Neuroprotective Role of Moringa oleifera in Alzheimer’s Disease: Insights into Mechanisms and Therapeutic Opportunities.

Neuroprotective Role of Moringa oleifera in Alzheimer’s Disease: Insights into Mechanisms and Therapeutic Opportunities. | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 2 December 2025 V1 Latest version Share on Neuroprotective Role of Moringa oleifera in Alzheimer’s Disease: Insights into Mechanisms and Therapeutic Opportunities. Authors : Hui Yu , Adeel Ahmed Abbasi , Hamid Khan , Hengji Hu , and Peiyuan Lu 0000-0001-8163-415X [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176468062.24514643/v1 819 views 198 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Alzheimer’s disease (AD) causes progressive cognitive decline, memory loss, and tau hyperphosphorylation. Studies have revealed that Moringa oleifera is an alternative neuroprotective agent in the therapy of AD. Moringa consists of phytochemicals, flavonoids (Quercetin and kaempferol), phenolic acids, alkaloids, and isothiocyanates, having antioxidant as well as anti-inflammatory activities. These bioactives prevent oxidative neuronal damage through the direct scavenging of free radicals and potent inhibition of the release of proinflammatory cytokines by blocking the NF-κB pathway. It has also been reported that some agents, such as isothiocyanates, can activate the Nrf2/ARE system with up-regulation of cytoprotective enzymes and promotion of brain endogenous antioxidant defences. Indeed, in vivo studies have shown that Moringa extracts possess anti-AchE properties and improve cholinergic transmission by reducing Aβ levels and enhancing cognitive performance in AD models. The modus of action comprises an inhibition of BACE1 activity and, in addition, a direct inhibition of the Aβ peptide aggregation into neurotoxic oligomers. It also functions as a modulator of mitochondrial activity. It increases the activity of endogenous antioxidant enzymes, such as SOD and catalase, enhancing neuronal energy metabolism while attempting to block apoptosis. These results suggest that M.O. is a useful approach for AD therapy through the modulation of major pathogenic factors. Further investigations, including similar cell studies and kinetics/pharmacokinetics study, as well as designing new human delivery devices for this valuable natural therapy, will be needed to confirm the efficacy, safety, and dosing schedule of this promising natural therapy. Neuroprotective Role of Moringa oleifera in Alzheimer’s Disease: Insights into Mechanisms and Therapeutic Opportunities Hui Yu 1 ,# , Adeel Ahmed Abbasi 2 ,# , Hamid Khan 2 , Hengji Hu 1 *, Peiyuan Lu 1 * School of Medicine, Shandong Xiehe University, Jinan 250109, PR China. Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China. #Equal contribution: Hui Yu and Adeel Ahmed Abbasi contribute equally as first authors. Correspondence* Dr. Peiyuan Lu , Email: peiyuanlu69hotmail.com Hengji Hu, Email: [email protected] Abstract Alzheimer’s disease (AD) causes progressive cognitive decline, memory loss, and tau hyperphosphorylation. Studies have revealed that Moringa oleifera is an alternative neuroprotective agent in the therapy of AD. Moringa consists of phytochemicals, flavonoids (Quercetin and kaempferol), phenolic acids, alkaloids, and isothiocyanates, having antioxidant as well as anti-inflammatory activities. These bioactives prevent oxidative neuronal damage through the direct scavenging of free radicals and potent inhibition of the release of proinflammatory cytokines by blocking the NF-κB pathway. It has also been reported that some agents, such as isothiocyanates, can activate the Nrf2/ARE system with up-regulation of cytoprotective enzymes and promotion of brain endogenous antioxidant defences. Indeed, in vivo studies have shown that Moringa extracts possess anti-AchE properties and improve cholinergic transmission by reducing Aβ levels and enhancing cognitive performance in AD models. The modus of action comprises an inhibition of BACE1 activity and, in addition, a direct inhibition of the Aβ peptide aggregation into neurotoxic oligomers. It also functions as a modulator of mitochondrial activity. It increases the activity of endogenous antioxidant enzymes, such as SOD and catalase, enhancing neuronal energy metabolism while attempting to block apoptosis. These results suggest that M.O. is a useful approach for AD therapy through the modulation of major pathogenic factors. Further investigations, including similar cell studies and kinetics/pharmacokinetics study, as well as designing new human delivery devices for this valuable natural therapy, will be needed to confirm the efficacy, safety, and dosing schedule of this promising natural therapy. Keywords: Moringa oleifera , Alzheimer’s disease, phytochemicals, anti-neuroinflammatory, neuroprotection, oxidative stress, acetylcholinesterase inhibition, β-amyloid, cognition. Introduction Alzheimer’s disease (AD) is one of the most significant health problems of this millennium (Dartigues 2009, Parsa 2011). The most common type of dementia is Alzheimer’s disease (AD) or dementia, accounting for 60-80% of cases and already affecting >55 million people all over the earth (Gustavsson, Norton et al. 2023, Xu, Jiang et al. 2025). The impact on an aging world population will be striking, with cases expected to triple by 2050 to nearly 139 million. It is a deadly clinical syndrome in which one forgets, has trouble with reasoning, and changes behavior, until the same thing that started all this occurs (Scheltens, De Strooper et al. 2021). The social and economic costs are enormous, with a global estimate that claims that >$1 trillion/year is needed to fix this disease, mostly from strain on health systems, caregivers, and the economy (Batsch and Mittelman 2012, Jia, Wei et al. 2018). The varied clinical spectrum depends on the multifactorial interrelation of primary neuropathogenic mechanisms (Matej, Tesar et al. 2019). The amyloid cascade hypothesis has held sway over AD research for more than 20 years, propounding that the aggregation and deposition of beta-amyloid (Aβ) peptides into soluble oligomers and insoluble plaques set in motion an unfortunate chain of events leading to synaptic failure followed by neuronal death (Hardy and Selkoe 2002). Meanwhile, the intracellular accumulation of hyperphosphorylated tau protein, which binds to proteins that transport cytoplasmic materials, aggregates into tangles of neurofibrils that block microtubule stability, disrupt axonal transport, and compromise neuronal viability (Iqbal, Liu et al. 2010). It is now accepted, however, that AD pathology includes more than Aβ/tom pathology (Gyimesi, Okolicsanyi et al. 2024). The inability to counteract the formation or removal of reactive oxygen species (ROS), known as oxidative stress, is the cause of lipid peroxidation, protein oxidation, and DNA breakage, ultimately leading to an increase in neuronal loss (Butterfield and Halliwell 2019). This is characterized by mitochondrial dysfunction, with impaired energy metabolism and increased oxidative damage (Swerdlow, Burns et al. 2014). Furthermore, the ongoing neuroinflammation, mediated by the recurrent activation of microglia and astrocytes, along with the release of proinflammatory cytokines, produces a toxic microenvironment that exacerbates rather than resolves the neurodegenerative process (Heneka, Carson et al. 2015). Finally, cholinergic neuron degeneration in the basal forebrain and acetylcholine deficit, a significant neurotransmitter for learning and memory, are the basis for dementia-specific cognitive symptoms being an inherent part of the dementogenic process (Hampel, Mesulam et al. 2018). This polyetiological pathogenesis makes AD a very challenging therapeutic target (Gong, Liu et al. 2018). The pharmacological armamentarium is weak and symptomatic in nature only for the treatment of AD. Cholinesterase inhibitors (such as donepezil, rivastigmine, or galantamine; AChEIs) work by increasing acetylcholine concentration in the synapse, resulting in limited and transient symptom alleviation (Birks, Dementia et al. 1996). The N-methyl-D-aspartate (NMDA) receptor antagonist memantine is used to modulate glutamate function, thereby protecting neurons from excitotoxic cell death (Kuns, Rosani et al. 2024). Although these medications offer some clinical benefit, there are several essential concerns: they do not stop or reverse the progression of the disease, their efficacy is usually short-lived, and adverse effects such as nausea, vomiting, and dizziness are reported (Yiannopoulou and Papageorgiou 2013). The recent approval of anti-amyloid immunotherapies (aducanumab, lecanemab) represents a move towards disease modification but is associated with substantial safety considerations, high costs, and modest clinical benefits, underscoring the unmet need for safer, more effective, and multi-target therapeutic approaches (Van Bokhoven, de Wilde et al. 2021). Moringa oleifera, commonly referred to as drumstick tree (Table 19.1), horseradish tree , or ben oil tree, is a fast-growing and drought-resistant family Moringaceae species with 13 known species in the genus (Fahey 2005). Taxonomically, it is categorized under: Kingdom Plantae; Division Magnoliophyta; Class Magnoliopsida; Order Brassicales; Family Moringaceae; Genus Moringa and Species M. oleifera (Leone, Spada et al. 2015). Moringa oleifera is native to the sub-Himalayan regions of India, Pakistan, Bangladesh, and Afghanistan, but it is now widely cultivated throughout tropical and subtropical areas due to its nutritional value. Soothing Tonic: Prepare a relaxing drink by boiling Moringa leaves in water until the water turns light green (Anwar, Latif et al. 2007). Nearly all parts of the plant, such as leaves, pods, seeds, and roots, have been employed in folk medicine and food applications, and its high vitamin, mineral, amino acid, and bioactive composition has established it as a “miracle tree” with versatile pharmacologic properties (Siddhuraju and Becker 2003). Examination of M. oleifera in AD can be justified due to its high nutritional value and a rich array of bioactive compounds, such as flavonoids (e.g., quercetin, kaempferol), phenolic acids, glucosinolates, and alkaloids, with documented potent antioxidant, anti-inflammatory, and AChE-inhibitory activities (Gopalakrishnan, Doriya et al. 2016). This multicomponent phytochemical profile positions M. oleifera as a potential favorable candidate acting as a multi-targeter towards several major pathological pathways of AD (Sharifi-Rad, Rapposelli et al. 2022, Zamani, Jam et al. 2025). The present review intends to summarize and critically appraise the available scientific evidence on the neuroprotective effects of M. oleifera in AD. Specifically, they will: Systematically define the multi-target mechanistic underpinnings by which M. oleifera and its bioactive components alleviate AD pathologies related to Aβ and tau aggregation, oxidative stress, neuroinflammation, and cholinergic insufficiency. Together and compare results from in vitro versus in vivo preclinical investigations. Discuss the current bottlenecks, including bioavailability and a lack of clinical data, and suggest new research avenues to bring this promising botanical agent from bench to bedside (Figure 1). Figure 1. Neuroprotective Role of Moringa oleifera in Alzheimer’s Disease. The schematic illustrates the progression from a normal brain to an Alzheimer’s-affected brain, characterized by amyloid-β plaque formation, tau hyperphosphorylation, microtubule