蟾蜍胆的化学成分及其生物合成研究进展  

A comprehensive review of chemicals and biosynthetic pathways in toad(Bufo)bile

作　　者：阮丽君 闫炳雄[1] 吴云秋 姚彩云 杨晓男[1] 宋志军 江仁望[2] RUAN Li-jun;YAN Bing-xiong;WU Yun-qiu;YAO Cai-yun;YANG Xiao-nan;SONG Zhi-jun;JIANG Ren-wang(National Engineering Research Center for Southwest Endangered Medicinal Materials Resources Development,Guangxi Botanical Garden of Medicinal Plants,Nanning 530023,China;State Key Laboratory of Bioactive Molecules and Draggability Assessment,College of Pharmacy,Jinan University,Guangzhou 510632,China)

机构地区：[1]广西壮族自治区药用植物园,西南濒危药材资源开发国家工程研究中心,广西南宁530023 [2]暨南大学药学院,生物活性分子和成药性评价全国重点实验室,广东广州510632

出　　处：《药学学报》2024年第6期1616-1626,共11页Acta Pharmaceutica Sinica

基　　金：广西自然科学基金资助项目(2021GXNSFBA220068);国家自然科学基金资助项目(81872760);广东省自然科学基金资助项目(2021A1515011251);广东省科学计划项目(2021A0505030032).

摘　　要：蟾蜍是一种药用价值很高的经济动物,其耳后腺分泌物(蟾酥)、干燥皮(蟾皮)、胆汁(蟾胆)等部位皆可入药,是名贵的传统动物类中药材。目前,关于蟾酥和蟾皮的化学成分及药效活性已有较多报道,而对蟾胆化学成分的综述报道相对较少。本文综述了蟾蜍属(Bufo)胆汁的化学成分,特别关注了胆甾烷类和蟾毒内酯类成分,并报道了这些成分的生物合成途径及药理活性研究进展。综述发现蟾胆存在一类特异的不饱和Δ22或Δ23-C27/C28胆甾酸,这类成分可能是蟾毒内酯C-17位α-吡喃酮形成的重要中间体。此外,还发现蟾胆中存在丰富的3α-OH构型蟾毒内酯,与以往从蟾酥或蟾皮分离的3β-OH构型不一致,这类成分的低毒性可能与蟾蜍的自我防御或生理调节相关。本综述为蟾胆资源的开发和利用提供科学依据,对药物先导化合物的发现、蟾毒内酯生物合成途径的解析和蟾蜍生理学研究提供有用借鉴。The toad,known for its various medicinal properties including parotid gland secretion(toad venom),dried skin,and gallbladder(toad bile),holds considerable medicinal applications as a valuable traditional Chinese animal medicine.Currently,in-depth attentions have been paid to the chemical composition and pharmacological properties of toad venom and skin;however,a lesser number of detailed analyses were concentrated on the toad bile.This review provides an overview of the chemical constituents in the bile of the Bufo genus,with a special focus on the cholestane and bufadienolides,and highlights the progress in their biosynthetic pathway and pharmacological activities.The analysis uncovers a distinct category of unsaturatedΔ22 orΔ23-C27/C28 bile acids in the toad gallbladder,potentially acting as key intermediaries in forming C-17α-pyrone of bufadienolides.Furthermore,the high presence of 3α-OH configured bufadienolides in toad bile,in contrast to the common 3β-OH configured found in toad venom or skin,indicates a possible link between their minimal toxicity and the toad's self-defensive or physiological control.This review provides scientific basis for the development and utilization of toad bile resources,and provides useful reference for the discovery of lead compounds,analysis of the biosynthetic pathway of bufadienolides,and research on toad physiology.

关 键 词：蟾蜍属 蟾胆 胆甾烷 蟾毒内酯 生物合成 

分 类 号：R931[医药卫生—生药学]