Lactucin alleviates liver fibrosis by regulating the TLR4-MyD88-MAPK/ NF-κB signaling pathway through intestinal flora

被引：0

作者：

Zhu, Liping ^{[1
]}

Lv, Bo ^{[2
]}

Gao, Yuefeng ^{[3
]}

Qin, Dongmei ^{[1
]}

机构：

[1] Shihezi Univ, Sch Pharm, Key Lab Xinjiang Phytomedicine Resource & Utilizat, Minist Educ, Shihezi, Peoples R China

[2] Shihezi Univ, Affiliated Hosp 1, Sch Med, Shihezi, Peoples R China

[3] Henan Univ Sci & Technol, Coll Appl Engn, Sanmenxia, Peoples R China

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2025年 / 766卷

基金：

中国国家自然科学基金;

关键词：

Gut microbiota; Gut-liver axis; Liver fibrosis; Lactucin; TLR4;

D O I：

10.1016/j.abb.2025.110341

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ethnopharmacological relevance: Cichorium glandulosum (CG) is a kind of traditional Chinese medicine, mainly produced in Xinjiang and Inner Mongolia, and its medicinal part is mainly the dried root of CG. CG is a commonly used medicine in Uygur medicine, which has good pharmacological effects. Lactucin (LC) in this study is the main sesquiterpene monomer compound obtained from the ethyl acetate extract of CG. The purity of LC obtained by our research group in the previous stage reached 98.1 %, which met the purity requirements of chemical control of traditional Chinese medicine. At present, the research on the pharmacological action of CG mainly focuses on the extract of CG, and there is little research on the monomer compounds and exact pharmacological action mechanism in CG. Aim of the study: The aim of this study is to investigate the mechanism of lactucin (LC) in alleviating liver fibrosis by regulating TLR4-related inflammatory pathway through intestinal flora-intestine-liver axis. Materials and methods: Firstly, the content of LC was determined by HPLC. In vitro, hepatic fibrosis cell model was induced and cytotoxicity was detected by MTT assay. QRT-PCR and Western Blot were used to detect the effect of LC on the expression of proteins related to TLR4-MyD88-MAPK/NF-kappa B signaling pathway. In vivo, carbon tetrachloride and dextran sodium sulfate were used to induce liver fibrosis and enteritis in rats. Detection of liver fibrosis index, H&E staining, Sirius red staining, immunofluorescence and Western Blot were used to detect the degree and action pathway of liver fibrosis. 16S rRNA analysis and bile acid targeted metabolism were used to explore the role of intestinal flora in liver fibrosis. Results: In vitro, LC can significantly inhibit the mRNA levels of TLR4 and related inflammatory factors, inhibit the expression of TLR4-MyD88-MAPK/NF-kappa B pathway protein, and reduce the level of intracellular reactive oxygen species, with the same effect as TLR4 inhibitors. In vivo, experimental results show that LC can reduce the degree of liver fibrosis and colitis, significantly reduce the levels of MDA and MPO in colon tissue, increase the level of SOD, reduce the activities of HYP, AKP, AST, ALT, TBA and gamma-GT in serum, and increase the level of Alb. LC can also inhibit the expression of TLR4-MyD88-MAPK/NF-kappa B pathway, and inhibit the expression of TLR4 protein in liver and increase the expression of ZO-1 protein in colon. In addition, LC can regulate the flora composition of liver fibrosis and improve bile acid metabolism. Conclusion: This study found that LC can alleviate liver fibrosis, and suggested that the beneficial effect of LC on liver fibrosis may be achieved by regulating TLR4-MyD88-MAPK pathway and improving intestinal flora through intestinal liver axis. At the same time, it is revealed that LC is the main component of CG for treating liver fibrosis, which lays a theoretical foundation for the research and development of new drugs and clinical research of CG in the later period.

引用

页数：14

共 28 条

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