Dihydromyrictin (DHM) is a dihydroflavonoids, which has many functions such as free radical removal, antioxidant and anti-inflammatory. Because its rich biological activity is widely used in the medical and health care fields, this paper reviews relevant studies on the neuroprotective effects of DHM to analyze its mechanisms and effects in the nervous system. Integrating the existing research results, including the effects of DHM on neurodevelopment, neuroprotection, neuroinflammation and neurodegenerative diseases, aims to summarize the potential application of DHM in the nervous system.

Cong Li, Canpeng Luo, Xiang Li, Bin Liang, Xiaoqing Yu, Xintai Chen. Repair of the nervous system by dihydromyricetin and the treatment of diseases. International Journal of Frontiers in Medicine (2024), Vol. 6, Issue 6: 60-67. https://doi.org/10.25236/IJFM.2024.060609.

[1] Guan S, Shen Y, Ge H, et al. Dihydromyricetin alleviates diabetic neuropathic pain and depression comorbidity symptoms by inhibiting P2X7 receptor[J]. Frontiers in Psychiatry, 2019, 10: 770.

[2] Tong H, Zhang X, Tan L, et al. Multitarget and promising role of dihydromyricetin in the treatment of metabolic diseases[J]. European journal of pharmacology, 2020, 870: 172888.

[3] Wang Yirong, Wang Junmin, Xiang Hongjiao, et al. Recent update on application of dihydromyricetin in metabolic related diseases [J]. Biomedicine & Pharmacotherapy, 2022, 148: 112771.

[4] He GX,et al.Studies on stability of dihydromyricetin[J].Chin J New Drugs, 2007, 16:1888-1890.

[5] Umair M, Jabbar S, Sultana T, et al. Chirality of the biomolecules enhanced its stereospecific action of dihydromyricetin enantiomers[J]. Food Science & Nutrition, 2020, 8(9): 4843-4856.

[6] Zhang Q, Liu J, Liu B, et al. Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism[J]. Scientific reports, 2014, 4(1): 4628.

[7] Li H, Li Q, Liu Z, et al. The versatile effects of dihydromyricetin in health[J]. Evidence‐Based Complementary and Alternative Medicine, 2017, 2017(1): 1053617.

[8] Liu M, Guo H, Li Z, et al. Molecular level insight into the benefit of myricetin and dihydromyricetin uptake in patients with Alzheimer's diseases[J]. Frontiers in Aging Neuroscience, 2020, 12: 601603.

[9] Shen N, Wang T, Gan Q, et al. Plant flavonoids: Classification, distribution, biosynthesis, and antioxidant activity[J]. Food chemistry, 2022, 383: 132531. 

[10] Liu D, Mao Y, Ding L, et al. Dihydromyricetin: A review on identification and quantification methods, biological activities, chemical stability, metabolism and approaches to enhance its bioavailability[J]. Trends in Food Science & Technology, 2019, 91: 586-597.

[11] Sferrazza G, Brusotti G, Zonfrillo M, et al. Hovenia dulcis Thumberg: Phytochemistry, pharmacology, toxicology and regulatory framework for its use in the European Union[J]. Molecules, 2021, 26(4): 903.

[12] Zhang Xiaonan, Zhang Lubin, Zhang Yingdi, et al. Extracting myricetin and dihydromyricetin simultaneously from Hovenia acerba seed by Ultrasound-Assisted extraction on a lab and small Pilot-Scale[J]. Ultrasonics Sonochemistry, 2023, 93:106304.

[13] Cheng Q C, Fan J, Deng X W, et al. Dihydromyricetin ameliorates chronic liver injury by reducing pyroptosis[J]. World Journal of Gastroenterology, 2020, 26(41): 6346.

[14] ZENG Y X,YU J P. Optimization of extraction methods of total flavonoids from rattan tea [J]. Journal ofmountain agricultural biology, 2013, 32(2): 153-158.

[15] WANG Y J,YAN J P,BAI F Z. Application progress of enzymatic method in extraction of traditional Chinese medicine [J]. Chinese Journal of traditional Chinese Medicine Information,2013,20( 9) : 110-112.

[16] CHEN Y M,YU H Z,LIU T F,et al. Enzymatic angraction of dihydromyricetin from the stem of rattan tea [J]. Applied Chemistry, 2016, 45(2) : 304-307.

[17] ZHENG C,QIU Y R,ZHAO Y H,et al. Study on microwave extraction and hypoglycemic effaot of dihydromyricetin in rattan tea [J].Journal of Guangzhou University ( Natural Science Edition) ,2007( 6) : 26-31.

[18] WANG Y W,GUO Q,CH N D,Et al. uptimization of tween-80 ultrasonic extract on process for dihydromyricetin from rattan tea [J]. Guangzhou Chemical Industry ,2016,44( 16) : 63 - 65.