disassembly, and neurofibrillary tangle accumulation. Such pathological processes give rise to neuroinflammation, hippocampal atrophy, synaptic dysfunction, and the subsequent progressive loss of cognitive faculties. Moringa oleifera is suggested as a neuroprotective agent that modulates such AD-related alterations and maintains brain structure and function integrity. Search strategy To systematically report the literature on the neuroprotective effects of Moringa oleifera in Alzheimer’s disease (AD). Search was performed on different electronic databases (PubMed, Scopus, Web of Science, ScienceDirect, Google Scholar, and Cochrane) from inception to January 2025. Bioactive compounds from Moringa oleifera and their phytochemical profile The incredible healing powers of Moringa oleifera can be primarily attributed to the presence of a diverse array of bioactive compounds with various properties (Chhikara, Kaur et al. 2021, Kumar, Khatak et al. 2025). These phytochemicals function independently and in combination to mediate a variety of pharmacological actions; thus, M. oleifera could be an ideal multi-target drug candidate for complex diseases, such as Alzheimer’s (Abbas, Mustafa et al. 2025, Goel 2025). This chapter is dedicated to the principal types of these neuroprotective substances and the plants in which they are mainly found. The phytochemical composition of M. oleifera is dominated by its broad classes of compounds, each of which is not insignificant in its contribution to providing a neuroprotective function (Azlan, Khairul Annuar et al. 2023, Goel 2025). Flavonoids. This category of polyphenolic compounds is likely one of the main contributors to the antioxidative and anti-inflammatory effects that Moringa can lead to (Coz-Bolaños, Campos-Vega et al. 2018, Saleem, Saleem et al. 2020). The leaves are particularly enriched in Quercetin and kaempferol (Vongsak, Sithisarn et al. 2013). It is a powerful antioxidant and free radical scavenger with the ability to block oxidative stress-mediated apoptosis in neurons. Quercetin can inhibit beta-amyloid fibrillogenesis in vitro (Ansari, Abdul et al. 2009). Kaempferol also has potent anti-inflammatory effects by inhibiting the NF-κB pathway, which is one of the most essential contributors to neuroinflammation in AD (Chen and Chen 2013). Phenolic Acids: Moringa is a rich source of phenolic acids, which are strong hydrogen donors that contribute significantly to the antioxidant capacity of the extract (Singh, Negi et al. 2013, He, Lv et al. 2020). Gallic acid and chlorogenic acid are two examples. Gallic acid has been demonstrated to abrogate Aβ-induced neurotoxicity and tau hyperphosphorylation in cellular models as well (Mansouri, Naghizadeh et al. 2013). Chlorogenic acid can pass through the blood-brain barrier and display its antioxidant properties, thereby improving cognitive function in animal models of age-dependent reactions and neurodegenerative disorders (Mikami and Yamazawa 2015). Glucosinolates and Isothiocyanates: This class of sulfuric compounds is typically present in the Moringaceae family. Glucotropaeolin, isothiocyanates, and dummy variables were reported to be transformed into active isothiocyanates upon enzymatic hydrolysis (e.g., chewing or processing) (Fahey, Olson et al. 2018). These molecules are known for their strong anti-inflammatory and cytoprotective properties. They do so through the Nrf2 pathway, a master regulator of cellular antioxidant defense that induces the expression of protective enzymes, such as heme oxygenase-1, resulting in increased resistance to oxidative stress in neurons (Fahey, Olson et al. 2018). Alkaloids and Saponins: Although not as well investigated as the polyphenols, alkaloids (e.g. moringinine) and saponins found in Moringa are also thought to contribute to its pharmacologic actions. Some alkaloids have demonstrated acetylcholinesterase (AChE) inhibitory activity in early screening tests, indicating a direct mode of action to potentiate cholinergic function (Nasution, Kalanjati et al. 2023). Saponins have anti-inflammatory and membrane-stabilizing effects that can support neural health indirectly (Bhadoriya, Mishra et al. 2012, Tsuchiya 2015). Vitamins and Minerals: Moringa leaves are an exceptional source of natural antioxidants, including high levels of Vitamin C and Vitamin E (Leone, Spada et al. 2015). These vitamins work synergistically with phenolic compounds to neutralize free radicals. Furthermore, Moringa accumulates essential minerals like Zinc and Selenium, which are crucial cofactors for endogenous antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), respectively. Adequate levels of these minerals are vital for maintaining neuronal redox homeostasis (Yang and Wang 2023) (Figure 2). Figure 2 . Chemical structures of key bioactive compounds in M. oleifera. The model depicts the molecular structure of the four core phytochemicals: Quercetin, which exhibits antioxidant activity by inhibiting hydroxyl radical production; Kaempferol, possessing neuroprotective and anti-inflammatory properties; Isothiocyanate, which acts in an anti-inflammatory and cytoprotective manner; and β-Carotene, a carotenoid with potent antioxidant effects. Such compounds contribute, overall, to the neuroprotective properties of Moringa oleifera, which are proposed herein as a potential defense against oxidative stress and neurodegenerative conditions. Neuroprotective properties of plant parts Diversity in the content and pattern of bioactive compounds across different parts of the Moringa tree may affect their respective properties in neuroprotection. Leaves: The leaves have attracted significant attention because they are the most well-studied and nutritionally rich part of the plant (Anwar, Latif et al. 2007, Saini, Sivanesan et al. 2016, He, Lv et al. 2020). They are rich in flavonoids, phenolic acids, vitamins, and proteins compared to other parts of the plant body and thus become an ideal source for the preparation of antioxidants-enriched extracts (Vongsak, Sithisarn et al. 2013, Leone, Spada et al. 2015). Among these leaf extracts, those of H. perforatum remain the primary candidate for AD drug discovery because most preclinical data showing cognitive-enhancing and neuroprotective properties were obtained with this plant extract. Seed: The seeds of Moringa are also rich in oil, tocopherols (Vitamin E), and oleic acid, which have a distinct profile of glucosinolates and cytokinins as well (Anwar and Bhanger 2003). Seed extracts, also widely acclaimed for their water-purifying and antidiabetic properties, have demonstrated substantial antioxidant and AChE inhibitory properties, but generally exhibit lesser activity compared to leaf extracts on a comparison basis (Sreelatha and Padma 2009, Santos 2021, Mahaman, Feng et al. 2022). Roots and Flowers - The roots and flowers also contain healing phytochemicals, but are less commonly used. The alkaloid content in the roots is significantly higher, even though potentially toxic substances are also present; therefore, we must be cautious when consuming it in high doses (Kasolo, Bimenya et al. 2010, Leone, Spada et al. 2015). The flowers are rich in flavonoids and used traditionally for their anti-inflammatory activity; however, the scientific reports endorsing it as a neuroprotective agent are limited (Mishra, Singh et al. 2011, Alhakmani, Kumar et al. 2013). Standardized Extracts for Research and Therapy. One important challenge in the use of M. oleifera in therapy is its lack of standardization (Villegas-Vazquez, Gómez-Cansino et al. 2025, Zamani, Jam et al. 2025). Phytochemical content differs with geographical region, soil quality, season, and postharvest of the product (Leone, Spada et al. 2015). The extracts need to be standardized in terms of some marker compounds (e.g., Quercetin, chlorogenic acid, or total phenolics) for reproducible efficacy and safety during clinical studies. If new research is to have value and lead to dependable and more translatable findings, such future studies should advance beyond crude extracts to better-defined preparations (Stohs and Hartman 2015). The mechanism of action of Moringa oleifera in the treatment of AD The advantage of Moringa oleifera on AD depends on its actions in various pathological pathways at the same time. Its diverse phytochemical profile results in a multitarget action in the multidirectional context of AD, comprising oxidative stress, neuroinflammation, proteinopathy, and synaptic dysfunction (Wei, Huang et al. 2020, Masukawa, Kitamura et al. 2023). The alleviation of oxidative stress The vulnerable nature of the brain to oxidative stress, which is a significant contributor to early AD pathology, may be due to its high metabolic rate and lipid composition. This can be mitigated by M. oleifera through several joint actions (Sreelatha and Padma 2009, Butterfield and Halliwell 2019). These flavonoids and phenolic acids from Moringa leaves could also act as direct ROS/RNS scavengers because of their high quantity, which can protect neuronal macromolecules from oxidative stress(Siddhuraju and Becker 2003, Sreelatha and Padma 2009, Adhikary, Mukhopadhyay et al. 2021). Besides their antioxidant scavenging activities, extracts of Moringa have also been shown to significantly upregulate the levels of critical endogenous antioxidants and enzymatic defenses, including SOD, CAT, and GPx, in scopolamine-induced (in streptozotocin) AD rat brain models (Sutalangka, Wattanathorn et al. 2013). This enhanced intracerebral antioxidative defense provides long-lasting protection by neutralizing free radicals. Its components prevent lipid peroxidation of the neuronal membrane, which leads to a decrease in malondialdehyde (MDA) level, an indicator of oxidative damage (Sutalangka, Wattanathorn et al. 2013). Moringa glucosinolate hydrolysis products, the isothiocyanates, are potent Nrf2 pathway activators (Kensler, Wakabayashi et al. 2007, Waterman, Cheng et al. 2014). Nrf2 moves to the nucleus when it is switched on. It binds to the Antioxidant Response Element (ARE) and triggers the transcription of more than 250 cytoprotective genes, enzymes mentioned above (Fahey, Olson et al. 2018, Silva Ferreira Da Costa and Barri 2018). The attenuation of inflammation in the brain Activated microglia and astrocytes are the drivers of chronic neuroinflammation, which continues to induce neuronal damage in AD (Kaur, Sharma et al. 2019, Leng and Edison 2021). M. oleifera possesses anti-inflammatory properties in the CNS (Azlan, Khairul Annuar et al. 2023, Mairuae, Buranrat et al. 2023). The bioactive constituents of Moringa, particularly Quercetin and isothiocyanates, suppressed the synthesis and release of essential molecules involved in pro-inflammation: tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 from microglial cell culture activated by Aβ or lipopolysaccharide (LPS) (Galuppo, Giacoppo et al. 2014). These cytokines are primarily inhibited by the suppression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. The degradation of IκBα is blocked by extracts from moringa, which sequesters NF-κB in the cytoplasm , preventing its nuclear translocation and repressing the activation of proinflammatory genes (Cheenpracha, Park et al. 2010). Additionally, M. oleifera suppresses oxidative stress-triggered inflammation, a pivotal role in the pathogenesis of neurodegeneration (Azlan, Khairul Annuar et al. 2023). The phenolic and flavonoid components, such as kaempferol, chlorogenic acid, ferulic acid, etc., from M. oleifera can further boost