{"paper_id":"8e2d30a3-ebbe-446d-ae83-67db7ad2d64d","body_text":"In recent decades, scientific\nresearch has been increasingly focusing\non investigating edible plants health-promoting benefits and potential\ntherapeutic applications. These species are rich in phytochemicals\nthat may help prevent or delay the onset of various diseases and provide\nvaluable support in their treatment.  Among\nthese plants, garlic ( Allium sativum L. ) has garnered\nconsiderable attention, partly due to its long-standing use in traditional\nmedicine for treating various ailments.  Nevertheless, fresh garlic (FG) consumption has declined due to\nits strong flavor and pungent odor, along with the gastrointestinal\ndiscomfort it may cause in certain individuals. \n , \n  To\naddress this issue, various garlic-based products have been developed\nto enhance its organoleptic attributes. Among the commercially available\ngarlic-derived products, black garlic (BG) is one of the most studied.\nAlthough the origin of BG remains unclear, historical evidence\nsuggests that it has been consumed in Asian countries since ancient\ntimes.  BG is obtained by aging fresh garlic\nbulbs at controlled high temperature (60–90 °C) and relative\nhumidity (70–90%) for 15 to 90 days, without the use of any\nadditives. \n , \n  During this transformation, garlic cloves\nacquire a dark color ( Figure  \n ), a sweeter flavor, and a chewy texture. \n , \n  The\ncolor change results from various chemical transformations, including\nthe Maillard reaction, caramelization, and the oxidation of phenols.\nChanges in the color of black garlic during the ripening\nprocess.\nIn contrast, changes in flavor and texture are\nprimarily associated\nwith the accumulation of reducing sugars and the degradation of cell\nwall polysaccharides under high-temperature conditions, ultimately\nresulting in a loss of tissue hardness.\nDuring this process, molecules responsible for the distinctive\naroma of FG, such as allicin, are converted into other compounds,\nincluding S-allyl- l -cysteine (SAC) and S-allylmercaptocysteine\n(SAMC), thereby reducing the unpleasant odor.\nThe transformation of FG into BG not only modifies its organoleptic\ncharacteristics but also enhances the content of bioactive substances,\nas polyphenols and organosulfur compounds.\nFresh garlic is widely recognized for its beneficial properties,\nincluding antibacterial,  antiviral,  antidiabetic,  antioxidant,  anti-inflammatory,  antihypertensive,  cardioprotective,  hypolipidemic,  and\nimmunomodulatory  effects.\nNevertheless,\nblack garlic displays distinct biological activity\nthat differs from that of fresh garlic. In particular, BG possesses\nhigher antioxidant activity  and exerts\nanti-inflammatory,  anticancer,  immunostimulatory,  antiallergic,  hepatoprotective,  antidiabetic,  and\nantiobesity  effects.\nTherefore,\nblack garlic could be proposed as a functional food,\noffering health benefits that extend beyond basic nutrition when regularly\nincluded in a balanced diet and consumed in appropriate amounts.\nThis review provides an overview of the\nmain mechanisms underlying\nBG production and their impact on its physicochemical properties and\nbioactivity. Relevant studies were retrieved through targeted searches\nin PubMed and ScienceDirect, with particular attention to research\naddressing processing conditions, chemical transformations, and the\nbiological activities of the resulting bioactive compounds. By integrating\ncurrent evidence, this work aims to clarify the functional potential\nof black garlic and outline areas requiring further investigation.\n\nCurrently,\nchallenges persist in obtaining a product with consistent\nqualitative characteristics and biological effects, primarily due\nto the lack of a standardized manufacturing method and a comprehensive\nunderstanding of the desired compounds formation mechanisms, aside\nfrom the well-established involvement of the Maillard reaction. \n ,\nThe Maillard reaction ( Figure  \n ) is a nonenzymatic browning reaction that occurs between\nthe carbonyl groups of reducing sugars and the amino groups of amino\nacids, peptides, and proteins. This process develops through three\nmain stages. Initially, reducing sugars react with amino acids, leading\nto the formation of Amadori or Heyns products, depending on whether\nthe sugar is an aldose or a ketose, respectively.  Yuan et al. observed a 40- to 100-fold increase in the\nmain Amadori and Heyns compounds in BG compared to FG.  In the second stage, sugar fragmentation and amino acid\ndegradation occur, resulting in the formation of various intermediates,\nsuch as 5-hydroxymethylfurfural (HMF). In the final phase, these compounds\npolymerize, leading to the production of high-molecular-weight brown\npolymers known as melanoidins.\nSchematic representation\nof the different stages of the Maillard\nreaction involved in black garlic ripening (modified from Yoon &\nBaek ). Created in BioRender. BORGATTI,\nM. (2025)  https://BioRender.com/sz5f9z4 .\nThe Maillard reaction contributes to changes in\nthe nutritional\nprofile, color, texture, and flavor of garlic. \n ,\nThese transformations are strongly influenced by temperature and\nrelative humidity, both of which play a decisive role in determining\nblack garlic quality attributes. \n , \n  Higher temperatures\naccelerate the ripening process and intensify the final products’\ncolor and flavor, but excessive heat (e.g., 90 °C) can lead to\na bitter taste due to the rapid depletion of reducing sugars, which\nare consumed to sustain the Maillard reaction. Instead, humidity critically\ndetermines the product texture, with optimal conditions achieved when\nthe water content reaches 400–500 g/kg. Conversely, when it\nfalls below 350 g/kg, BG becomes too hard to be consumed.\nProcessing conditions also alter the concentration\nof bioactive\ncompounds in black garlic. \n , \n  For example, subjecting\nfresh garlic to a temperature of 60 °C enhances the levels of\nSAC, the primary antioxidant compound in BG.  However, the accumulation of HMF, another significant antioxidant\nmolecule, occurs at a considerably slower rate at this temperature.  HMF production also depends on the duration\nof the ripening period; indeed, its concentration increases more than\n6-fold when the period has been extended from 25 to 90 days.\nA detailed overview of the mechanisms\nbehind BG ripening could\nhelp identify optimal production conditions to enhance organoleptic\nproperties, nutritional value, and bioactivity.