Dammarane-type triterpenoid saponins isolated from Gynostemma pentaphyllum ameliorate liver fibrosis via agonizing PP2Cαand inhibiting deposition of extracellular matrix  

作　　者：LIU Yue YANG Yating WANG Hanghang LI Han LV Qi WANG Xiachang WU Dalei HU Lihong ZHANG Yinan 

机构地区：[1]Jiangsu Key Laboratory for Functional Substances of Chinese Medicine,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China [2]Helmholtz International Lab,State Key Laboratory of Microbial Technology,Shandong University,Qingdao 266237,China

出　　处：《Chinese Journal of Natural Medicines》2023年第8期599-609,共11页中国天然药物（英文版）

基　　金：supported by the National Key R&D Program(No.2018YFC1707900);the National Natural Science Foundation of China(No.22177052);Jiangsu Provincial Science and Technology Development Project of Chinese Medicine(No.ZD202002);Jiangsu postgraduate scientific research innovation program(No.KYCX21_1721).

摘　　要：Gypenosides,structurally analogous to ginsenosides and derived from a sustainable source,are recognized as the principal active compounds found in Gynostemma pentaphyllum,a Chinese medicinal plant used in the treatment of the metabolic syndrome.By bioactive tracking isolation of the plants collected from different regions across China,we obtained four new gypenosides(1−4),together with nine known gypenosides(5−13),from the methanol extract of the plant.The structures of new gypenosides were elucidated by one-dimensional(1D)and two-dimensional(2D)nuclear magnetic resonance(NMR)spectra,complemented by chemical degradation experiments.Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cαactivity assays,we established a definitive structure-activity relationship for these dammarane-type triterpenoids,affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix(ECM)deposition within hepatic stellate cells.Further in vivo study on the CCl4-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration.These results underscore the potential of dammarane-type triterpenoids as prospective antifibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.

关 键 词：Dammarane-type triterpenoid GYPENOSIDE Liver fibrosis Extracellular matrix 

分 类 号：R284[医药卫生—中药学] R965[医药卫生—中医学]