was used to facilitate the efficient and blinded screening of titles and abstracts based on predefined eligibility criteria. Duplicate entries were automatically identified and removed by the Rayyan system before the screening commenced. The selection process followed three sequential stages: title screening, abstract screening, and full-text review. Each article was assessed for relevance against the established inclusion and exclusion criteria and any disagreements during screening were resolved through discussion and consensus among the reviewers. Screening and selection were conducted in strict adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Only studies that met all eligibility criteria at each screening level were included for final qualitative synthesis. Articles that failed to meet the criteria were excluded at the appropriate stage, with exclusion reasons documented systematically. Two independent reviewers screened and extracted data from each included article using a predefined data extraction form. Disagreements were resolved through discussion, and no automation tools were used in the data collection process. Inclusion and exclusion criteria Studies that investigated the role of flavonoids in amnesia, including those that evaluated any flavonoid compound for the treatment or management of amnesia, were included. Eligible studies specifically targeted flavonoid-based interventions and reported on the protective functions or therapeutic roles of flavonoids in amnesia. Only studies that presented quantitative outcomes related to the severity of amnesia, were published in peer-reviewed journals in English, and demonstrated clear methodology with detailed reporting regarding the administration of flavonoids or formulations, compounds, or extracts with flavonoid activity were considered for inclusion. Studies that did not focus on flavonoids, lacked experimental models of amnesia (with clinical trials also excluded), or investigated therapies unrelated to flavonoid interventions were excluded. Additionally, studies published in languages other than English, studies without clear reporting of outcomes or methodology, and secondary sources such as review articles, editorials, commentaries, and conference abstracts were excluded from the review. Data synthesis and analysis Extracted data were tabulated and categorized under distinct headings for clarity. Descriptive synthesis was employed to summarize the outcomes, focusing on experimental models, types of flavonoids, behavioral assessments, biochemical markers, gene expression, and affected brain regions. Frequencies and percentages were calculated for key variables, and where possible, trends and correlations were discussed. The Rayyan platform facilitated structured data management throughout the analysis process. Results Search results A total of 593 articles were retrieved from three databases: 98 from Web of Science, 440 from Scopus, and 55 from PubMed. After the removal of 394 duplicates, 199 articles proceeded to the screening stage. Screening of titles and abstracts resulted in the exclusion of 139 articles. The full texts of the remaining 60 articles were then assessed for eligibility, leading to the exclusion of 35 articles that did not meet the inclusion criteria. In the end, 25 articles were included in the final review after completing the eligibility and quality assessment process as depicted in Figure 1 . Figure 1. PRISMA study selection flow chart. Study characteristics These studies were conducted across various countries, demonstrating considerable diversity in animal models, species, sample sizes, sexes, and age groups used in the research. The studies spanned multiple countries, including Brazil, Pakistan, Cameroon, India, China, Saudi Arabia, South Korea, Tunisia, Romania, Egypt, the United Arab Emirates, and Mongolia, along with contributions from unspecified locations. A variety of animal models were employed, with rats and mice being the most commonly used. Zebrafish and gerbils were also utilized in several studies. Among the mouse models, specific strains included Swiss albino mice, Laca mice, and transgenic APP/PS1 mice. For rat models, Wistar and Sprague-Dawley strains were frequently used. The majority of studies predominantly used male animals, though some included both sexes. Sample sizes varied widely, ranging from as few as six animals per group to larger cohorts of over 100 animals. Animal ages were also diverse, with studies reporting precise age ranges or weights. For instance, some studies focused on young adult animals, while others used aged animals to model disease progression. Several studies also detailed treatment initiation and assessment at specific age milestones. Full details of species, strains, sex distribution, sample sizes, and ages are summarized in Table 1 . Table 1. Study Characteristics. S/N Reference Country Animal species Animal type Gender of animals Sample size Age of animals (wks) 1 8 Brazil Swiss Mice Mice Male 82 8 wks 2 9 Pakistan Sprague-Dawley Rats Male 30 3 10 India Mice Swiss mice NA NA NA 4 11 Cameroon Mice Swiss albino mice Both sexes 35 mice 2-2.5 months old 5 12 NA Mice Swiss albino mice NA NA NA 6 13 NA Rats NA NA NA NA 7 14 China Rats Sprague Dawley rats Female 60 rats 6 months old 8 15 NA Rats Wistar rats Males 40 rats 60 days old 9 16 NA Mice APP/PS1 transgenic mice and wild-type mice NA NA Treatment at 5 months assay at 7 months 10 17 South Korea Gerbils Mongolian gerbils Male 106 gerbils (varied across groups) Six months old 11 18 NA Mice NA NA NA NA 12 7 NA Rats Sprague-Dawley rats Sprague-Dawley rats NA NA 13 19 NA Rats Wistar rats Male 12 rats per group Adult 14 6 NA Mice Institute of Cancer Research (ICR) mice NA NA 4 weeks old 15 20 NA Mice Swiss albino mice NA NA NA 16 20 NA Rats NA NA NA NA 17 5 NA Zebrafish Danio rerio NA NA NA 18 21 NA Mice NA NA NA Adult 19 22 Tunisia, Romania, Egypt, United Arab Emirates Zebrafish Danio rerio NA Eight animals per group NA 20 23 India Rats Wistar rats Male 6 rats per group 12 months old 21 24 Pakistan Mice Swiss albino mice Male 144 mice 25-30 g body weight 22 25 NA Mice Laca mice Male 6 mice per group 3-4 months old 23 26 NA Mice Swiss albino mice NA NA NA 24 27 Iran Rats Male rats Male NA NA 25 28 Mongolia Mice NA NA NA NA Behavioral tests and animal models utilized The analysis of behavioral models employed across the reviewed studies demonstrates a clear preference for specific memory and learning assessment paradigms as depicted by Figure 2 . The Morris Water Maze (MWM) was the most frequently utilized test, reflecting its robust sensitivity for evaluating spatial learning and memory functions, particularly hippocampus-dependent processes. 25 The Novel Object Recognition Test (NORT) and Y-Maze Test (YMT) also featured prominently, emphasizing the importance of assessing recognition memory and spontaneous alternation behavior as measures of cognitive flexibility. 30 Other commonly used models included the Elevated Plus Maze (EPM) and Passive Avoidance Test (PAT), suggesting a broader interest in anxiety-related memory retention and avoidance learning. Less frequently employed tests, such as the Radial Arm Maze and Object-Location Memory Test, provide complementary assessments of working memory and object-place associations. Overall, the distribution of behavioral models indicates that researchers prioritized multi-dimensional evaluation of memory, integrating spatial, recognition, and emotional memory paradigms to capture the complexity of amnesia-related cognitive deficits. Figure 2. Frequency of behavioral tests used in flavonoid-amnesia studies. Genes expressed Oxidative stress markers assessed The evaluation of oxidative stress markers across the included studies highlights the critical role of oxidative damage in amnesia and the potential antioxidative benefits of flavonoid interventions as depicted by Figure 3 . Malondialdehyde (MDA) was the most frequently measured marker, reflecting its well-established role as a sensitive indicator of lipid peroxidation and cellular oxidative injury. 