Rhapontigenin is a potent and selective inactivator of cytochrome P4501A1 with an IC50 of 0.4μM. It is 400-fold and 23-fold more selective for P4501A1 than P4501A2 and P4501B1, respectively[1]. Rhapontigenin is a natural analog of resveratrol and has anticancer, antioxidant, antifungal and antibacterial activities[2, 3].
In vitro, treatment of PC3 cells with Rhapontigenin (0, 2.5, 5, 10, 20μM) for 30min inhibited the expression of HIF-1α protein in a concentration-dependent manner and reduced the protein levels of epithelial-mesenchymal transition (EMT)-related markers N-cadherin, vimentin and the HIF-1α target gene anhydrous carbonate IX (CA9)[4]. Rhapontigenin (0-250μg/mL) treated HepG2 cells for 24h, inhibited cell viability in a concentration-dependent manner, with an IC50 of 115μg/mL[5].
In vivo, Rhapontigenin (1, 2.5, 5mg/kg/day) was injected into the tail vein to treat rats with myocardial infarction for 8 days, which improved the myocardial infarction area, heart/body mass index, creatine kinase (CK), lactate dehydrogenase (LD) and cardiac troponin-T (CTT) in rats, and significantly downregulated the expression levels of TNF-α, IL-6, MDA, SOD, p38 and iNOS[6]. Rhapontigenin (1-5mg/kg) was orally treated with hyperlipidemic rats for 4 weeks, which dose-dependently improved the pathological characteristics of degenerative fatty liver in rats and significantly reduced serum lipid levels[7].
References:
[1] Chun Y J, Ryu S Y, Jeong T C, et al. Mechanism-based inhibition of human cytochrome P450 1A1 by rhapontigenin[J]. Drug Metabolism and Disposition, 2001, 29(4): 389-393.
[2] Chen D, Liu J R, Cheng Y, et al. Metabolism of rhaponticin and activities of its metabolite, rhapontigenin: a review[J]. Current Medicinal Chemistry, 2020, 27(19): 3168-3186.
[3] Sun Y, Liang X, Cheng H, et al. Review of characteristics, pharmacology, determination and pharmacokinetics of rhaponticin[J]. Mini-Reviews in Organic Chemistry, 2017, 14(1): 24-34.
[4] Yeh Y H, Wang S W, Yeh Y C, et al. Rhapontigenin inhibits TGF-β-mediated epithelial mesenchymal transition via the PI3K/AKT/mTOR pathway and is not associated with HIF-1α degradation[J]. Oncology Reports, 2016, 35(5): 2887-2895.
[5] Roupe K A, Helms G L, Halls S C, et al. Preparative enzymatic synthesis and HPLC analysis of rhapontigenin: Applications to metabolism, pharmacokinetics and anti-cancer studies[J]. J. Pharm. Pharm. Sci, 2005, 8(3): 374-386.
[6] Fan Y. Cardioprotective effect of rhapontigenin in isoproterenol-induced myocardial infarction in a rat model[J]. Pharmacology, 2019, 103(5-6): 291-302.
[7] Jo S P, Kim J K, Lim Y H. Antihyperlipidemic effects of rhapontin and rhapontigenin from rheum undulatum in rats fed a high-cholesterol diet[J]. Planta medica, 2014, 80(13): 1067-1071.
Rhapontigenin（丹叶大黄素）是一种有效的细胞色素P4501A1选择性灭活剂，IC50为0.4μM，对P4501A1的选择性分别是P4501A2和P4501B1的400倍和23倍[1]。Rhapontigenin是白藜芦醇的天然类似物，具有抗癌、抗氧化、抗真菌和抗菌活性[2, 3]。
在体外，Rhapontigenin（0, 2.5, 5, 10, 20μM）处理PC3细胞30min，以浓度依赖性方式抑制HIF-1α蛋白的表达，降低了上皮间质转化（EMT）相关标记物N-钙粘蛋白、波形蛋白和HIF-1α靶基因无水碳酸IX（CA9）的蛋白质水平[4]。Rhapontigenin（0-250μg/mL）处理HepG2细胞24h，浓度依赖性地抑制了细胞活力，IC50为 115μg/mL[5]。
在体内，Rhapontigenin（1, 2.5, 5mg/kg/day）通过尾静脉注射治疗心肌梗死大鼠8天，改善了大鼠心肌梗死面积、心脏/体重指数、肌酸激酶（CK）、乳酸脱氢酶（LD）和心肌肌钙蛋白-T（CTT），显著下调了TNF-α、IL-6、MDA、SOD、p38和iNOS的表达水平[6]。Rhapontigenin（1-5mg/kg）通过口服治疗高脂血症大鼠4周，剂量依赖性地改善了大鼠退化性脂肪肝的病理特征，显著降低了血清脂质水平[7]。