the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities to increase the antioxidant defense system in Aβ wounded neuronal cells (Sreelatha and Padma 2011). This repolarization maintains redox balance while decreasing the production of ROS that are involved in the subsequent activation of NF-κB and inflammatory cascades (He, He et al. 2017, Bellanti, Coda et al. 2025). In vivo studies using rodent Aβ-induced models have demonstrated that the leaf extract of M. oleifera significantly reduces lipid peroxidation and GFAP expression, indicating reduced astrocytic activation and oxidative stress (Goel 2025). Moreover, M. oleifera modulates NLRP3 inflammasome, which is essential for the innate immune response system and implicated in the progression of AD (Yang, Liu et al. 2023). Moringa isothiocynates and flavonoids also inhibit NLRP3-mediated activation, Caspase-1 cleavage, microglial maturation, as well as the release of IL-1β and IL-18 (Shoaib, Ansari et al. 2023). This leads to amelioration of chronic neuroinflammation and apoptosis in hippocampal neurons. Furthermore, there are actually some corroborative reports that M. oleifera extracts can attenuate the MAPK signaling pathway via the suppression of p38 MAPK and c-Jun N-terminal kinase (JNK) phosphorylation leading to down-regulation of proinflammatory mediators synthesis(Al-Malki and El Rabey 2015). Taken together, these data revealed that M. oleifera exerts a multi-targeted anti-inflammatory and anti-oxidant interaction in the brain, implicating it as a protective agent to regulate neuroinflammation and AD. A mechanism for inhibiting beta-amyloid pathology The initiation and deposition of Aβ plaques a hallmarks of AD (Sadigh-Eteghad, Sabermarouf et al. 2015, Walker 2020). M. oleifera intervenes at various stages of the amyloidogenic pathway (Zamani, Jam et al. 2025). In vitro, compounds such as Quercetin and gallic acid bind to Aβ peptides, preventing their aggregation into toxic aggregates (Ansari et al., 2009). There are a few potential pieces of evidence that Moringa extracts may affect amyloidogenic processing of APP (Mahaman, Feng et al. 2022, Zamani, Jam et al. 2025). Other studies found that β-secretase (BACE1)-mediated inactivation also promoted the reorientation of APP processing to a non-amyloidogenic pathway and reduced Aβ generation (Mahaman, Huang et al. 2018). Although poorly studied, Moringa has anti-inflammatory and antioxidant effects that may have an indirect effect on microglial phagocytosis, leading to the clearance of Aβ plaques , but requires experimental confirmation (Butterfield and Halliwell 2019, Wei, Huang et al. 2020). Furthermore, M. oleifera has also been found to act as a neuroprotective by controlling amyloidogenesis enzymes and signal pathways (Goel 2025, Zamani, Jam et al. 2025). Ethanolic and aqueous extracts of M. oleifera leaves considerably mitigate Aβ1-42 burden in the hippocampus and cortex of transgenic AD mouse models by down-regulation of BACE1 and γ-secretases gene expression (Mahaman, Feng et al. 2022). This enzymatic switch is accompanied by increased α-secretase (ADAM10) expression that, under physiological conditions, mediates the non-amyloidogenic cleavage of APP and leads to the generation of soluble neuroprotective sAPP-α fragment. Moreover, polyphenolic compounds (e.g., chlorogenic acid and kaempferol) demonstrate synergetic inhibitory actions in the APP catabolism stabilization and Aβ-mediated mitochondrial dysfunction abrogation, reducing neuro-apoptotic cell death and cognitive impairment (Kara, Marks et al. 2018, Zeng, Zhang et al. 2021). In addition to preventing plaque formation, M. oleifera enhances the clearance of accumulated amyloid deposits by stimulating autophagic and proteasomal pathways (Chen, Gao et al. 2020, Zamani, Jam et al. 2025). In vivo and in vitro studies have shown that Moringa extracts upregulate the expression of autophagy-related genes (Beclin-1, LC3-II) and lysosomal enzymes such as cathepsin D, leading to the degradation of aggregated Aβ species (Bopape, Tiloke et al. 2023, Rajendran, Renu et al. 2024). Furthermore, these effects are also supported by the activation of PI3K/Akt/mTOR signalling pathway that sustains neuronal survival and intracellular proteostasis under Aβ stress, altogether, these studies demonstrate that M. oleifera not only hampers the synthesis and aggregation of amyloid peptides but also ascertains its clearance, suggesting a two–pronged treatment against AD pathology (Aswani, Lemahieu et al. 2018, Biswkarma and Wadhawan 2025, Zamani, Jam et al. 2025) (Figure 3). Figure 3. Mechanism for inhibiting beta-amyloid pathology. The diagram illustrates the inhibition of primary enzymes involved in cholinergic and amyloid metabolism, such as AChE and BACE. AChE inhibitors increase acetylcholine (ACh) concentration, thereby promoting cholinergic neurotransmission. At the same time, β-secretase inhibition will lower the amyloidogenic processing of APP and thereby also attenuate the formation of amyloid plaques. Altogether, these findings demonstrate the potential of Moringa oleifera as a treatment for improving cognitive functions and attenuating AD pathology. Tau hyperphosphorylation modulation The hyperphosphorylation of tau protein and its formation into neurofibrillary tangles are closely correlated with cognitive decline in AD (Metcalfe and Figueiredo‐Pereira 2010, Wang, Xia et al. 2012). Key flavonoids in Moringa , such as Quercetin, have been shown to inhibit the activity of glycogen synthase kinase-3 beta (GSK-3β), a primary kinase responsible for tau hyperphosphorylation (Bhullar and Rupasinghe 2013). Additionally, some compounds may promote the activity of protein phosphatase 2A (PP2A), the main tau phosphatase, thereby facilitating the dephosphorylation of tau and stabilizing microtubules (Martin, Latypova et al. 2013, Chen, Lu et al. 2025). Besides, flavonoid-rich Moringa (e.g., Quercetin and others) has a strong capacity toward inhibiting the tau hyperphosphorylation via acting on the upstream kinases (Goel 2025, Zamani, Jam et al. 2025). Overactive GSK-3β is a major tau kinase in AD, causing abnormal phosphorylation at numerous sites and disassembly of microtubules (Hernandez, Lucas et al. 2012). For example, Quercetin was found to reduce tau phosphorylation at Thr205 and Ser396 in neuronal cell models through the activation of the PI3K/Akt pathway, which results in the inhibition of GSK-3β by promoting its phosphorylation at Ser9 and inhibiting its phosphorylation at Tyr216 (Ansari, Abdul et al. 2009). While the direct relation of Moringa extracts to GSK-3β regulation in vivo has not yet been completely elucidated, the presence of these flavonoids provides a putative mechanism by which Moringa may down-regulate tau-kinase activity and break the cycle of tau-driven cytoskeletal pathology (Luo, Zhou et al. 2022, Wen, Liu et al. 2022). Simultaneously, modulation of tau dephosphorylation pathways provides an alternative avenue for therapeutic intervention (Kalra and Khan 2015, Guha, Johnson et al. 2020). The primary tau phosphatase, Protein phosphatase 2A (PP2A), is reduced in AD pathogenesis, leading to the hyperphosphorylation of tau and neurofibrillary tangle (NFT) formation (Liu, Grundke‐Iqbal et al. 2005, Sontag and Sontag 2014). It has been reported in other systems that some natural flavonoids increase PP2A activity and/or expression, leading to tau dephosphorylation, stabilising microtubules and thus reducing cytoskeletal damage (Zhou, Fu et al., Anschuetz, Schwab et al. 2025). A literature search that demonstrated Moringa-based compounds upregulating PP2A in neuronal models is explicitly limited; however, the anti-oxidant and anti-inflammatory environment created by Moringa does have the potential to be conducive to maintaining normal PP2A function (as oxidative stress and inflammation inhibit phosphatase activity) (Goel 2025, Kumar, Khatak et al. 2025). The act of adding Moringa bioactives might therefore aid in the decrease of tau phosphorylation, which is kinase-driven, and help restore phosphatase-mediated dephosphorylation of tau derived from evidence described above (Ansari, Abdul et al. 2009, Sontag and Sontag 2014). Acetylcholinesterase (AChE) Inhibition and Cholinergic Enhancement Augmentation of cholinergic neurotransmission is a central aspect of the standard treatment for AD symptomology (Mufson, Counts et al. 2008, Giacobini, Cuello et al. 2022). Some in vitro and ex vivo studies have previously demonstrated that methanol and aqueous extracts of Moringa leaves possess activities against AChE, and the activity is dose-related (Idoga, Ambali et al. 2018, Nwidu, Elmorsy et al. 2018). Moringa leaf extract treatment of AD animal models has been shown not only to reduce brain AChE (Rahmath, Rajan et al. 2015, Nwidu, Elmorsy et al. 2018), but also to improve cognitive function (Nwidu et al., 2018; Rahmath et al., 2015). Moringa leaf extract treatment of AD animal models has been shown not only to reduce brain AChE (Sutalangka, Wattanathorn et al. 2013, Senthilkumar, Karuvantevida et al. 2018, Djiogue, Youmbi et al. 2022), but also to improve cognitive function (Djiogue et al., 2022; Senthilkumar et al., 2018; Sutalangka et al., 2013). In addition to its AChE inhibitory action, Moringa oleifera has the potential to modulate the global cholinergic network through pre- and post-synaptic actions (Onasanwo, Adamaigbo et al. 2021, Worku and Tolossa 2024). Phytochemicals, like Quercetin, niaziminin, and isothiocyanates, have been reported to increase acetylcholine (ACh) levels by decreasing oxidative breakdown of cholinergic neurons and increasing choline acetyltransferase (ChAT) expression, the enzyme responsible for ACh synthesis(Khan, Amin et al. 2018, Walczak-Nowicka and Herbet 2021, Singh, Kumar et al. 2024). These cognitive effects of M. oleifera were associated with significant restoration of hippocampal ACh content, enhanced muscarinic receptor sensitivity, and decreased malondialdehyde (MDA) level in its streptozotocin-streptozotocin-induced model as well as scopolamine-induced model, indicating cholinergic enhancement was closely related to antioxidant and anti-inflammatory activities (Adebayo, Wopara et al. 2021, Onasanwo, Adamaigbo et al. 2021). These results suggest that M. oleifera may act not only as a AChE inhibitor but also as a neuromodulator, which can maintain cholinergic tone and synaptic plasticity, thereby supporting pharmacological therapy in AD (Kumar, Kumar et al. 2025, Zamani, Jam et al. 2025). Mitochondrial Protection and Anti-Apoptotic Effects Safeguarding mitochondrial activity is crucial due to the connection between mitochondrial dysfunction and neuronal damage (Nicholls and Budd 2000, Rose, Brian et al. 2017). Moringa extracts have also recently been shown to reverse mitochondrial membrane potential, increase ATP generation, and induce mitochondrial biogenesis in models of neuronal stress , thereby preserving cellular energy homeostasis (Balit, Thonabulsombat et al. 2024, Hirao 2024). The phytochemicals of the plant work by inhibiting apoptosis through the regulation of Bcl-2 family proteins (Christodoulou, K Kontos et al. 2014, Shenoy and Abdul Salam 2025). The evidence from research studies indicates that treatment with Moringa extract upregulates Bcl-2 while downregulating the pro-apoptotic protein Bax, thereby reducing the activation of executioner caspase-3 and arresting apoptotic cascades (Fakurazi, Sharifudin et al. 2012, Adhikary, Mukhopadhyay et al. 2021). Besides stabilizing mitochondrial membrane potential, Moringa