31 , 32 Glutathione (GSH) and superoxide dismutase (SOD) were also commonly assessed, underscoring the importance of endogenous antioxidant defenses in maintaining neuronal integrity. 33 Other markers such as lipid peroxidase (LPO), catalase (CAT), and nitric oxide (NO) were frequently utilized, further emphasizing the multifactorial nature of oxidative damage pathways in cognitive dysfunction. 34 Less frequently assessed indicators, including FRAP, DPPH, and reactive oxygen species (ROS), provided complementary measures of overall antioxidant capacity and free radical scavenging activity. 35 Overall, the pattern of biomarker evaluation supports that oxidative stress modulation is a central mechanism through which flavonoids exert neuroprotective effects against amnesia. Figure 3. Frequency of oxidative stress markers measured in flavonoid-amnesia studies. Plant extracts, phytochemicals, dosages, and routes of administration The reviewed studies demonstrate the diverse use of plant extracts and isolated flavonoid compounds in the experimental management of amnesia, as summarised in Table 3 . Oral administration emerged as the predominant route, reflecting its practicality and relevance for translational research into human therapies. Most studies utilized ethanolic or methanolic extracts (e.g., Averrhoa carambola , Grewia asiatica , Cyamopsis tetragonoloba ), highlighting the solubility of active flavonoids in polar solvents and the richness of polyphenolic compounds in these preparations. 10 , 9 , 12 Doses ranged widely from low concentrations (e.g., 5 mg/kg for Biochanin A) to relatively high doses (e.g., 800 mg/kg for Lavandula stoechas extract), suggesting differences in extract potency, bioavailability, and experimental design across studies. 18 Standardized compounds such as quercetin, kaempferol, silibinin, and pycnogenol® were also assessed, providing insights into the neuroprotective potential of purified flavonoids. 7 , 17 , 19 Less common administration methods, such as intraperitoneal injection ( Pinus pinaster , Glycine max ) and immersion ( Tribulus terrestris ), highlight methodological adaptations for certain experimental models. Notably, several studies did not report dosage or administration details, which may affect reproducibility and interpretation. 17 Overall, the data suggest that both crude extracts and purified flavonoid compounds confer neuroprotective effects against amnesia through varied dosing strategies and predominantly oral delivery, supporting their therapeutic potential. Table 2. Genes expressed from studies. S/N Gene expression Organ Reference 1 AChE and ChAT enzyme gene expression N/A 8 2 Bcl-2, Bax, Caspase-3 Hippocampus 14 3 bdnf, npy, egr-1, nfr2α, creb1 Brain 5 4 ERK and beta-actin proteins Hippocampus 29 5 Extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), BDNF Hippocampus 6 6 Silent information regulator 1 (SIRT1), Nuclear factor kappa B (NF-κB), p53, Forkhead box O (FOXO-1) Hippocampus 19 7 Immediate early gene cFos, mitochondrial dynamic markers (Dynamin-related protein-1, Mitofusins 1 and 2) Hippocampus 27 8 Nrf2, Bcl2, Bax, cleaved caspase-3 Hippocampus 19 Table 3. Plant extracts, phytochemicals, dosages, and routes of administration from various studies. S/N Plant name Extract/phytochemicals used Dosage of administration Route of administration Reference 1 Averrhoa carambola Ethanolic extract 100 mg/kg, 200 mg/kg, and 400 mg/kg Oral 10 2 Baicalein ( Scutellaria baicalensis ) Flavonoid (baicalein) NA Oral (via drinking water) 20 3 Biochanin A (Red clover, cabbage) Biochanin A (BCA) 5 mg/kg, 20 mg/kg, and 60 mg/kg Oral gavage 14 4 Blackcurrant ( Ribes nigrum L.) NA 50 mg/kg Oral 8 5 Cajanus cajan Ethanol seed extract 50, 100, or 200 mg/kg Oral 21 6 Capparis sepiaria Aqueous lyophilisate 10 mg/kg and 40 mg/kg Oral gavage 11 7 Carthamus tinctorius L. Kaempferol 50 mg/kg Oral 19 8 Citrus limon Juice 0.6 ml/kg/day and 1.2 ml/kg/day Oral 3 9 Cyamopsis tetragonoloba Methanolic tender green pod extract 100 mg/kg and 200 mg/kg Oral 12 10 Dimorphandra mollis Flavonoids NA NA 8 11 Elaeagnus umbellate Methanolic extract 200 mg/kg (CHF Ext), 30 mg/kg (Chlorogenic) Oral 24 12 French maritime pine ( Pinus pinaster ) Pycnogenol® 30, 40, and 50 mg/kg Intraperitoneal injection 17 13 Glycine max (soybean) Textured soy protein (TSP) extract 100 mg/kg, 200 mg/kg, and 400 mg/kg Intraperitoneal (i.p.) 27 14 Grewia asiatica L. Quercetin, Anthocyanin 200 mg/kg Oral 9 15 Lactuca sativa (LS) Ethanol extract of fresh LS leaves (LSEE) 50, 100, and 200 mg/kg (LSEE); 15 mg/kg (n-Bu) Oral 36 16 Lavandula stoechas Methanolic extract 800 mg/kg Oral 18 17 Lawsonia inermis Leaves extract NA NA 20 18 Limonia acidissima Methanolic extract NA NA 13 19 Manihot esculenta Crantz Cassava leaves' extract NA Oral 15 20 Milk thistle Silibinin (silybin) NA NA 16 21 Ocimum species Hydro-methanol extract 200 mg/kg and 400 mg/kg Oral 31 22 Onion (Quergold cultivar) Quercetin NA Oral 23 23 Sesbania grandiflora Ethanolic extract NA Oral 37 24 Soybean Soy isoflavones 40 mg/kg Oral 6 25 Tribulus terrestris Ethanolic extract 1, 3, and 6 mg/L Immersion 22 Animal models utilized The distribution of animal models in the reviewed studies highlights a predominant reliance on rats (40.74%) and Swiss albino mice (37.04%) for evaluating the protective effects of flavonoids against amnesia, as depicted in Figure 4 . This preference reflects the extensive validation of these models in behavioral neuroscience, particularly in memory and learning paradigms. Among rat models, Wistar rats (14.81%) and Sprague Dawley rats (7.41%) were commonly employed due to their well-characterized cognitive profiles and reproducibility in experimental settings. 29 , 30 The use of Danio rerio (zebrafish) (7.41%) illustrates emerging trends favoring alternative, cost-effective models for high-throughput behavioral screening. 21 , 22 Less frequently used models, including Mongolian gerbils, APP/PS1 transgenic mice, ICR mice, Laca mice, and aged wild-type mice (each at 3.70%), reflect specific study designs targeting particular aspects of neurodegeneration, aging, or genetic predisposition to memory deficits. Overall, the data indicate a strong preference for traditional rodent models, with growing exploration of alternative species to diversify cognitive research in amnesia. Figure 4. Distribution of animal models used in studies investigating flavonoid effects on amnesia. Discussion This systematic review critically evaluated the neuroprotective potential of flavonoids against amnesia, integrating findings from behavioral assessments, oxidative stress biomarkers, gene expression studies, plant-based interventions, and animal models. Overall, the evidence consistently supports that flavonoids exert multi-targeted therapeutic actions, highlighting their promise as candidates for managing cognitive impairment. Behavioral assessments revealed that the Morris Water Maze (MWM) was the most widely employed model, emphasizing its sensitivity to hippocampus-dependent spatial memory loss. This observation aligns with prior studies 25 , 30 Which have established MWM as a gold standard in memory research. Additionally, the frequent use of the Novel Object Recognition Test (NORT) and Y-Maze Test (YMT) reflects a growing trend toward adopting multidimensional cognitive testing that captures both spatial and recognition memory domains. 