Letter to the editor
Recent studies on myricetin and its biological and pharmacological activities
Priscilla Nadalin1, Jae Kwang Kim2, Sang Un Park1[*]
1Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea2Division of Life Sciences and Convergence Research Center for Insect Vectors, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea
EXCLI J 2023;22:Doc1223
Flavonoids are compounds characterized by a 15-carbon skeleton structure (also abbreviated as C6-C3-C6) containing two aromatic ring systems (A and B rings) and a heterocyclic ring (C) (Kumar and Pandey, 2013[37]; Dias et al., 2021[19]). Among these, flavonols have an unsaturated C ring at the C2-C3 position, which is hydroxylated at C3 and oxidized at C4. The main flavonols are myricetin (MYR), quercetin, kaempferol, isorhamnetin, and fisetin (Kim et al., 2006[35]; Spiegel et al., 2020[61]).
MYR (3,3′,4′,5,5′,7-hexahydroxyflavone) is a flavonol (Ong and Khoo, 1997[48]) derived from the parent compound taxifolin, which is turned into the (+)-dihydromyricetin intermediate and can be further chemically modified to produce laricitrin and then syringetin, both molecules in the flavonol class of flavonoids (Flamini et al., 2013[21]).
MYR is present in various fruits, vegetables, tea, berries and red wine. MYR's augmented biological activity in comparison with other flavonols is due to the pyrogallol B-ring, and the more hydroxylated structure. MYR is found in the Myricaceae, Anacardiaceae, Polygonaceae, Pinaceae and Primulaceae families (Gupta et al., 2020[24]; Taheri et al., 2020[65]). MYR displays an array of biological and pharmacological activities such as antioxidant, anti-amyloidogenic, antibacterial, antiviral, antidiabetic, anticancer, anti-inflammatory, anti-epileptic and anti-ulcer (Imran et al., 2021[28]; Pluta et al., 2021[52]; Agraharam et al., 2022[1]; Javed et al., 2022[30]). Because of such a range of properties, MYR has been the object of great attention in recent years for its uses in the pharmaceutical, food, and cosmetic industries. The present letter summarizes recent key research on the biological and pharmacological properties of MYR (Table 1(Tab. 1); References in Table 1: Ahmad et al., 2022[2]; Akhtar et al., 2020[3]; Alidadi et al., 2022[4]; Alqarni et al., 2022[5]; Aminzadeh and Bashiri, 2020[6]; Aminzadeh and Salarinejad, 2021[8]; Aminzadeh et al., 2023[7]; Anwar et al., 2022[9]; Arafah et al., 2022[10]; Bai et al., 2021[11]; Berköz et al., 2020[12]; Chen et al., 2021[13], 2023[14]; Choi et al., 2021[15]; Dai et al., 2021[16]; Dang et al., 2023[17]; Deng et al., 2021[18]; Dubey et al., 2020[20]; Gao et al., 2023[22]; Gaspar et al., 2020[23]; Han et al., 2022[25]; Huang et al., 2020[26]; Ikeji et al., 2023[27]; Jang et al., 2020[29]; Ji et al., 2022[31]; Jing et al., 2021[32]; Kan et al., 2021[33]; Kang et al., 2020[34]; Kimura et al., 2021[36]; Lalitha et al., 2020[38]; Li et al., 2022[39], 2023[40]; Lin et al., 2020[41]; Liu et al., 2022[42], 2023[43]; Lv et al., 2021[44]; Ma et al., 2021[45]; Nafee et al., 2020[46]; Nie et al., 2023[47]; Pan et al., 2023[49]; Park et al., 2021[50]; Peng et al., 2022[51]; Prajapati et al., 2020[53]; Qu et al., 2020[54]; Rajendran et al., 2021[55]; Rostami et al., 2023[56]; Salimi et al., 2021[57]; Sharma et al., 2023[58]; Soleimani and Sajedi, 2020[59]; Song et al., 2021[60]; Sun et al., 2021[62]; Sur and Lee, 2022[63][64]; Wang et al., 2020[67], 2022[66], 2023[68]; Xiao et al., 2021[69]; Xu et al., 2022[70]; Yang et al., 2022[71]; Yao et al., 2022[72]; Ying et al., 2020[73]; Zhang et al., 2020[74]; Zhao et al., 2022[75]; Zhu et al., 2020[76]).