[19] WANG H B,XIONG W I,HU J W,et al. Study on the technology of extracting polysaccangide and Dihydromyricetin from rattan tea by ultrasound and low temperature [J]. Food industry ,2015,36( 8) : 81-85.

[20] YAO M J,HUANG J H. Ulthengnic assisted solvent extraction of dihydromyricetin [J]. Journal of Food and Biotechnology ,2007 ( 3) : 20-23

[21] Zhang Q, Zhao Y, Zhang M, et al. Recent advances in research on vine tea, a potential and functional herbal tea with dihydromyricetin and myricetin as major bioactive compounds[J]. Journal of Pharmaceutical Analysis, 2021, 11(5): 555-563.

[22] Matouk Asmaa I, Awad Eman M, Kamel Amr A, et al. Dihydromyricetin protects against gentamicin-induced nephrotoxicity via upregulation of renal SIRT3 and PAX2.[J]. Life sciences, 2023, 336:122318.

[23] Zhang Q Y, Li R, Zeng G F, et al. Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression[J]. World journal of gastroenterology: WJG, 2014, 20(29): 10082. 

[24] Mao J, Yang J, Zhang Y, et al. Arsenic trioxide mediates HAPI microglia inflammatory response and subsequent neuron apoptosis through p38/JNK MAPK/STAT3 pathway[J]. Toxicology and Applied Pharmacology, 2016, 303: 79-89. 

[25] Lu Y, Zhang X S, Zhang Z H, et al. Peroxiredoxin 2 activates microglia by interacting with Toll-like receptor 4 after subarachnoid hemorrhage[J]. Journal of neuroinflammation, 2018, 15: 1-10.

[26] Wang J, Chen H, Cao P, et al. Inflammatory cytokines induce caveolin‐1/β‐catenin signalling in rat nucleus pulposus cell apoptosis through the p38 MAPK pathway[J]. Cell proliferation, 2016, 49(3): 362-372.

[27] Tan S N, Sim S P, Khoo A S B. Potential role of oxidative stress-induced apoptosis in mediating chromosomal rearrangements in nasopharyngeal carcinoma[J]. Cell & Bioscience, 2016, 6: 1-16.

[28] Wang S M, Lim S W, Wang Y H, et al. Astrocytic CCAAT/Enhancer-binding protein delta contributes to reactive oxygen species formation in neuroinflammation[J]. Redox biology, 2018, 16: 104-112.

[29] Liu Xia, Li Yunjie, Chen Shiling, et al. Dihydromyricetin attenuates intracerebral hemorrhage by reversing the effect of LCN2 via the system Xc- pathway.[J]. Phytomedicine: international journal of phytotherapy and phytopharmacology, 2023, 115:154756.

[30] Ling H, Zhu Z, Yang J, et al. Dihydromyricetin improves type 2 diabetes-induced cognitive impairment via suppressing oxidative stress and enhancing brain-derived neurotrophic factor-mediated neuroprotection in mice[J]. Acta Biochimica et Biophysica Sinica, 2018, 50(3): 298-306.

[31] Hui-Jie L, Ze-Mei Z, Wei-Zhao C, et al. Dihydromyricetin inhibits high glucose induced pc12 cells apoptosis by down-regulating JNK pathway[J]. PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS, 2018, 45(6): 663-671.

[32] Wang Z, Feng S, Li Q, et al. Dihydromyricetin alleviates hippocampal ferroptosis in type 2 diabetic cognitive impairment rats via inhibiting the JNK-inflammatory factor pathway[J]. Neuroscience Letters, 2023, 812: 137404.

[33] Kawamoto Y, Nakamura S, Nakano S, et al. Immunohistochemical localization of brain-derived neurotrophic factor in adult rat brain[J]. Neuroscience, 1996, 74(4): 1209-1226. 

[34] Kapczinski F, Frey B N, Andreazza A C, et al. Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes[J]. Brazilian Journal of Psychiatry, 2008, 30: 243-245. 

[35] Ling Hongyan, Zhu Zemei, Yang Jihua, et al. Dihydromyricetin improves type 2 diabetes-induced cognitive impairment via suppressing oxidative stress and enhancing brain-derived neurotrophic factor-mediated neuroprotection in mice.[J]. Acta biochimica et biophysica Sinica, 2018, 50(3):298-306.

[36] Amanollahi Mobina, Jameie Melika, Heidari Arash, et al. The Dialogue Between Neuroinflammation and Adult Neurogenesis: Mechanisms Involved and Alterations in Neurological Diseases.[J]. Molecular neurobiology, 2022, 60(2):923-959.

[37] Sun Z Z, Huang X X, Lin N, et al. Dihydromyricin alleviates doxorubicin-induced myocardial injury by inhibiting NLRP3 inflammasome in rats[J]. Zhonghua Bing li xue za zhi= Chinese Journal of Pathology, 2020, 49(10): 1046-1051.

