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Luteolin-7-diglucuronide, a novel PTP1B inhibitor, ameliorates hepatic stellate cell activation and liver fibrosis in mice

文献类型：期刊论文

作者Tang, Bi-xi4,5; Zhang, Yong4; Sun, Dan-dan4; Liu, Qin-yi3,4; Li, Cong4; Wang, Pei-pei4; Gao, Li-xin4; Zhang, Xue-mei5; Li, Jia2,3,4; Zhu, Wei-liang4
刊名ACTA PHARMACOLOGICA SINICA
出版日期2024-08-05
页码12
关键词liver fibrosis phytochemical luteolin 7-diglucuronide HSC activation PTP1B
ISSN号1671-4083
DOI10.1038/s41401-024-01351-3
通讯作者Zhang, Xue-mei(xuemzhang@fudan.edu.cn) ; Li, Jia(jli@simm.ac.cn) ; Zhu, Wei-liang(wlzhu@simm.ac.cn) ; Zang, Yi(yzang@lglab.ac.cn)
英文摘要Liver fibrosis, one of the leading causes of morbidity and mortality worldwide, lacks effective therapy. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. Luteolin-7-diglucuronide (L7DG) is the major flavonoid extracted from Perilla frutescens and Verbena officinalis. Their beneficial effects in the treatment of liver diseases were well documented. In this study we investigated the anti-fibrotic activities of L7DG and the potential mechanisms. We established TGF-beta 1-activated mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 as in vitro liver fibrosis models. Co-treatment with L7DG (5, 20, 50 mu M) dose-dependently decreased TGF-beta 1-induced expression of fibrotic markers collagen 1, alpha-SMA and fibronectin. In liver fibrosis mouse models induced by CCl4 challenge alone or in combination with HFHC diet, administration of L7DG (40, 150 mgkg-1d-1, i.g., for 4 or 8 weeks) dose-dependently attenuated hepatic histopathological injury and collagen accumulation, decreased expression of fibrogenic genes. By conducting target prediction, molecular docking and enzyme activity detection, we identified L7DG as a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 2.10 mu M. Further studies revealed that L7DG inhibited PTP1B activity, up-regulated AMPK phosphorylation and subsequently inhibited HSC activation. This study demonstrates that the phytochemical L7DG may be a potential therapeutic candidate for the treatment of liver fibrosis.
资助项目Shanghai Institute of Materia Medica, Chinese Academy of Sciences[CASIMM0120225006-2] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM0120232001] ; Shanghai Municipal Science and Technology Major Project[TM202301H002] ; Shanghai Committee of Science and Technology[22ZR1415200]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001283863800001
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/312571]  
专题中国科学院上海药物研究所
通讯作者Zhang, Xue-mei; Li, Jia; Zhu, Wei-liang; Zang, Yi
作者单位1.Lingang Lab, Shanghai 201203, Peoples R China
2.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Stake Key Lab Chem Biol, Shanghai 201203, Peoples R China
5.Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Tang, Bi-xi,Zhang, Yong,Sun, Dan-dan,et al. Luteolin-7-diglucuronide, a novel PTP1B inhibitor, ameliorates hepatic stellate cell activation and liver fibrosis in mice[J]. ACTA PHARMACOLOGICA SINICA,2024:12.
APA Tang, Bi-xi.,Zhang, Yong.,Sun, Dan-dan.,Liu, Qin-yi.,Li, Cong.,...&Zang, Yi.(2024).Luteolin-7-diglucuronide, a novel PTP1B inhibitor, ameliorates hepatic stellate cell activation and liver fibrosis in mice.ACTA PHARMACOLOGICA SINICA,12.
MLA Tang, Bi-xi,et al."Luteolin-7-diglucuronide, a novel PTP1B inhibitor, ameliorates hepatic stellate cell activation and liver fibrosis in mice".ACTA PHARMACOLOGICA SINICA (2024):12.

入库方式： OAI收割

来源：上海药物研究所

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