\nAlthough the changes underlying BG production are\nlargely attributed\nto nonenzymatic reactions driven by heat and humidity, emerging evidence\nsuggests that endophytic microorganisms may also contribute to the\nripening process. Only a few studies have examined the microbial species\nfound in garlic, which primarily belong to the  Bacillus  genus, a bacterial strain commonly found in soil, water sources\nand plants. More specifically, Qiu and colleagues isolated 78 endophytic\nstrains during black garlic processing and found that  Bacillus\nsubtilis  remained dominant throughout, with  B. methylotrophicus  and  B. amyloliquefaciens  also contributing significantly\nto the microbial community.  Additionally,\nbacteria from the genera  Thermus ,  Corynebacterium ,  Streptococcus , and  Brevundimonas  have been identified.\nThese microorganisms\ncan adapt to various carbon sources and exhibit\nsignificant heat resistance. Therefore, they could play a role in\nthe development of compounds that contribute to the flavor and bioactivity\nof BG. \n ,\nIn a subsequent study, Qiu et al.\nselected the most relevant endophytes\nidentified in black garlic, based on their relative abundance and\npreliminary experimental findings, to examine their contributions\nduring the aging process. The investigation involved four  B.  strains, including the three previously mentioned, with\nthe addition of  B. licheniformis , and confirmed their\nability to proliferate across a broad temperature range (20–50\n°C) and pH spectrum (5–9). Notably, when the temperature\nreaches 50 °C, the growth of both  B. subtilis  and  B. amyloliquefaciens  undergo a marked decline,\nwhereas  B. licheniformis  and  B. methylotrophicus  growth appear less sensitive. Moreover, the inoculation of the four\nstrains with garlic polysaccharide and garlic juice media demonstrated\ntheir capacity to hydrolyze garlic polysaccharides, thereby increasing\nthe percentage of reducing sugars. Finally, by inoculating the endophytes\nwith fresh garlic cloves, the authors illustrated that, in comparison\nto controls,  B. methylotrophicus ,  B. amyloliquefaciens , and  B. subtilis  can slightly accelerate the formation\nof black garlic (0.8–2.8%), in contrast to  B. licheniformis , which delays the browning process. Collectively, these findings\nunderscore the potential impact of endophytes on aging dynamics, although\nfurther research is necessary to provide deeper insights into this\nphenomenon.\nIn addition to ripening\nconditions and microbial influences, the\nintrinsic characteristics of fresh garlic contribute significantly\nto the physicochemical and bioactive properties of the final product.\nIn particular, garlic variety affects moisture content, polyphenol\nconcentration, total soluble solids, pH, antioxidant activity, texture,\nand color. Nevertheless, most fresh garlic traits are not reliable\npredictors of BG quality. Consequently, additional studies are required\nto clarify which specific attributes of fresh garlic are decisive\nin determining the final characteristics of black garlic. \n ,\n\nThe chemical profile of fresh garlic changes\nsignificantly due\nto several factors, including variety, cultivation location and practices,\nseason, and climate. \n , \n  FG mainly comprises carbohydrates\n(26–30%, with 1.5% of dietary fiber), proteins (1.5–2.1%),\nlipids (0.1–0.2%), sulfur compounds (1.1–3.5%), phenols\n(17.16–42.53 mg of gallic acid equivalent (GAE)/g), and more\ncomplex substances such as saponins (0.04–0.11%). It also contains\nvitamins (0.015%) and minerals (0.7%), such as C, E, B-group vitamins,\ncalcium, sodium, potassium, magnesium, phosphorus, zinc, copper, iron,\nsulfur, manganese, and selenium. \n −\nFresh garlic is particularly\nrich in γ-glutamylcysteine,\nwhich undergoes hydrolysis and oxidation to form alliin. Actions like\ncutting, crushing, or chewing garlic can disrupt its cellular structure,\nresulting in the release of alliinase, an enzyme stored in vacuoles.\nThis enzyme catalyzes the conversion of alliin into allicin, which\nimparts the characteristic pungent odor of garlic. This reaction also\nproduces pyruvic acid as a byproduct. Allicin and other thiosulfinates\nare rapidly converted into several compounds, such as diallyl sulfide,\ndiallyl disulfide, diallyl trisulfide, dithiins, and ajoene. Simultaneously,\nγ-glutamylcysteine is converted into SAC. \n ,\nThe conversion from FG to BG induces substantial changes in\nits\nchemical profile ( Table  \n ), which are influenced by processing conditions.\nData are presented as mean ±\nSD or %. Abbreviations: BG, black garlic; FG, fresh garlic; GAE, gallic\nacid equivalent; HMF, 5-hydroxymethylfurfural; SAC, S-allyl- l -cysteine.\nDuring the ripening of black garlic, polysaccharides\nare degraded\ninto oligosaccharides, disaccharides, and monosaccharides. Fructans\nprogressively degrade under high-temperature conditions and the action\nof fructan exohydrolase. Specifically, Lu et al. highlighted that\nthis phenomenon is largely attributable to the thermal treatment,\nwhile enzymatic hydrolysis plays a secondary role, as the enzyme is\nrapidly inactivated at the temperatures employed.  Consequently, BG contains more reducing sugars than FG,\nimparting a sweeter taste to the final product. \n , \n  The content of these sugars also depends on their consumption during\nthe Maillard reaction.  The predominant\nreducing sugars in black garlic are fructose (57.14%), sucrose (7.62%),\nand glucose (6.78%).\nFurthermore,\nNassur et al. observed a minor increase in protein\ncontent in BG compared to FG.  Nevertheless,\nprotein degradation may also occur from enzymatic or nonenzymatic\nhydrolysis, leading to an initial increment in amino acids content.  Although the amino acid profile varies significantly\ndepending on the ripening conditions, Kang documented a change in\nthe total amount of 14 free amino acids from 843.11 ± 3.75 to\n167.65 ± 1.08 mg/100 g of substance.  An accumulation of certain amino acids – such as leucine,\nisoleucine, and phenylalanine – has been observed, accompanied\nby a reduction in others. In particular, the depletion of cysteine\nand tyrosine may be attributed to their involvement in the Maillard\nreaction.  In conjunction with the degradation\nof hexoses in an acidic environment, this process contributes to the\nformation of HMF. Additionally, it produces melanoidins, which cause\ngarlic browning. \n , \n  Kang reported a rise in the melanoidin\ncontent during the thermal process.