[38] Chang Y, Yuan L, Liu J, et al. Dihydromyricetin attenuates Escherichia coli lipopolysaccharide-induced ileum injury in chickens by inhibiting NLRP3 inflammasome and TLR4/NF-κB signalling pathway[J]. Veterinary Research, 2020, 51: 1-12.

[39] Lu M, Liu R, Chen Z, et al. Effects of dietary dihydromyricetin on growth performance, antioxidant capacity, immune response and intestinal microbiota of shrimp (Litopenaeus vannamei)[J]. Fish & Shellfish Immunology, 2023, 142: 109086.

[40] Guo T , Zhang D, Zeng Y , et al. Molecular and cellular mecha-nisms underlying the pathogenesis of Alzheimer's disease[J]. WolNeurodegener ,2020 ,15(1) :40.

[41] Prajit R, Sritawan N, Suwannakot K, et al. Chrysin protects against memory and hippocampal neurogenesis depletion in D-galactose-induced aging in rats[J]. Nutrients, 2020, 12(4): 1100.

[42] Qian Jianan, Wang Xue, Cao Ji, et al. Dihydromyricetin attenuates D-galactose-induced brain aging of mice via inhibiting oxidative stress and neuroinflammation.[J]. Neuroscience letters, 2021, 756:135963.

[43] Gibson C J, Hossain M M, Richardson J R, et al. Inflammatory regulation of ATP binding cassette efflux transporter expression and function in microglia[J]. Journal of Pharmacology and Experimental Therapeutics, 2012, 343(3): 650-660.

[44] Pei H, Han C, Bi J, et al. Dihydromyricetin suppresses inflammatory injury in microglial cells to improve neurological behaviors of Alzheimer's disease mice via the TLR4/MD2 signal[J]. International Immunopharmacology, 2023, 118: 110037.

[45] Al Omran A J, Watanabe S, Hong E C, et al. Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF[J]. Neurobiology of Stress, 2022, 21: 100499.

[46] Wei Y, Hu Y, Qi K, et al. Dihydromyricetin improves LPS-induced sickness and depressive-like behaviors in mice by inhibiting the TLR4/Akt/HIF1a/NLRP3 pathway[J]. Behavioural Brain Research, 2022, 423: 113775.

[47] Jia Longgang, Wang Ying, Sang Jingcheng, et al. Dihydromyricetin inhibits α-synuclein aggregation, disrupts preformed fibrils and protects neuronal cells in culture against amyloid-induced cytotoxicity.[J]. Journal of agricultural and food chemistry, 2019, 67(14):3946-3955.

[48] Su DL,et al.The acute toxicological evaluation of dihydromyricetin and its control effect for alcoholic hepatic injury[J].Hunan Agric Sci,2009,230:90-93.

[49] Zhong ZX,et al.Experimental research on total flavone of Ampelopsis grossedentata from Guangxi in liver protection[J].Guangxi Sci,2002,9:57-59.

[50] Zhou YC,et al.Toxicological assessment on Ampelopsis grossedentata and its immune regulation study[J].Pract Prev Med,2001,8:412-414.

[51] El Banna N, Hatem E, Heneman-Masurel A, et al. Redox modifications of cysteine-containing proteins, cell cycle arrest and translation inhibition: involvement in vitamin C-induced breast cancer cell death[J]. Redox biology, 2019, 26: 101290.

[52] Akbay E, Erdem B, Ünlü A, et al. Effects of N-acetyl cysteine, vitamin E and vitamin C on liver glutathione levels following amiodarone treatment in rats[J]. Kardiochirurgia i Torakochirurgia Polska/Polish Journal of Thoracic and Cardiovascular Surgery, 2019, 16(2): 88-92.

[53] Li W, Sang H, Xu X, et al. Protective effect of dihydromyricetin on vascular smooth muscle cell apoptosis induced by hydrogen peroxide in rats[J]. Perfusion, 2023, 38(3): 491-500.

[54] Zhang J, Wu J, Liu F, et al. Neuroprotective effects of anthocyanins and its major component cyanidin-3-O-glucoside (C3G) in the central nervous system: An outlined review[J]. European journal of pharmacology, 2019, 858: 172500.

[55] Zhang J, Yu J, Chen Y, et al. Exogenous hydrogen sulfide supplement attenuates isoproterenol‐induced myocardial hypertrophy in a Sirtuin 3‐dependent manner[J]. Oxidative Medicine and Cellular Longevity, 2018, 2018(1): 9396089.

[56] Zhang X, Bi X. Post-stroke cognitive impairment: a review focusing on molecular biomarkers[J]. Journal of Molecular Neuroscience, 2020, 70(8): 1244-1254.