Zheng Xi-Yuan, Yang Ying-Fan, Li Wan, Zhao Xin, Sun Yi, Sun Hua, Wang Yue-Hua, Pu Xiao-Ping
National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China; Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, PR China.
National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China.
J Ethnopharmacol. 2014 May 14;153(3):854-63. doi: 10.1016/j.jep.2014.03.058. Epub 2014 Mar 29.
Swertia punicea Hemsl. (Gentianaceae) is more commonly known as "Ganyan-cao" and used mainly as a traditional Chinese folk medicine for the treatment of acute bilious hepatitis, cholecystitis, fever, intoxification and jaundice.
The active hepatoprotective constituents of Swertia punicea were purified using various column chromatography techniques. The structures of two isolated compounds were determined on the basis of spectroscopic data interpretation such as NMR analysis. The hepatoprotective activities of isolated compounds were evaluated by using hepatotoxicity in vitro and dimethylnitrosamine-induced rat hepatic fibrosis in vivo, respectively.
Two xanthones, 1, 7-dihydroxy-3, 4, 8-trimethoxyxanthone (1) and bellidifolin (2) were isolated from the stems of Swertia punicea. The compounds 1 and 2 exhibited notable hepatoprotective activities against carbon tetrachloride (CCl4) -induced HepG2 cell damage, and effectively alleviated the levels of aspartate transaminase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malonic dialdehyde (MDA) induced by CCl₄ in a concentration-dependent manner. Co-treatment with compound 2 significantly increased the cell viability compared with N-acetyl-p-aminophenol (APAP) treatment. Compound 2 also alleviated APAP-induced hepatotoxicity by increasing glutathione (GSH) content and decreasing hydroxyl free radical (·OH) levels and reactive oxygen specises (ROS) production. In addition, the protective effect of compound 1 significantly alleviated DMN-induced liver inflammation and fibrosis. Oral administration of compound 1 recovered the reduction of albumin (ALB) and reversed the elevation of serum alanine transaminase (ALT), AST and total bilirubin (TBIL) in dimethylnitrosamine (DMN)-induced fibrotic rats. Severe oxidative stress induced in fibrotic rats was evidenced by a 1.5-fold elevation in MDA and a fall in the SOD activity, and treatment with compound 1 protected against these adverse effects. Recovery of rat liver tissue against DMN-induced hepatocellular necrosis, inflammatory changes and hepatic fibrosis by compound 1 is also confirmed by H&E and Masson stained histopathological evaluation of liver tissue.
Two xanthones from Swertia punicea exhibited hepatoprotective activities in vitro (compounds 1 and 2) and in vivo (compound 1), respectively.
紫红獐牙菜（龙胆科）更为人所知的名称是“肝炎草”，主要作为一种传统的中国民间药物用于治疗急性胆汁性肝炎、胆囊炎、发热、中毒和黄疸。
采用各种柱色谱技术对紫红獐牙菜的活性保肝成分进行纯化。基于核磁共振分析等光谱数据解释确定了两种分离化合物的结构。分别通过体外肝毒性实验和二甲基亚硝胺诱导的大鼠肝纤维化实验对分离化合物的保肝活性进行评估。
从紫红獐牙菜茎中分离得到两种呫吨酮，1,7 - 二羟基 - 3,4,8 - 三甲氧基呫吨酮（1）和雏菊叶龙胆酮（2）。化合物1和2对四氯化碳（CCl₄）诱导的HepG2细胞损伤表现出显著的保肝活性，并以浓度依赖的方式有效降低了CCl₄诱导的天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）和丙二醛（MDA）水平。与N - 乙酰对氨基酚（APAP）处理相比，化合物2联合处理显著提高了细胞活力。化合物2还通过增加谷胱甘肽（GSH）含量、降低羟自由基（·OH）水平和活性氧（ROS）生成来减轻APAP诱导的肝毒性。此外，化合物1的保护作用显著减轻了二甲基亚硝胺（DMN）诱导的肝脏炎症和纤维化。口服化合物1可恢复二甲基亚硝胺（DMN）诱导的纤维化大鼠血清白蛋白（ALB）的降低，并逆转血清丙氨酸转氨酶（ALT）、AST和总胆红素（TBIL）的升高。纤维化大鼠中严重的氧化应激表现为MDA升高1.5倍和SOD活性下降，而化合物1的处理可预防这些不良反应。通过对肝组织进行苏木精 - 伊红（H&E）染色和马松（Masson）染色的组织病理学评估，也证实了化合物1对大鼠肝组织DMN诱导的肝细胞坏死、炎症变化和肝纤维化具有恢复作用。
紫红獐牙菜中的两种呫吨酮分别在体外（化合物1和2）和体内（化合物1）表现出保肝活性。
