Affiliation:
1. Department of Endocrinology, Shanghai TCM-Integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai,
China
2. Department of Pharmacy, Shanghai Sixth People Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China
Abstract
Background::
Cholangiopathies comprise a spectrum of diseases without curative treatments. Pharmacological treatments based on bile acid (BA) metabolism
regulation represent promising therapeutic strategies for the treatment of cholangiopathies. Gentiopicroside (GPS), derived from the Chinese
medicinal herb Gentianae Radix, exerts pharmacological effects on bile acid metabolism regulation and oxidative stress.
Objective::
The present study aims to investigate the effect of GPS on 3,5-diethoxycarbonyl-1,4dihydrocollidine (DDC)-induced cholangiopathy.
Methods::
Two independent animal experiments were designed to evaluate the comprehensive effect of GPS on chronic DDC diet-induced cholangiopathy,
including bile duct obliteration, ductular reaction, BA metabolism reprogramming, liver fibrosis, oxidative stress and inflammatory responses.
Results::
In the first pharmacological experiment, three doses of GPS (5, 25 and 125 mg/kg) were injected intraperitoneally into mice fed a DDC diet for 14
days. DDC induced a typical ductular reaction, increased periductal fibrosis and mixed inflammatory cell infiltration in the portal areas. GPS
treatment showed dose-dependent improvements in the ductular reaction, BA metabolism, fibrosis, oxidative stress and inflammatory response. In
the second experiment, a high dose of GPS was injected intraperitoneally into control mice for 28 days, resulting in no obvious histologic changes
and significant serologic abnormalities in liver function. However, GPS inhibited DDC-induced oxidative stress, serum and hepatic BA
accumulation, proinflammatory cytokine production, and immunocyte infiltration. Specifically, the GPS-treated groups showed decreased
infiltration of monocyte-derived macrophages and CD4+ and CD8+ T lymphocytes, as well as preserved Kupffer cells.
Conclusion::
GPS alleviated chronic DDC diet-induced cholangiopathy disorder by improving the ductular reaction, periductal fibrosis, oxidative stress and
inflammatory response. Its dosage-dependent pharmacological effects indicated that GPS warrants its further evaluation in clinical trials for
cholangiopathy.
Funder
National Natural Science Foundation of China
Shanghai Pujiang Talent Program
Shanghai Three-Year Action Plan of Specialty Cultivation and Promotion Project
Clinical Medicine Outstanding Young Talents of HongKou
HongKou District Health Committee Project
Project of Shanghai TCM-Integrated Hospital
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology,Molecular Medicine
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献