Notes
Priscilla Nadalin and Jae Kwang Kim contributed equally as first author.
Declaration
Acknowledgments
This study was carried out with the support of 'R&D Program for Forest Science Technology (Project No. 2021379B10-2123-BD02)' provided by Korea Forest Service (Korea Forestry Promotion Institute).
Conflict of interest
The authors declare no conflict of interest.
References
1. Agraharam G, Girigoswami A, Girigoswami K. Myricetin: a multifunctional flavonol in biomedicine. Curr Pharmacol Rep. 2022;8(1):48-61
2. Ahmad SB, Rashid SM, Wali AF, Ali S, Rehman MU, Maqbool MT, et al. Myricetin (3, 3′, 4′, 5, 5′, 7-hexahydroxyflavone) prevents ethanol-induced biochemical and inflammatory damage in the liver of Wistar rats. Hum Exp Toxicol. 2022;41:09603271211066843
3. Akhtar S, Najafzadeh M, Isreb M, Newton L, Gopalan RC, Anderson D. An in vitro investigation into the protective and genotoxic effects of myricetin bulk and nano forms in lymphocytes of MGUS patients and healthy individuals. Toxicol Lett. 2020;327:33-40
4. Alidadi H, Ashtari A, Samimi A, Karami MA, Khorsandi L. Myricetin loaded in solid lipid nanoparticles induces apoptosis in the HT-29 colorectal cancer cells via mitochondrial dysfunction. Mol Biol Rep. 2022;49:8537-45
5. Alqarni MH, Foudah AI, Muharram MM, Alam A, Labrou NE. Myricetin as a potential adjuvant in chemotherapy: studies on the inhibition of human glutathione transferase A1–1. Biomolecules. 2022;12(10):1364
6. Aminzadeh A, Bashiri H. Myricetin ameliorates high glucose‐induced endothelial dysfunction in human umbilical vein endothelial cells. Cell Biochem Funct. 2020;38(1):12-20
7. Aminzadeh A, Darijani MH, Bashiri H. Investigating the effect of myricetin against arsenic-induced cardiac toxicity in rats. Toxicol Res (Camb). 2023;12(1):117-23
8. Aminzadeh A, Salarinejad A. Effects of myricetin against cadmium-induced neurotoxicity in PC12 cells. Toxicol Res (Camb). 2021;10(1):84-90
9. Anwar S, Khan S, Anjum F, Shamsi A, Khan P, Fatima H, et al. Myricetin inhibits breast and lung cancer cells proliferation via inhibiting MARK4. J Cell Biochem. 2022;123:359-74
10. Arafah A, Rehman MU, Ahmad A, AlKharfy KM, Alqahtani S, Jan BL, et al. Myricetin (3, 3′, 4′, 5, 5′, 7-Hexahydroxyflavone) Prevents 5-Fluorouracil-Induced Cardiotoxicity. ACS Omega. 2022;7:4514-24
11. Bai Y, Liu X, Chen Q, Chen T, Jiang N, Guo Z. Myricetin ameliorates ox-LDL-induced HUVECs apoptosis and inflammation via lncRNA GAS5 upregulating the expression of miR-29a-3p. Sci Rep. 2021;11(1):19637
12. Berköz M, Yıldırım M, Yalın S, İlhan M, Yunusoğlu O. Myricetin inhibits angiotensin converting enzyme and induces nitric oxide production in HUVEC cell line. Gen Physiol Biophys. 2020;39:249-58
13. Chen G, Xu H, Wu Y, Han X, Xie L, Zhang G, et al. Myricetin suppresses the proliferation and migration of vascular smooth muscle cells and inhibits neointimal hyperplasia via suppressing TGFBR1 signaling pathways. Phytomedicine. 2021;92:153719
14. Chen T, Hu Y, Lu L, Zhao Q, Tao X, Ding B, et al. Myricetin attenuates hypoxic-ischemic brain damage in neonatal rats via NRF2 signaling pathway. Front Pharmacol. 2023;14:1134464
