Hepatotoxicity of Eupatorium adenophorum extracts and the identification of major hepatotoxic components.

Eupatorium adenophorum can induce liver toxicity in animals. For the safe utilisation of the weed, the hepatotoxic components need to be discovered. In this study, in vitro hepatotoxicity of different extracts from E. adenophorum were determined on human hepatocyte cell line L02 and hepatocellular carcinoma cell line HepG2. The results showed that water extracts of E. adenophorum exhibited no hepatotoxicity in vitro while high concentrations of the organic solvent extracts had obvious hepatotoxicity. Sesquiterpenes may contribute to the toxicity based on the comparison of composition analysis. Three cadinene sesquiterpenes were purified and identified as 9-oxo-10,11-dehydroageraphorone, 10Hα-9-oxo-ageraphorone and 10Hß-9-oxo-ageraphorone. In vitro hepatotoxic effects of these components were investigated, the IC50 of the three compounds were 122.53, 87.52, and 108.80 µM in L02 cells and 151.92, 104.48, and 138.08 µM in HepG2 cells by Cell Counting Kit-8 (CCK-8) assay. The three components were confirmed to be, at least partial, hepatotoxic components.

Antioxidant activity and protective effect of fructus trichosanthis extracts with different solvent on myocardial ischemia reperfusion injury in rats / 中国药学杂志

OBJECTIVE: To study the chemical constituents of different solvent extracts from Fructus Trichosanthis, and to study their antioxidant activity and protection of myocardial ischemia reperfusion injury in rats. METHODS: The chemical constituents in different solvent extracts were determined by UV-Vis spectrophotometry. Myocardial ischemia reperfusion model was made by ligation of left coronary artery in rats. Rats were randomly divided into 6 groups, with 6 rats in each group. The sham operation group and the model groups were respectively given normal saline, Fructus Trichosanthis (equivalent to crude drug 22.5 g·kg-1), compound Danshen dripping pill group(0.085 g·kg-1). Medicines were given once a day for 7 d. After the last drug 1 h, left coronary artery was ligated for 30 min and then reperfusion was established for 120 min by removing the ligation. During this time, ECG was recorded. At the end, animals were euthanized. Blood was collected to evaluate the contents of CK-MB, MYO-MB, cTnT. The heart was removed and fixed to observe the changes of myocardial tissue by optical microscope. RESULTS: Compared with the water extract group and the alcohol extract group of Fructus Trichosanthis, the total amino acids content of Fructus Trichosanthis dichloromethane extract was not detected, but the content of total flavonoids is higher (P < 0.01). Compared with the water extraction liquid of Fructus Trichosanthis, the antioxidant properties on DPPH radical of Fructus Trichosanthis dichloromethane extract group is lower (P < 0.01), and the antioxidant activity on-OH free radical of the alcohol extract of Fructus Trichosanthis group is lower (P < 0.01). Compared with model group, the elevation of ST segment of electrocardiogram was significantly suppressed in each group during reperfusion (P < 0.01 or P < 0.05). The plasma CK-MB, cTnT and MYO-MB in water extract group were significant lowered (P < 0.05). CONCLUSION: The extraction of Fructus Trichosanthis is able to decrease the production of oxidants. The water extract of Fructus Trichosanthis could ameliorate myocardial ischemia reperfusion injury.