oleifera bioactive components, particularly Quercetin, kaempferol, and phenolic acids, have been reported to modulate mitochondrial redox homeostasis and prevent reactive oxygen species (ROS) generation (Ercan, Gecesefa et al. 2021, Goel 2025, Kumar, Khatak et al. 2025). Moringa scavenges superoxide radicals and upregulates the expression of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, to prevent mitochondrial lipid peroxidation and DNA damage in neuronal cells under oxidative stress conditions (Sreelatha and Padma 2011, Fakurazi, Sharifudin et al. 2012). By attenuating the activities of mitochondrial respiratory chain complexes, treatment with Moringa oleifera leaf extract was also shown to ward off mitochondrial dysfunction, an event that has been documented to precede neuronal apoptosis in scopolamine and aluminum chloride-induced neurodegeneration models (Ausina, Da Silva et al. 2018, Adhikary, Mukhopadhyay et al. 2021). These results indicate that Moringa maintains the structure and function of mitochondria, leading to neuronal survival under pathological stress conditions (Balit, Thonabulsombat et al. 2024, Goel 2025). Additionally, Moringa oleifera exhibits significant anti-apoptotic effects by interacting with a wide array of signaling pathways that regulate apoptosis (Shah and Oza 2022, Kumar, Verma et al. 2023, Zhou and Huang 2025). Upregulation of Bcl-2 and reduction in the expression of Bax and caspase-3 have also been documented after the administration of Moringa extracts against several neurotoxicity models such as kainic acid, ultraviolet A, rotenone, or β-amyloid-induced neuronal injury (Ausina, Da Silva et al. 2018, Adhikary, Mukhopadhyay et al. 2021). This regulation is believed to be mediated through a turnover of PI3K/Akt signaling cascade (which mediates neuronal survival and hinders the pro-apoptotic transducers) (Rai, Dilnashin et al. 2019, Kumar and Bansal 2022). Furthermore, Moringa flavonoids reduce mitochondrial cytochrome c release and block the activation of c-Jun N-terminal kinase (JNK), all being linked to apoptotic cascade in Alzheimer’s disease (Azlan, Khairul Annuar et al. 2023, Kumar, Kaur et al. 2024, Biswkarma and Wadhawan 2025). All these mitochondrial and anti-apoptotic activities may contribute to reduction of neuronal death in neurodegenerative diseases like AD (Sarkar, Rana et al. 2024, Goel 2025, Zamani, Jam et al. 2025). Evidence from Preclinical Studies There is a mounting evidence from in vitro and in vivo preclinical studies that Moringa oleifera harbors neuroprotective activity against Alzheimer’s disease pathology (Goel 2025, Zamani, Jam et al. 2025). These studies serve as important proof-of-concept, demonstrating the specific mechanistic and functional activity of Moringa extracts and their components in model systems that mimic features of AD (Shabbir, Naveed et al. 2024, Goel 2025, Zamani, Jam et al. 2025). In Vitro Models Cell-based investigations have enabled the identification of potential targets for M. oleifera components and their protective effects when primary hippocampal neurons and SH-SY5Y neuroblastoma cells were exposed to Aβ1-42 oligomers. Pretreatment with Moringa leaf extract or its major flavonoid quercetin significantly reduced cell death. This protection is also achieved by a decrease in oxidative stress markers, including ROS and lipid peroxidation levels, and inhibition of caspase-3 activation (Akhtar, Dhanalekshmi et al. 2024, Mohan and Kumar 2025, Singh, Kumar et al. 2025). The Moringa extract also exerted strong anti-inflammatory effects in LPS- or Aβ-stimulated BV-2 microglial cells (Sivaprakasam, Ganesan et al. 2019, Mairuae, Buranrat et al. 2023). Proinflammatory cytokine production, such as TNF-α, IL-6, and IL-1β, was downregulated in the treatment, while NO was downregulated through the downregulation of iNOS expression (Das, Acharya et al. 2022). This effect was mechanistically associated with inhibition of NF-κB signaling (Galuppo, Giacoppo et al. 2014). In vitro evaluations using enzyme assays and cell culture systems have demonstrated that Moringa compounds, such as Quercetin and gallic acid, directly block the activity of β-secretase (BACE1), the rate-limiting enzyme responsible for Aβ peptide generation (Bhullar and Rupasinghe 2013). In Vivo Animal Models These mechanistic analyses are reinforced by in vivo findings and have translated into a behavioral benefit, as observed in learning and memory (Mathews, Chang et al. 2023, Polis and Samson 2024). This pharmacologically induced model of cholinergic dysfunction and oxidative stress has been used extensively as an assay for screening potential cognitive enhancers (Fond, Micoulaud-Franchi et al. 2015, Shahanenko, Lukianenko et al. 2025). Moringa oleifera leaf extract (200-400 mg/kg, p.o.) significantly ameliorated memory deficits in scopolamine-administered rats and mice (Onasanwo, Adamaigbo et al. 2021, Djiogue, Youmbi et al. 2022). This was accompanied by a marked enhancement in performance in various behavioral tasks, including the Morris Water Maze (spatial learning and memory), Y-Maze (spatial short-term/working memory), and Passive Avoidance task (long-term retention) (Bakre, Aderibigbe et al. 2013). Biochemically, this enhancement of cognitive functions was linked to a drastic decline in brain AChE activity and an increase in GSH (glutathione) and SOD (superoxide dismutase) in the hippocampus and cortex (Bakre, Aderibigbe et al. 2013, Sutalangka, Wattanathorn et al. 2013). The disease-modifying potential is supported by studies in genetically engineered models, such as APP/PS1 mice, which produce progressive Aβ plaques. A survey by Mahaman et al. (2022) reported that chronic supplementation of M. oleifera leaf powder in an APP/PS1 mouse model caused a noticeable decrease in the cerebral Aβ plaque load and reduction of hyperphosphorylated tau (Mahaman, Huang et al. 2018). These pathological benefits were correlated with improved performance in the Morris Water Maze. The work also correlated these benefits with the activation of the Nrf2 antioxidant pathway and a decrease in the levels of neuroinflammatory markers (Mahaman, Huang et al. 2018). In various animal models, the administration of Moringa extracts has consistently abrogated key AD-like biochemical features (Mahaman, Feng et al. 2022, Aktary, Jeong et al. 2025). This comprises not only the mentioned decline in AChE activity and reduction in oxidative stress, but also the pro-apoptotic Bax, caspase-3 repression, and anti-apoptotic upregulation of Bcl-2, which contribute to a wide-spectrum neuroprotective and pro-survival effect (Chen, Zhao et al. 2022, Dailah 2022, Kumar and Bansal 2022). Neuroprotective potential of Moringa oleifera: Integrating phytochemistry, AI, and clinical research. The possible neuroprotective role of Moringa oleifera could be attributed to the relatively complex and synergetic composition of phytochemicals, including flavonoids (e.g, Quercetin), phenolic acids (gallic acid), and specific glucosinolates typical of this species (Camilleri and Blundell 2024, Goel 2025). These compounds target multiple pathological hubs of neurodegenerative diseases, exhibiting antioxidant, anti-inflammatory, and antiamyloidogenic , as well as cholinesterase inhibitory activities (Jana, Bhattacharjee et al. 2022, Cacabelos, Martínez-Iglesias et al. 2024). However, the conventional bioassay-guided discovery paradigm can only partially elucidate such a complex polypharmacology of this multi-component mixture (Koehn and Carter 2005, Atanasov, Waltenberger et al. 2015). This is where AI and ML can have the most significant impact in terms of revolutionizing the industry, providing computational references for multi-target interaction prediction, synergy detection, and large-scale integration of phytochemistry and biology data (Chen, Engkvist et al. 2018, Vamathevan, Clark et al. 2019, Zhang, Huai et al. 2019). AI platforms can combine large datasets of genomics, transcriptomics, and metabolomics to predict novel bioactive compounds present in Moringa, infer their specific molecular targets, and define possible synergistic interactions among them (Chen, Mias et al. 2012, Chen, Engkvist et al. 2018, Vamathevan, Clark et al. 2019). For example, through network pharmacology analyses the ”compound-target-pathway” network of Moringa can be constructed to illustrate how its matrix makes it modulate these three aspects (Nrf2 antioxidant pathway, NF-κB inflammatory signaling and BACE1 activity) simultaneously based on a systems biological approach (Hopkins 2008, Li, Fan et al. 2014, Zhang, Zhu et al. 2019). This in-silico driven discovery can rapidly promote the most promising of lead compounds and formulations for experimental validation, thus reducing the time spent on early phase development (Chen, Engkvist et al. 2018, Ekins, Puhl et al. 2019, Vamathevan, Clark et al. 2019). The eventual conversion of these findings into clinical neuroprotectants will depend on overcoming the significant obstacle of bioavailability and achieving success in human clinical trials. AI can also help design more sophisticated drug delivery systems, such as lipid nanoparticles/phytosomal complexes , tailored to improve brain Moringa bioactives by predicting their physicochemical properties and absorption parameters (Aljabali et al., 2025; Dube et al., 2011; Esentürk-. Despite the promising preclinical data, there is limited clinical data regarding Moringa in neurodegenerative diseases (Stohs and Hartman 2015). As such, a key next step is the initiation of well-designed, randomized, and placebo-controlled clinical trials using standardized Moringa extracts characterized by their AI-predicted markers of activity. Such trials will need to include strong biomarker endpoints, such as neuroimaging techniques and fluid-based Aβ- or tau-specific markers, to independently measure target engagement and disease modification in preclinical or early Alzheimer’s populations (Jack Jr, Bennett et al. 2018, Del Prete, Beatino et al. 2020, Cummings, Zhou et al. 2023). With the merger of phytochemistry and AI, and with a focus on rigorous clinical validation, Moringa oleifera is poised to become a traditional remedy for a next-generation evidence-based neurotherapeutic (Shukla, Potharaju et al., Mukherjee 2022, KADİROĞLU 2023). Current Challenges and Limitations While the preclinical data detailing the neuroprotective effects of Moringa oleifera are impressive, several key challenges must be overcome to capitalize on these findings and turn promise into a proven clinical therapy (Camilleri and Blundell 2024, Zamani, Jam et al. 2025). The path from traditional use and laboratory discoveries to a standardized, evidence-based medicine is strewn with significant pharmacological and clinical challenges. Bioavailability and Pharmacokinetics One of the significant stumbling blocks a the clinical efficacy of M. oleifera is the low bioavailability of its critical bioactive compounds. Among some of the most potent phytochemicals present in Moringa, Quercetin and other flavonoids have a low aqueous solubility, poor intestinal absorption, and high pre-systemic metabolism (Manach, Scalbert et al. 2004, D’Archivio, Filesi et al. 2010, Figueira, Menezes et al. 2017). They are metabolized very quickly by phase I and phase II enzymes (i.e., glucuronidation and sulfation) in the gut and liver, which largely prevents their systemic circulation and eventual delivery to the brain (Scalbert, Morand et al. 2002, Lambert, Hong et al. 2004). The blood-brain barrier (BBB) penetration