15. Choi HN, Shin JY, Kim JI. Ameliorative effect of myricetin on nonalcoholic fatty liver disease in ob/ob mice. J Med Food. 2021;24:1092-9
16. Dai B, Zhong T, Chen ZX, Chen W, Zhang N, Liu XL, et al. Myricetin slows liquid–liquid phase separation of tau and activates ATG5-dependent autophagy to suppress tau toxicity. J Biol Chem. 2021;297(4):101222
17. Dang B, Hu S, Zhang Y, Huang Y, Zhang T, An H. Myricetin served as antagonist for negatively regulate MRGPRX2 mediated pseudo-allergic reactions through CD300f/SHP1/SHP2 phosphorylation. Int Immunopharmacol. 2023;118:110034
18. Deng H, Liu S, Pan D, Jia Y, Ma ZG. Myricetin reduces cytotoxicity by suppressing hepcidin expression in MES23. 5 cells. Neural Regen Res. 2021;16:1105-10
19. Dias MC, Pinto DC, Silva AM. Plant flavonoids: Chemical characteristics and biological activity. Molecules. 2021;26(17):5377
20. Dubey R, Kulkarni SH, Dantu SC, Panigrahi R, Sardesai DM, Malik N, et al. Myricetin protects pancreatic β-cells from human islet amyloid polypeptide (hIAPP) induced cytotoxicity and restores islet function. Biol Chem. 2020;402:179-94
21. Flamini R, Mattivi F, De Rosso M, Arapitsas P, Bavaresco L. Advanced knowledge of three important classes of grape phenolics: anthocyanins, stilbenes and flavonols. Int J Mol Sci. 2013;14:19651-69
22. Gao L, Tang Z, Li T, Wang J. Myricetin exerts anti-biofilm activity and attenuates osteomyelitis by inhibiting the TLR2/MAPK pathway in experimental mice. Microb Pathog. 2023;182:106165
23. Gaspar RS, da Silva SA, Stapleton J, Fontelles JLdL, Sousa HR, Chagas VT, et al. Myricetin, the main flavonoid in Syzygium cumini leaf, is a novel inhibitor of platelet thiol isomerases PDI and ERp5. Front Pharmacol. 2020;10:1678
24. Gupta G, Siddiqui MA, Khan MM, Ajmal M, Ahsan R, Rahaman MA, et al. Current pharmacological trends on myricetin. Drug Res (Stuttg). 2020;70:448-54
25. Han J, Cheng C, Zhang J, Fang J, Yao W, Zhu Y, et al. Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells. Front Pharmacol. 2022;13:959938
26. Huang P, Zhou M, Cheng S, Hu Y, Gao M, Ma Y, et al. Myricetin possesses anthelmintic activity and attenuates hepatic fibrosis via modulating TGFβ1 and Akt signaling and shifting Th1/Th2 balance in Schistosoma japonicum-infected mice. Front Immunol. 2020;11:593
27. Ikeji CN, Adedara IA, Farombi EO. Dietary myricetin assuages atrazine-mediated hypothalamic-pituitary–testicular axis dysfunction in rats. Environ Sci Pollut Res Int. 2023;30:15655-70
28. Imran M, Saeed F, Hussain G, Imran A, Mehmood Z, Gondal TA, et al. Myricetin: A comprehensive review on its biological potentials. Food Sci Nutr. 2021;9:5854-68
29. Jang JH, Lee SH, Jung K, Yoo H, Park G. Inhibitory effects of myricetin on lipopolysaccharide-induced neuroinflammation. Brain Sci. 2020;10(1):32
30. Javed Z, Khan K, Herrera-Bravo J, Naeem S, Iqbal MJ, Raza Q, et al. Myricetin: targeting signaling networks in cancer and its implication in chemotherapy. Cancer Cell Int. 2022;22(1):239
