二氢杨梅素药理作用研究进展
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摘要
二氢杨梅素是藤茶中的主要活性成分之一,属于黄酮类化合物,既往研究证实具有抗肿瘤、抗氧化、抗炎、抗微生物等作用,近年来研究发现其药理作用多样,有抗皮肤老化、解酒、保肝、降血糖、保护心血管及神经系统等功效,表明二氢杨梅素极具药用及保健价值。本文就其药理作用研究进展作一综述,以期促进其药理作用的开发利用。
Dihydromyricetin is one of the main active constituents of vine tea,belonging to flavonoids.Previous studies have proved that it has anti-tumor,antioxidant,anti-inflammatory,and anti-microbial effects. In recent years,a variety of pharmacological effects have been found,such as anti-skin aging,alcoholism,liver prptection,blood sugar reduction,protection of cardiovascular and nervous systems,indicating that dihydromyricetin is of great medicinal and health value. In this paper,the pharmacological action and mechanism of dihydromyricetin are reviewed,so as to promote the development and clinical application of dihydromyricetin.
Dihydromyricetin is one of the main active constituents of vine tea,belonging to flavonoids.Previous studies have proved that it has anti-tumor,antioxidant,anti-inflammatory,and anti-microbial effects. In recent years,a variety of pharmacological effects have been found,such as anti-skin aging,alcoholism,liver prptection,blood sugar reduction,protection of cardiovascular and nervous systems,indicating that dihydromyricetin is of great medicinal and health value. In this paper,the pharmacological action and mechanism of dihydromyricetin are reviewed,so as to promote the development and clinical application of dihydromyricetin.
引文
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[2] WU S,LIU B,ZHANG Q,et al. Dihydromyricetin reduced Bcl-2 expression via p53 in human hepatoma HepG2 cells[J]. PloS One,2013,8(11):e76886.
[3] LIU B,ZHOU W,CHEN X,et al. Dihydromyricetin induces mouse hepatoma Hepal-6 cell apoptosis via the transforming growth factor-βpathway[J]. Mol Med Rep,2015,11(3):1609-1614.
[4] XIA J,GUO S,FANG T,et al. Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of m TOR and regulating its upstream pathways[J]. Food Chem Toxicol,2014,66(4):7-13.
[5] CHEN XM,XIE XB,ZHAO Q,et al. Ampelopsin induces apoptosis by regulating multiple c-Myc/S-phase kinase-associated protein 2/F-box and WD repeat-containing protein 7/histone deacetylase 2 pathways in human lung adenocarcinoma cells[J].Mol Med Rep,2015,11(1):105-112.
[6] QI S,KOU X,LV J,et al. Ampelopsin induces apoptosis in HepG2 human hepatoma cell line through extrinsic and intrinsic pathways:Involvement of P38 and ERK[J]. Environ Toxicol Pharmacol,2015,40(3):847-854.
[7] LIU C,ZHAO P,YANG Y,et al. Ampelopsin suppresses TNF-α-induced migration and invasion of U2OS osteosarcoma cells[J].Mol Med Rep,2016,13(6):4729-4736.
[8] ZHANG QY,LI R,ZENG GF,et al. Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression[J]. World J Gastroenterol 2014,20(29):10082-10093.
[9] HUANG H,HU M,ZHAO R,et al. Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathway[J]. Oncol Rep,2013,30(5):2467-2475.
[10] NI F,GONG Y,LI L,et al. Flavonoid ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice[J].PLoS One,2012,7(6):e38802.
[11] ALTIERI DC. Validating survivin as a cancer therapeutic target[J]. Nat Rev Cancer,2003,3(1):46-54.
[12] XU Y,WANG S,CHAN HF,et al. Dihydromyricetin induces apoptosis and reverses drug resistance in ovarian cancer cells by p53-mediated downregulation of survivin[J]. Sci Rep,2017,7:46060.
[13] WANG Z,SUN X,FENG Y,et al. Dihydromyricetin reverses MRP2-mediated MDR and enhances anticancer activity induced by oxaliplatin in colorectal cancer cells[J]. Anticancer Drugs,2017,28(3):281-288.
[14] HE MH,ZHANG Q,SHU G,et al. Dihydromyricetin sensitizes human acute myeloid leukemia cells to retinoic acid-induced myeloid differentiation by activating STAT1[J]. Biochem Biophys Res Commun,2018,495(2):1702-1707.