capability of these compounds or their metabolites into the brain at therapeutic concentrations is poorly defined (Youdim, Dobbie et al. 2003, Faria, Mateus et al. 2012). Although some compounds, including gallic acid and chlorogenic acid, have been shown to cross the BBB (Mikami and Yamazawa 2015). The bioavailability profile generally indicates that levels reaching the CNS may be sub-therapeutic without highly sophisticated formulation strategies (OC, if not an abbreviation of ”advanced delivery systems”). This PK limitation questions the extent to which in vitro effects can be recapitulated in vivo after oral dosing. Lack of Standardization and Clinical Evidence The field is currently limited by a lack of standardization and a gap in human clinical data. The phytochemical profile of M. oleifera has been reported as highly heterogeneous, depending on various factors, including geographical area, soil conditions, climate, and season of collection, as well as the part used (leaf or seed) (Leone, Spada et al. 2015). This variation complicates comparisons of results with those obtained in other studies, and the reproducibility of findings may be called into question (Heinrich, Lardos et al. 2018). There are numerous animal models, but a dearth of high-quality, randomized, double-masked, placebo-controlled clinical trials for these antioxidants in humans with either MCI or AD (Stohs and Hartman 2015, Heinrich, Lardos et al. 2018, Cummings, Zhou et al. 2023). The human studies that have already been conducted on Moringa are primarily concerned with its nutritional or metabolic aspects (e.g., in diabetes). At the same time, its cognitive effects are described informally or as secondary outcomes without a formal neuropsychological test battery (Gopalakrishnan, Doriya et al. 2016). It can’t be sufficiently tested in humans without those trials to prove how well it works and the right dose to use. Safety and Potential Drug-Herb Interactions While these extracts are generally considered safe when consumed as food, a potential for unknown toxicity exists in concentrated products used for medicinal purposes. Toxicity: Most toxicological investigations of M. oleifera leaf extracts describe a wide margin of safety, with no adverse effects reported at moderate doses in acute and sub-acute studies (Stohs and Hartman 2015). Nevertheless, the extracts from root and bark are to be used with caution because they might contain particular alkaloids (e.g., moringinine) and have uterotrophic effects (Caceres, Cabrera et al. 1991, Fahey 2005). The possibility of interaction between Moringa and standard AD drugs is a crucial point (Meireles, Gomes et al. 2020, Pareek, Pant et al. 2023). This inhibitory effect on CYP3A4 and other P450 enzymes can at least modify the metabolism of such drugs, since donepezil use is accompanied by CYP3A4 alkylation (Stohs and Hartman 2015). Additionally, due to its reported hypoglycemic and hypotensive effects, concomitant use with antidiabetic or antihypertensive drugs might enhance the action of such medications, requiring close monitoring (Vergara-Jimenez, Almatrafi et al. 2017). And the absence of well-performed interaction studies means that these risks are not yet fully quantified. Table 1 . Neuroprotective Mechanisms of Moringa oleifera and its Bioactive Compounds in Alzheimer’s Disease Antioxidant Defense Direct free radical scavenging. Upregulation of endogenous antioxidants (SOD, Catalase, Glutathione). Activation of the Nrf2/ARE signaling pathway. Flavonoids (Quercetin, Kaempferol), Phenolic acids (Gallic acid), Isothiocyanates. (Vongsak, Sithisarn et al. 2013, Fahey, Olson et al. 2018) Anti-neuroinflammatory Effects Suppression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Inhibition of microglial activation. Downregulation of the NF-κB signaling pathway. Flavonoids, Isothiocyanates. (Cheenpracha, Park et al. 2010, Galuppo, Giacoppo et al. 2014) Anti-Amyloidogenic Activity Inhibition of BACE1 (β-secretase) activity. Reduction of Aβ peptide production. Inhibition of Aβ aggregation and fibril formation. Quercetin, Gallic acid, other phenolic compounds. (Ansari, Abdul et al. 2009, Mahaman, Feng et al. 2022) Cholinergic Enhancement Inhibition of Acetylcholinesterase (AChE) activity. Increased synaptic Acetylcholine (ACh) levels. Improved cholinergic transmission. Alkaloids, Flavonoids. (Bakre, Aderibigbe et al. 2013, Igado and Olopade 2016) Anti-Tau & Microtubule Stabilization Inhibition of GSK-3β kinase. Reduction of Tau protein hyperphosphorylation. Prevention of Neurofibrillary Tangle (NFT) formation. Quercetin, Gallic acid. (Bhullar and Rupasinghe 2013, Mansouri, Naghizadeh et al. 2013) Mitochondrial Protection & Anti-Apoptosis Improved mitochondrial membrane potential and function. Upregulation of anti-apoptotic Bcl-2 protein. Downregulation of pro-apoptotic Bax and Caspase-3. Flavonoids, Phenolic acids. (Ahmed, Rabbee et al. 2021, Ghimire, Subedi et al. 2021, Khan, Joshi et al. 2023) Future Perspectives and Conclusion The pre-clinical studies on Moringa oleifera are encouraging and warrant transition to clinical trials. Additional research should also be devoted to overcoming its major drawback, which is the poor bioavailability of its active components. This could be due to the use of new formulation approaches, such as encapsulation systems (nanoencapsulation systems, phospholipid complexes), which increase bioavailability and stability and reduce rapid metabolization and BBB passage. Furthermore, more standardized and well-characterized preparations of the drugs are required to ensure reproducibility of results, rather than crude extracts, which vary in composition. The logical next translation step involves stringent, biomarker-driven studies in the clinic. Finally, such trials should not be limited to cognitive endpoints, but include the use of neuroimaging and fluid biomarkers for objective assessment of the impact of Moringa on classic AD pathologic processes, including cerebral Aβ deposition, accumulation of tau tangles, and neuroinflammation in the human brain. Future long-term studies are necessary to obtain additional data on its safety/ies and drug-herb interactions with standard AD drugs. Collectively, the associated mechanistic insights suggest that Moringa oleifera is no longer a symptomatic remedy but may serve as a potential attractive multi-target therapeutic. Its unique phytochemical group acts in a same manner against several pathological pathways of Alzheimer’s disease, such as oxidative damage reduction, neuroinflammation attenuation, acetylcholinesterase inhibition, control of amyloid-beta production, and tau-hyperphosphorylation. This pleiotropic effect is a clear advantage over single-target drugs. Despite obstacles, there is a significant amount of preclinical evidence that firmly places the Moringa yerba´s perceived role in the fight against this disease as an adjuvant, preventive, or even as a disease-modifying strategy. This miracle tree that has been revered for so long may become an important evidence-based weapon in the fight against Alzheimer’s when approached collectively and through translational science. References Abbas, K., M. Mustafa, M. Alam, S. Habib, W. Ahmad, M. Adnan, M. I. Hassan and N. Usmani (2025). ”Multi-target approach to Alzheimer’s disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid-modulating mechanisms.” Neurogenetics 26 (1): 1-20.Adebayo, O. G., I. Wopara, W. Aduema, O. T. Ebo and E. B. Umoren (2021). ”Long-term consumption of Moringa oleifera-supplemented diet enhanced neurocognition, suppressed oxidative stress, acetylcholinesterase activity and neuronal degeneration in rat’s hippocampus.” Drug metabolism and personalized therapy 36 (3): 223-231.Adhikary, M., K. Mukhopadhyay and B. Sarkar (2021). ”Flavonoid‐rich wheatgrass (Triticum aestivum L.) diet attenuates diabetes by modulating antioxidant genes in streptozotocin‐induced diabetic rats.” Journal of Food Biochemistry 45 (4): e13643.Ahmed, S. R., M. F. Rabbee, A. Roy, R. Chowdhury, A. Banik, K. Kubra, M. M. Hassan Chowdhury and K.-H. Baek (2021). ”Therapeutic promises of medicinal plants in Bangladesh and their bioactive compounds against ulcers and inflammatory diseases.” Plants 10 (7): 1348.Akhtar, M. J., U. Dhanalekshmi, T. Alam, M. S. Akhtar and S. A. Khan (2024). Phytochemistry and Neuroprotective Spectrum of a Medicinal Food Product: Crocus sativus Linn. Plants as Medicine and Aromatics, CRC Press : 118-167.Aktary, N., Y. Jeong, S. Oh, Y. Shin, Y. Sung, M. Rahman, L. Ramos Santiago, J. Choi, H. G. Song and F. Nurkolis (2025). ”Unveiling the therapeutic potential of natural products in Alzheimer’s disease: insights from in vitro, in vivo, and clinical studies.” Frontiers in Pharmacology 16 : 1601712.Al-Malki, A. L. and H. A. El Rabey (2015). ”The antidiabetic effect of low doses of Moringa oleifera Lam. seeds on streptozotocin induced diabetes and diabetic nephropathy in male rats.” BioMed research international 2015 (1): 381040.Alhakmani, F., S. Kumar and S. A. Khan (2013). ”Estimation of total phenolic content, in–vitro antioxidant and anti–inflammatory activity of flowers of Moringa oleifera.” Asian Pacific journal of tropical biomedicine 3 (8): 623-627.Ansari, M. A., H. M. Abdul, G. Joshi, W. O. Opii and D. A. Butterfield (2009). ”Protective effect of quercetin in primary neurons against Aβ (1–42): relevance to Alzheimer’s disease.” The Journal of nutritional biochemistry 20 (4): 269-275.Anschuetz, A., K. Schwab, C. R. Harrington, C. M. Wischik and G. Riedel (2025). ”Proteomic and non-proteomic changes of presynaptic proteins in animal models of Alzheimer’s disease: A meta-analysis 2015–2023.” Journal of Alzheimer’s Disease 107 (2): 452-476.Anwar, F. and M. Bhanger (2003). ”Analytical characterization of Moringa oleifera seed oil grown in temperate regions of Pakistan.” Journal of Agricultural and food Chemistry 51 (22): 6558-6563.Anwar, F., S. Latif, M. Ashraf and A. H. Gilani (2007). ”Moringa oleifera: a food plant with multiple medicinal uses.” Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives 21 (1): 17-25.Aswani, S., A. Lemahieu and W. H. Sauer (2018). ”Global trends of local ecological knowledge and future implications.” PloS one 13 (4): e0195440.Atanasov, A. G., B. Waltenberger, E.