31. Ji A, Hu L, Ma D, Qiang G, Yan D, Zhang G, et al. Myricetin induces apoptosis and protective autophagy through endoplasmic reticulum stress in hepatocellular carcinoma. Evid Based Complement Alternat Med. 2022;2022:3115312
32. Jing S, Wang L, Wang T, Fan L, Chen L, Xiang H, et al. Myricetin protects mice against MRSA-related lethal pneumonia by targeting ClpP. Biochem Pharmacol. 2021;192:114753
33. Kan X, Liu J, Chen Y, Guo W, Xu D, Cheng J, et al. Protective effect of myricetin on LPS-induced mastitis in mice through ERK1/2 and p38 protein author. Naunyn Schmiedebergs Arch Pharmacol. 2021;394:1727-35
34. Kang HR, Moon JY, Ediriweera MK, Song YW, Cho M, Kasiviswanathan D, et al. Dietary flavonoid myricetin inhibits invasion and migration of radioresistant lung cancer cells (A549‐IR) by suppressing MMP‐2 and MMP‐9 expressions through inhibition of the FAK‐ERK signaling pathway. Food Sci Nutr. 2020;8:2059-67
35. Kim JD, Liu L, Guo W, Meydani M. Chemical structure of flavonols in relation to modulation of angiogenesis and immune-endothelial cell adhesion. J Nutr Biochem. 2006;17:165-76
36. Kimura AM, Tsuji M, Yasumoto T, Mori Y, Oguchi T, Tsuji Y, et al. Myricetin prevents high molecular weight Aβ1-42 oligomer-induced neurotoxicity through antioxidant effects in cell membranes and mitochondria. Free Radic Biol Med. 2021;171:232-44
37. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal. 2013;2013:162750
38. Lalitha N, Sadashivaiah B, Ramaprasad TR, Singh SA. Anti-hyperglycemic activity of myricetin, through inhibition of DPP-4 and enhanced GLP-1 levels, is attenuated by co-ingestion with lectin-rich protein. PloS One. 2020;15(4):e0231543
39. Li L, Ma H, Li D, Shu Q, Wang T, Song X, et al. Myricetin alleviates the formaldehyde-enhanced Warburg effect in tumor cells through inhibition of HIF-1α. Toxicol Appl Pharmacol. 2022;454:116246
40. Li T, Wang L, Wu L, Xie Y, Chang M, Wang D, et al. Integrated metabolomics and network pharmacology investigation of cardioprotective effects of myricetin after 1-week high-intensity exercise. Nutrients. 2023;15(6):1336
41. Lin X, Lin CH, Liu R, Li C, Jiao S, Yi X, et al. Myricetin against myocardial injury in rat heat stroke model. Biomed Pharmacother. 2020;127:110194
42. Liu JS, Fang WK, Yang SM, Wu MC, Chen TJ, Chen CM, et al. Natural product myricetin is a pan-KDM4 inhibitor which with poly lactic-co-glycolic acid formulation effectively targets castration-resistant prostate cancer. J Biomed Sci. 2022;29(1):29
43. Liu P, Zhou Y, Shi J, Wang F, Yang X, Zheng X, et al. Myricetin improves pathological changes in 3× Tg-AD mice by regulating the mitochondria-NLRP3 inflammasome-microglia channel by targeting P38 MAPK signaling pathway. Phytomedicine. 2023;115:154801
44. Lv Q, Lv Y, Dou X, Wassy SL, Jia G, Wei L, et al. Myricetin inhibits the type III secretion system of Salmonella enterica serovar typhimurium by downregulating the Salmonella pathogenic island I gene regulatory pathway. Microb Pathog. 2021;150:104695
45. Ma H, Song X, Huang P, Zhang W, Ling X, Yang X, et al. Myricetin protects natural killer cells from arsenite induced DNA damage by attenuating oxidative stress and retaining poly (ADP-Ribose) polymerase 1 activity. Mutat Res Genet Toxicol Environ Mutagen. 2021;865:503337
