Bracteanolide A以及龍眼花萃取物對不同肝損傷大鼠模式之預防效應

Abstract

肝損傷為國人重要的醫療問題，許多疾病都可導致肝損傷，包括外科手術或肝臟移植之治療方式所引發的肝損傷和代謝症候群導致的肝損傷。近年來代謝症候群日趨盛行，且經證明會造成肝代謝異常、肝癌及肝內膽囊癌的發生。本研究目的旨在探討肝臟的預防效應，首先利用蛋白質體學分析龍眼花水萃物 (Longan flower water extract, LFWE) 前置處理預防高果糖飲食誘導大鼠代謝症候群之肝臟影響。結果顯示，高果糖飲食會誘導大鼠代謝症候群中蛋白質變化，如：增加果糖代謝、醣解作用、脂肪生成、內質網壓力及發炎反應；減少脂肪酸氧化、抗氧化能力，而導致代謝症候群的發生；使用LFWE處理後，則降低脂肪堆積、發炎反應；提高抗氧化能力，改善血脂異常，顯示出LFWE可經由上述作用路徑抑制高果糖飲食誘導大鼠的代謝症候群。另進一步評估龍眼花萃取物 (Longan flower ethyl acetate extract, LFEE) 和白花水竹草萃取物 (Bracteanolide A) 是否可降低大鼠肝臟缺血再灌流的損傷，評估Aspartate aminotransferase、Alanine aminotransferase、Interleukin-1β、Interleukin-6、Interleukin-10、Tumor necrosis factor-α、Inducible nitric oxide synthase和Cyclooxygenase-2的活性，其數值在缺血再灌流後會顯著的增加，而給予LFEE或Bracteanolide A會有顯著的降低。此外，缺血再灌流會顯著降低肝臟Glutathione濃度，而給予LFEE或Bracteanolide A則可顯著的改善。病理組織學的結果也發現給予LFEE或Bracteanolide A可以有效改善缺血再灌流導致的損傷。因此，LFEE或Bracteanolide A的前置處理可為肝臟缺血再灌流的損傷過程中，如肝臟手術或移植，提供一個新的治療方式。

Liver injury, which can be caused by liver surgery, liver transplantation, and diseases such as metabolic syndrome (MetS), is considered an important medical issue in Taiwan. The increasing prevalence of MetS in recent years has been tightly associated with the development of abnormal liver metabolism and hepatocellular carcinoma. Thus, our current studies focus on the protection of hepatic injury. In this study, we used proteomic approaches to investigate the preventive effects of longan flower water extract (LFWE) on high fructose (HF)-induced MetS in rats. The results show that fructose metabolism, glycolysis, lipogenesis, endoplasmic reticulum stress, inflammatory activities, fatty acid oxidation and antioxidant capacity are significantly altered in rats with MetS; however, the abnormal protein expression pattern could been rescued with LFWE supplementation. We further investigated the protective effects of longan flower ethyl acetate extract (LFEE) and Bracteanolide A pretreatment in a rat hepatic I/R injury model. The results display that both LFEE and Bracteanolide A can ameliorate I/R injury-mediated increase of aspartate aminotransferase, alanine aminotransferase, interleukin-1β, interleukin-6, interleukin-10, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 activities, while at the time elevating hepatic glutathione levels after I/R injury. Histological results indicate that both LFEE and Bracteanolide A are effective in improving liver morphology during I/R injury. Therefore, LFEE and Bracteanolide A might offer a novel intervention for patients suffering from hepatic I/R injury caused by hepatectomy and liver transplantation.