[15]黄晔,游淑梅,沈杨炳.二氢杨梅素通过SIRT1/JNK途径提高耐药恶性黑素瘤细胞对卡铂的敏感性[J].中国现代应用药学,2017,34(12):1689-1694.
[16] ZHU H,LUO P,FU Y,et al. Dihydromyricetin prevents cardiotoxicity and enhances anticancer activity induced by adriamycin[J].Oncotarget,2015,6(5):3254-3267.
[17] WU F,LI Y,SONG H,et al. Preventive effect of dihydromyricetin against cisplatin-induced nephrotoxicity in vitro and in vivo[J].Evid Based Complement Alternat Med,2016,2016:7937385.
[18] YE XL,LU LQ,LI W,et al. Oral administration of ampelopsin protects against acute brain injury in rats following focal cerebral ischemia[J]. Exp Ther Med,2017,13(5):2373-2374.
[19] LIU P,ZOU D,CHEN K,et al. Dihydromyricetin improves hypobaric hypoxia-induced memory impairment via modulation of SIRT3 signaling[J]. Mol Neurobiol,2016,54(3):7200-7212.
[20] ZHU X. Inhibition of catechol-o-methyltransferase(COMT)by myricetin,dihydromyricetin, and myricitrin[J]. Pharmazie,2014,69(3):183-186.
[21] REN ZX,ZHAO YF,CAO T. Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson's disease by suppressing glycogen synthase kinase-3 beta activity[J]. Acta Pharmacol Sin,2017,38(5):733.
[22] MU S,LI Y,LIU B,et al. Dihydromyricetin ameliorates 3NP-induced behavioral deficits and striatal injury in rats[J]. J Mol Neurosci,2016,60(2):267-275.
[23] LIANG J,LPEZ-VALDS HE,MARTNEZ-CORIA H,et al. Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of transgenic mouse models of Alzheimer's disease[J].Neurochem Res,2014,39(6):1171-1181.
[24] REN Z,YAN P,ZHU L,et al. Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of euroinflammation[J]. Psychopharmacology(Berl),2018,235(1):233-244.
[25] WU Y,BAI J,ZHONG K,et al. A dual antibacterial mechanism involved in membrane disruption and DNA binding of 2R,3R-dihydromyricetin from pine needles of Cedrus deodara against Staphylococcus aureus[J]. Food Chem,2017,218:463-470.
[26]傅若秋,卢来春,李卓恒,等. 31种中药单体对耐甲氧西林金黄色葡萄球菌的抗菌作用研究[J].中国药业,2014,23(4):20-22.
[27] DALCIN AJF,SANTOS CG,GNDEL SS,et al. Anti biofilm effect of dihydromyricetin-loaded nanocapsules on urinary catheterinfected by Pseudomonas aeruginosa[J]. Colloids Surf B Biointerfaces,2017,156(5):282-291.
[28] LIU DY,YE JT,YANG WH,et al. Ampelopsin,a small molecule inhibitor of HIV-1 infection targeting HIV entry[J]. Biomed Environ Sci,2004,17(2):153-164.
[29] SHI L,ZHANG T,ZHOU Y,et al. Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway[J]. Endocrine,2015,50(2):378-389.
[30] LE L,JIANG B,WAN W,et al. Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity[J]. Sci Rep,2016,6:36184.
[31] LIU L,WAN J,LANG H,et al. Dihydromyricetin delays the onset of hyperglycemia and ameliorates insulin resistance without excessive weight gain in Zucker diabetic fatty rats[J]. Mol Cell Endocrinol,2017,439(C):105-115.
[32] XIE C,CHEN Z,ZHANG C,et al. Dihydromyricetin ameliorates oleic acid-induced lipid accumulation in L02 and HepG2 cells by inhibiting lipo genesis and oxidative stress[J]. Life Sci,2016,157:131-139.
[33] QIU P,DONG Y,LI B,et al. Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate ethanol-induced hepatic injury[J]. Toxicol Lett,2017,274:31-41.
[34] WANG Y,FU L,WANG L,et al. Electrophysiological study on the antiarrhythmic mechanism of ampelopsin in rats[J]. Zhonghua Xin Xue Guan Bing Za Zhi,2014,42(8):675-679.
[35] LI Q,WANG J,ZHU X,et al. Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in rats[J]. Biomed Pharmacother,2017,96:825-833.
[36] WU B,LIN J,LUO J,et al. Dihydromyricetin protects against diabetic cardiomyopathy in streptozotocin-induced diabetic mice[J].Biomed Res Int,2017,2017(1):1-13.
[37] WENG L,ZHANG H,LI X,et al. Ampelopsin attenuates lipopolysaccharide-induced inflammatory response through the inhibition of the NF-κB and JAK2/STAT3 signaling pathways in microglia[J]. Int Immunopharmacol,2017,44:1-8.
[38]蔡祯艳,刘赫男,王虹,等.二氢杨梅素乙酰化衍生物的合成及其抗氧化活性研究[J].中国医药工业杂志,2016,47(1):18-21.
[39] XU B,HUANG S,WANG C,et al. Antiinflammatory effects of dihydromyricetin in a mouse model of asthma[J]. Mol Med Rep,2017,15(6):3674-3680.
[40] SONG Q,LIU L,YU J,et al. Dihydromyricetin attenuated Ang II induced cardiac fibroblasts proliferation related to inhibitory of oxidative stress[J]. Eur J Pharmacol,2017,807:159-167.
[41] RAGGATT LJ,PARTRIDGE NC. Cellular and molecular mechanisms of bone remodeling[J]. J Biol Chem,2010,285(33):25103-25108.
[42] ZHAO L,CAI C,WANG J,et al. Dihydromyricetin protects against bone loss in ovariectomized mice by suppressing osteoclast activity[J]. Front Pharmacol,2017,8:928.
[43] ZHANG W,WANG S,YIN H,et al. Dihydromyricetin enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro partially via the activation of Wnt/β-catenin signaling pathway[J]. Fundam Clin Pharmacol,2016,30(6):596-606.
[44] HE Z,ZHANG L,ZHUO C,et al. Apoptosis inhibition effect of Dihydromyricetin against UVA-exposed human keratinocyte cell line[J]. J Photochem Photobiol B,2016,161:40-49.
[45] MOON NR,KANG S. Consumption of ellagic acid and dihydromyricetin synergistically protects against UV-B induced photoaging,possibly by activating both TGF-β1 and wnt signaling pathways[J]. J Photochem Photobiol B,2017,178:92-100.
[46] LIU L,YIN X,WANG X,et al. Determination of dihydromyricetin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study[J]. Pharmaceutical Biology,2017,55(1):657-662.
[47]黄华艺,查锡良.黄酮类化合物抗肿瘤作用研究进展[J].中国新药与临床杂志,2002,21(7):428-433.
[48]何桂霞,裴刚,李斌,等.二氢杨梅素的稳定性研究[J].中国新药杂志,2007,16(22):1888-1890.
[49]黄郁梅,洪正善,杨柯,等.二氢杨梅素稳定性影响因素及抑菌活性研究进展[J].药学研究,2017,36(9):531-533,537.
[2] WU S,LIU B,ZHANG Q,et al. Dihydromyricetin reduced Bcl-2 expression via p53 in human hepatoma HepG2 cells[J]. PloS One,2013,8(11):e76886.
[3] LIU B,ZHOU W,CHEN X,et al. Dihydromyricetin induces mouse hepatoma Hepal-6 cell apoptosis via the transforming growth factor-βpathway[J]. Mol Med Rep,2015,11(3):1609-1614.
[4] XIA J,GUO S,FANG T,et al. Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of m TOR and regulating its upstream pathways[J]. Food Chem Toxicol,2014,66(4):7-13.
[5] CHEN XM,XIE XB,ZHAO Q,et al. Ampelopsin induces apoptosis by regulating multiple c-Myc/S-phase kinase-associated protein 2/F-box and WD repeat-containing protein 7/histone deacetylase 2 pathways in human lung adenocarcinoma cells[J].Mol Med Rep,2015,11(1):105-112.
[6] QI S,KOU X,LV J,et al. Ampelopsin induces apoptosis in HepG2 human hepatoma cell line through extrinsic and intrinsic pathways:Involvement of P38 and ERK[J]. Environ Toxicol Pharmacol,2015,40(3):847-854.
[7] LIU C,ZHAO P,YANG Y,et al. Ampelopsin suppresses TNF-α-induced migration and invasion of U2OS osteosarcoma cells[J].Mol Med Rep,2016,13(6):4729-4736.
[8] ZHANG QY,LI R,ZENG GF,et al. Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression[J]. World J Gastroenterol 2014,20(29):10082-10093.
[9] HUANG H,HU M,ZHAO R,et al. Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathway[J]. Oncol Rep,2013,30(5):2467-2475.
[10] NI F,GONG Y,LI L,et al. Flavonoid ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice[J].PLoS One,2012,7(6):e38802.
[11] ALTIERI DC. Validating survivin as a cancer therapeutic target[J]. Nat Rev Cancer,2003,3(1):46-54.
[12] XU Y,WANG S,CHAN HF,et al. Dihydromyricetin induces apoptosis and reverses drug resistance in ovarian cancer cells by p53-mediated downregulation of survivin[J]. Sci Rep,2017,7:46060.
[13] WANG Z,SUN X,FENG Y,et al. Dihydromyricetin reverses MRP2-mediated MDR and enhances anticancer activity induced by oxaliplatin in colorectal cancer cells[J]. Anticancer Drugs,2017,28(3):281-288.
[14] HE MH,ZHANG Q,SHU G,et al. Dihydromyricetin sensitizes human acute myeloid leukemia cells to retinoic acid-induced myeloid differentiation by activating STAT1[J]. Biochem Biophys Res Commun,2018,495(2):1702-1707.
[15]黄晔,游淑梅,沈杨炳.二氢杨梅素通过SIRT1/JNK途径提高耐药恶性黑素瘤细胞对卡铂的敏感性[J].中国现代应用药学,2017,34(12):1689-1694.
[16] ZHU H,LUO P,FU Y,et al. Dihydromyricetin prevents cardiotoxicity and enhances anticancer activity induced by adriamycin[J].Oncotarget,2015,6(5):3254-3267.
[17] WU F,LI Y,SONG H,et al. Preventive effect of dihydromyricetin against cisplatin-induced nephrotoxicity in vitro and in vivo[J].Evid Based Complement Alternat Med,2016,2016:7937385.
[18] YE XL,LU LQ,LI W,et al. Oral administration of ampelopsin protects against acute brain injury in rats following focal cerebral ischemia[J]. Exp Ther Med,2017,13(5):2373-2374.
[19] LIU P,ZOU D,CHEN K,et al. Dihydromyricetin improves hypobaric hypoxia-induced memory impairment via modulation of SIRT3 signaling[J]. Mol Neurobiol,2016,54(3):7200-7212.
[20] ZHU X. Inhibition of catechol-o-methyltransferase(COMT)by myricetin,dihydromyricetin, and myricitrin[J]. Pharmazie,2014,69(3):183-186.
[21] REN ZX,ZHAO YF,CAO T. Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson's disease by suppressing glycogen synthase kinase-3 beta activity[J]. Acta Pharmacol Sin,2017,38(5):733.
[22] MU S,LI Y,LIU B,et al. Dihydromyricetin ameliorates 3NP-induced behavioral deficits and striatal injury in rats[J]. J Mol Neurosci,2016,60(2):267-275.
[23] LIANG J,LPEZ-VALDS HE,MARTNEZ-CORIA H,et al. Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of transgenic mouse models of Alzheimer's disease[J].Neurochem Res,2014,39(6):1171-1181.
[24] REN Z,YAN P,ZHU L,et al. Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of euroinflammation[J]. Psychopharmacology(Berl),2018,235(1):233-244.
[25] WU Y,BAI J,ZHONG K,et al. A dual antibacterial mechanism involved in membrane disruption and DNA binding of 2R,3R-dihydromyricetin from pine needles of Cedrus deodara against Staphylococcus aureus[J]. Food Chem,2017,218:463-470.
[26]傅若秋,卢来春,李卓恒,等. 31种中药单体对耐甲氧西林金黄色葡萄球菌的抗菌作用研究[J].中国药业,2014,23(4):20-22.
[27] DALCIN AJF,SANTOS CG,GNDEL SS,et al. Anti biofilm effect of dihydromyricetin-loaded nanocapsules on urinary catheterinfected by Pseudomonas aeruginosa[J]. Colloids Surf B Biointerfaces,2017,156(5):282-291.
[28] LIU DY,YE JT,YANG WH,et al. Ampelopsin,a small molecule inhibitor of HIV-1 infection targeting HIV entry[J]. Biomed Environ Sci,2004,17(2):153-164.
[29] SHI L,ZHANG T,ZHOU Y,et al. Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway[J]. Endocrine,2015,50(2):378-389.
[30] LE L,JIANG B,WAN W,et al. Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity[J]. Sci Rep,2016,6:36184.
[31] LIU L,WAN J,LANG H,et al. Dihydromyricetin delays the onset of hyperglycemia and ameliorates insulin resistance without excessive weight gain in Zucker diabetic fatty rats[J]. Mol Cell Endocrinol,2017,439(C):105-115.
[32] XIE C,CHEN Z,ZHANG C,et al. Dihydromyricetin ameliorates oleic acid-induced lipid accumulation in L02 and HepG2 cells by inhibiting lipo genesis and oxidative stress[J]. Life Sci,2016,157:131-139.
[33] QIU P,DONG Y,LI B,et al. Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate ethanol-induced hepatic injury[J]. Toxicol Lett,2017,274:31-41.
[34] WANG Y,FU L,WANG L,et al. Electrophysiological study on the antiarrhythmic mechanism of ampelopsin in rats[J]. Zhonghua Xin Xue Guan Bing Za Zhi,2014,42(8):675-679.
[35] LI Q,WANG J,ZHU X,et al. Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in rats[J]. Biomed Pharmacother,2017,96:825-833.
[36] WU B,LIN J,LUO J,et al. Dihydromyricetin protects against diabetic cardiomyopathy in streptozotocin-induced diabetic mice[J].Biomed Res Int,2017,2017(1):1-13.
[37] WENG L,ZHANG H,LI X,et al. Ampelopsin attenuates lipopolysaccharide-induced inflammatory response through the inhibition of the NF-κB and JAK2/STAT3 signaling pathways in microglia[J]. Int Immunopharmacol,2017,44:1-8.
[38]蔡祯艳,刘赫男,王虹,等.二氢杨梅素乙酰化衍生物的合成及其抗氧化活性研究[J].中国医药工业杂志,2016,47(1):18-21.
[39] XU B,HUANG S,WANG C,et al. Antiinflammatory effects of dihydromyricetin in a mouse model of asthma[J]. Mol Med Rep,2017,15(6):3674-3680.
[40] SONG Q,LIU L,YU J,et al. Dihydromyricetin attenuated Ang II induced cardiac fibroblasts proliferation related to inhibitory of oxidative stress[J]. Eur J Pharmacol,2017,807:159-167.
[41] RAGGATT LJ,PARTRIDGE NC. Cellular and molecular mechanisms of bone remodeling[J]. J Biol Chem,2010,285(33):25103-25108.
[42] ZHAO L,CAI C,WANG J,et al. Dihydromyricetin protects against bone loss in ovariectomized mice by suppressing osteoclast activity[J]. Front Pharmacol,2017,8:928.
[43] ZHANG W,WANG S,YIN H,et al. Dihydromyricetin enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro partially via the activation of Wnt/β-catenin signaling pathway[J]. Fundam Clin Pharmacol,2016,30(6):596-606.
[44] HE Z,ZHANG L,ZHUO C,et al. Apoptosis inhibition effect of Dihydromyricetin against UVA-exposed human keratinocyte cell line[J]. J Photochem Photobiol B,2016,161:40-49.
[45] MOON NR,KANG S. Consumption of ellagic acid and dihydromyricetin synergistically protects against UV-B induced photoaging,possibly by activating both TGF-β1 and wnt signaling pathways[J]. J Photochem Photobiol B,2017,178:92-100.
[46] LIU L,YIN X,WANG X,et al. Determination of dihydromyricetin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study[J]. Pharmaceutical Biology,2017,55(1):657-662.
[47]黄华艺,查锡良.黄酮类化合物抗肿瘤作用研究进展[J].中国新药与临床杂志,2002,21(7):428-433.
[48]何桂霞,裴刚,李斌,等.二氢杨梅素的稳定性研究[J].中国新药杂志,2007,16(22):1888-1890.
[49]黄郁梅,洪正善,杨柯,等.二氢杨梅素稳定性影响因素及抑菌活性研究进展[J].药学研究,2017,36(9):531-533,537.