46. Nafee N, Gaber DM, Elzoghby AO, Helmy MW, Abdallah OY. Promoted antitumor activity of myricetin against lung carcinoma via nanoencapsulated phospholipid complex in respirable microparticles. Pharm Res. 2020;37(4):82
47. Nie N, Li Z, Li W, Huang X, Jiang Z, Shen Y. Myricetin ameliorates experimental autoimmune myocarditis in mice by modulating immune response and inhibiting MCP-1 expression. Eur J Pharmacol. 2023;942:175549
48. Ong KC, Khoo HE. Biological effects of myricetin. Gen Pharmacol. 1997;29:121-6
49. Pan H, He J, Yang Z, Yao X, Zhang H, Li R, et al. Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice. Phytomedicine. 2023;116:154858
50. Park HS, Seo CS, Baek EB, Rho JH, Won YS, Kwun HJ. Gastroprotective effect of myricetin on ethanol-induced acute gastric injury in rats. Evid Based Complement Alternat Med. 2021;2021:9968112
51. Peng S, Fang C, He H, Song X, Zhao X, Zou Y, et al. Myricetin exerts its antiviral activity against infectious bronchitis virus by inhibiting the deubiquitinating activity of papain-like protease. Poult Sci. 2022;101(3):101626
52. Pluta R, Januszewski S, Czuczwar SJ. Myricetin as a promising molecule for the treatment of post-ischemic brain neurodegeneration. Nutrients. 2021;13(2):342
53. Prajapati KP, Singh AP, Dubey K, Ansari M, Temgire M, Anand BG, et al. Myricetin inhibits amyloid fibril formation of globular proteins by stabilizing the native structures. Colloids Surf B Biointerfaces. 2020;186:110640
54. Qu X, Li Q, Song Y, Xue A, Liu Y, Qi D, et al. Potential of myricetin to restore the immune balance in dextran sulfate sodium-induced acute murine ulcerative colitis. J Pharm Pharmacol. 2020;72:92-100
55. Rajendran P, Maheshwari U, Muthukrishnan A, Muthuswamy R, Anand K, Ravindran B, et al. Myricetin: Versatile plant based flavonoid for cancer treatment by inducing cell cycle arrest and ROS–reliant mitochondria-facilitated apoptosis in A549 lung cancer cells and in silico prediction. Mol Cell Biochem. 2021;476:57-68
56. Rostami A, Baluchnejadmojarad T, Roghani M. Hepatoprotective effect of myricetin following lipopolysaccharide/DGalactosamine: Involvement of autophagy and sirtuin 1. Curr Mol Pharmacol. 2023;16:419-33
57. Salimi A, Jamali Z, Shabani M. Antioxidant potential and inhibition of mitochondrial permeability transition pore by myricetin reduces aluminium phosphide-induced cytotoxicity and mitochondrial impairments. Front Pharmacol. 2021;12:719081
58. Sharma S, Tomar VR, Deep S. Myricetin: A potent anti-amyloidogenic polyphenol against superoxide dismutase 1 aggregation. ACS Chem Neurosci. 2023;14:2461-75
59. Soleimani M, Sajedi N. Myricetin apoptotic effects on T47D breast cancer cells is a P53-independent approach. Asian Pac J Cancer Prev. 2020;21:3697-704
60. Song X, Rao H, Guo C, Yang B, Ren Y, Wang M, et al. Myricetin exhibit selective anti-lymphoma activity by targeting BTK and is effective via oral administration in vivo. Phytomedicine. 2021;93:153802
61. Spiegel M, Andruniów T, Sroka Z. Flavones’ and flavonols’ antiradical structure–activity relationship—A quantum chemical study. Antioxidants (Basel). 2020;9(6):461
62. Sun WL, Li XY, Dou HY, Wang XD, Li JD, Shen L, et al. Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota. Cell Rep. 2021;36(9):109641
63. Sur B, Lee B. Myricetin Inhibited fear and anxiety-like behaviors by HPA axis regulation and activation of the BDNF-ERK signaling pathway in posttraumatic stress disorder rats. Evid Based Complement Alternat Med. 2022;2022:8320256
64. Sur B, Lee B. Myricetin prevents sleep deprivation-induced cognitive impairment and neuroinflammation in rat brain via regulation of brain-derived neurotropic factor. Korean J Physiol Pharmacol. 2022;26:415-25
65. Taheri Y, Suleria HAR, Martins N, Sytar O, Beyatli A, Yeskaliyeva B, et al. Myricetin bioactive effects: Moving from preclinical evidence to potential clinical applications. BMC Complement Med Ther. 2020;20(1):241
66. Wang M, Ren S, Bi Z, Zhang L, Cui M, Sun R, et al. Myricetin reverses epithelial–endothelial transition and inhibits vasculogenic mimicry and angiogenesis of hepatocellular carcinoma by directly targeting PAR1. Phytother Res. 2022;36:1807-21
67. Wang T, Zhang P, Lv H, Deng X, Wang J. A natural dietary flavone myricetin as an α-hemolysin inhibitor for controlling Staphylococcus aureus infection. Front Cell Infect Microbiol. 2020;10:330
68. Wang X, Sun Y, Li P, Wu Z, Chen Y, Fu Y, et al. The protective effects of myricetin against acute liver failure via inhibiting inflammation and regulating oxidative stress via Nrf2 signaling. Nat Prod Res. 2023;37:798-802
69. Xiao T, Cui M, Zheng C, Wang M, Sun R, Gao D, et al. Myricetin inhibits SARS-CoV-2 viral replication by targeting Mpro and ameliorates pulmonary inflammation. Front Pharmacol. 2021;12:669642
70. Xu B, Mo X, Chen J, Yu H, Liu Y. Myricetin inhibits α‐synuclein amyloid aggregation by delaying the liquid‐to‐solid phase transition. Chembiochem. 2022;23(16):e202200216
71. Yang W, Yang M, Tian Y, Jiang Q, Loor JJ, Cao J, et al. Effect of myricetin on lipid metabolism in primary calf hepatocytes challenged with long-chain fatty acids. Metabolites. 2022;12(11):1071
72. Yao X, Zhang J, Lu Y, Deng Y, Zhao R, Xiao S. Myricetin restores Aβ-induced mitochondrial impairments in N2a-SW cells. ACS Chem Neurosci. 2022;13:454-63
73. Ying X, Chen X, Wang T, Zheng W, Chen L, Xu Y. Possible osteoprotective effects of myricetin in STZ induced diabetic osteoporosis in rats. Eur J Pharmacol. 2020;866:172805
74. Zhang S, Xiao L, Lv L, Sang S. Trapping methylglyoxal by myricetin and its metabolites in mice. J Agric Food Chem. 2020;68:9408-14
75. Zhao Z, Chen Y, Li X, Zhu L, Wang X, Li L, et al. Myricetin relieves the symptoms of type 2 diabetes mice and regulates intestinal microflora. Biomed Pharmacother. 2022;153:113530
76. Zhu Ml, Zhang PM, Jiang M, Yu SW, Wang L. Myricetin induces apoptosis and autophagy by inhibiting PI3K/Akt/mTOR signalling in human colon cancer cells. BMC Complement Med Ther. 2020;20(1):209
[*] Corresponding Author:
Sang Un Park, Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea; Tel.: +82-42-821-5730, Fax: +82-42-822-2631, eMail: supark@cnu.ac.kr