Apigenin (API), or 4′,5,7-trihydroxyflavone, is a bioactive flavonoid present in many plants, known for its anti-inflammatory, antioxidant, and anticancer properties. Apigenin is a competitive inhibitor of CYP2C9, with a Ki of 2 µM[1]. It inhibits the activation of the Wnt/β-catenin signaling pathway and the activity of NF-κB, and blocks the phosphorylation of c-Met and its downstream effectors[2].
In vitro, apigenin (6.25-100 µM) shows dose- and time-dependent cytotoxic effects on malignant mesothelioma (MM) cell lines[2]. After 72 hours of treatment with apigenin, the IC50 values for MM-B1, MM-F1, and H-Meso-1 cells were 49.16 ± 2.52µM, 46.95 ± 1.69µM, and 34.31 ± 1.55µM, respectively[2]. Treatment of SGC-7901 cells with apigenin for 48 hours at concentrations of 20, 40, and 80µmol/L resulted in apoptosis rates of 5.76%, 19.17%, and 29.30%, respectively. Apigenin exhibited dose-dependent effects on the growth, colony formation, and proliferation of SGC-7901 cells[3]. Apigenin (0-50 µg/ml) inhibited the proliferation of T-24 cells in a dose-dependent manner and, after 12 hours, increased the levels of ROS while depleting GSH in T-24 cells[4].
In vivo, treatment with apigenin (20mg/kg, intraperitoneally) in C57BL/6 mice reduced the growth of transplanted malignant mesothelioma MM cell lines in the peritoneal cavity of the mice[2]. Treatment with apigenin at doses of 125mg/kg or 250mg/kg in mice with ADR-induced cardiomyopathy via gastric gavage for 17 days increased the phosphorylation of AKT and mTOR in cardiac cells, as well as the expression of PI3K, and reduced apoptosis and autophagy in cardiac cells[5].
References:
[1] Si D, Wang Y, et al. Mechanism of CYP2C9 inhibition by flavones and flavonols. Drug Metab Dispos. 2009 Mar;37(3):629-34.
[2] Laura M , Monica B , Rosanna M ,et al. In Vitro and In Vivo Anti-tumoral Effects of the Flavonoid Apigenin in Malignant Mesothelioma[J].Frontiers in Pharmacology, 2017.8:373.
[3] Wu K, et al. Inhibitory effects of apigenin on the growth of gastric carcinoma SGC-7901 cells. World J Gastroenterol. 2005 Aug 7;11(29):4461-4.
[4] Shi M D , Shiao C K , Lee Y C ,et al.Apigenin, a dietary flavonoid, inhibits proliferation of human bladder cancer T-24 cells via blocking cell cycle progression and inducing apoptosis[J].BioMed Central, 2015(1).
[5] Wei Y , Huirong S , Wenliang Z ,et al.Apigenin Attenuates Adriamycin-Induced Cardiomyocyte Apoptosis via the PI3K/AKT/mTOR Pathway[J].Evidence-based Complementary and Alternative Medicine, 2017, 2017:1-9.
芹菜素(Apigenin,API)(4′,5,7-三羟基黄酮)是一种具有生物活性的类黄酮,存在于许多植物中,具有抗炎、抗氧化和抗癌特性。芹菜素是一种竞争性 CYP2C9 抑制剂,Ki 为2 µM[1]。芹菜素抑制Wnt/β-连环蛋白信号通路的激活和NF-κB的活性,阻断c-Met及其下游效应物的磷酸化[2]。
在体外,芹菜素(6.25-100 µM)对恶性间皮瘤(MM)细胞系的毒性作用具有剂量和时间依赖性[2]。芹菜素处理MM-B1、MM-F1和H-Meso-1细胞72 h后,IC50分别为49.16 ± 2.52µM、46.95 ± 1.69和34.31 ± 1.55µM[2]。芹菜素处理SGC-7901细胞48 h后,20、40、80µmol/L组细胞凋亡率分别为5.76%、19.17%和29.30%。芹菜素对SGC-7901细胞的生长、克隆形成和增殖均呈剂量依赖性作用[3]。芹菜素(0-50 µg/ml)以剂量依赖性方式抑制 T-24 细胞增殖,并在12 h时增加了T-24细胞的ROS水平并耗尽了GSH[4]。
在体内,芹菜素(20mg/kg,i.p.)处理C57BL/6小鼠,减少了移植到小鼠腹膜中的恶性间皮瘤MM 细胞系的生长[2]。芹菜素125mg/kg或250mg/kg对ADR诱导的心肌病小鼠胃管饲法治疗17天后,上调了心肌细胞AKT和mTOR的磷酸化,以及PI3K的表达,减少了心肌细胞凋亡和自噬[5]。