-M. Pferschy-Wenzig, T. Linder, C. Wawrosch, P. Uhrin, V. Temml, L. Wang, S. Schwaiger and E. H. Heiss (2015). ”Discovery and resupply of pharmacologically active plant-derived natural products: A review.” Biotechnology advances 33 (8): 1582-1614.Ausina, P., D. Da Silva, D. Majerowicz, P. Zancan and M. Sola-Penna (2018). ”Insulin specifically regulates expression of liver and muscle phosphofructokinase isoforms.” Biomedicine & Pharmacotherapy 103 : 228-233.Azlan, U. K., N. A. Khairul Annuar, A. Mediani, W. M. Aizat, H. A. Damanhuri, X. Tong, D. Yanagisawa, I. Tooyama, W. Z. Wan Ngah and I. Jantan (2023). ”An insight into the neuroprotective and anti-neuroinflammatory effects and mechanisms of Moringa oleifera.” Frontiers in Pharmacology 13 : 1035220.Bakre, A. G., A. O. Aderibigbe and O. G. Ademowo (2013). ”Studies on neuropharmacological profile of ethanol extract of Moringa oleifera leaves in mice.” Journal of ethnopharmacology 149 (3): 783-789.Balit, T., C. Thonabulsombat and P. Dharmasaroja (2024). ”Moringa oleifera leaf extract suppresses TIMM23 and NDUFS3 expression and alleviates oxidative stress induced by Aβ1-42 in neuronal cells via activation of Akt.” Research in Pharmaceutical Sciences 19 (1): 105-120.Batsch, N. and M. Mittelman (2012). Alzheimer’s Disease International: World Alzheimer Report, The International Federation of Alzheimer’s Disease and Related Disorders ….Bellanti, F., A. R. D. Coda, M. I. Trecca, A. Lo Buglio, G. Serviddio and G. Vendemiale (2025). ”Redox imbalance in inflammation: the interplay of oxidative and reductive stress.” Antioxidants 14 (6): 656.Bhadoriya, S. S., V. Mishra, S. Raut, A. Ganeshpurkar and S. K. Jain (2012). ”Anti-inflammatory and antinociceptive activities of a hydroethanolic extract of Tamarindus indica leaves.” Scientia pharmaceutica 80 (3): 685.Bhullar, K. S. and H. V. Rupasinghe (2013). ”Polyphenols: multipotent therapeutic agents in neurodegenerative diseases.” Oxidative medicine and cellular longevity 2013 (1): 891748.Birks, J. S., C. Dementia and C. I. Group (1996). ”Cholinesterase inhibitors for Alzheimer’s disease.” Cochrane database of systematic reviews 2016 (3).Biswkarma, V. K. and S. Wadhawan (2025). ”Phytoconstituents Ameliorates Alzheimer’s Disease and Cognitive Impairments: A Review of Preclinical Studies.” Current Bioactive Compounds 21 (5): E140624231042.Bopape, M., C. Tiloke and C. Ntsapi (2023). ”Moringa oleifera and autophagy: evidence from in vitro studies on chaperone-mediated autophagy in HepG2 cancer cells.” Nutrition and Cancer 75 (10): 1822-1847.Butterfield, D. A. and B. Halliwell (2019). ”Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease.” Nature Reviews Neuroscience 20 (3): 148-160.Cacabelos, R., O. Martínez-Iglesias, N. Cacabelos, I. Carrera, L. Corzo and V. Naidoo (2024). ”Therapeutic options in Alzheimer’s disease: from classic acetylcholinesterase inhibitors to multi-target drugs with pleiotropic activity.” Life 14 (12): 1555.Caceres, A., O. Cabrera, O. Morales, P. Mollinedo and P. Mendia (1991). ”Pharmacological properties of Moringa oleifera. 1: Preliminary screening for antimicrobial activity.” Journal of ethnopharmacology 33 (3): 213-216.Camilleri, E. and R. Blundell (2024). ”A comprehensive review of the phytochemicals, health benefits, pharmacological safety and medicinal prospects of Moringa oleifera.” Heliyon 10 (6).Cheenpracha, S., E.-J. Park, W. Y. Yoshida, C. Barit, M. Wall, J. M. Pezzuto and L. C. Chang (2010). ”Potential anti-inflammatory phenolic glycosides from the medicinal plant Moringa oleifera fruits.” Bioorganic & medicinal chemistry 18 (17): 6598-6602.Chen, A. Y. and Y. C. Chen (2013). ”A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention.” Food chemistry 138 (4): 2099-2107.Chen, B., J. Zhao, R. Zhang, L. Zhang, Q. Zhang, H. Yang and J. An (2022). ”Neuroprotective effects of natural compounds on neurotoxin-induced oxidative stress and cell apoptosis.” Nutritional neuroscience 25 (5): 1078-1099.Chen, H., O. Engkvist, Y. Wang, M. Olivecrona and T. Blaschke (2018). ”The rise of deep learning in drug discovery.” Drug discovery today 23 (6): 1241-1250.Chen, R., G. I. Mias, J. Li-Pook-Than, L. Jiang, H. Y. Lam, R. Chen, E. Miriami, K. J. Karczewski, M. Hariharan and F. E. Dewey (2012). ”Personal omics profiling reveals dynamic molecular and medical phenotypes.” Cell 148 (6): 1293-1307.Chen, S.-Y., Y. Gao, J.-Y. Sun, X.-L. Meng, D. Yang, L.-H. Fan, L. Xiang and P. Wang (2020). ”Traditional Chinese medicine: role in reducing β-amyloid, apoptosis, autophagy, neuroinflammation, oxidative stress, and mitochondrial dysfunction of Alzheimer’s disease.” Frontiers in Pharmacology 11 : 497.Chen, Z., Y. Lu, Y. Wang, Q. Wang, L. Yu and J. Liu (2025). ”Natural Products Targeting Tau Protein Phosphorylation: A Promising Therapeutic Avenue for Alzheimerʼs Disease.” Planta Medica.Chhikara, N., A. Kaur, S. Mann, M. Garg, S. A. Sofi and A. Panghal (2021). ”Bioactive compounds, associated health benefits and safety considerations of Moringa oleifera L.: An updated review.” Nutrition & Food Science 51 (2): 255-277.Christodoulou, M.-I., C. K Kontos, M. Halabalaki, A.-L. Skaltsounis and A. Scorilas (2014). ”Nature promises new anticancer agents: Interplay with the apoptosis-related BCL2 gene family.” Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 14 (3): 375-399.Coz-Bolaños, X., R. Campos-Vega, R. Reynoso-Camacho, M. Ramos-Gómez, G. F. Loarca-Piña and S. Guzmán-Maldonado (2018). ”Moringa infusion (Moringa oleifera) rich in phenolic compounds and high antioxidant capacity attenuate nitric oxide pro-inflammatory mediator in vitro.” Industrial Crops and Products 118 : 95-101.Cummings, J., Y. Zhou, G. Lee, K. Zhong, J. Fonseca and F. Cheng (2023). ”Alzheimer’s disease drug development pipeline: 2023.” Alzheimer’s & Dementia: Translational Research & Clinical Interventions 9 (2): e12385.D’Archivio, M., C. Filesi, R. Varì, B. Scazzocchio and R. Masella (2010). ”Bioavailability of the polyphenols: status and controversies.” International journal of molecular sciences 11 (4): 1321-1342.Dailah, H. G. (2022). ”Potential of therapeutic small molecules in apoptosis regulation in the treatment of neurodegenerative diseases: An updated review.” Molecules 27 (21): 7207.Dartigues, J. F. (2009). ”Alzheimer’s disease: a global challenge for the 21st century.” The Lancet Neurology 8 (12): 1082-1083.Das, S. K., R. Acharya and K. Sen (2022). ”Phytosomes: a cutting-edge technique for herbal drug delivery and its clinical applications.”Del Prete, E., M. F. Beatino, N. Campese, L. Giampietri, G. Siciliano, R. Ceravolo and F. Baldacci (2020). ”Fluid candidate biomarkers for Alzheimer’s disease: A precision medicine approach.” Journal of Personalized Medicine 10 (4): 221.Djiogue, S., K. Youmbi, E. Seke, K. Kandeda, G. Zemo, T. Motoum, R. Tadah and N. Dieudonne (2022). ”Neuroprotective Effects of the Aqueous Extract of Leaves of Moringa oleifera (Moringaceae) in Scopolamine-Treated Rats.” BioMed 14 : 486.Ekins, S., A. C. Puhl, K. M. Zorn, T. R. Lane, D. P. Russo, J. J. Klein, A. J. Hickey and A. M. Clark (2019). ”Exploiting machine learning for end-to-end drug discovery and development.” Nature materials 18 (5): 435-441.Ercan, K., O. F. Gecesefa, M. E. Taysi, O. A. Ali Ali and S. Taysi (2021). ”Moringa oleifera: a review of its occurrence, pharmacological importance and oxidative stress.” Mini Reviews in Medicinal Chemistry 21 (3): 380-396.Fahey, J. W. (2005). ”Moringa oleifera: a review of the medical evidence for its nutritional, therapeutic, and prophylactic properties. Part 1.” Trees for life Journal 1 (5): 1-15.Fahey, J. W., M. E. Olson, K. K. Stephenson, K. L. Wade, G. M. Chodur, D. Odee, W. Nouman, M. Massiah, J. Alt and P. A. Egner (2018). ”The diversity of chemoprotective glucosinolates in Moringaceae (Moringa spp.).” Scientific reports 8 (1): 7994.Fakurazi, S., S. A. Sharifudin and P. Arulselvan (2012). ”Moringa oleifera hydroethanolic extracts effectively alleviate acetaminophen-induced hepatotoxicity in experimental rats through their antioxidant nature.” Molecules 17 (7): 8334-8350.Faria, A., N. Mateus and C. Calhau (2012). ”Flavonoid transport across blood-brain barrier: Implication for their direct neuroprotective actions.” Nutrition and Aging 1 (2): 89-97.Figueira, I., R. Menezes, D. Macedo, I. Costa and C. Nunes dos Santos (2017). ”Polyphenols beyond barriers: a glimpse into the brain.” Current neuropharmacology 15 (4): 562-594.Fond, G., J.-A. Micoulaud-Franchi, L. Brunel, A. Macgregor, S. Miot, R. Lopez, R. Richieri, M. Abbar, C. Lancon and D. Repantis (2015). ”Innovative mechanisms of action for pharmaceutical cognitive enhancement: a systematic review.” Psychiatry research 229 (1-2): 12-20.Galuppo, M., S. Giacoppo, G. R. De Nicola, R. Iori, M. Navarra, G. E. Lombardo, P. Bramanti and E. Mazzon (2014). ”Antiinflammatory activity of glucomoringin isothiocyanate in a mouse model of experimental autoimmune encephalomyelitis.” Fitoterapia 95 : 160-174.Ghimire, S., L. Subedi, N. Acharya and B. P. Gaire (2021). ”Moringa oleifera: A tree of life as a promising medicinal plant for neurodegenerative diseases.” Journal of agricultural and food chemistry 69 (48): 14358-14371.Giacobini, E., A. C. Cuello and A. Fisher (2022). ”Reimagining cholinergic therapy for Alzheimer’s disease.” Brain 145 (7): 2250-2275.Goel, F. (2025). ”Exploring the therapeutic role of Moringa oleifera in neurodegeneration: antioxidant, anti-inflammatory, and neuroprotective mechanisms: Exploring the therapeutic role of Moringa oleifera in neurodegeneration.” Inflammopharmacology: 1-17.Gong, C.-X., F. Liu and K. Iqbal (2018). ”Multifactorial hypothesis and multi-targets for Alzheimer’s disease.” Journal of Alzheimer’s Disease 64 (s1): S107-S117.Gopalakrishnan, L., K. Doriya and D. S. Kumar (2016). ”Moringa oleifera: A review on nutritive importance and its medicinal application.” Food science and human wellness 5 (2): 49-56.Guha, S., G. V. Johnson and K. Nehrke (2020). ”The crosstalk between pathological tau phosphorylation and mitochondrial dysfunction as a key to understanding and treating Alzheimer’s disease.” Molecular neurobiology 57 (12): 5103-5120.Gustavsson, A., N. Norton, T. Fast, L. Frölich, J. Georges, D. Holzapfel, T. Kirabali, P. Krolak‐Salmon, P. M. Rossini and M. T. Ferretti (2023). ”Global estimates on the number of persons across the Alzheimer’s disease continuum.” Alzheimer’s & Dementia 19 (2): 658-670.Gyimesi, M., R. Okolicsanyi and L. Haupt (2024). ”Beyond amyloid and tau: rethinking Alzheimer’s disease through less explored avenues.” Open biology 14 (6): 240035.Hampel, H., M.-M. Mesulam, A. C. Cuello, M. R. Farlow, E. Giacobini, G. T. Grossberg, A. S. Khachaturian, A. Vergallo, E. Cavedo and P. J. Snyder (2018). ”The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease.” Brain 141 (7): 1917-1933.Hardy, J. and D. J. Selkoe (2002). ”The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics.” science 297 (5580): 353-356.He, L., T. He, S. Farrar, L. Ji, T. Liu and X. Ma (2017). ”Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species.” Cellular Physiology and Biochemistry 44 (2): 532-553.He, L., H. Lv, N. Chen, C. Wang, W. Zhou, X. Chen and Q. Zhang (2020). ”Improving fermentation, protein preservation and antioxidant activity of Moringa oleifera leaves silage with gallic acid and tannin acid.” Bioresource Technology 297 : 122390.Heinrich, M., A. Lardos, M. Leonti, C. Weckerle, M. Willcox, W. Applequist, A. Ladio, C. L. Long, P. Mukherjee and G. Stafford (2018). ”Best practice in research: consensus statement on ethnopharmacological field studies–ConSEFS.” Journal of ethnopharmacology 211 : 329-339.Heneka, M. T., M. J. Carson, J. El Khoury, G. E. Landreth, F. Brosseron, D. L. Feinstein, A. H. Jacobs, T. Wyss-Coray, J. Vitorica and R. M. Ransohoff (2015). ”Neuroinflammation in Alzheimer’s disease.” The Lancet Neurology 14 (4): 388-405.Hernandez, F., J. J. Lucas and J. Avila (2012). ”GSK3 and tau: two convergence points in Alzheimer’s disease.” Journal of Alzheimer’s disease 33 (s1): S141-S144.Hirao, D. (2024). ”Moringa Oleifera and Mitochondria–A Short Literature Review.” American Journal of Medical and Clinical Research & Reviews 3 (12): 1-16.Hopkins, A. L. (2008). ”Network pharmacology: the next paradigm in drug discovery.” Nature chemical biology 4 (11): 682-690.Idoga, E. S., S. F. Ambali, J. O. Ayo and A. Mohammed (2018). ”Assessment of antioxidant and neuroprotective activities of methanol extract of Moringa oleifera Lam. leaves in subchronic chlorpyrifos-intoxicated rats.” Comparative Clinical Pathology 27 (4): 917-925.Igado, O. and J. Olopade (2016). ”A review on the possible neuroprotective effects of Moringa oleifera leaf extract.” Nigerian Journal of Physiological Sciences 31 (2): 183-187.Iqbal, K., F. Liu, C.