异泽兰黄素的药理作用研究进展
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摘要
异泽兰黄素是从菊科蒿属植物中分离得到的一种黄酮苷元,大量研究表明异泽兰黄素具有多种显著的药理活性,包括抗炎、抗氧化、抗肿瘤、抗过敏等,文章总结了近年来国内外关于异泽兰黄素的药理作用及其机制研究进展,以期对它的深入研究和开发提供参考。
Eupatilin is a flavonoid aglycone isolated from Artemisia species. Previous studies have shown that eupatilin has many significant pharmacological activities, including anti-inflammatory, anti-oxidation, anti-tumor and anti-allergy effects. This paper summarized the research progress on the pharmacological effects and mechanisms of eupatilin in recent years, which will provide reference for its in-depth study and new drug development.
Eupatilin is a flavonoid aglycone isolated from Artemisia species. Previous studies have shown that eupatilin has many significant pharmacological activities, including anti-inflammatory, anti-oxidation, anti-tumor and anti-allergy effects. This paper summarized the research progress on the pharmacological effects and mechanisms of eupatilin in recent years, which will provide reference for its in-depth study and new drug development.
引文
[1] Kupchan SM,Sigel CW,Hemingway RJ,et al.Tumor inhibitors-XXXIII :Cytotoxic flavones from eupatorium species[J].Tetrahedron,1969,25(8) :1603.
[2] Choi EJ,Lee S,Chae JR,et al.Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages[J].Life Sci,2011,88(25) :1121.
[3] Jung J,Ko SH,Yoo DY,et al.5,7-Dihydroxy-3,4,6-trimethoxyflavone inhibits intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 via the Akt and nuclear factor-κB-dependent pathway,leading to suppression of adhesion of monocytes and eosinophils to bronchial epithet[J].Immunology,2012,137(1) :98.
[4] Jeon JI,Ko SH,Kim YJ,et al.The flavone eupatilin inhibits eotaxin expression in an NF-κB-dependent and STAT6-independent manner[J].Scand J Immunol,2015,81(3) :166.
[5] Yu K,Li XM,Xu XL,et al.Eupatilin protects against tumor necrosis factor-α-mediated inflammation in human umbilical vein endothelial cells[J].Int J Clin Exp Med,2014,8(12) :22191.
[6] Qiao HB,Li J,Lv LJ,et al.Eupatilin inhibits microglia activation and attenuates brain injury in intracerebral hemorrhage[J].Exp Ther Med,2018,16(5) :4005.
[7] Joo M,Kim HS,Kwon TH,et al.Anti-inflammatory effects of flavonoids on TNBS-induced colitis of rats[J].Korean J Physiol Pha,2015,19(1) :43.
[8] Zhou K,Cheng R,Liu B,et al.Eupatilin ameliorates dextran sulphate sodium-induced colitis in mice partly through promoting AMPK activation[J].Phytomedicine,2018,46:46.
[9] Jeong JH,Moon SJ,Jhun JY,et al.Eupatilin exerts antinociceptive and chondroprotective properties in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes[J].Plos One,2015,10(6) :e0130882.
[10] Giangaspero A,Ponti C,Pollastro F,et al.Topical anti-inflammatory activity of eupatilin,a lipophilic flavonoid from mountain wormwood (Artemisia umbelliformis Lam.) [J].J Agr Food Chem,2009,57(17) :7726.
[11] Lee J H,Lee YJ,Lee JY,et al.Topical application of eupatilin ameliorates atopic dermatitis-like skin lesions in NC/Nga Mice [J].Ann Dermatol,2017,29(1) :61.
[12] Jegal KH,Ko HL,Park SM,et al.Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress[J].Apoptosis,2016,21(5) :642.
[13] Park JY,Lee D,Jang HJ,et al.Protective effect of Artemisia asiatica extract and its active compound eupatilin against cisplatin-induced renal damage[J].Evid-Based Compl Alt,2015 ,2015 (4):483980.
[14] Du L,Chen J,Xing Y.Eupatilin prevents H2O2-induced oxidative stress and apoptosis in human retinal pigment epithelial cells [J].Biomed Pharmacoth,2017,85:136.