24 Compared to older reviews that emphasized single-task paradigms, the diversification seen here suggest a methodological advancement. In parallel with behavioral outcomes, biochemical findings consistently demonstrated that oxidative stress plays a central role in amnesia pathogenesis. Malondialdehyde (MDA) was the most frequently measured biomarker, reinforcing its established position as an indicator of lipid peroxidation and neuronal oxidative injury. 38 Alongside MDA, antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were commonly evaluated, highlighting the importance of maintaining redox balance in memory preservation. Compared to earlier studies that mainly focused on MDA as a damage marker, the broader antioxidant profiling observed here indicates a more complex understanding of oxidative dynamics. 39 These findings imply that flavonoids’ ability to simultaneously suppress oxidative stress and enhance antioxidant defenses could offer a dual-layered strategy superior to conventional single-mechanism antioxidants. 2 Molecular evidence from gene expression studies as depicted by Table 2 further strengthened these observations. Flavonoid interventions upregulated key neurotrophic and memory-related genes, notably BDNF, CREB1, and NPY, while downregulating pro-apoptotic markers such as Bax and cleaved caspase-3. This dual modulation of neuroplasticity and survival pathways reflects a complex neuroprotective mechanism, consistent with findings reported by Ref. 3 . In contrast to earlier polyphenol studies that focused narrowly on BDNF activation, the broader pathway engagement observed here suggests that flavonoids may offer more robust synaptic resilience. 4 This suggests that the ability of flavonoids to target multiple molecular pathways simultaneously makes them particularly advantageous for treating complex neurodegenerative conditions like Alzheimer’s disease, where several mechanisms of cognitive decline occur together. 40 The diversity of plant-derived interventions is summarized in Table 4 , which presents the key findings and conclusions from studies involving flavonoid-rich extracts and compounds. The reviewed studies consistently demonstrated that flavonoids improved memory functions, enhanced antioxidant defenses, modulated apoptosis, and supported cholinergic neurotransmission. 21 , 30 , 39 Some compounds, such as biochanin A, baicalein, kaempferol, and soy isoflavones, showed effects comparable to conventional anti-amnesic agents like donepezil, suggesting that flavonoids can offer similar therapeutic efficacy with fewer side effects. 12 , 26 Moreover, several studies such also demonstrated synergistic effects when flavonoids were combined with standard therapies, indicating potential as adjunct treatments. 41 Table 4. Key findings and conclusions from the included studies. S/N Reference Key findings/outcomes Conclusion 1 8 Blackcurrant improved memory and oxidative balance by cholinergic modulation. Promising natural supplement for memory impairment. 2 9 G. asiatica flavonoids boosted acetylcholine, reduced stress, enhanced memory. Effective for neuroprotection and cognitive recovery. 3 10 Naringenin improved memory and redox status in cadmium-treated mice. Protects against cadmium-induced neurotoxicity. 4 11 C. sepiaria enhanced brain antioxidants and reduced AChE. Shows anti-amnesic potential via antioxidant and cholinergic effects. 5 12 Cyamopsis extract reversed memory loss like donepezil. Multi-target cognitive impairment therapy candidate. 6 13 Limonia extract enhanced behavior, decreased AChE, improved brain histology. Enhances memory in Alzheimer’s models. 7 14 Biochanin A improved cognition, redox balance, and apoptosis markers. Neuroprotective for postmenopausal cognitive decline. 8 15 Cassava leaves extract preserved memory and antioxidant levels in the hippocampus. Preventive potential in Alzheimer’s disease. 9 15 Baicalein restored LTP, reduced Aβ, tau, and synaptic deficits. Promising oral therapy for Alzheimer’s. 10 17 Pycnogenol® protected memory and neurons from ischemic damage via antioxidants. Effective post-stroke neuroprotectant. 11 18 Lavandula stoechas improved memory and increased SOD, CAT, GSH. Stabilizes memory via cholinergic and antioxidant support. 12 7 Silibinin reduced inflammation, improved autophagy, and prevented memory loss. Promising for Alzheimer’s treatment. 13 19 Kaempferol improved behavior, antioxidant markers, and signaling regulation. Neuroprotection through PTEN, AMPK, Akt/mTOR pathway. 14 6 Soy isoflavones enhanced cognition, reduced stress, upregulated BDNF, ERK, CREB. Powerful neuroprotectant in memory dysfunction. 15 20 Lawsonia inermis enhanced cholinergic activity and antioxidant defenses. Boosts memory via neurotransmission and redox pathways. 16 20 Baicalin reduced oxidative stress, apoptosis, and improved learning. Potential agent for Alzheimer’s disease. 17 5 Rhoifolin improved memory and increased gene expression in zebrafish. Promising for amnesia and anxiety treatment. 18 21 Cajanus cajan enhanced working memory and antioxidant enzymes, lowered AChE. Improves cognition via cholinergic and antioxidant effects. 19 22 Tribulus terrestris showed anxiolytic effects via MAO-A interaction. Herb has antidepressant and anxiolytic potential. 20 23 Quercetin + donepezil improved cognition, reduced AChE and oxidative stress. Combined therapy enhances anti-amnesic effects. 21 24 Elaeagnus umbellata improved spatial memory and novel object recognition. Chlorogenic acid is an effective anti-amnesic compound. 22 25 Lactuca sativa reversed memory loss in scopolamine models. Validates its traditional use as memory enhancer. 23 26 Ocimum basilicum reduced AChE, boosted antioxidants, and improved memory. Neuroprotective and anti-amnesic herb. 24 27 TSP extract improved learning and antioxidant defense. Enhances memory via isoflavone-based pathways. 25 28 RDP decreased ROS, prevented apoptosis, and activated BDNF/TrkB pathway. Antioxidant-rich supplement for neurodegenerative disorders. Furthermore, plant-based interventions showed substantial diversity, including both crude extracts and isolated flavonoids such as quercetin, kaempferol, baicalein, and silibinin. 8 , 9 , 42 Oral administration was the predominant route, consistent with natural dietary intake and supporting pharmacokinetic evidence that flavonoids exhibit moderate to good oral bioavailability. 1 Although a few studies used intraperitoneal or immersion methods, these alternative routes may limit clinical translation. Compared to earlier flavonoid studies that often-lacked route standardization, the predominance of oral administration here reflects a growing focus on translational relevance. It implies that optimizing oral delivery systems, including nano-formulations or bioenhancers, should be a future research priority to maximize therapeutic effectiveness. Animal model analysis demonstrated a strong preference for traditional rodents, with rats (40.74%) and Swiss albino mice (37.04%) most commonly used. This mirrors established trends in cognitive neuroscience due to the reliability and depth of behavioral characterization available for these models. However, the emerging use of zebrafish (Danio rerio) and transgenic APP/PS1 mice suggests a shift toward models that better represent aging, genetic vulnerability, and high-throughput capabilities. In contrast to older research that relied almost exclusively on rodents, the diversification observed here reflects an important methodological evolution. The implication is that using a broader range of models can improve the generalizability and translational relevance of preclinical flavonoid research. 