源于中药的胰脂肪酶抑制剂研究进展  

Recent advances on pancreatic lipase inhibitors from Chinese herbs

作　　者：侯旭东 胡情 马丽娟 于浩楠 葛广波 侯洁 HOU Xu-dong;HU Qing;MA Li-juan;YU Hao-nan;GE Guang-bo;HOU Jie(Department of Biotechnology,College of Basic Medical Sciences,Dalian Medical University,Dalian 116044,China;Institute of Interdisciplinary Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]大连医科大学基础医学院生物技术系,辽宁大连116044 [2]上海中医药大学交叉科学研究院,上海201203

出　　处：《药学学报》2020年第7期1478-1493,共16页Acta Pharmaceutica Sinica

基　　金：科技部“中医药现代化研究”重点专项(2017YFC1700200,2017YFC1702000);国家自然科学基金资助项目(81922070,81973286);上海市优秀学术带头人计划(18XD1403600);大连市支持高层次人才创新创业项目(2017RQ121);辽宁省自然科学基金资助项目(20180530025)。

摘　　要：肥胖是高血压、高脂血症、动脉硬化、2型糖尿病以及多种癌症等代谢性疾病的重要诱因,抗肥胖药物一直是新药研发领域的热点。胰脂肪酶(又称三酰基甘油酰基水解酶)负责水解胃肠中50%~70%膳食脂肪,是防治肥胖的一个关键靶点。胰脂肪酶抑制剂可通过降低该酶的水解活性减少消化器官中膳食脂肪的分解和吸收,进而改善肥胖和高脂血症等代谢性疾病的症状。虽然目前临床上已有胰脂肪酶抑制剂(奥利司他)上市,但其长期服用后会出现显著的胃肠道不良反应。因此,有必要研发抑制作用强且安全性好的新型胰脂肪酶抑制剂。近年来,国内外大量研究发现部分中草药提取物及其化学成分能够通过抑制胰脂肪酶达到调节脂质代谢和防治肥胖的效果。本文结合近年来胰脂肪酶抑制剂研发领域的国内外研究进展,着重汇总了具有胰脂肪酶抑制效应的中药提取物及其化学成分,并对其抑制效应和抑制机制等进行了归纳总结。此外,作者还对该领域面临的挑战和未来降脂药物的研发方向进行了展望。上述信息不仅有助于药物化学家从中药化学成分中发现强效的胰脂肪酶抑制剂进而用于肥胖防治药物的研发,同时也为中草药及其制品防治肥胖及肥胖相关代谢性疾病提供了新思路和启示。Obesity is an important cause of a panel of metabolic diseases,such as hypertension,hyperlipidemia,arteriosclerosis,type 2 diabetes and various cancers.Discovery of anti-obesity agents has always been a hot spot in the field of new drug research and development.Pancreatic lipase(PL,also named triacylglycerol acyl hydrolase),a key enzyme responsible for the hydrolysis of 50%-70%dietary fats in the gastrointestinal system,which has been recognized as a crucial target for the prevention and treatment of obesity.PL inhibitors can reduce the decomposition and absorption of dietary fat in the digestive organs by decreasing the hydrolytic activity of this key enzyme,which can alleviate the symptoms of metabolic diseases such as obesity and hyperlipidemia.Although a potent PL inhibitor(orlistat)has been marketed,it may trigger gastrointestinal side effects after long-term use.Therefore,it is necessary to develop more new PL inhibitors with strong inhibition potency and safety.In recent years,a large number of studies have found that some Chinese herbal extracts and their constituents can regulate lipid metabolism and treat obesity via inhibiting PL.In this paper,the research progress in the field pancreatic lipase inhibitors,as well as the extracts of Chinese herbs and their constituents with pancreatic lipase inhibitory effects were summarized.Meanwhile,the PL inhibition activities and inhibitory mechanisms of herbal constitutes were also summarized systematically.In addition,the authors also highlight the challenges in this field and the future research directions.All information and knowledge presented in this review will be very helpful for the medicinal chemists to find more potent PL inhibitors from herbs or to develop next generation anti-obesity drugs,as well as helpful for the prevention and treatment of obesity and other related metabolic diseases using herba medicines or related products.

关 键 词：胰脂肪酶 肥胖 中药 天然成分 抑制剂 

分 类 号：R284[医药卫生—中药学]