[15] Choi E J,Oh HM,Na BR,et al.Eupatilin protects gastric epithelial cells from oxidative damage and down-regulates genes responsible for the cellular oxidative stress[J].Pharm Res,2008,25(6):1355.
[16] Kim M,Min YS,Sohn UD.Cytoprotective effect of eupatilin against indomethacin-induced damage in feline esophageal epithelial cells:relevance of HSP27 and HSP70[J].Arch Pharm Res,2018,41(10):1019
[17] Lee S J,Kim JI,Cheung DY,et al.Inhibitory effect of eupatilin isolated from Artemisia princeps,on NSAID induced small intestinal mucosal injury in rat[J].Eur J Intern Med,2013,24(Suppl 1) :e77.
[18] Zhong WF,Wang XH,Pan B,et al.Eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways[J].Oncol Lett,2016,12(4) :2894.
[19] Wang X,Zhu Y,Zhu L,et al.Eupatilin inhibits the proliferation of human esophageal cancer TE1 cells by targeting the Akt GSK3β and MAPK/ERK signaling cascades[J].Oncol Rep,2018,39(6).
[20] Li Y Y,Wu H,Dong YG,et al.Application of eupatilin in the treatment of osteosarcoma[J].Oncol Lett,2015,10(4) :2505.
[21] Cho J H,Lee JG,Yang YI,et al.Eupatilin,a dietary flavonoid,induces G2/M cell cycle arrest in human endometrial cancer cells[J].Food Chem Toxicol,2011,49(8) :1737.
[22] Wang Y,Hou H,Ming LI,et al.Anticancer effect of eupatilin on glioma cells through inhibition of the Notch-1 signaling pathway [J].Mol Med Rep,2016,13(2) :1141.
[23] Choi E J,Oh HM,Wee H,et al.Eupatilin exhibits a novel anti-tumor activity through the induction of cell cycle arrest and differentiation of gastric carcinoma AGS cells[J].Differentiation,2009,77(4) :412.
[24] Park B B,Yoon JS,Kim ES,et al.Inhibitory effects of eupatilin on tumor invasion of human gastric cancer MKN-1 cells[J].Tumor Biol,2013,34(2) :875.
[25] Park JY,Park DH,Jeon Y,et al.Eupatilin inhibits angiogenesis-mediated human hepatocellular metastasis by reducing MMP-2 and VEGF signaling[J].Bioorg Med Chem Lett,2018,28(19):3150.
[26] Qiao Z,Xu YW,Yang J.Eupatilin inhibits the apoptosis in H9c2 cardiomyocytes via the Akt/GSK-3β pathway following hypoxia/reoxygenation injury [J].Biomed Pharmacother,2016,82 :373.
[27] Jeong E K,Jang HJ,Kim SS,et al.Protective effect of eupatilin against renal ischemia-reperfusion injury in mice[J].Transpl Proc,2015,47(3) :757.
[28] Lee HM,Jang HJ,Kim SS,et al.Protective effect of eupatilin pretreatment against hepatic ischemia-reperfusion injury in mice[J].Transpl Proc,2016,48(4) :1226.
[29] Cai M,Phan P TT,Hong J G,et al.The neuroprotective effect of eupatilin against ischemia/reperfusion-induced delayed neuronal damage in mice[J].Eur J Pharmacol,2012,689(1-3) :104.
[30] Sapkota A,Gaire BP,Cho KS,et al.Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation[J].Plos One,2017,12(2) :e0171479.
[31] Song EH,Chung KS,Kang YM,et al.Eupatilin suppresses the allergic inflammatory response in vitro and in vivo [J].Phytomedicine,2017,42 :1.
[32] Kim J Y,Lee MS,Baek JM,et al.Massive elimination of multinucleated osteoclasts by eupatilin is due to dual inhibition of transcription and cytoskeletal rearrangement [J].Bone Rep,2015,3(Suppl 2) :83.