43 Additionally, the cumulative outcomes from the reviewed studies confirm that flavonoids improve cognitive performance, enhance antioxidant defenses, modulate key neurotrophic and apoptotic signaling pathways, and preserve cholinergic function. 18 , 19 Compared to traditional antioxidant strategies or single-target drugs, flavonoids appear to operate across multiple pathological processes simultaneously. This observation aligns with broader polyphenol research and highlights the potential of flavonoids to offer superior, multi-faceted interventions for memory disorders. 44 Importantly, the inclusion of studies demonstrating synergistic effects between flavonoids and standard therapies (e.g., quercetin combined with donepezil) suggests that flavonoids could complement existing treatments rather than replace them, providing an additive benefit. Conclusion This systematic review provides strong evidence that flavonoids possess significant neuroprotective properties against amnesia through multi-targeted mechanisms. The reviewed studies consistently demonstrated that flavonoid interventions improve cognitive performance by reducing oxidative stress, enhancing antioxidant defenses, promoting synaptic plasticity, and regulating apoptotic pathways. Both crude plant extracts and isolated flavonoid compounds showed remarkable efficacy across various animal models, predominantly through oral administration routes, suggesting their translational potential for human therapy. The modulation of key molecular pathways, including upregulation of BDNF, CREB1, and Nrf2, highlights flavonoids’ ability to support neurogenesis and cognitive resilience. These findings are consistent with broader polyphenol research and emphasize that flavonoids offer a holistic approach to mitigating cognitive decline, superior to single-target interventions. Despite encouraging results, substantial heterogeneity exists in experimental designs, dosages, and extract standardization. Future research should focus on harmonizing methodologies, enhancing bioavailability, and conducting rigorous clinical trials to validate these promising preclinical outcomes. The integration of flavonoids into clinical practice could offer a safe, accessible, and effective strategy for preventing and managing amnesia and related neurodegenerative conditions, especially in aging populations. Overall, flavonoids represent a promising class of natural compounds with the potential to significantly advance cognitive health interventions. Limitations This systematic review is limited by its exclusive focus on preclinical experimental studies conducted in animal models, which restricts the generalizability of the findings to human populations. The lack of clinical trials highlights a translational gap that must be addressed to confirm these results in clinical settings. There was considerable heterogeneity across the included studies in terms of animal species, flavonoid types, dosages, routes of administration, and behavioral assessment tools. This variability hindered direct comparisons across studies and made meta-analysis infeasible. Many studies did not provide detailed phytochemical characterization or standardization of the flavonoid content in their extracts. This absence of consistency affects the reproducibility and pharmacological interpretation of the findings. In several cases, the duration of treatment and follow-up periods was either unclear or not reported, limiting conclusions about the sustainability of effects over time. Risk of bias assessments and certainty grading of evidence, such as the use of GRADE, were not conducted, which weakens the ability to critically appraise the overall strength of the evidence. The review was also limited to studies published in English, which may have introduced language bias and excluded potentially relevant findings from non-English sources. These limitations emphasize the importance of methodological standardization, clinical translation, and broader inclusion criteria in future systematic reviews on this topic. Recommendations Future research should prioritize the standardization of flavonoid preparations and dosing protocols to enhance comparability. Rigorous pharmacokinetic and pharmacodynamic studies are necessary to optimize bioavailability and therapeutic windows. To enhance clinical relevance, translational studies, including well-designed human trials, should be conducted to validate the neuroprotective efficacy of flavonoids in amnesia and related cognitive disorders. Combining flavonoids with current pharmacotherapies should also be explored for potential synergistic effects. Additionally, the development of flavonoid-based nutraceuticals or supplements with well-defined compositions and safety profiles may offer accessible interventions, especially in aging or at-risk populations. Finally, future reviews should consider broader inclusion criteria, such as non-English studies and grey literature, to capture a more holistic evidence base. Disclosure statement The authors declare that the content of this systematic review is solely the result of their independent academic work. No external influence or conflict affected the integrity of the data interpretation, synthesis, or reporting. Ethical approval This study is based exclusively on the synthesis of previously published preclinical studies and did not involve any direct research with human participants or animals conducted by the authors. Therefore, ethical approval and participant consent were not required. Data availability Underlying data No data associated with this article. Reporting guidelines PRSIMA: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW, DOI: 10.6084/m9.figshare.29351495.v1 45 This dataset is available under the terms of the Creative Commons Attribution 4.0 International license (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. References 1. Thilakarathna SH, Vasantha Rupasinghe HP: Flavonoid Bioavailability and Attempts for Bioavailability Enhancement. Nutrients. 2013 Aug 28 [cited 2025 Apr 28]; 5 (9): 3367–3387. PubMed Abstract | Publisher Full Text | Free Full Text 2. Hassanpour SH, Doroudi A: Review of the antioxidant potential of flavonoids as a subgroup of polyphenols and partial substitute for synthetic antioxidants. Avicenna J. Phytomed. 2023 Jan 1 [cited 2025 Apr 28]; 13 (4): 354–376. PubMed Abstract | Publisher Full Text Reference Source 3. Amiri B, Yazdani Tabrizi M, Naziri M, et al. : Neuroprotective effects of flavonoids: endoplasmic reticulum as the target. Front. Neurosci. Frontiers Media SA; 2024; 18 . PubMed Abstract | Publisher Full Text | Free Full Text 4. Carrillo JÁ, Arcusa R, Xandri-Martínez R, et al. : Impact of Polyphenol-Rich Nutraceuticals on Cognitive Function and Neuroprotective Biomarkers: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2025 Feb 1 [cited 2025 Apr 28]; 17 (4). PubMed Abstract | Publisher Full Text | Free Full Text 5. Brinza I, Boiangiu RS, Mihasan M, et al. : Rhoifolin, baicalein 5,6-dimethyl ether and agathisflavone prevent amnesia induced in scopolamine zebrafish (Danio rerio) model by increasing the mRNA expression of bdnf, npy, egr-1, nfr2α, and creb1 genes. Eur. J. Pharmacol. 2024 Dec 5 [cited 2025 Apr 25]; 984 : 177013. Publisher Full Text Reference Source 6. Lu C, Wang Y, Wang D, et al. : Neuroprotective Effects of Soy Isoflavones on Scopolamine-Induced Amnesia in Mice. Nutrients. 2018 Jul 1 [cited 2025 Apr 25]; 10 (7): 853. PubMed Abstract | Publisher Full Text | Free Full Text 7. Liu X, Wang C, Liu W, et al. : Oral Administration of Silibinin Ameliorates Cognitive Deficits of Parkinson’s Disease Mouse Model by Restoring Mitochondrial Disorders in Hippocampus. Neurochem. Res. 2021 Sep 1 [cited 2025 Apr 25]; 46 (9): 2317–2332. PubMed Abstract | Publisher Full Text 8. da Costa P , Schetinger MRC, Baldissarelli J, et al. : Blackcurrant (Ribes nigrum L.) improves cholinergic signaling and protects against chronic Scopolamine-induced memory impairment in mice. J. Psychopharmacol. 