\nIn addition, an almost 4-fold increase in crude lipid content was\nobserved when the bulbs were subjected to the aging process. Nonetheless,\nfurther studies are required to elucidate the changes in the lipid\nprofile.\nThe transformation of FG\ninto BG also results in a 1.15- to 1.92-fold\nrise in water-soluble vitamin content. Nevertheless, thermal treatment\nunder high-humidity conditions and increased acidity causes a reduction\nin certain vitamins. This includes thiamine (vitamin B1), biotin (vitamin\nB7), cobalamin (vitamin B12), vitamin C, and a wide array of fat-soluble\nvitamins. Conversely, an augmented concentration of niacin (vitamin\nB3) and pantothenic acid (vitamin B5) has been recorded. The former\nmay be attributed to its release following the disruption of cell\nmembranes, while the latter might arise due to the concentration effect\nresulting from reduced moisture content.\nThis process also leads to a concomitant rise in the quantity\nof\nminerals, particularly sodium, potassium, iron, and calcium.\nAdditionally, BG contains high levels\nof β-carboline alkaloids,\nwhich are derived from tryptophan. These compounds are only found\nin trace amounts in FG, yet during ripening 1,2,3,4-tetrahydro-β-carboline\nderivatives are formed, thus contributing to its antioxidant activity. \n ,\nAs Zhang et al. observed, the organic acid content varies\nfrom\n4.6 to 33.61, 37.50, 30.96, and 36.37 g/kg when FG is transformed\ninto BG at 60 °C, 70 °C, 80 °C, and 90 °C, respectively.  Particularly, levels of acetic and formic acids\nincrease, which affects the flavor of garlic.  Furthermore, Bae et al. reported a decrease in pH from 6.42 to 5.00\nand 3.05 after exposing FG to 40 and 85 °C for 45 days.\nAmong dietary vegetables, garlic is particularly\nrich in phenolic\ncompounds, which are known for their antioxidant properties. \n , \n  The aging of FG into BG increases their concentration, enhancing\nits antioxidant activity.  Choi et al.\ndocumented a rise in total polyphenols from 13.91 mg GAE/g to 25.81–58.33\nmg GAE/g, depending on processing conditions.  This may be attributed to the release of bound phenolics and enhanced\nextractability resulting from the disruption of cellular structures\nduring thermal treatment.  Kim et al.\nidentified hydroxycinnamic acid derivatives as the primary phenolic\nacids in black garlic, with flavanols being the predominant flavonoid\nclass.  However, extended exposure to\nhigh temperatures can reduce certain phenolic compounds.\nIn addition, pyruvate levels also increase\nduring garlic ripening,\ncontributing to BG antioxidant activity.  This compound is typically produced by the alliin-allicin pathway.\nFurthermore, BG exhibits lower allicin\nlevels than FG, as this\ncompound is unstable and rapidly produces other organosulfur compounds.\nAllicin also reacts with  l -cysteine to form S-allylmercaptocysteine.\nLastly, thermal treatment leads to a 4-\nto 6-fold rise in S-allyl- l -cysteine content, depending on\nthe temperature applied. Indeed,\nBae et al. found that SAC reached 124.67 μg/g of dry matter\nwhen garlic was subjected to a temperature of 40 °C for 45 days,\nbut dropped to 85.46 μg/g at 85 °C.  This variation occurs since at lower temperatures (30–50\n°C) SAC is primarily produced through the enzymatic hydrolysis\nof γ-glutamyl-S-allylcysteine (GSAC) by γ-glutamyl transpeptidase\n(GGT), whereas at higher temperatures SAC formation occurs through\nthe nonenzymatic hydrolysis of GSAC and, to a lesser extent, by the\nreduction of alliin, as GGT becomes inactive under these conditions. \n ,\nAn overview of the effects of the ripening process on black\ngarlic\nquality attributes and chemical composition is provided in  Table  \n .\nAbbreviations: HMF, 5-hydroxymethylfurfural;\nSAC, S-allyl- l -cysteine; SAMC, S-allylmercaptocysteine; T,\ntemperature.\n\nBlack garlic and its derivatives exhibit a wide range of biological\nactivities ( Figure  \n ), primarily due to bioactive constituents that modulate key cellular\nsignaling pathways. In recent decades, numerous preclinical studies\nhave underscored the therapeutic potential of BG in the prevention\nand treatment of various diseases.\nThe principal biological effects of black\ngarlic. Created in BioRender.\nBORGATTI, M. (2025)  https://BioRender.com/gnxe36x .\nIn living organisms,\noxidative processes naturally generate free radicals, including reactive\noxygen species (ROS), which are typically neutralized by the antioxidant\ndefense system. However, when free radical accumulation exceeds the\ncapacity of these defenses, oxidative stress ensues, contributing\nto the development of chronic diseases such as cancer.\nSeveral constituents of black garlic have\nbeen shown to manifest substantial antioxidant activity. Jeong et\nal. highlighted the remarkable ability of BG to neutralize free radicals  in vitro  through 2,2-diphenyl-1-picrylhydrazyl and 2,2’-azinobis­(3-ethylbenzothiazoline-6-sulfonic\nacid) radical scavenging assays, with 50% inhibition (IC 50 ) values of 166.3 ± 1.3 μg/mL and 108.1 ± 0.9 μg/mL,\nrespectively. These values are approximately two- and 3-fold lower\nthan those of the fresh garlic extracts.  Additionally, at a dosage of 100 μg/mL, BG extracts maintain\na strong capability to inhibit lipid peroxidation even after 5 days,\nwhereas the same concentration of fresh garlic extracts showed a marked\ndecline in inhibitory activity starting from day 3.\nFurthermore, experiments conducted on cell lines\nhave demonstrated\nthat BG extracts decrease hydrogen peroxide-induced ROS synthesis\nin murine macrophages RAW264.7 at 1000 μg/mL  and counteract lipid peroxidation triggered by tert-butyl\nhydroperoxide in rat hepatocytes in a dose-dependent manner, at concentrations\nranging from 2.5 to 10 μg/mL.  In\naddition to  in vitro  studies,  in vivo  analyses have been conducted to evaluate the antioxidant properties\nof black garlic. Specifically, Lee et al. reported that BG consumption\n(administered through the diet, containing 5% of freeze-dried garlic\nor aged black garlic) significantly reduces hepatic levels of lipid\nperoxidation products in a murine model. This effect was more pronounced\nin the group treated with black garlic than in the one treated with\nfresh garlic. Simultaneously, an increase was observed in the activity\nof antioxidant enzymes such as superoxide dismutase (SOD), glutathione\nperoxidase (GPx), and catalase (CAT).