中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Peptidoglycan isolated from the fruit of Lycium barbarum alleviates liver fibrosis in mice by regulating the TGF-β/Smad7 signaling and gut microbiota

文献类型:期刊论文

作者Nie, Ying-min6,7; Zhou, Wan-qi4,5,7; Niu, Ting3,7; Mao, Meng-fei6,7; Zhan, Yu-xue2; Li, Yun6,7; Wang, Kai-ping2; Li, Mei-xia6,7; Ding, Kan1,4,5,6,7
刊名ACTA PHARMACOLOGICA SINICA
出版日期2025-01-20
页码16
关键词liver fibrosis Lycium barbarum peptidoglycan LBPW TGF-beta/Smad7 Akkermansia muciniphila
ISSN号1671-4083
DOI10.1038/s41401-024-01454-x
英文摘要The hepatoprotective effect of the fruit of Lycium barbarum has been documented in China over millennia. Lycium barbarum polysaccharides (LBPs) were the first macromolecules reported to mitigate liver fibrosis in carbon tetrachloride (CCl4)-treated mice. Herein, a neutral peptidoglycan, named as LBPW, was extracted from the fruit of Lycium barbarum. In this study, we investigated the hepatoprotective mechanisms of LBPW. CCl4-induced liver fibrosis mice were administered LBPW (50, 100, 200 mg kg-1 d-1, i.p.) or (100, 200, 300 mg kg-1 d-1, i.g.) for 6 weeks. We showed that either i.p. or i.g. administration of LBPW dose-dependently attenuated liver damage and fibrosis in CCl4-treated mice. Pharmacokinetic analysis showed that cyanine 5.5 amine (Cy5.5)-labeled LBPW (Cy5.5-LBPW) could be detected in the liver through i.p. and i.g. administration with i.g.-administered Cy5.5-LBPW mainly accumulating in the intestine. In TGF-beta 1-stimulated LX-2 cells as well as in the liver of CCl4-treated mice, we demonstrated that LBPW significantly upregulated Smad7, a negative regulator of TGF-beta/Smad signaling, to retard the activation of hepatic stellate cells (HSCs) and prevent liver fibrosis. On the other hand, LBPW significantly boosted the abundance of Akkermansia muciniphila (A. muciniphila) and fortified gut barrier function. We demonstrated that A. muciniphila might be responsible for the efficacy of LBPW since decreasing the abundance of this bacterium by antibiotics (Abs) blocked the effectiveness of LBPW. Overall, our results show that LBPW may exert the hepatoprotective effect via rebalancing TGF-beta/Smad7 signaling and propagating gut commensal A. muciniphila, suggesting that LBPW could be leading components to be developed as new drug candidates or nutraceuticals against liver fibrosis.
WOS关键词AKKERMANSIA-MUCINIPHILA ; NONALCOHOLIC STEATOHEPATITIS ; STELLATE CELLS ; CROSS-TALK ; SMAD7 ; EXPRESSION ; FIBROGENESIS ; ANTAGONIST ; ACTIVATION ; DYSBIOSIS
资助项目Zhongshan Municipal Bureau of Science and Technology
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001400810200001
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/315878]  
专题新药研究国家重点实验室
通讯作者Wang, Kai-ping; Li, Mei-xia; Ding, Kan
作者单位1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, SSIP Healthcare & Med Demonstrat Zone, Zhongshan 528400, Peoples R China
2.Huazhong Univ Sci & Technol, Tongji Med Coll Pharm, Hubei Key Lab Nat Med Chem & Resource Evaluat, Wuhan 430030, Peoples R China
3.Naval Med Univ, Changzheng Hosp, Dept Pancreat Biliary Surg, Shanghai 200003, Peoples R China
4.Lingang Lab, Shanghai 201203, Peoples R China
5.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201210, Peoples R China
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai 201203, Peoples R China
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Nie, Ying-min,Zhou, Wan-qi,Niu, Ting,et al. Peptidoglycan isolated from the fruit of Lycium barbarum alleviates liver fibrosis in mice by regulating the TGF-β/Smad7 signaling and gut microbiota[J]. ACTA PHARMACOLOGICA SINICA,2025:16.
APA Nie, Ying-min.,Zhou, Wan-qi.,Niu, Ting.,Mao, Meng-fei.,Zhan, Yu-xue.,...&Ding, Kan.(2025).Peptidoglycan isolated from the fruit of Lycium barbarum alleviates liver fibrosis in mice by regulating the TGF-β/Smad7 signaling and gut microbiota.ACTA PHARMACOLOGICA SINICA,16.
MLA Nie, Ying-min,et al."Peptidoglycan isolated from the fruit of Lycium barbarum alleviates liver fibrosis in mice by regulating the TGF-β/Smad7 signaling and gut microbiota".ACTA PHARMACOLOGICA SINICA (2025):16.

入库方式: OAI收割

来源:上海药物研究所

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