[33] Kang YJ,Jung UJ,Lee MK,et al.Eupatilin,isolated from Artemisia princeps Pampanini,enhances hepatic glucose metabolism and pancreatic β-cell function in type 2 diabetic mice[J].Diabetes Res Clin P,2008,82(1) :25.
[34] 李响,刘宏伟,梁杰,等.异泽兰黄素抑制瘢痕组织成纤维细胞增殖的机制[J].中国老年学杂志,2017,37(22):5495.
[35] 张朝凤,陶丽君,曹娟.异泽兰黄素在制备抗肺纤维化药物中的应用[P].中国专利,105663115A,2016 6 15.
[36] 薛燕芳,杨丽霞,范强,等.中药黄酮类化合物抗糖尿病作用机制研究述评[J].时珍国医国药,2017,28(8):1967.
[2] Choi EJ,Lee S,Chae JR,et al.Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages[J].Life Sci,2011,88(25) :1121.
[3] Jung J,Ko SH,Yoo DY,et al.5,7-Dihydroxy-3,4,6-trimethoxyflavone inhibits intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 via the Akt and nuclear factor-κB-dependent pathway,leading to suppression of adhesion of monocytes and eosinophils to bronchial epithet[J].Immunology,2012,137(1) :98.
[4] Jeon JI,Ko SH,Kim YJ,et al.The flavone eupatilin inhibits eotaxin expression in an NF-κB-dependent and STAT6-independent manner[J].Scand J Immunol,2015,81(3) :166.
[5] Yu K,Li XM,Xu XL,et al.Eupatilin protects against tumor necrosis factor-α-mediated inflammation in human umbilical vein endothelial cells[J].Int J Clin Exp Med,2014,8(12) :22191.
[6] Qiao HB,Li J,Lv LJ,et al.Eupatilin inhibits microglia activation and attenuates brain injury in intracerebral hemorrhage[J].Exp Ther Med,2018,16(5) :4005.
[7] Joo M,Kim HS,Kwon TH,et al.Anti-inflammatory effects of flavonoids on TNBS-induced colitis of rats[J].Korean J Physiol Pha,2015,19(1) :43.
[8] Zhou K,Cheng R,Liu B,et al.Eupatilin ameliorates dextran sulphate sodium-induced colitis in mice partly through promoting AMPK activation[J].Phytomedicine,2018,46:46.
[9] Jeong JH,Moon SJ,Jhun JY,et al.Eupatilin exerts antinociceptive and chondroprotective properties in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes[J].Plos One,2015,10(6) :e0130882.
[10] Giangaspero A,Ponti C,Pollastro F,et al.Topical anti-inflammatory activity of eupatilin,a lipophilic flavonoid from mountain wormwood (Artemisia umbelliformis Lam.) [J].J Agr Food Chem,2009,57(17) :7726.
[11] Lee J H,Lee YJ,Lee JY,et al.Topical application of eupatilin ameliorates atopic dermatitis-like skin lesions in NC/Nga Mice [J].Ann Dermatol,2017,29(1) :61.
[12] Jegal KH,Ko HL,Park SM,et al.Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress[J].Apoptosis,2016,21(5) :642.
[13] Park JY,Lee D,Jang HJ,et al.Protective effect of Artemisia asiatica extract and its active compound eupatilin against cisplatin-induced renal damage[J].Evid-Based Compl Alt,2015 ,2015 (4):483980.
[14] Du L,Chen J,Xing Y.Eupatilin prevents H2O2-induced oxidative stress and apoptosis in human retinal pigment epithelial cells [J].Biomed Pharmacoth,2017,85:136.
[15] Choi E J,Oh HM,Na BR,et al.Eupatilin protects gastric epithelial cells from oxidative damage and down-regulates genes responsible for the cellular oxidative stress[J].Pharm Res,2008,25(6):1355.
[16] Kim M,Min YS,Sohn UD.Cytoprotective effect of eupatilin against indomethacin-induced damage in feline esophageal epithelial cells:relevance of HSP27 and HSP70[J].Arch Pharm Res,2018,41(10):1019
[17] Lee S J,Kim JI,Cheung DY,et al.Inhibitory effect of eupatilin isolated from Artemisia princeps,on NSAID induced small intestinal mucosal injury in rat[J].Eur J Intern Med,2013,24(Suppl 1) :e77.