\nAmong\nits multiple biological properties, black garlic also exhibits anti-inflammatory\nactivity. In particular, 2-linoleoylglycerol isolated from BG (tested\nat concentrations between 5 and 20 μg/mL) has been shown to\nreduce the levels of nitric oxide (NO), prostaglandin E2 (PGE2), and\ninflammatory mediators such as interleukin (IL)-6, IL-1β, and\ntumor necrosis factor-alpha (TNF-α), as well as the expression\nof inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2),\nin lipopolysaccharide (LPS)-activated murine macrophages RAW264.7.\nThis anti-inflammatory effect appears to be mediated through the inhibition\nof phosphorylation of mitogen-activated protein kinases (MAPK; MAPKs)\nextracellular signal-regulated kinase (ERK) and p38.\nAdditional  in vitro  studies have\ndemonstrated that 30 and 50 μg/mL of BG extract also suppresses\ncell cycle progression and proliferation in TNF-α-activated\nhuman endometrial stromal cells by inhibiting ERK and c-Jun N-terminal\nkinase activity. This process is accompanied by reduced expression\nof intracellular adhesion molecule-1 and vascular cell adhesion molecules-1,\nwhich may play a crucial role in the pathological process underlying\nendometriosis. Moreover, a decrease in IL-6 secretion was observed,\nlikely due to inhibition of nuclear factor kappa B (NF-κB) and\nactivator protein-1, two key transcription factors involved in inflammatory\nresponses.\nIn vivo  studies have also revealed that BG extract\n(120 mg/kg, orally administrated) protects mice from LPS-induced septic\nshock by reducing the production of TNF-α and IL-6.  These findings suggest that black garlic may\nserve as a supportive treatment for various inflammation-related conditions,\nincluding sepsis and endometriosis.\nCancer remains\none of the leading causes of mortality worldwide. Conventional treatments\n– such as surgery, chemotherapy, radiotherapy and hormonal\ntherapy – are often associated with severe adverse effects\nthat compromise patients quality of life.  In recent years, researchers have begun to explore the integration\nof plant-derived natural compounds into conventional oncological regimens.\nCarcinogenesis is influenced by external\nand internal factors. Among internal contributors, excessive free\nradical accumulation constitutes a major etiological agent. Oxidative\nstress is frequently associated with chronic inflammation, which may\ninduce genetic mutations in adjacent cells, leading to increased proliferation\nand the establishment of a microenvironment conducive to cancer development.  Accordingly, the antioxidant and anti-inflammatory\nproperties of black garlic may indirectly hinder cancer progression.  In addition to these indirect mechanisms, BG\nappears to exert direct anticancer effects, as evidenced by numerous\nstudies highlighting its antiproliferative, antimetastatic, and pro-apoptotic\nactivities. \n , ,\nSeveral  in vitro  experiments have shown that\nblack\ngarlic inhibits the proliferation of various cancer cell lines. For\ninstance, BG extract has been found to suppress the growth of HT-29\nhuman colon cancer cells in a time- (24, 48, and 72 h) and dose-dependent\n(20, 50, and 100 mg/mL) manner, and promote apoptosis by acting on\nthe phosphoinositide 3-kinase/protein kinase B (Akt) signaling pathway.  Similarly, black garlic extract induced apoptosis\nin SGC-7901 human gastric cancer cells and even reduced tumor mass\nin a murine model, starting from the lowest tested dose of 200 mg/kg\n(intraperitoneally administered).\nLow doses (4, 6, and 10 μg/mL) of hexane extracts derived\nfrom BG have also demonstrated pro-apoptotic activity in human leukemic\nU937 cells by upregulating death receptor 4 and Fas ligand, thereby\nactivating the extrinsic apoptotic pathway. Concurrently, the extract\nincreased the expression of the pro-apoptotic protein Bcl-2 associated\nX-protein (Bax) and decreased the levels of the antiapoptotic protein\nB-cell lymphoma 2 (Bcl-2), promoting the intrinsic apoptotic pathway.\nRecent evidence indicates that 100 mg/mL\nof BG extract inhibits\nproliferation, migration, invasion, and metastasis of MCF-7 and MDA-MB-361\nhuman cells derived from breast adenocarcinoma. These effects are\nassociated with downregulation of antiapoptotic proteins myeloid cell\nleukemia-1 (Mcl-1) and Bcl-2, and upregulation of pro-apoptotic proteins\nBcl-2-interacting mediator of cell death (Bim) and Bcl-2 homologous\nantagonist/killer (Bak).\nShin et\nal. demonstrated that 0.5 mg/mL of BG extract has the ability\nto impede the invasion and metastasis of AGS human gastric cancer\ncells through the suppression of matrix metalloproteinases 2 and 9.\nThese enzymes play a pivotal role in the extracellular matrix degradation\nprocess, a critical step in the invasion of surrounding tissues by\ncancer cells and their subsequent dissemination to distant sites. \n , \n  Finally, Purev et al. reported a dose-dependent (100–500\nμg/mL) cytotoxic effect of BG extract against multiple cancer\ncell lines, including lung carcinoma A549, gastric adenocarcinoma\nAGS, and hepatocarcinoma HepG2 cells.\nBlack\ngarlic has also been shown to act as an immunostimulant – a\nterm that refers to substances capable of enhancing the immune system\n– making it potentially beneficial for the prevention and treatment\nof various diseases. Indeed, treatment with BG extract <100 μg/mL\nhas been observed to increase human lymphocyte proliferation, as well\nas TNF-α release and NO production by macrophages. These immunostimulatory\neffects may also contribute to its anticancer activity.\nIn recent years,\nthe number of individuals affected by allergies has increased, prompting\na growing interest in functional foods with potential antiallergic\neffects.\nAllergic responses are\nclassified into four types based on the immune mechanisms involved.\nType I hypersensitivity reaction is mediated by the activation of\nthe high-affinity immunoglobulin E receptor, which is localized on\nthe plasma membrane of mast and basophilic cells. Upon activation,\nthis receptor triggers the release of mediators such as histamine,\nwhich are responsible for allergic symptoms. In addition, β-hexosaminidase\n– an established marker of cell degranulation – is released.  Kim et al. demonstrated that BG extract inhibits\nβ-hexosaminidase release in RBL-2H3 cells, a widely used  in vitro  model for studying allergic responses. However,\nwhen directly compared under identical conditions, FG extracts exerted\na stronger inhibitory effect at both tested concentrations (10 and\n100 μg/mL), suggesting that the transformation of fresh garlic\ninto black garlic may reduce, at least in part, its antiallergic potential.\nFurthermore, an  in vivo  study showed that an ethyl\nacetate fraction of BG extract significantly reduced the cutaneous\nanaphylactic reaction in a murine model, but only at the highest tested\ndose of 66.7 mg/kg.\nHepatic\ndiseases represent a significant global health burden due to their\nhigh morbidity and mortality rates.  Various\nsubstances, including dietary components, pharmaceuticals, alcohol,\nand pollutants, are known to induce both acute and chronic liver diseases. \n − \n \n \n  Despite advances in modern medicine, effective therapeutic strategies\nto stimulate hepatic function, protect the liver, or promote hepatic\ncell regeneration remain limited. Consequently, great attention has\nbeen directed toward identifying natural compounds capable of mitigating\nhepatic injury.  In this context, some\nstudies have demonstrated that black garlic also has hepatoprotective\neffects. \n ,\nFor example, Shin et al. reported\nthat chronic dietary administration of BG extract at 100 and 200 mg/kg\nfor 4 weeks reduced aspartate aminotransferase and alanine aminotransferase\nlevels – which are widely used markers of hepatocellular damage\n– in the liver of rats treated with carbon tetrachloride and  d -galactosamine to cause liver injury, in a dose dependent manner.\nSimilar results were observed in mice fed a high-fat diet.\nDiabetes mellitus\nis a metabolic disorder characterized by chronic hyperglycemia and\nabnormalities in carbohydrate, fat, and protein metabolism due to\ndefects in insulin secretion and/or action.  Sustained hyperglycemia represents a major contributor to oxidative\nstress, with elevated levels of free radicals playing a crucial role\nin the pathogenesis and complications of diabetes.\nWithin this context, the antidiabetic potential of\nblack garlic and its effects on conventional diabetes markers have\nbeen investigated. \n , \n  For example, Kang et al. demonstrated\nthat BG extract added to the diet (1% and 3% of the total food amount)\nof streptozotocin-induced diabetic rats reduced blood glucose and\nglycosylated hemoglobin levels.\nObesity has\nemerged as a pressing public health concern and is associated with\nvarious diseases.  In this framework,\nan  in vitro  study revealed that BG extract at 2 and\n4 mg/mL suppresses adipogenesis by inhibiting key pro-adipogenic transcription\nfactors in 3T3-L1 preadipocytes  and,\nat similar doses, promotes lipolysis in mature adipocytes.\nAdditionally, an  in vivo  study showed that BG administered in the diet at low (0.2%), medium\n(0.6%), and high (1.2%) concentrations reduces body weight, peritoneal\nfat, and serum triglycerides while improving hepatic lipid profiles\n(total lipids, triglycerides, and cholesterol) in rats with high-fat\ndiet-induced obesity.\nAnalogous\nfindings were reported by Ha et al.,  who\nobserved a reduction in body weight and an improvement\nin lipid profile in rats fed a high-fat diet and supplemented with\n0.5% or 1.5% of BG extract, compared to the control group. Specifically,\nin order to investigate the underlying mechanism, hepatic sterol regulatory\nelement-binding protein 1c (SREBP-1c) mRNA expression was measured\nand found to be reduced following BG treatment.\nSREBP-1c is\na pivotal transcription factor that induces the expression\nof various genes involved in lipid metabolism, including acetyl-CoA\ncarboxylase, fatty acid synthase, and glucose-6-phosphate dehydrogenase.\nConsequently, the levels of these enzymes were found to be significantly\nlower in the treated mice than in controls. This suggests that their\ninhibition contributes to a reduction in hepatic lipid synthesis.\nThe mechanism in question was also associated with a decrease in plasma\ntriglyceride levels. In addition, a reduction in the hepatic expression\nof hydroxymethylglutaryl-coenzyme A reductase and acyl-coenzyme A\ncholesterol acyltransferase was observed compared to the control group.\nThis result was related to reduced total cholesterol levels. Conversely,\nan increase in high-density lipoprotein cholesterol – known\nfor its protective effects on lipid metabolism – was reported.\nIn\naddition to the biological activities previously discussed, black\ngarlic has shown potential neuroprotective properties. These effects\nhave been attributed to its ability to enhance spatial memory and\nincrease the number of pyramidal cells in the hippocampus and Purkinje\ncells in the cerebellum of rats exposed to monosodium glutamate –\na well-known neurotoxic compound – at all the tested doses\n(2.5, 5, and 10 mg/200 g of body weight). \n ,\nFurthermore, at 50 mg/mL black garlic has demonstrated antihypertensive\nactivity by inhibiting the angiotensin-converting enzyme (ACE)  in vitro .  This enzyme catalyzes\nthe conversion of angiotensin I into angiotensin II. The latter acts\nas a potent vasoconstrictor and stimulates aldosterone secretion from\nthe adrenal cortex, leading to sodium retention in the kidneys and\nincreased blood pressure.\nEmerging\ndata also suggests that BG may have beneficial effects\non gastrointestinal function. For example, Chen et al. reported that\nits administration at low (200 mg/mL) and high (400 mg/mL) doses improves\nintestinal motility in rats.\n\nThe health-promoting effects of black garlic are primarily\nattributed\nto its rich profile of bioactive compounds ( Figure  \n ), which exert a broad spectrum of biological\nfunctions that have been investigated through both  in vitro  and  in vivo  studies ( Table  \n ).\nChemical structures of key bioactive compounds\nidentified in black\ngarlic.\nAbbreviations: 4-HNE, 4-hydroxy-2-nonenal;\nACE, angiotensin-converting enzyme; Akt, protein kinase B; ATGL, adipose\ntriacylglyceride lipase; Bad, Bcl-2-associated death promoter; Bax,\nBcl-2 associated X-protein; Bcl-2, B-cell lymphoma 2; Bim, Bcl-2-interacting\nmediator of cell death; CAT, catalase; CDK, cyclin dependent kinase;\nCOX, cyclooxygenase; CYPs, cytochrome P450; DNMTs, DNA methyltransferases;\nEMT, epithelial-mesenchymal transition; FAS, fatty acid synthase;\nGPx, glutathione peroxidase; GSH, glutathione; GST, glutathione S-transferase:\nHATs, histone acetyltransferases; HbA1c, hemoglobin A1c; HDACs, histone\ndeacetylases; HIF-α, hypoxia inducible factor-alpha; HIV, immunodeficiency\nvirus; HMF, 5-hydroxymethylfurfural; HSL, hormone sensitive lipase;\nICAM-1, intercellular adhesion molecule-1; IL, interleukin; iNOS,\ninducible nitric oxide synthase; JAK, Janus kinase; LOX, lipoxygenase;\nMAPK, mitogen-activated protein kinase; MDA, malondialdehyde; MMP,\nmetalloproteinase; mTOR, mammalian target of rapamycin; NF-κB,\nnuclear factor kappa-B; NLRP3, NLR family pyrin domain containing\n3; NO, nitric oxide; NOX, NADPH oxidase; PDGF, platelet-derived growth\nfactor; PGE2, prostaglandin E2; PI3K, phosphoinositide 3-kinase; PLA 2 , phospholipase A2; Rb, retinoblastoma protein; RNS, reactive\nnitrogen species; ROS, reactive oxygen species; SAC, S-allyl- l -cysteine; SAMC, S-allylmercaptocysteine; STAT, signal transducer\nand activator of transcription; TBARS, thiobarbituric acid reactive\nsubstances; TGF-β, transforming growth factor-beta; TLR, toll-like\nreceptor; TNF-α, tumor necrosis factor-alpha; TREM-1, triggering\nreceptor expressed on myeloid cells-1; VCAM-1, vascular cell adhesion\nmolecule-1; VEGF, vascular endothelial growth factor.\nAmong the principal bioactive compounds in black garlic, S-allyl- l -cysteine has attracted particular interest. In fact, this\nsulfur-containing amino acid exhibits multiple biological activities.\nFirst of all, the antioxidant properties of SAC have been deeply investigated\nboth  in vitro  and  in vivo . The  in vitro  studies demonstrate its ability to scavenge ROS\nand hypochlorous acid, thereby protecting LLC-PK1 kidney cells from\npotassium dichromate-induced oxidative damage.  The  in vivo  studies corroborated these\nfindings by assessing the activities of the antioxidant enzymes SOD,\nCAT, and GPx: following the administration of SAC (150 mg/kg) for\n45 days, diabetic Wistar rats exhibited enhanced activity of these\nenzymes in liver and kidney tissues.  Beyond\nits antioxidant action, SAC also demonstrates anticancer activity  in vitro  through several mechanisms of action, such as the\ninduction of carcinogen detoxification,  inhibition of cell proliferation,  induction\nof apoptosis, \n − \n \n  and suppression of epithelial-mesenchymal\ntransition and invasion \n , \n  of cancer cells.\nSimilar evidence has been observed in animal models, where SAC consumption\nwas shown to suppress the growth of lung carcinoma in xenografted\nBALB/CAnN-Foxn1 nude mice.\nFurther  in vivo  studies extend these findings,\nhighlighting how SAC is also effective in lowering blood glucose in\nstreptozotocin-induced diabetic rats,  reducing serum triglyceride and cholesterol levels,  and exerting neuroprotection. Regarding this\nlast aspect, it has been demonstrated that SAC reduces lipid peroxidation,\nROS production, and dopamine loss in the striatum, thereby improving\nmotor deficits in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,\na toxin used to induce Parkinson’s disease in animal models.  Likewise, Ashafaq et al. demonstrated SAC’s\nability to reduce oxidative damage and improve neurological deficits\nin a rat model of focal cerebral ischemia.\nS-allyl- l -cysteine also exhibits hepatoprotective\nproperties.\nFor example, it has been shown to protect BRL-3A rat liver cells against\nalcohol-induced apoptosis.  Furthermore,\nSAC reduces the levels of pro-inflammatory cytokines such as IL-1β,\nIL-6, and TNF-α, demonstrating anti-inflammatory activity in\nmice. \n , \n  Additional reported benefits  in\nvivo  include nephroprotective,  cardioprotective,  and antihypertensive\nactivities.\nS-allylmercaptocysteine is a water-soluble organosulfur compound\nwith demonstrated antioxidant properties both  in vitro  and  in vivo . Specifically, it scavenges hydroxyl\nradical and singlet oxygen, inhibits lipid peroxidation  in\nvitro , and mitigates kidney damage in rats treated with gentamicin,\nan antibiotic known to induce nephrotoxicity via oxidative stress.\nThese nephroprotective effects are associated with the prevention\nof decreases in antioxidant enzymes such as glutathione reductase\nand manganese superoxide dismutase.\nSAMC also exhibits hepatoprotective activity  in vivo , as evidenced by its ability to protect the liver of rats affected\nby nonalcoholic fatty liver disease against chronic injury through\ninhibition of apoptosis and enhancement of autophagy.\nIts anti-inflammatory effects were demonstrated\nby Yang et al.,\nwho observed reduced levels of the pro-inflammatory cytokines IL-1β,\nIL-6, and TNF-α in the serum of mice treated with posaconazole,\nsuggesting its capacity to attenuate this antifungal drug-adverse\neffects.\nThe anticancer potential\nof SAMC has also been widely studied.\nIt has been shown to reduce the onset and progression of various tumors\nthrough multiple mechanisms,  in vitro  and  in vivo . \n , \n  For instance, SAMC prevents\nbenzo­(a)­pyrene-induced carcinogenesis in human lung A549 cells by\nreducing ROS formation, increasing SOD activity, inhibiting NF-κB,\nsuppressing cell proliferation, and regulating the cell cycle.  Additionally, SAMC has also proven to be effective\nagainst cancer cells derived from multiple organs, including the colon,\nprostate, liver, breast, stomach, bladder, thyroid, and ovary. \n − \n \n \n \n \n \n \n  Finally, in xenografted mice SAMC could effectively suppress the\ngrowth and metastasis of colorectal cancer cells.\nβ-carboline alkaloids are known for their wide range of biological\nactivities, including anticancer, antiviral, antimicrobial, antiparasitic,\nand anxiolytic effects. \n − \n \n \n  Among them, 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic\nacid (THβC) has been identified in black garlic. This compound\nlikely forms during the ripening process through a condensation reaction\nbetween acetaldehyde – a byproduct of the Maillard reaction\n– and tryptophan. \n , \n  A salient property\nof THβC is its substantial antioxidant activity  in vitro , which encompasses the scavenging of hydrogen peroxide and the inhibition\nof lipid peroxidation.  To date, direct  in vivo  confirmation is still lacking.\nPyruvate is abundant in\nblack garlic and contributes significantly to its antioxidant properties.\nIndeed, it not only suppresses ROS generation but also reduces NO\nand PGE2 production induced by LPS in RAW264.7 cells. These findings\nsuggest that pyruvate has anti-inflammatory effects. Also  in vivo,  multiple studies have demonstrated that exogenous\npyruvate exerts diverse biological effects, including antioxidant,  anti-inflammatory,  and neuroprotective activities.  However,\nthe properties observed in black garlic appear to be less prominent\nthan those exerted by pyruvate alone, indicating that other BG constituents\nmight interfere with its activity.\n5-Hydroxymethylfurfural\nis a furanic compound formed as an intermediate in the Maillard reaction.  The process of formation is of pivotal significance\nin the characteristic color transition of garlic during thermal treatment.\nIn particular, when HMF levels reach approximately 4 g/kg, BG acquires\nits distinctive dark appearance.\nAlthough it remains unclear whether HMF exposure poses a health risk,\nit seems that it possesses weak genotoxic and mutagenic potential\nonly at high concentration. \n , \n  Despite these concerns,\na mounting body of evidence suggests that HMF concurrently engenders\nmultiple beneficial effects.  For instance,\nZhao et al. reported that HMF exhibits a strong antioxidant activity.\nIt reduces ROS production and lipid peroxidation while enhancing the\nactivity of the antioxidant enzymes GPx, SOD, and CAT in human erythrocytes\ntreated with 2,2′-azobis­(2-amidinopropane) dihydrochloride,\na compound employed to induce oxidative damage. These observations\nindicate a protective effect against oxidative stress  in vitro .\nFurthermore, HMF also displays\nanti-inflammatory properties through\nthe suppression of NO, PGE 2 , TNF-α, IL-1β,\nand IL-6 production in LPS-stimulated RAW264.7. In addition, it downregulates\nthe expression of iNOS and COX-2, key mediators of inflammation. The\nanti-inflammatory effect of HMF appears to be mediated by the inhibition\nof the MAPK, NF-κB, and Akt/mammalian target of rapamycin (mTOR)\nsignaling pathways.\nAdditionally,\nHMF has demonstrated anticancer activity through\nG 0 /G 1  phase arrest and induction of apoptosis,\nas evidenced by its antiproliferative effects on human melanoma A375\ncells.\nHowever,  in vivo  validation is still limited and\npartly contradictory. For example, Zhang et al. demonstrated that\nthe intraperitoneal injection of HMF in mouse models of acute-lung\ninjury ameliorated disease conditions by exerting anti-inflammatory\nand protective effects.  Conversely,\na study conducted on Brown Norway rats highlighted the nonallergic\nanaphylaxis induced by HMF, underlying its related immunotoxic risks.  However, most evidence remains restricted to\ncell-based analysis and further investigations are necessary to clarify\nthese aspects.\nMelanoidins are heterogeneous,\nnitrogen-containing brown polymers. Similarly to 5-hydroxymethylfurfural,\nthese pigments are synthesized during the final stages of the Maillard\nreaction and contribute to the characteristic dark color of thermally\nprocessed garlic. \n ,\nBeyond their role in color\ndevelopment, melanoidins have attracted considerable interest due\nto their diverse biological activities. Notably, melanoidins have\nexhibited antihypertensive properties, which are attributed to their\ncapacity to inhibit ACE activity  in vitro .\nAdditionally, they have demonstrated\nantimicrobial effects against\nboth Gram-positive ( Staphylococcus aureus  and  Listeria monocytogenes ) \n , \n  and Gram-negative\n( Salmonella enteritis  and  Escherichia coli )  bacteria. Interestingly, melanoidins\nact as bacteriostatic agents at low concentrations and display bactericidal\nactivity at higher doses.\nFurthermore,\nmelanoidins derived from black garlic have shown promising\nantiobesity effects.  In vivo  studies have shown that\nmelanoidin supplementation significantly reduces body weight and white\nadipose tissue accumulation, while also decreasing blood glucose levels\nand improving lipid profile.\nFinally,\nmelanoidins exhibit significant antioxidant capacity,\nmainly through metal-chelating and radical-scavenging mechanisms demonstrated\nby  in vitro  studies. \n ,\nPolyphenols are naturally\noccurring compounds derived from the secondary metabolism of plants,\nwhere they serve a critical function in mitigating various environmental\nstressors, including ultraviolet radiation and pathogen aggression.  Structurally, these phytochemicals feature\none or more aromatic rings substituted with hydroxyl groups.\nPolyphenols are broadly classified into\ntwo groups: flavonoids and nonflavonoids. Each class comprises several\nsubcategories, defined by the number of phenolic units in their molecular\nstructure, the nature of substituent groups, and/or the linkage type\nbetween phenolic units.\nFlavonoids share a common diphenylpropane\n(C6–C3–C6)\nskeleton, consisting of two benzene rings connected by a three-carbon\nunit that typically forms an oxygen-containing heterocyclic ring.\nVariations in the hydroxylation pattern and the oxidation state of\nthe central ring allow further classification into flavanols, anthocyanidins,\nisoflavones, flavones, flavonols, flavanones, flavanonols, neoflavonoids,\nand chalcones. \n ,\nIn contrast, nonflavonoids\ngenerally exhibit simpler structures,\noften consisting of a single aromatic ring. This group includes phenolic\nacids, stilbenes, and lignans. Among these, phenolic acids represent\nthe principal subgroup and are primarily derived from benzoic and\ncinnamic acids.\nPolyphenols are\ncommon constituents of plant-based foods and beverages,\nand their content is influenced by numerous factors such as environmental\nconditions, harvest ripeness, storage methods, and culinary processing. \n − \n \n  Garlic subjected to various thermal treatments has been found to\ncontain significantly higher total polyphenol content compared to\nfresh garlic. According to Kim et al., flavanols (catechin, epicatechin,\nand epigallocatechin gallate) are the most abundant flavonoids in\nBG, followed by flavonols (myricetin, morin, and quercetin). Regarding\nphenolic acids, derivatives of hydroxycinnamic acid (caffeic acid,\np-coumaric, m-coumaric, o-coumaric, and ferulic acid) are the most\nprevalent, although hydroxybenzoic acid derivatives (gallic and vanillic\nacid) have also been identified.\nThe health-promoting potential of polyphenols is well-documented.\nDiets rich in polyphenol-containing foods are associated with a reduced\nincidence of chronic diseases, including cancer, cardiovascular disorders,\nand neurodegenerative conditions.  Oxidative\nstress has been implicated as a common etiological factor among many\nof these diseases.  