2024 Dec 1 [cited 2025 Mar 22]; 38 (12): 1170–1183. PubMed Abstract | Publisher Full Text 9. Imran I, Javaid S, Waheed A, et al. : Grewia asiatica Berry Juice Diminishes Anxiety, Depression, and Scopolamine-Induced Learning and Memory Impairment in Behavioral Experimental Animal Models. Front. Nutr. 2021 Jan 15 [cited 2025 Mar 22]; 7 . PubMed Abstract | Publisher Full Text | Free Full Text 10. Kumar A, Dogra S, Prakash A: Protective effect of naringin, a citrus flavonoid, against colchicine-induced cognitive dysfunction and oxidative damage in rats. J. Med. Food. 2010 Aug 1 [cited 2025 Apr 25]; 13 (4): 976–984. PubMed Abstract | Publisher Full Text 11. Yassi FB, Ngoupaye GT, Kom TD, et al. : Capparis sepiaria’s root bark aqueous lyophilisate shows antiamnesic properties on scopolamine induce cognitive impairment in mice. IBRO Neurosci. Rep. 2023 Dec 1; 15 : 355–363. PubMed Abstract | Publisher Full Text | Free Full Text 12. Kraeuter AK, Guest PC, Sarnyai Z: The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods Mol. Biol. 2019 [cited 2025 Apr 25]; 1916 : 105–111. PubMed Abstract | Publisher Full Text 13. Mali KK, Sutar GV, Dias RJ, et al. : Evaluation of Nootropic Activity of Limonia acidissima Against Scopolamine-induced Amnesia in Rats. Turk. J. Pharm. Sci. 2021 [cited 2025 Apr 25]; 18 (1): 3–9. Publisher Full Text Reference Source 14. He X, Sun J, Huang X: Expression of caspase-3, Bax and Bcl-2 in hippocampus of rats with diabetes and subarachnoid hemorrhage. Exp. Ther. Med. 2018 Jan 1 [cited 2025 Apr 25]; 15 (1): 873–877. PubMed Abstract | Publisher Full Text 15. Carrazoni GS, Garces NB, Cadore CR, et al. : Supplementation with Manihot esculenta Crantz (Cassava) leaves’ extract prevents recognition memory deficits and hippocampal antioxidant dysfunction induced by Amyloid-β. Nutr. Neurosci. 2023; 27 (9): 942–950. PubMed Abstract | Publisher Full Text 16. Cho J, Bin HE, Kim YS, et al. : Baicalin and baicalein from Scutellaria baicalensis Georgi alleviate aberrant neuronal suppression mediated by GABA from reactive astrocytes. CNS Neurosci. Ther. 2024 May 1 [cited 2025 Apr 25]; 30 (5): e14740. PubMed Abstract | Publisher Full Text | Free Full Text 17. Kim B, Lee TK, Park CW, et al. : Pycnogenol® Supplementation Attenuates Memory Deficits and Protects Hippocampal CA1 Pyramidal Neurons via Antioxidative Role in a Gerbil Model of Transient Forebrain Ischemia. Nutrients. 2020 Aug 1 [cited 2025 Apr 25]; 12 (8): 2477. PubMed Abstract | Publisher Full Text | Free Full Text 18. Mushtaq A, Anwar R, Ahmad M: Lavandula stoechas (L) a very potent antioxidant attenuates dementia in scopolamine induced memory deficit mice. Front. Pharmacol. 2018 Nov 23 [cited 2025 Apr 25]; 9 (NOV): 367938. Publisher Full Text Reference Source 19. El-kott AF, Bin-Meferij MM, Eleawa SM, et al. : Kaempferol Protects Against Cadmium Chloride-Induced Memory Loss and Hippocampal Apoptosis by Increased Intracellular Glutathione Stores and Activation of PTEN/AMPK Induced Inhibition of Akt/mTOR Signaling. Neurochem. Res. 2020 Feb 1 [cited 2025 Apr 25]; 45 (2): 295–309. PubMed Abstract | Publisher Full Text 20. Balaei-Kahnamoei M, Saeedi M, Rastegari A, et al. : Phytochemical Analysis and Evaluation of Biological Activity of Lawsonia inermis Seeds Related to Alzheimer’s Disease. Evid. Based Complement. Alternat. Med. 2021 [cited 2025 Apr 25]; 2021 : 1–10. Publisher Full Text Reference Source 21. Dumitru G, El-Nashar HAS, Mostafa NM, et al. : Agathisflavone isolated from Schinus polygamus (Cav.) Cabrera leaves prevents scopolamine-induced memory impairment and brain oxidative stress in zebrafish (Danio rerio). Phytomedicine. 2019 May 1 [cited 2025 Apr 25]; 58 : 152889. PubMed Abstract | Publisher Full Text 22. Bouabdallah S, Brinza I, Boiangiu RS, et al. : The Effect of a Tribulus-Based Formulation in Alleviating Cholinergic System Impairment and Scopolamine-Induced Memory Loss in Zebrafish (Danio rerio): Insights from Molecular Docking and In Vitro/In Vivo Approaches. Pharmaceuticals (Basel). 2024 Feb 1 [cited 2025 Apr 25]; 17 (2). PubMed Abstract | Publisher Full Text | Free Full Text 23. Saberi-Hasanabadi P, Sedaghatnejad R, Mohammadi H: Protective Effect of Quercetin against Paraquat-induced Brain Mitochondrial Disruption in Mice. Curr. Drug Saf. 2024 [cited 2025 Apr 25]; 19 (1): 44–50. PubMed Abstract | Publisher Full Text 24. Nazir N, Zahoor M, Uddin F, et al. : Chemical composition, in vitro antioxidant, anticholinesterase, and antidiabetic potential of essential oil of Elaeagnus umbellata Thunb. BMC Complement. Med. Ther. 2021 Dec 1 [cited 2025 Apr 25]; 21 (1): 73. PubMed Abstract | Publisher Full Text | Free Full Text 25. Iranshahy M, Javadi B: Diet therapy for the treatment of Alzheimer’s disease in view of traditional Persian medicine: A review. Iran J. Basic Med. Sci. 2019 [cited 2025 Apr 25]; 22 (10): 1102. Reference Source 26. Minocha T, Birla H, Obaid AA, et al. : Flavonoids as Promising Neuroprotectants and Their Therapeutic Potential against Alzheimer’s Disease. Oxidative Med. Cell. Longev. 2022 Jan 1 [cited 2025 Mar 22]; 2022 (1): 6038996. PubMed Abstract | Publisher Full Text | Free Full Text 27. Mandegary A, Sharififar F, Sheibani V, et al. : Ameliorating Effect of Standardized Extract From Textured Soy Protein (Glycine max L.) on Memory Deficit and Learning Insufficiency in Scopolamine-induced Amnesia. Basic Clin. Neurosci. 2022 Jul 1 [cited 2025 Apr 25]; 13 (4): 501–510. PubMed Abstract | Publisher Full Text | Free Full Text 28. Kim NY, Cheong SH, Lee KJ, et al. : Anti-Inflammatory Effects of Ribes diacanthum Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal Model. Antioxidants. 2020 Jul 1 [cited 2025 Apr 25]; 9 (7): 622. PubMed Abstract | Publisher Full Text | Free Full Text 29. Hernández-Mercado K, Zepeda A: Morris Water Maze and Contextual Fear Conditioning Tasks to Evaluate Cognitive Functions Associated With Adult Hippocampal Neurogenesis. Front. Neurosci. 2022 Jan 3 [cited 2025 Apr 28]; 15 : 782947. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source 30. Othman MZ, Hassan Z, Has ATC: Morris water maze: a versatile and pertinent tool for assessing spatial learning and memory. Exp. Anim. 2022 Jul 1 [cited 2025 Apr 28]; 71 (3): 264–280. PubMed Abstract | Publisher Full Text | Free Full Text 31. Minocha T, Birla H, Obaid AA, et al. : Flavonoids as Promising Neuroprotectants and Their Therapeutic Potential against Alzheimer’s Disease. Oxidative Med. Cell. Longev. 2022 Jan 1 [cited 2025 Mar 22]; 2022 (1): 6038996. PubMed Abstract | Publisher Full Text | Free Full Text 32. Sahab Uddin M, Tanvir Kabir M, Niaz K, et al. : Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease. Molecules. 2020 Mar 11 [cited 2025 Mar 22]; 25 (6): 1267. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source 33. Mubangizi V, Maling S, Obua C, et al. : Prevalence and correlates of Alzheimer’s disease and related dementias in rural Uganda: Cross-sectional, population-based study. BMC Geriatr. 2020 Feb 10 [cited 2025 Mar 22]; 20 (1): 1–7. PubMed Abstract | Publisher Full Text | Free Full Text 34. Sahab Uddin M, Tanvir Kabir M, Niaz K, et al. : Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease. Molecules. 2020 Mar 11 [cited 2025 Mar 22]; 25 (6): 1267. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source 35. Ramezani M, Meymand AZ, Khodagholi F, et al. : A role for flavonoids in the prevention and/or treatment of cognitive dysfunction, learning, and memory deficits: a review of preclinical and clinical studies. Nutr. Neurosci. 