Khamphaya Tanaporn, Chansela Piyachat, Piyachaturawat Pawinee, Suksamrarn Apichart, Nathanson Michael H, Weerachayaphorn Jittima
Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand.
Department of Anatomy, Phramongkutklao College of Medicine, Bangkok, Thailand.
Eur J Pharmacol. 2016 Oct 15;789:254-264. doi: 10.1016/j.ejphar.2016.07.032. Epub 2016 Jul 27.
Cholestasis is a cardinal manifestation of liver diseases but effective therapeutic approaches are limited. Therefore, alternative therapy for treating and preventing cholestatic liver diseases is necessary. Andrographolide, a promising anticancer drug derived from the medicinal plant Andrographis paniculata, has diverse pharmacological properties and multi-spectrum therapeutic applications. However, it is unknown whether andrographolide has a hepatoprotective effect on intrahepatic cholestasis. The aims of this study were to investigate the protective effect and possible mechanisms of andrographolide in a rat model of acute intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT). Andrographolide was administered intragastrically for four consecutive days, with a single intraperitoneal injection of ANIT on the second day. Liver injury was evaluated biochemically and histologically together with hepatic gene and protein expression analysis. Rats pretreated with andrographolide prior to ANIT injection demonstrated lower levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, as well as bilirubin and bile acids as compared to rats treated with ANIT alone. Andrographolide also decreased the incidence and extent of periductular fibrosis and bile duct proliferation. Analysis of protein expression in livers from andrographolide-treated cholestatic rats revealed markedly decreased expression of alpha-smooth muscle actin and nuclear factor kappa-B (NF-κB). In conclusion, andrographolide has a potent protective property against ANIT-induced cholestatic liver injury. The mechanisms that underlie this protective effect are mediated through down-regulation of NF-κB expression and inhibition of hepatic stellate cell activation. These findings suggest that andrographolide could be a promising therapeutic option in prevention and slowing down the progression of cholestatic liver diseases.
胆汁淤积是肝脏疾病的主要表现，但有效的治疗方法有限。因此，治疗和预防胆汁淤积性肝病的替代疗法是必要的。穿心莲内酯是一种从药用植物穿心莲中提取的有前景的抗癌药物，具有多种药理特性和多谱治疗应用。然而，穿心莲内酯对肝内胆汁淤积是否具有肝保护作用尚不清楚。本研究的目的是探讨穿心莲内酯在α-萘异硫氰酸酯（ANIT）诱导的急性肝内胆汁淤积大鼠模型中的保护作用及可能机制。连续四天灌胃给予穿心莲内酯，第二天腹腔注射一次ANIT。通过生化、组织学以及肝脏基因和蛋白质表达分析来评估肝损伤。与单独用ANIT治疗的大鼠相比，在注射ANIT之前用穿心莲内酯预处理的大鼠血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、碱性磷酸酶、γ-谷氨酰转移酶以及胆红素和胆汁酸水平较低。穿心莲内酯还降低了汇管区周围纤维化和胆管增生的发生率和程度。对穿心莲内酯治疗的胆汁淤积大鼠肝脏中的蛋白质表达分析显示，α-平滑肌肌动蛋白和核因子κB（NF-κB）的表达明显降低。总之，穿心莲内酯对ANIT诱导的胆汁淤积性肝损伤具有强大的保护作用。这种保护作用的潜在机制是通过下调NF-κB表达和抑制肝星状细胞活化介导的。这些发现表明，穿心莲内酯可能是预防和减缓胆汁淤积性肝病进展的一种有前景的治疗选择。