[18] Zhong WF,Wang XH,Pan B,et al.Eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways[J].Oncol Lett,2016,12(4) :2894.
[19] Wang X,Zhu Y,Zhu L,et al.Eupatilin inhibits the proliferation of human esophageal cancer TE1 cells by targeting the Akt GSK3β and MAPK/ERK signaling cascades[J].Oncol Rep,2018,39(6).
[20] Li Y Y,Wu H,Dong YG,et al.Application of eupatilin in the treatment of osteosarcoma[J].Oncol Lett,2015,10(4) :2505.
[21] Cho J H,Lee JG,Yang YI,et al.Eupatilin,a dietary flavonoid,induces G2/M cell cycle arrest in human endometrial cancer cells[J].Food Chem Toxicol,2011,49(8) :1737.
[22] Wang Y,Hou H,Ming LI,et al.Anticancer effect of eupatilin on glioma cells through inhibition of the Notch-1 signaling pathway [J].Mol Med Rep,2016,13(2) :1141.
[23] Choi E J,Oh HM,Wee H,et al.Eupatilin exhibits a novel anti-tumor activity through the induction of cell cycle arrest and differentiation of gastric carcinoma AGS cells[J].Differentiation,2009,77(4) :412.
[24] Park B B,Yoon JS,Kim ES,et al.Inhibitory effects of eupatilin on tumor invasion of human gastric cancer MKN-1 cells[J].Tumor Biol,2013,34(2) :875.
[25] Park JY,Park DH,Jeon Y,et al.Eupatilin inhibits angiogenesis-mediated human hepatocellular metastasis by reducing MMP-2 and VEGF signaling[J].Bioorg Med Chem Lett,2018,28(19):3150.
[26] Qiao Z,Xu YW,Yang J.Eupatilin inhibits the apoptosis in H9c2 cardiomyocytes via the Akt/GSK-3β pathway following hypoxia/reoxygenation injury [J].Biomed Pharmacother,2016,82 :373.
[27] Jeong E K,Jang HJ,Kim SS,et al.Protective effect of eupatilin against renal ischemia-reperfusion injury in mice[J].Transpl Proc,2015,47(3) :757.
[28] Lee HM,Jang HJ,Kim SS,et al.Protective effect of eupatilin pretreatment against hepatic ischemia-reperfusion injury in mice[J].Transpl Proc,2016,48(4) :1226.
[29] Cai M,Phan P TT,Hong J G,et al.The neuroprotective effect of eupatilin against ischemia/reperfusion-induced delayed neuronal damage in mice[J].Eur J Pharmacol,2012,689(1-3) :104.
[30] Sapkota A,Gaire BP,Cho KS,et al.Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation[J].Plos One,2017,12(2) :e0171479.
[31] Song EH,Chung KS,Kang YM,et al.Eupatilin suppresses the allergic inflammatory response in vitro and in vivo [J].Phytomedicine,2017,42 :1.
[32] Kim J Y,Lee MS,Baek JM,et al.Massive elimination of multinucleated osteoclasts by eupatilin is due to dual inhibition of transcription and cytoskeletal rearrangement [J].Bone Rep,2015,3(Suppl 2) :83.
[33] Kang YJ,Jung UJ,Lee MK,et al.Eupatilin,isolated from Artemisia princeps Pampanini,enhances hepatic glucose metabolism and pancreatic β-cell function in type 2 diabetic mice[J].Diabetes Res Clin P,2008,82(1) :25.
[34] 李响,刘宏伟,梁杰,等.异泽兰黄素抑制瘢痕组织成纤维细胞增殖的机制[J].中国老年学杂志,2017,37(22):5495.
[35] 张朝凤,陶丽君,曹娟.异泽兰黄素在制备抗肺纤维化药物中的应用[P].中国专利,105663115A,2016 6 15.
[36] 薛燕芳,杨丽霞,范强,等.中药黄酮类化合物抗糖尿病作用机制研究述评[J].时珍国医国药,2017,28(8):1967.