2023 [cited 2025 Mar 22]; 26 (2): 156–172. Publisher Full Text Reference Source 36. Harsha SN, Anilakumar KR: Anxiolytic property of hydro-alcohol extract of Lactuca sativa and its effect on behavioral activities of mice. J. Biomed. Res. 2012 [cited 2025 Apr 29]; 27 (1): 37. Publisher Full Text Reference Source 37. Sharma S, Semwal BC, Mazumder A: Evaluation of toxicity studies of Sesbania grandiflora leaves extracts in Wistar albino rats. J. Appl. Pharm. Res. 2024 Feb 29 [cited 2025 Apr 29]; 12 (1): 42–51. Publisher Full Text Reference Source 38. Tsikas D: Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal. Biochem. 2017 May 1 [cited 2025 Apr 28]; 524 : 13–30. PubMed Abstract | Publisher Full Text 39. Tekin S, Seven E: Assessment of serum catalase, reduced glutathione, and superoxide dismutase activities and malondialdehyde levels in keratoconus patients. Eye. 2021 Oct 1 [cited 2025 Apr 28]; 36 (10): 2062–2066. Publisher Full Text Reference Source 40. Nguyen-Thi PT, Vo TK, Pham THT, et al. : Natural flavonoids as potential therapeutics in the management of Alzheimer’s disease: a review. 3 Biotech. 2024 Mar 1 [cited 2025 Apr 28]; 14 (3): 68. PubMed Abstract | Publisher Full Text | Free Full Text 41. Asnaashari S, Amjad E, Sokouti B: Synergistic effects of flavonoids and paclitaxel in cancer treatment: a systematic review. Cancer Cell Int. 2023 Dec 1 [cited 2025 Apr 28]; 23 (1): 211. PubMed Abstract | Publisher Full Text | Free Full Text 42. Mir NT, Saleem U, Anwar F, et al. : Lawsonia Inermis Markedly Improves Cognitive Functions in Animal Models and Modulate Oxidative Stress Markers in the Brain. Medicina (Kaunas). 2019 May 1 [cited 2025 Apr 25]; 55 (5). Publisher Full Text Reference Source 43. Karl T, Nithianantharajah J, Weber-Stadlbauer U: Editorial: Looking at the Complete Picture: Tackling Broader Factors Important for Advancing the Validity of Preclinical Models in Disease. Front. Behav. Neurosci. 2022 Apr 26 [cited 2025 Apr 28]; 16 : 905327. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source 44. Zahra M, Abrahamse H, George BP: Flavonoids: Antioxidant Powerhouses and Their Role in Nanomedicine. Antioxidants. 2024 Aug 1 [cited 2025 Apr 28]; 13 (8): 922. PubMed Abstract | Publisher Full Text | Free Full Text 45. Terkimbi S, Mujinya R, Otu Oka V, et al. : The Protective Role of Flavonoid in Amnesia Final – Manuscript.docx. Dataset. figshare. 2025. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 21 Jul 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of Physiology, Faculty of Biomedical sciences, Kampala International University - Western Campus, Bushenyi, Western Region, P.O Box. 71, Uganda 2 Department of Physiological, Equator University of Science and Technology, Masaka, Masaka, B.O. `box 21, Uganda 3 Department of Biochemistry, Faculty of Biomedical Sciences, Kampala International University - Western Campus, Bushenyi, Western Region, B.O Box. 71, Uganda 4 Department of Human Anatomy, Faculty of Biomedical sciences, Kampala International University - Western Campus, Bushenyi, Western Region, P.O.Box 71, Uganda Regan Mujinya Roles: Conceptualization, Formal Analysis, Methodology, Resources, Software, Writing – Original Draft Preparation, Writing – Review & Editing Swase Dominic Terkimbi Roles: Conceptualization, Formal Analysis, Methodology, Visualization, Writing – Review & Editing Victor Otu Oka Roles: Conceptualization, Investigation, Methodology, Resources, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Monday Etukudo Ekon Roles: Conceptualization, Investigation, Resources, Software, Visualization, Writing – Original Draft Preparation Makena Wusa Roles: Formal Analysis, Investigation, Methodology, Software, Writing – Original Draft Preparation, Writing – Review & Editing Elna Owembabazi Roles: Conceptualization, Formal Analysis, Investigation, Project Administration, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Patrick Aja Maduabuchi Roles: Conceptualization, Investigation, Methodology, Software, Supervision, Validation, Writing – Original Draft Preparation Daniel Udofia Owu Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 21 Jul 2025, 14:716 https://doi.org/10.12688/f1000research.164798.1 Copyright © 2025 Mujinya R et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Mujinya R, Dominic Terkimbi S, Otu Oka V et al. THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.12688/f1000research.164798.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 21 Jul 2025 Views 0 Cite How to cite this report: Hou Y. Reviewer Report For: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.5256/f1000research.181373.r408295 ) The direct URL for this report is: https://f1000research.com/articles/14-716/v1#referee-response-408295 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 16 Sep 2025 Yujun Hou , Tongji University, Shanghai, Shanghai, China Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.181373.r408295 The authors present a PRISMA-compliant systematic review of pre-clinical studies (2010–2024) investigating flavonoid-based interventions in animal models of amnesia. Out of 593 screened records, 25 rodent and zebrafish studies were included. The review highlights consistent improvements in behavioral performance, reductions ... Continue reading READ ALL The authors present a PRISMA-compliant systematic review of pre-clinical studies (2010–2024) investigating flavonoid-based interventions in animal models of amnesia. Out of 593 screened records, 25 rodent and zebrafish studies were included. The review highlights consistent improvements in behavioral performance, reductions in oxidative stress markers, and modulation of neuroplasticity and apoptosis-related genes. Based on these findings, the authors suggest that flavonoids represent promising multi-target neuroprotectants with translational potential. While the topic is of high relevance and the synthesis provides useful insights, there are several methodological and reporting issues that must be addressed to improve the rigor, clarity, and overall impact of the work. Major Comments Table 1 contains numerous “NA” entries, which limits transparency and reproducibility. The authors should attempt to retrieve missing information, for example by contacting study authors, or explicitly state when details were not reported in the primary papers. The mechanistic discussion is relatively superficial. A more integrated synthesis of how specific flavonoids modulate pathways such as BDNF/CREB, Nrf2, or apoptosis would considerably enhance the scientific contribution of the review. The review does not include a risk-of-bias assessment. Pre-clinical systematic reviews are expected to evaluate study quality using tools such as SYRCLE or CAMARADES. A domain-based appraisal for each study, summarized in a figure or table and discussed in relation to the findings, is essential to strengthen confidence in the conclusions. The translational perspective could be expanded. Beyond noting the absence of clinical trials, the authors should propose specific next steps, such as identifying candidate flavonoids, clarifying dosing strategies, or considering formulation approaches that could guide early human studies. Minor Comments Figure 1 contains inconsistencies between the numbers shown in the flow diagram and those reported in the main text; these should be corrected. The main table would be more informative if it included the direction of change (up- or down-regulation) and the specific flavonoid associated with each effect. Some in-text citations (e.g., [25], [30]) do not correspond to the reference list, suggesting formatting or numbering errors that should be revised. The manuscript treats all behavioral assays as equivalent. Adding a supplementary table that classifies each test by memory domain, validation status, and sensitivity to flavonoid effects would provide important context. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Aging and neurodegenerative disease I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Hou Y. Reviewer Report For: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.5256/f1000research.181373.r408295 ) The direct URL for this report is: https://f1000research.com/articles/14-716/v1#referee-response-408295 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Kaur R. Reviewer Report For: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.5256/f1000research.181373.r408299 ) The direct URL for this report is: https://f1000research.com/articles/14-716/v1#referee-response-408299 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 Sep 2025 Rajwinder Kaur , Chitkara University, Rajpura, Punjab, India Approved VIEWS 0 https://doi.org/10.5256/f1000research.181373.r408299 This manuscript is a robust and valuable addition to the literature on natural compounds in cognitive health. With minor additional reporting clarifications, it meets the scientific and methodological standards for systematic reviews and provides a thorough synthesis supporting further translation ... Continue reading READ ALL This manuscript is a robust and valuable addition to the literature on natural compounds in cognitive health. With minor additional reporting clarifications, it meets the scientific and methodological standards for systematic reviews and provides a thorough synthesis supporting further translation of flavonoids in amnesia research. Following areas can be considered for improvement: The review would benefit from a more detailed presentation of excluded studies and reasons for exclusion (e.g., a supplementary PRISMA table). While heterogeneity is thoroughly discussed, more structured narrative on the impact of model variations on outcome comparability would enhance clarity. Clear mention of review registration (e.g., PROSPERO, if applicable) would strengthen method transparency.Following areas can be considered for improvement: While heterogeneity is thoroughly discussed, a more structured narrative on the impact of model variations on outcome comparability would enhance clarity. A clear mention of review registration (e.g., PROSPERO, if applicable) would strengthen the method transparency. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Anticancer, neurodegenerative diseases, inflammatory diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kaur R. Reviewer Report For: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.5256/f1000research.181373.r408299 ) The direct URL for this report is: https://f1000research.com/articles/14-716/v1#referee-response-408299 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Banu Z. Reviewer Report For: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.5256/f1000research.181373.r405522 ) The direct URL for this report is: https://f1000research.com/articles/14-716/v1#referee-response-405522 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 05 Sep 2025 Zeenath Banu , RBVRR Women's College of Pharmacy, Hyderabad, Telangana, India Approved VIEWS 0 https://doi.org/10.5256/f1000research.181373.r405522 This systematic review (2010–2024) synthesizes 25 studies on flavonoids in amnesia. Flavonoids enhanced cognition, biochemical markers, and gene expression in animal models through antioxidant, anti-inflammatory, and neurotrophic effects. Following PRISMA 2020, the review details species, interventions, and ... Continue reading READ ALL This systematic review (2010–2024) synthesizes 25 studies on flavonoids in amnesia. Flavonoids enhanced cognition, biochemical markers, and gene expression in animal models through antioxidant, anti-inflammatory, and neurotrophic effects. Following PRISMA 2020, the review details species, interventions, and outcomes; however, it describes animal models but not the specific induction methods of amnesia (e.g., scopolamine, Aβ injection, trauma, ischemia) and the plant names should be written in italics(Table 4).Inconsistent use of in-text citations (sometimes just "Ref. 3") Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Partly Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Neuropharmacology, Neuroscience I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Banu Z. Reviewer Report For: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.5256/f1000research.181373.r405522 ) The direct URL for this report is: https://f1000research.com/articles/14-716/v1#referee-response-405522 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 15 Oct 2025 prince swase Dominic , Department of Biochemistry, Faculty of Biomedical Sciences, Kampala International University - Western Campus, Bushenyi, B.O Box. 71, Uganda 15 Oct 2025 Author Response Thank you so much for this comments Competing Interests: not applicable Thank you so much for this comments Thank you so much for this comments Competing Interests: not applicable Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 15 Oct 2025 prince swase Dominic , Department of Biochemistry, Faculty of Biomedical Sciences, Kampala International University - Western Campus, Bushenyi, B.O Box. 71, Uganda 15 Oct 2025 Author Response Thank you so much for this comments Competing Interests: not applicable Thank you so much for this comments Thank you so much for this comments Competing Interests: not applicable Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 21 Jul 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 1 21 Jul 25 read read read Zeenath Banu , RBVRR Women's College of Pharmacy, Hyderabad, India Rajwinder Kaur , Chitkara University, Rajpura, India Yujun Hou , Tongji University, Shanghai, China Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Hou Y. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 Sep 2025 | for Version 1 Yujun Hou , Tongji University, Shanghai, Shanghai, China 0 Views copyright © 2025 Hou Y. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors present a PRISMA-compliant systematic review of pre-clinical studies (2010–2024) investigating flavonoid-based interventions in animal models of amnesia. Out of 593 screened records, 25 rodent and zebrafish studies were included. The review highlights consistent improvements in behavioral performance, reductions in oxidative stress markers, and modulation of neuroplasticity and apoptosis-related genes. Based on these findings, the authors suggest that flavonoids represent promising multi-target neuroprotectants with translational potential. While the topic is of high relevance and the synthesis provides useful insights, there are several methodological and reporting issues that must be addressed to improve the rigor, clarity, and overall impact of the work. Major Comments Table 1 contains numerous “NA” entries, which limits transparency and reproducibility. The authors should attempt to retrieve missing information, for example by contacting study authors, or explicitly state when details were not reported in the primary papers. The mechanistic discussion is relatively superficial. A more integrated synthesis of how specific flavonoids modulate pathways such as BDNF/CREB, Nrf2, or apoptosis would considerably enhance the scientific contribution of the review. The review does not include a risk-of-bias assessment. Pre-clinical systematic reviews are expected to evaluate study quality using tools such as SYRCLE or CAMARADES. A domain-based appraisal for each study, summarized in a figure or table and discussed in relation to the findings, is essential to strengthen confidence in the conclusions. The translational perspective could be expanded. Beyond noting the absence of clinical trials, the authors should propose specific next steps, such as identifying candidate flavonoids, clarifying dosing strategies, or considering formulation approaches that could guide early human studies. Minor Comments Figure 1 contains inconsistencies between the numbers shown in the flow diagram and those reported in the main text; these should be corrected. The main table would be more informative if it included the direction of change (up- or down-regulation) and the specific flavonoid associated with each effect. Some in-text citations (e.g., [25], [30]) do not correspond to the reference list, suggesting formatting or numbering errors that should be revised. The manuscript treats all behavioral assays as equivalent. Adding a supplementary table that classifies each test by memory domain, validation status, and sensitivity to flavonoid effects would provide important context. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Aging and neurodegenerative disease I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Hou Y. Peer Review Report For: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.5256/f1000research.181373.r408295) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-716/v1#referee-response-408295 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Kaur R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 12 Sep 2025 | for Version 1 Rajwinder Kaur , Chitkara University, Rajpura, Punjab, India 0 Views copyright © 2025 Kaur R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This manuscript is a robust and valuable addition to the literature on natural compounds in cognitive health. With minor additional reporting clarifications, it meets the scientific and methodological standards for systematic reviews and provides a thorough synthesis supporting further translation of flavonoids in amnesia research. Following areas can be considered for improvement: The review would benefit from a more detailed presentation of excluded studies and reasons for exclusion (e.g., a supplementary PRISMA table). While heterogeneity is thoroughly discussed, more structured narrative on the impact of model variations on outcome comparability would enhance clarity. Clear mention of review registration (e.g., PROSPERO, if applicable) would strengthen method transparency.Following areas can be considered for improvement: While heterogeneity is thoroughly discussed, a more structured narrative on the impact of model variations on outcome comparability would enhance clarity. A clear mention of review registration (e.g., PROSPERO, if applicable) would strengthen the method transparency. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Anticancer, neurodegenerative diseases, inflammatory diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Kaur R. Peer Review Report For: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.5256/f1000research.181373.r408299) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-716/v1#referee-response-408299 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Banu Z. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 05 Sep 2025 | for Version 1 Zeenath Banu , RBVRR Women's College of Pharmacy, Hyderabad, Telangana, India 0 Views copyright © 2025 Banu Z. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This systematic review (2010–2024) synthesizes 25 studies on flavonoids in amnesia. Flavonoids enhanced cognition, biochemical markers, and gene expression in animal models through antioxidant, anti-inflammatory, and neurotrophic effects. Following PRISMA 2020, the review details species, interventions, and outcomes; however, it describes animal models but not the specific induction methods of amnesia (e.g., scopolamine, Aβ injection, trauma, ischemia) and the plant names should be written in italics(Table 4).Inconsistent use of in-text citations (sometimes just "Ref. 3") Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Partly Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Neuropharmacology, Neuroscience I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 15 Oct 2025 prince swase Dominic, Department of Biochemistry, Faculty of Biomedical Sciences, Kampala International University - Western Campus, Bushenyi, B.O Box. 71, Uganda Thank you so much for this comments View more View less Competing Interests not applicable reply Respond Report a concern Banu Z. Peer Review Report For: THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW [version 1; peer review: 2 approved, 1 approved with reservations] . F1000Research 2025, 14 :716 ( https://doi.org/10.5256/f1000research.181373.r405522) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-716/v1#referee-response-405522 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with F1000Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://f1000research.com/articles/14-716/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://f1000research.com/articles/14-716/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://f1000research.com/articles/14-716/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Mujinya R et al.'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://f1000research.com/articles/14-716/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://f1000research.com/articles/14-716", templates : { twitter : "THE PROTECTIVE ROLE OF FLAVONOIDS IN AMNESIA -SYSTEMATIC REVIEW. Mujinya R et al., published by " + "@F1000Research" + ", https://f1000research.com/articles/14-716/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/164798/181373") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "181373"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { "405518": 0, "405519": 0, "405517": 0, "402838": 0, "405526": 0, "402839": 0, "402836": 0, "405524": 0, "402837": 0, "405525": 0, "405522": 7, "405523": 0, "405520": 0, "405521": 0, "402844": 0, "402845": 0, "402842": 0, "402843": 0, "402840": 0, "402841": 0, "408294": 0, "408295": 5, "408293": 0, "408302": 0, "408300": 0, "408301": 0, "408298": 0, "408299": 5, "408296": 0, "408297": 0, }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "9f463ced-bc00-4a63-be09-037e3c2aa1ec"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); An innovative open access publishing platform offering rapid publication and open peer review, whilst supporting data deposition and sharing. Browse Gateways Collections How it Works Contact For Developers Cookie Notice Privacy Notice RSS Submit Your Research Follow us © 2012-2026 F1000 Research Ltd. ISSN 2046-1402 | Legal | Partner of Research4Life • CrossRef • ORCID • FAIRSharing R.templateTests.simpleTemplate = R.template(' $text $text $text $text $text '); R.templateTests.runTests(); var F1000platform = new F1000.Platform({ name: "f1000research", displayName: "F1000Research", hostName: "f1000research.com", id: "1", editorialEmail: "[email protected]", infoEmail: "[email protected]", usePmcStats: true }); $(function(){R.ui.dropdowns('.dropdown-for-authors, .dropdown-for-about, .dropdown-for-myresearch');}); // $(function(){R.ui.dropdowns('.dropdown-for-referees');}); $(document).ready(function () { if ($(".cookie-warning").is(":visible")) { $(".sticky").css("margin-bottom", "35px"); $(".devices").addClass("devices-and-cookie-warning"); } $(".cookie-warning .close-button").click(function (e) { $(".devices").removeClass("devices-and-cookie-warning"); $(".sticky").css("margin-bottom", "0"); }); $("#tweeter-feed .tweet-message").each(function (i, message) { var self = $(message); self.html(linkify(self.html())); }); $(".partner").on("mouseenter mouseleave", function() { $(this).find(".gray-scale, .colour").toggleClass("is-hidden"); }); }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });