# Pharmacological mechanisms and potential clinical applications of Dihydromyricetin in neurological disorders **Authors:** Yike Zhang, Tingting Zhang, Manli Zhao, Peichun Li, Tao Liu, Jiangbo Xie PMC · DOI: 10.3389/fphar.2025.1618623 · Frontiers in Pharmacology · 2025-07-16 ## TL;DR This paper reviews the potential of Dihydromyricetin (DHM) as a treatment for neurological disorders like Alzheimer's and Parkinson's due to its antioxidant and neuroprotective effects. ## Contribution The paper provides a systematic review of DHM's pharmacological mechanisms and therapeutic potential in neurological disorders. ## Key findings - DHM exhibits antioxidant, anti-inflammatory, and neuroprotective properties in preclinical studies. - DHM shows promise as a novel therapeutic agent for central nervous system disorders. - The review highlights current knowledge gaps and challenges in DHM's clinical application. ## Abstract Neurological disorders (e.g., Alzheimer’s disease, Parkinson’s disease, and stroke) have complex pathogenesis and affect a substantial proportion of the population; yet, available treatments have poor or limited efficacy, and the patients have a poor prognosis, with high morbidity and mortality. Dihydromyricetin (DHM), a flavonoid compound extracted from plants, has received widespread attention in recent years because of its diverse pharmacological effects. In vitro and in vivo studies have revealed its substantial antioxidant, anti-inflammatory, and neuroprotective properties, making it a promising candidate for the treatment of central nervous system disorders through multiple mechanisms and pleiotropic effects. Therefore, there is an urgent need to develop novel therapeutic strategies. DHM is an attractive candidate for the management of neurological disorders, but there is a lack of a systematic summary of the knowledge status and gaps. Therefore, to address this challenge, we systematically reviewed the pharmacological mechanisms of DHM in central nervous system disorders and its potential applications in related conditions. We analyzed the therapeutic potential and current challenges of DHM to provide a reference for its development and application as a novel therapeutic agent. The review suggests that DHM possesses significant potential for the management of neurological disorders. ## Linked entities - **Chemicals:** Dihydromyricetin (PubChem CID 161557) - **Diseases:** Alzheimer’s disease (MONDO:0004975), Parkinson’s disease (MONDO:0005180), stroke (MONDO:0005098) ## Full-text entities - **Genes:** Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 56637] {aka 7330414F15Rik, 8430431H08Rik, GSK-3, GSK-3beta, GSK3}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Renbp (renin binding protein) [NCBI Gene 19703] {aka Age, Rnbp}, Ly96 (lymphocyte antigen 96) [NCBI Gene 17087] {aka ESOP-1, MD-2, MD2}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Hspg2 (perlecan (heparan sulfate proteoglycan 2)) [NCBI Gene 15530] {aka HSPG, Pcn, Plc, per}, Foxo3 (forkhead box O3) [NCBI Gene 56484] {aka 1110048B16Rik, 2010203A17Rik, FKHRL1, Fkhr2, Foxo3a}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Ache (acetylcholinesterase) [NCBI Gene 11423], Gphn (gephyrin) [NCBI Gene 268566] {aka 5730552E08Rik, C230040D23, GPH, GPHRYN, geph}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, P2RX7 (purinergic receptor P2X 7) [NCBI Gene 5027] {aka P2X7}, Fnip1 (folliculin interacting protein 1) [NCBI Gene 216742] {aka A730024A03Rik}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56718] {aka Frap1, RAFT1}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, Mir665 (microRNA 665) [NCBI Gene 751555] {aka Mirn665, mir-665, mmu-mir-665}, Nox4 (NADPH oxidase 4) [NCBI Gene 50490], Snhg10 (small nucleolar RNA host gene 10) [NCBI Gene 69434] {aka 1700026B20Rik}, Fadd (Fas associated via death domain) [NCBI Gene 14082] {aka Mort1/FADD}, Rassf5 (Ras association (RalGDS/AF-6) domain family member 5) [NCBI Gene 54354] {aka 1300019G20Rik, Maxp1, Nore1, Nore1A, Nore1B, Rapl}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 287362] {aka Cias1}, Slc2a4 (solute carrier family 2 (facilitated glucose transporter), member 4) [NCBI Gene 20528] {aka GT2, Glut-4, Glut4, twgy}, AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, Ldlr (low density lipoprotein receptor) [NCBI Gene 16835] {aka Hlb301}, Ulk1 (unc-51 like kinase 1) [NCBI Gene 22241] {aka Unc51.1, mKIAA0722}, Apoe (apolipoprotein E) [NCBI Gene 11816] {aka Apo-E}, Fasl (Fas ligand) [NCBI Gene 14103] {aka APT1LG1, CD178, CD95-L, CD95L, Fas-L, Faslg}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Irs1 (insulin receptor substrate 1) [NCBI Gene 16367] {aka G972R, IRS-1}, Ddah1 (dimethylarginine dimethylaminohydrolase 1) [NCBI Gene 69219] {aka 2410006N07Rik, 2510015N06Rik}, F2 (coagulation factor II) [NCBI Gene 14061] {aka Cf-2, Cf2, FII}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Bid (BH3 interacting domain death agonist) [NCBI Gene 12122] {aka 2700049M22Rik}, KRT18 (keratin 18) [NCBI Gene 3875] {aka CK-18, CYK18, K18}, Ephb2 (Eph receptor B2) [NCBI Gene 13844] {aka Cek5, Drt, ETECK, Erk, Hek5, Nuk}, Ntrk2 (neurotrophic receptor tyrosine kinase 2) [NCBI Gene 25054] {aka RATTRKB1, TRKB1, Tkrb, trk-B, trkB}, Bace1 (beta-site APP cleaving enzyme 1) [NCBI Gene 23821] {aka ASP2, Bace}, Bace1 (beta-secretase 1) [NCBI Gene 29392] {aka Bace}, Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], Sirt1 (sirtuin 1) [NCBI Gene 309757] {aka Sir2}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Nos3 (nitric oxide synthase 3, endothelial cell) [NCBI Gene 18127] {aka 2310065A03Rik, Nos-3, eNOS, ecNOS}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Mme (membrane metallo-endopeptidase) [NCBI Gene 24590] {aka CD10, Nep, SFE}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 19225] {aka COX2, Cox-2, PES-2, PGHS-2, PHS II, PHS-2}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, Cybb (cytochrome b-245, beta polypeptide) [NCBI Gene 13058] {aka CGD91-phox, Cgd, Cyd, Nox2, gp91-1, gp91phox}, FNDC5 (fibronectin type III domain containing 5) [NCBI Gene 252995] {aka FRCP2, irisin}, Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225], Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1} - **Diseases:** pain (MESH:D010146), hearing loss (MESH:D034381), sleep deprivation (MESH:D012892), neuronal oxidative damage (MESH:D016472), alcohol (MESH:D000437), OD (OMIM:165800), nerve damage (MESH:D000080902), Neuralgia (MESH:D009437), myocardial ischemia (MESH:D017202), hyperlipidemia (MESH:D006949), NAFLD (MESH:D065626), OGD (MESH:C536050), anxiety (MESH:D001007), auditory disorders (MESH:D006311), neurotoxicity (MESH:D020258), neuropsychiatric complications (MESH:D008107), depression (MESH:D003866), tumor metastasis (MESH:D009362), diabetic cardiomyopathy (MESH:D058065), nasopharyngeal carcinoma (MESH:D000077274), AD (MESH:D000544), PD (MESH:D010300), cerebral infarction (MESH:D002544), diabetic neuropathy (MESH:D003929), metabolic syndrome (MESH:D024821), hepatic steatosis (MESH:D005234), Neurological disorders (MESH:D009461), atherosclerotic plaques (MESH:D058226), Insulin resistance (MESH:D007333), stroke (MESH:D020521), brain tissue damage (MESH:D017695), neurofibrillary tangles (MESH:D055956), acute kidney injury (MESH:D058186), psychological disorders (MESH:D000067073), ischemic brain injury (MESH:D001930), carotid artery injury (MESH:D020212), sciatic nerve compression (MESH:D009408), hepatic inflammation (MESH:D007249), cancer (MESH:D009369), endothelial injury (MESH:D057772), central nervous system diseases (MESH:D002493), Cerebral and subarachnoid hemorrhages (MESH:D013345), metabolic diseases (MESH:D008659), cerebral hemorrhage (MESH:D002543), fibrosis (MESH:D005355), breast, liver, ovarian, and other cancers (MESH:D061325), disorders (MESH:D009358), bradykinesia (MESH:D018476), rheumatoid arthritis (MESH:D001172), tremors (MESH:D014202), cardiotoxicity (MESH:D066126), reperfusion injury (MESH:D015427), myocardial infarction (MESH:D009203), obese (MESH:D009765), memory dysfunction (MESH:D008569), Anxiety disorder (MESH:D001008), dyslipidemia (MESH:D050171), cerebral ischemia (MESH:D002545), multiple sclerosis (MESH:D009103), hypertension (MESH:D006973) - **Chemicals:** alpha-lipoic acid (MESH:D008063), Brusatol (MESH:C020237), alloxan (MESH:D000496), lipid (MESH:D008055), lipopolysaccharide (MESH:D008070), ROS (MESH:D017382), free radical (MESH:D005609), dexamethasone (MESH:D003907), palmitic acid (MESH:D019308), FeCl3 (MESH:C024555), prostaglandin E2 (MESH:D015232), water (MESH:D014867), MDA (MESH:D008315), aminoglycoside (MESH:D000617), phosphatidylserine (MESH:D010718), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MESH:D015632), dopamine (MESH:D004298), D-galactose (MESH:D005690), corticosterone (MESH:D003345), fat (MESH:D005223), nitric oxide (MESH:D009569), LY294002 (MESH:C085911), sodium nitroprusside (MESH:D009599), ethanol (MESH:D000431), glutamate (MESH:D018698), glycogen (MESH:D006003), cyclodextrin (MESH:D003505), blood glucose (MESH:D001786), DHM (MESH:C472036), glutathione (MESH:D005978), hydroxytyrosol (MESH:C005975), Flavonoids (MESH:D005419), O2 - (MESH:D010100), GABA (MESH:D005680), calcium (MESH:D002118), cholesterol (MESH:D002784), glucose (MESH:D005947), NO (MESH:D009614), iron (MESH:D007501), ATP (MESH:D000255), phospholipid (MESH:D010743), levodopa (MESH:D007980), DMY (-), 1-methyl-4-phenylpyridinium (MESH:D015655), streptozotocin (MESH:D013311), H2O2 (MESH:D006861) - **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Oryza sativa (Asian cultivated rice, species) [taxon 4530], Mus musculus (house mouse, species) [taxon 10090], Nekemias grossedentata (species) [taxon 416090], Homo sapiens (human, species) [taxon 9606] - **Mutations:** cysteine-aspartic acid - **Cell lines:** BV-2 — Mus musculus (Mouse), Transformed cell line (CVCL_0182), HT22 — Mus musculus (Mouse), Transformed cell line (CVCL_0321), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12308142/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12308142/full.md ## References 134 references — full list in the complete paper: https://tomesphere.com/paper/PMC12308142/full.md --- Source: https://tomesphere.com/paper/PMC12308142