-X. Gong and I. Grundke-Iqbal (2010). ”Tau in Alzheimer disease and related tauopathies.” Current Alzheimer Research 7 (8): 656-664.Jack Jr, C. R., D. A. Bennett, K. Blennow, M. C. Carrillo, B. Dunn, S. B. Haeberlein, D. M. Holtzman, W. Jagust, F. Jessen and J. Karlawish (2018). ”NIA‐AA research framework: toward a biological definition of Alzheimer’s disease.” Alzheimer’s & dementia 14 (4): 535-562.Jana, A., A. Bhattacharjee, S. S. Das, A. Srivastava, A. Choudhury, R. Bhattacharjee, S. De, A. Perveen, D. Iqbal and P. K. Gupta (2022). ”Molecular insights into therapeutic potentials of hybrid compounds targeting Alzheimer’s disease.” Molecular Neurobiology 59 (6): 3512-3528.Jia, J., C. Wei, S. Chen, F. Li, Y. Tang, W. Qin, L. Zhao, H. Jin, H. Xu and F. Wang (2018). ”The cost of Alzheimer’s disease in China and re‐estimation of costs worldwide.” Alzheimer’s & Dementia 14 (4): 483-491.KADİROĞLU, A. K. (2023). General Internal Medicine IV, Akademisyen Kitabevi.Kalra, J. and A. Khan (2015). ”Reducing Aβ load and tau phosphorylation: Emerging perspective for treating Alzheimer’s disease.” European journal of pharmacology 764 : 571-581.Kara, E., J. D. Marks and A. Aguzzi (2018). ”Toxic protein spread in neurodegeneration: reality versus fantasy.” Trends in molecular medicine 24 (12): 1007-1020.Kasolo, J. N., G. S. Bimenya, L. Ojok, J. Ochieng and J. W. Ogwal-Okeng (2010). ”Phytochemicals and uses of Moringa oleifera leaves in Ugandan rural communities.”Kaur, D., V. Sharma and R. Deshmukh (2019). ”Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer’s disease.” Inflammopharmacology(4): 663-677.Kensler, T. W., N. Wakabayashi and S. Biswal (2007). ”Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway.” Annu. Rev. Pharmacol. Toxicol. 47 (1): 89-116.Khan, F., A. Joshi, H. P. Devkota, V. Subramaniyan, V. Kumarasamy and J. Arora (2023). ”Dietary glucosinolates derived isothiocyanates: chemical properties, metabolism and their potential in prevention of Alzheimer’s disease.” Frontiers in Pharmacology 14 : 1214881.Khan, H., S. Amin, M. A. Kamal and S. Patel (2018). ”Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and future prospects.” Biomedicine & Pharmacotherapy 101 : 860-870.Koehn, F. E. and G. T. Carter (2005). ”The evolving role of natural products in drug discovery.” Nature reviews Drug discovery 4 (3): 206-220.Kumar, A., M. Kumar, A. Verma, R. Joshi, M. Bidlan and R. Singh (2025). ”Pathophysiology of Alzheimer’s Disease: Herbal Neurogenesis and Synthetic Molecular Interventions.” Current Behavioral Neuroscience Reports 12 (1): 17.Kumar, M. and N. Bansal (2022). ”Implications of phosphoinositide 3-kinase-Akt (PI3K-Akt) pathway in the pathogenesis of Alzheimer’s disease.” Molecular neurobiology 59 (1): 354-385.Kumar, M., S. Kaur and S. Kaur (2024). ”c-Jun N-terminal kinase (JNK), p38, and caspases: promising therapeutic targets for the regulation of apoptosis in cancer cells by phytochemicals.” Current Cancer Therapy Reviews 20 (2): 200-211.Kumar, R., S. Khatak, Vandana, A. K. Shukla, S. Panwar and A. Kumar (2025). ”Deciphering of nutritional profile, therapeutic potential, and networking of bioactive compounds of Moringa oleifera: A comprehensive review.” Food Biomacromolecules 2 (3): 271-287.Kumar, S., P. K. Verma, A. Shukla, R. K. Singh, A. K. Patel, L. Yadav, S. Kumar, N. Kumar and A. Acharya (2023). ”Moringa oleifera L. leaf extract induces cell cycle arrest and mitochondrial apoptosis in Dalton’s Lymphoma: An in vitro and in vivo study.” Journal of Ethnopharmacology 302 : 115849.Kuns, B., A. Rosani, P. Patel and D. Varghese (2024). Memantine. StatPearls [Internet], StatPearls Publishing.Lambert, J. D., J. Hong, D. H. Kim, V. M. Mishin and C. S. Yang (2004). ”Piperine enhances the bioavailability of the tea polyphenol (−)-epigallocatechin-3-gallate in mice.” The Journal of nutrition 134 (8): 1948-1952.Leng, F. and P. Edison (2021). ”Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?” Nature Reviews Neurology 17 (3): 157-172.Leone, A., A. Spada, A. Battezzati, A. Schiraldi, J. Aristil and S. Bertoli (2015). ”Cultivation, genetic, ethnopharmacology, phytochemistry and pharmacology of Moringa oleifera leaves: An overview.” International journal of molecular sciences 16 (6): 12791-12835.Li, S., T.-P. Fan, W. Jia, A. Lu and W. Zhang (2014). ”Network pharmacology in traditional Chinese medicine.” Evidence-based complementary and alternative medicine: eCAM 2014 : 138460.Liu, F., I. Grundke‐Iqbal, K. Iqbal and C. X. Gong (2005). ”Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation.” European Journal of Neuroscience 22 (8): 1942-1950.Luo, X., L. Zhou, S. Wang, J. Yuan, Z. Chang, Q. Hu, Y. Chen, Y. Liu, Y. Huang and B. Wang (2022). ”The therapeutic effect and the potential mechanism of flavonoids and phenolics of Moringa oleifera Lam. Leaves against hyperuricemia mice.” Molecules 27 (23): 8237.Mahaman, Y. A. R., J. Feng, F. Huang, M. T. M. Salissou, J. Wang, R. Liu, B. Zhang, H. Li, F. Zhu and X. Wang (2022). ”Moringa oleifera alleviates Aβ burden and improves synaptic plasticity and cognitive impairments in APP/PS1 mice.” Nutrients 14 (20): 4284.Mahaman, Y. A. R., F. Huang, M. Wu, Y. Wang, Z. Wei, J. Bao, M. T. M. Salissou, D. Ke, Q. Wang and R. Liu (2018). ”Moringa oleifera alleviates homocysteine-induced Alzheimer’s disease-like pathology and cognitive impairments.” Journal of Alzheimer’s Disease 63 (3): 1141-1159.Mairuae, N., B. Buranrat, S. Yannasithinon and P. Cheepsunthorn (2023). ”Antioxidant and anti-inflammatory effects of Aegle marmelos fruit and Moringa oleifera leaf extracts on lipopolysaccharide-stimulated BV2 microglial cells.” Tropical Journal of Pharmaceutical Research 22 (6).Manach, C., A. Scalbert, C. Morand, C. Rémésy and L. Jiménez (2004). ”Polyphenols: food sources and bioavailability.” The American journal of clinical nutrition 79 (5): 727-747.Mansouri, M. T., B. Naghizadeh, B. Ghorbanzadeh, Y. Farbood, A. Sarkaki and K. Bavarsad (2013). ”Gallic acid prevents memory deficits and oxidative stress induced by intracerebroventricular injection of streptozotocin in rats.” Pharmacology biochemistry and behavior 111 : 90-96.Martin, L., X. Latypova, C. M. Wilson, A. Magnaudeix, M.-L. Perrin and F. Terro (2013). ”Tau protein phosphatases in Alzheimer’s disease: the leading role of PP2A.” Ageing research reviews 12 (1): 39-49.Masukawa, D., S. Kitamura, R. Tajika, H. Uchimura, M. Arai, Y. Takada, T. Arisawa, M. Otaki, K. Kanai and K. Kobayashi (2023). ”Coupling between GPR143 and dopamine D2 receptor is required for selective potentiation of dopamine D2 receptor function by L‐3, 4‐dihydroxyphenylalanine in the dorsal striatum.” Journal of Neurochemistry 165 (2): 177-195.Matej, R., A. Tesar and R. Rusina (2019). ”Alzheimer’s disease and other neurodegenerative dementias in comorbidity: a clinical and neuropathological overview.” Clinical biochemistry 73 : 26-31.Mathews, J., A. J. Chang, L. Devlin and M. Levin (2023). ”Cellular signaling pathways as plastic, proto-cognitive systems: Implications for biomedicine.” Patterns 4 (5).Meireles, D., J. Gomes, L. Lopes, M. Hinzmann and J. Machado (2020). ”A review of properties, nutritional and pharmaceutical applications of Moringa oleifera: integrative approach on conventional and traditional Asian medicine.” Advances in Traditional Medicine 20 (4): 495-515.Metcalfe, M. J. and M. E. Figueiredo‐Pereira (2010). ”Relationship between tau pathology and neuroinflammation in Alzheimer’s disease.” Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine: A Journal of Translational and Personalized Medicine 77 (1): 50-58.Mikami, Y. and T. Yamazawa (2015). ”Chlorogenic acid, a polyphenol in coffee, protects neurons against glutamate neurotoxicity.” Life sciences 139 : 69-74.Mishra, G., P. Singh, R. Verma, S. Kumar, S. Srivastav, K. Jha and R. Khosa (2011). ”Traditional uses, phytochemistry and pharmacological properties of Moringa oleifera plant: An overview.” Der Pharmacia Lettre 3 (2): 141-164.Mohan, G. S. and R. Kumar (2025). ”Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer’s Disease: Mechanisms, Implications, and Potential Therapies.” Aging and Disease 16 (5): 2553.Mufson, E. J., S. E. Counts, S. E. Perez and S. D. Ginsberg (2008). ”Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications.” Expert review of neurotherapeutics 8 (11): 1703-1718.Mukherjee, P. K. (2022). Evidence-based validation of herbal medicine: translational research on botanicals, Elsevier.Nasution, M. H. F., V. P. Kalanjati, A. Abdurachman, D. M. N. Aditya, D. B. B. Pamungkas and M. R. Syamhadi (2023). ”The Effects of Methotrexate, Moringa oleiferaLeaf Extract, and Andrographis paniculata Leaf Extract on the Testes of Hyperglycemic Wistar Rat.” Tropical Journal of Natural Product Research (TJNPR) 7 (6): 3140-3146.Nicholls, D. G. and S. L. Budd (2000). ”Mitochondria and neuronal survival.” Physiological reviews 80 (1): 315-360.Nwidu, L. L., E. Elmorsy, J. S. Aprioku, I. Siminialayi and W. G. Carter (2018). ”In vitro anti-cholinesterase and antioxidant activity of extracts of Moringa oleifera plants from Rivers State, Niger Delta, Nigeria.” Medicines 5 (3): 71.Onasanwo, S. A., V. O. Adamaigbo, O. G. Adebayo and S. E. Eleazer (2021). ”Moringa oleifera-supplemented diet protect against cortico-hippocampal neuronal degeneration in scopolamine-induced spatial memory deficit in mice: role of oxido-inflammatory and cholinergic neurotransmission pathway.” Metabolic Brain Disease 36 (8): 2445-2460.Pareek, A., M. Pant, M. M. Gupta, P. Kashania, Y. Ratan, V. Jain, A. Pareek and A. A. Chuturgoon (2023). ”Moringa oleifera: An updated comprehensive review of its pharmacological activities, ethnomedicinal, phytopharmaceutical formulation, clinical, phytochemical, and toxicological aspects.” International journal of molecular sciences 24 (3): 2098.Parsa, N. (2011). ”Alzheimer’s disease: A medical challenge of 21st century.” Journal of Arak University of Medical Sciences 14 (2): 100-108.Polis, B. and A. O. Samson (2024). ”Addressing the discrepancies between animal models and human Alzheimer’s disease pathology: implications for translational research.” Journal of Alzheimer’s Disease 98 (4): 1199-1218.Rahmath, A., N. Rajan, M. A. Shahal, T. Seena and E. Sreekumaran (2015). ”Neuroprotective effect of Moringa oleifera in scopolamine induced cognitive impairment and oxidative stress in Wistar albino rats.”Rai, S. N., H. Dilnashin, H. Birla, S. S. Singh, W. Zahra, A. S. Rathore, B. K. Singh and S. P. Singh (2019). ”The role of PI3K/Akt and ERK in neurodegenerative disorders.” Neurotoxicity research 35 (3): 775-795.Rajendran, P., K. Renu, E. M. Ali, M. A. M. Genena, V. Veeraraghavan, R. Sekar, A. K. Sekar, S. Tejavat, P. Barik and B. M. Abdallah (2024). ”Promising and challenging phytochemicals targeting LC3 mediated autophagy signaling in cancer therapy.” Immunity, Inflammation and Disease 12 (10): e70041.Rose, J., C. Brian, J. Woods, A. Pappa, M. I. Panayiotidis, R. Powers and R. Franco (2017). ”Mitochondrial dysfunction in glial cells: Implications for neuronal homeostasis and survival.” Toxicology 391 : 109-115.Sadigh-Eteghad, S., B. Sabermarouf, A. Majdi, M. Talebi, M. Farhoudi and J. Mahmoudi (2015). ”Amyloid-beta: a crucial factor in Alzheimer’s disease.” Medical principles and practice 24 (1): 1-10.Saini, R. K., I. Sivanesan and Y.-S. Keum (2016). ”Phytochemicals of Moringa oleifera: a review of their nutritional, therapeutic and industrial significance.” 