18β-glycyrrhetinic acid exhibit protective effect against triptolide-induced hepatotoxicity:role in oxidative stress,inflammation and apoptosis
作者单位：Guangzhou Unversity of Chinese Medicine The First Affiliated Hospital of Chinese MedicineGuangzhou University of Chinese Medicine
会议名称：《第十一届全国免疫学学术大会》
会议日期：2016年
学科分类：1006[医学-中西医结合] 10[医学] 100602[医学-中西医结合临床]
关 键 词：Triptolide 18β-Glycyrrhetinic acid hepatotoxicity anti-oxidation anti-inflammation anti-apoptos
摘 要：Objective: Tripterygium wilfordii Hook F(TWHF) has been widely used in traditional Chinese medicine to treat rheumatoid arthritis, systemic lupus erythematosus and immune complex nephritis, and to prolong allograft survival in organtransplants. Triptolide(TP), the major active component of TWHF, possesses promising pharmacological effects such as immuno-suppression, anti-inflammation and anti-tumor activity. However, the toxicities of TP, particularly the hepatotoxicity, limit its clinical application. 18β-Glycyrrhetinic acid(GA) is the main bioactive ingredient of Licorice(Glycyrrhizza glabra L.), a herbal medicine well-known for its detoxification. The present study aims to investigate the protective effect of GA against TP-induced hepatotoxicity and its possible mechanism. Methods: 40 male Wistar rats were randomly divided into 4 groups. TP-intoxicated rats received 2.4 mg/kg of TP for 3 days p.o. Protection group pretreated with GA for 6 days p.o. ALT, AST and ALP were detected as biomarkers in the blood to indicate hepatic injury. MDA, SOD, CAT and GPx were evaluated for oxidative stress in liver injury. Liver tissue TNF-α, IL-1β, IL-6 and IFN-γ levels were measured for inflammation in hepatic injury. Light microscopy for histopathological studies and TUNEL assay was also done. Results: TP markedly elevated the serum levels of ALT, AST and ALP, and led to evident histopathological changes in liver. The hepatic activities of SOD, CAT, GSH-Px were significantly decreased in TP group, whereas, the levels of MDA, TNF-α, IL-6, IL-1β and IFN-γ were elevated in TP-injured liver. TUNEL assay showed that TP induced severe apoptosis in rat hepatocytes. In contrast, GA pretreatment significantly reversed the above biochemical and pathological changes caused by TP.Conclusions: Overall, the findings indicate that GA exhibits a protective effect against TP-induced hepatotoxicity in rats by enhancing anti-oxidation, suppressing the inflammatory response and protecting hepatocytes from apoptosis.