Within this framework,\npolyphenols have demonstrated potent antioxidant properties by scavenging\nfree radicals, acting as reducing agents, hydrogen donors, and singlet\noxygen quenchers. Furthermore, they chelate transition metals such\nas ferrous ion (Fe 2+ ), thereby preventing the formation\nof additional free radicals via the Fenton reaction, which occurs\nbetween Fe 2+  and hydrogen peroxide. Moreover, polyphenols\ncontribute to redox homeostasis by regenerating vitamin E. \n , − \n \n \n In vivo  studies have shown\nthat polyphenols also increase serum levels of antioxidant enzymes\nsuch as SOD, GPx, and CAT, while reducing lipid peroxidation. \n −\nNeuroprotective effects have also been attributed to polyphenols,\npotentially reducing the incidence of Parkinson’s and delaying\nthe onset of Alzheimer’s disease, primarily due to their antioxidant\ncapabilities. \n , −\nBeyond their antioxidant activity, polyphenols exhibit notable\nimmunomodulatory and anti-inflammatory effects,  in vitro  and  in vivo . They influence immune cell populations,\nregulate cytokine production, and modulate the expression of pro-inflammatory\ngenes. \n , − \n \n  For instance, polyphenols\ninterfere with the NF-κB and MAPK signaling pathways, reducing\nthe formation of pro-inflammatory cytokines. \n , \n  They also modulate the expression and activity of cyclooxygenase\nand 5-lipoxygenase, leading to a reduction in the synthesis of prostaglandins\nand leukotrienes – two major mediators of inflammation. \n , ,\nDue to this broad range\nof bioactivities, polyphenols have garnered\nincreasing attention for their chemopreventive potential. Their protective\neffects stem primarily from their capacity to mitigate oxidative stress,\na critical factor in carcinogenesis and cancer progression.  Furthermore, they inhibit procarcinogens activation\nby reducing the activity of phase I metabolizing enzymes, while facilitating\ndetoxification from carcinogenic substances through the induction\nof phase II metabolizing enzymes.  These\naspects were confirmed  in vivo , as reported in a\nstudy on green tea polyphenols, which upregulated the expression of\ndetoxifying enzymes such as heme oxygenase 1 and NAD­(P)H quinone oxidoreductase,\nwhile reducing transaminases and total bilirubin levels in the liver\nof Kunming mice.\nBeyond these\ndetoxifying properties, polyphenols also influence\nepigenetic regulation, which is pivotal in cancer development as it\nmodulates gene expression without altering the underlying DNA sequence.\nSpecifically, they are capable of inhibiting DNA methyltransferases\nand histone deacetylases, as well as modulating histone acetyltransferases.\nThis leads to the reactivation of tumor suppressor genes and the downregulation\nof oncogenes transcription  in vitro \n \n , \n  and  in vivo . \n ,\nAlthough\nwidely recognized for their antioxidant activity, polyphenols\ncan also exhibit prooxidant effects under certain conditions, particularly\nat high concentrations, elevated pH, and in the presence of transition\nmetals. Such behavior is attributed to the formation of an unstable\naroxyl radical, which may react with oxygen to generate superoxide\nanion (O 2 \n •‑ ). Beyond direct ROS\ngeneration, some polyphenols promote oxidative stress by stimulating\nintracellular ROS production via NADPH oxidase or through the reduction\nof metal ions involved in redox-cycling.\nThis dual redox behavior has particular relevance in the context\nof cancer. Compared to normal cells, cancer cells frequently display\nelevated oxidative stress and disrupted redox homeostasis. This imbalance\nhas the potential to stimulate cell proliferation and activate adaptive\nresponses that may contribute to tumorigenesis, metastasis, and treatment\nresistance. However, further exposure to ROS has been demonstrated\nto trigger cell death in cancer cells. Conversely, normal cells are\ntypically less sensitive to ROS-inducing stimuli, as they maintain\nredox homeostasis through efficient adaptive mechanisms.  Accordingly, the prooxidant activity of polyphenols\nmay contribute to apoptosis induction and cell cycle arrest in cancer\ncells. In addition, they suppress specific signaling pathways involved\nin cell proliferation, which are typically hyperactivated during tumorigenesis.\nFurther  in vitro  studies\nhave indicated that some\npolyphenols also possess the ability to inhibit DNA replication, transcription,\nand repair in cancer cells. \n , \n  They also counteract\nangiogenesis by downregulating pro-angiogenic molecules such as vascular\nendothelial growth factor and exert antimetastatic effects through\nthe suppression of metalloproteinase expression and the modulation\nof epithelial-to-mesenchymal transition. \n ,\nIn another domain, polyphenols exhibit antimicrobial activity\nthrough\nmultiple mechanisms, including disruption of bacterial membrane integrity\nand inhibition of certain enzymes. Although the exact pathways remain\nincompletely elucidated, it has been hypothesized that polyphenols\ncan selectively induce the death of pathogenic species while promoting\nthe growth of beneficial microorganisms. \n , \n  Some polyphenols have also demonstrated antiviral activity. For\ninstance, epigallocatechin gallate exhibit activity against human\nimmunodeficiency virus, influenza virus, and hepatitis C virus.\nPhenolic compounds are additionally recognized\nfor their potential\nto reduce the risk of cardiovascular disease, particularly through\ntheir antihypertensive properties. These include the enhancement of\nNO-mediated vasodilation, inhibition of ACE, and attenuation of oxidative\nstress.\nFurthermore, polyphenols\nhave demonstrated antiobesity effects\nby decreasing lipogenesis, suppressing triglyceride accumulation,\npromoting lipolysis, and stimulating fatty acid β-oxidation.  Multiple studies conducted on animal models\nand human subjects, in fact, highlight how these compounds reduce\nmultiple obesity-related parameters, including the adipose tissue\nweight and the fat accumulation. \n −\nIn addition,\na growing body of evidence from both  in vitro  and  in vivo  studies supports their role in the\nprevention and management of type 2 diabetes. Indeed, polyphenols\nenhance insulin secretion and sensitivity, thereby improving glycemic\ncontrol.\nIn light of this compelling\nevidence, it can be concluded that\npolyphenols represent an extremely diversified array of bioactive\nmolecules with extensive health-promoting effects. Many of these biological\nproperties are consistent with those attributed to black garlic, further\nsupporting its relevance as a potential functional food.\n\nThe health benefits\nof black garlic have been extensively documented.\nHowever, the specific bioactive constituents responsible for its various\nbiological effects, as well as the molecular mechanisms underlying\ntheir activity, remain only partially understood. Furthermore, the\npotential synergistic interactions among these compounds have received\nlimited attention. Hence, further research is necessary to elucidate\nthe contribution of individual key constituents and their potential\ninteractions.","source_license":"CC-BY-4.0","license_restricted":false}