3 Biotech 6 (2): 203.Saleem, A., M. Saleem and M. F. Akhtar (2020). ”Antioxidant, anti-inflammatory and antiarthritic potential of Moringa oleifera Lam: An ethnomedicinal plant of Moringaceae family.” South African Journal of Botany 128 : 246-256.Santos, B. O. (2021). ”Perfil químico do pericarpo de pequi (Caryocar brasiliense Camb.) in natura e na forma de farinha e o efeito da digestibilidade in vitro na bioacessibilidade dos compostos fenólicos.”Sarkar, B., N. Rana, C. Singh and A. Singh (2024). ”Medicinal herbal remedies in neurodegenerative diseases: an update on antioxidant potential.” Naunyn-Schmiedeberg’s Archives of Pharmacology 397 (8): 5483-5511.Scalbert, A., C. Morand, C. Manach and C. Rémésy (2002). ”Absorption and metabolism of polyphenols in the gut and impact on health.” Biomedicine & Pharmacotherapy 56 (6): 276-282.Scheltens, P., B. De Strooper, M. Kivipelto, H. Holstege, G. Chételat, C. E. Teunissen, J. Cummings and W. M. van der Flier (2021). ”Alzheimer’s disease.” The Lancet 397 (10284): 1577-1590.Senthilkumar, A., N. Karuvantevida, L. Rastrelli, S. S. Kurup and A. J. Cheruth (2018). ”Traditional uses, pharmacological efficacy, and phytochemistry of Moringa peregrina (Forssk.) Fiori.—a review.” Frontiers in pharmacology 9 : 465.Shabbir, M. A., M. Naveed, M. Manzoor, H. M. Hurraira and F. Zaidi (2024). Therapeutic Application of Natural Products in Alzheimer’s Disease Using Computational Methods. Computational and Experimental Studies in Alzheimer’s Disease, CRC Press : 138-154.Shah, K. H. and M. J. Oza (2022). ”Comprehensive review of bioactive and molecular aspects of Moringa Oleifera lam.” Food Reviews International 38 (7): 1427-1460.Shahanenko, R., K. Lukianenko, O. Yeroshenko, N. Kozii, V. Shahanenko, A. Antipov, V. Goncharenko and V. Koziy (2025). ”Pharmacological correction of cognitive dysfunctions in animals.” Regulatory Mechanisms in Biosystems 16 (3): e25119-e25119.Sharifi-Rad, J., S. Rapposelli, S. Sestito, J. Herrera-Bravo, A. Arancibia-Diaz, L. A. Salazar, B. Yeskaliyeva, A. Beyatli, G. Leyva-Gómez and C. González-Contreras (2022). ”Multi-target mechanisms of phytochemicals in Alzheimer’s disease: Effects on oxidative stress, neuroinflammation and protein aggregation.” Journal of Personalized Medicine 12 (9): 1515.Shenoy, T. N. and A. A. Abdul Salam (2025). ”Therapeutic potential of dietary bioactive compounds against anti-apoptotic Bcl-2 proteins in breast cancer.” Critical Reviews in Food Science and Nutrition 65 (25): 4915-4940.Shoaib, S., M. A. Ansari, A. A. Fatease, A. Y. Safhi, U. Hani, R. Jahan, M. N. Alomary, M. N. Ansari, N. Ahmed and S. Wahab (2023). ”Plant-derived bioactive compounds in the management of neurodegenerative disorders: challenges, future directions and molecular mechanisms involved in neuroprotection.” Pharmaceutics 15 (3): 749.Shukla, C. P., R. Potharaju, V. Nikam and M. H. Khodade ”Botanical Insights: From Traditional Knowledge to Modern Science.”Siddhuraju, P. and K. Becker (2003). ”Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves.” Journal of agricultural and food chemistry 51 (8): 2144-2155.Silva Ferreira Da Costa, T. and F. Barri (2018). ”Lama guanicoe remains from the Chaco ecoregion (Córdoba, Argentina): An osteological approach to the characterization of a relict wild population.”Singh, D. K., B. Kumar, S. Sinha and K. Fatima (2024). ”Phytochemicals for the Improvement of Cognitive Function through Cholinergic Anti-inflammatory Pathway.” Current Indian Science: e2210299X2309791.Singh, R. G., P. S. Negi and C. Radha (2013). ”Phenolic composition, antioxidant and antimicrobial activities of free and bound phenolic extracts of Moringa oleifera seed flour.” Journal of functional foods 5 (4): 1883-1891.Singh, V., A. Kumar, P. Sood, H. Singh, G. Singh, L. Kaur, S. Kaur, G. Kaur, G. Singh and B. Singh (2025). Anti-Apoptotic Natural Products for the Management of Alzheimer’s Disease. Neuro-Nutraceuticals and Drug Discovery and Delivery in Alzheimer’s Disease, Apple Academic Press : 111-151.Sivaprakasam, G., P. Ganesan, K. Muniandy, S.-Y. Park, D.-Y. Cho, J.-S. Kim, P. Arulselvan and D.-K. Choi (2019). ”Attenuation of lipopolysaccharide-induced neuroinflammatory events in BV-2 microglial cells by Moringa oleifera leaf extract.” Asian Pacific Journal of Tropical Biomedicine 9 (3): 109-115.Sontag, J.-M. and E. Sontag (2014). ”Protein phosphatase 2A dysfunction in Alzheimer’s disease.” Frontiers in molecular neuroscience 7 : 16.Sreelatha, S. and P. Padma (2009). ”Antioxidant activity and total phenolic content of Moringa oleifera leaves in two stages of maturity.” Plant foods for human nutrition 64 (4): 303-311.Sreelatha, S. and P. Padma (2011). ”Modulatory effects of Moringa oleifera extracts against hydrogen peroxide-induced cytotoxicity and oxidative damage.” Human & experimental toxicology 30 (9): 1359-1368.Stohs, S. J. and M. J. Hartman (2015). ”Review of the safety and efficacy of Moringa oleifera.” Phytotherapy Research 29 (6): 796-804.Sutalangka, C., J. Wattanathorn, S. Muchimapura and W. Thukham-mee (2013). ”Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age‐related dementia.” Oxidative medicine and cellular longevity 2013 (1): 695936.Swerdlow, R. H., J. M. Burns and S. M. Khan (2014). ”The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives.” Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1842 (8): 1219-1231.Tsuchiya, H. (2015). ”Membrane interactions of phytochemicals as their molecular mechanism applicable to the discovery of drug leads from plants.” Molecules 20 (10): 18923-18966.Vamathevan, J., D. Clark, P. Czodrowski, I. Dunham, E. Ferran, G. Lee, B. Li, A. Madabhushi, P. Shah and M. Spitzer (2019). ”Applications of machine learning in drug discovery and development.” Nature reviews Drug discovery 18 (6): 463-477.Van Bokhoven, P., A. de Wilde, L. Vermunt, P. S. Leferink, S. Heetveld, J. Cummings, P. Scheltens and E. G. Vijverberg (2021). ”The Alzheimer’s disease drug development landscape.” Alzheimer’s Research & Therapy 13 (1): 186.Vergara-Jimenez, M., M. M. Almatrafi and M. L. Fernandez (2017). ”Bioactive components in Moringa oleifera leaves protect against chronic disease.” Antioxidants 6 (4): 91.Villegas-Vazquez, E. Y., R. Gómez-Cansino, G. Marcelino-Pérez, D. Jiménez-López and L. I. Quintas-Granados (2025). ”Unveiling the miracle tree: therapeutic potential of Moringa oleifera in chronic disease management and beyond.” Biomedicines 13 (3): 634.Vongsak, B., P. Sithisarn, S. Mangmool, S. Thongpraditchote, Y. Wongkrajang and W. Gritsanapan (2013). ”Maximizing total phenolics, total flavonoids contents and antioxidant activity of Moringa oleifera leaf extract by the appropriate extraction method.” Industrial crops and products 44 : 566-571.Walczak-Nowicka, Ł. J. and M. Herbet (2021). ”Acetylcholinesterase inhibitors in the treatment of neurodegenerative diseases and the role of acetylcholinesterase in their pathogenesis.” International journal of molecular sciences 22 (17): 9290.Walker, L. C. (2020). ”Aβ plaques.” Free neuropathology 1 : 31.Wang, J.-Z., Y.-Y. Xia, I. Grundke-Iqbal and K. Iqbal (2012). ”Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration.” Journal of Alzheimer’s Disease 33 (s1): S123-S139.Waterman, C., D. M. Cheng, P. Rojas-Silva, A. Poulev, J. Dreifus, M. A. Lila and I. Raskin (2014). ”Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro.” Phytochemistry 103 : 114-122.Wei, Z., L. Huang, L. Cui and X. Zhu (2020). ”Mannose: Good player and assister in pharmacotherapy.” Biomedicine & Pharmacotherapy 129 : 110420.Wen, Y., Y. Liu, Q. Huang, R. Liu, J. Liu, F. Zhang, S. Liu and Y. Jiang (2022). ”Moringa oleifera Lam. seed extract protects kidney function in rats with diabetic nephropathy by increasing GSK-3β activity and activating the Nrf2/HO-1 pathway.” Phytomedicine 95 : 153856.Worku, B. and N. Tolossa (2024). ”A Review on the Neuroprotective Effect of Moringa oleifera.” Oxidative medicine and cellular longevity 2024 (1): 7694516.Xu, C., C. Jiang, X. Liu, W. Shi, J. Bai, S. Mubarik and F. Wang (2025). ”Epidemiological and sociodemographic transitions in the global burden and risk factors for Alzheimer’s disease and other dementias: a secondary analysis of GBD 2021.” International journal for equity in health 24 (1): 149.Yang, Z., J. Liu, S. Wei, J. Deng, X. Feng, S. Liu and M. Liu (2023). ”A novel strategy for bioactive natural products targeting NLRP3 inflammasome in Alzheimer’s disease.” Frontiers in Pharmacology 13 : 1077222.Yang, Z. and L. Wang (2023). ”Current, emerging, and potential therapies for non-alcoholic steatohepatitis.” Frontiers in Pharmacology 14 : 1152042.Yiannopoulou, K. G. and S. G. Papageorgiou (2013). ”Current and future treatments for Alzheimer’s disease.” Therapeutic advances in neurological disorders 6 (1): 19-33.Youdim, K. A., M. S. Dobbie, G. Kuhnle, A. R. Proteggente, N. J. Abbott and C. Rice‐Evans (2003). ”Interaction between flavonoids and the blood–brain barrier: in vitro studies.” Journal of neurochemistry 85 (1): 180-192.Zamani, N. I. S. M., F. A. Jam, L. J. Yi, C. W. Yi, T. Rajendran, P. W. Wong, A. T. Y. Ying, U. K. Azlan, H. S. Hamezah and A. Mediani (2025). ”Advancing Alzheimer’s Therapy with Moringa oleifera: Bioactive Insights, Mechanistic Pathways, and Strategies for Efficacy and Standardization.” The Open Medicinal Chemistry Journal 19 (1).Zeng, L., D. Zhang, Q. Liu, J. Zhang, K. Mu, X. Gao, K. Zhang, H. Li, Q. Wang and Y. Zheng (2021). ”Alpha-asarone improves cognitive function of APP/PS1 mice and reducing Aβ42, P-tau and neuroinflammation, and promoting neuron survival in the hippocampus.” Neuroscience 458 : 141-152.Zhang, R., X. Zhu, H. Bai and K. Ning (2019). ”Network pharmacology databases for traditional Chinese medicine: review and assessment.” Frontiers in pharmacology 10 : 123.Zhang, W., Y. Huai, Z. Miao, A. Qian and Y. Wang (2019). ”Systems pharmacology for investigation of the mechanisms of action of traditional Chinese medicine in drug discovery.” Frontiers in pharmacology 10 : 743.Zhou, M.-L. and K. Huang (2025). ”Modulating Neural Pathways: Moringa oleifera Oil’s Role in Neuroprotection Beyond Nutritional Support.” Frontline Medical Sciences and Pharmaceutical Journal 5 (07): 1-7.Zhou, M., G. Fu, W. Yu, S. Wang and S. Cheng ”Natural Glycosides as Multi-Target Neuroprotective Agents in Alzheimer’s Disease: Bridging Mechanistic Insights and Translational Potential.” Gangying and Yu, Wengjing and Wang, Shanshan and Cheng, Shaowu and song, zhenyan, Natural Glycosides as Multi-Target Neuroprotective Agents in Alzheimer’s Disease: Bridging Mechanistic Insights and Translational Potential. Information & Authors Information Version history V1 Version 1 02 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords alzheimer's alzheimer's disease animal model amyloid precursor protein animal models of depression Authors Affiliations Hui Yu Shandong Xiehe University View all articles by this author Adeel Ahmed Abbasi Shandong First Medical University View all articles by this author Hamid Khan Shandong First Medical University View all articles by this author Hengji Hu Shandong Xiehe University View all articles by this author Peiyuan Lu 0000-0001-8163-415X [email protected] Shandong Xiehe University View all articles by this author Metrics & Citations Metrics Article Usage 819 views 198 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Hui Yu, Adeel Ahmed Abbasi, Hamid Khan, et al. Neuroprotective Role of Moringa oleifera in Alzheimer’s Disease: Insights into Mechanisms and Therapeutic Opportunities.. Authorea . 02 December 2025. DOI: https://doi.org/10.22541/au.176468062.24514643/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.176468062.24514643/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9fe9e48d5b3caa64',t:'MTc3OTI2NDkxOA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();