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苹果多酚通过调控肠道菌群抑制 TLR4/NF-κB/TGF-β 信号通路缓解酒精性肝纤维化的作用及机制

Effect and Mechanism of Apple Polyphenols in Regulating Intestinal Flora and Inhibiting the TLR4/NF-κB/TGF-β Signaling Pathway to Alleviate Alcoholic Liver Fibrosis.

机构信息

Shenyang Pharmaceutical University, Shenyang, 110016, China.

Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, China.

出版信息

Plant Foods Hum Nutr. 2024 Dec;79(4):915-919. doi: 10.1007/s11130-024-01235-1. Epub 2024 Sep 19.

DOI:10.1007/s11130-024-01235-1
PMID:39298074
Abstract

Apple polyphenols (APs) have gained attention for their various bioactivities, while no studies on anti-liver fibrosis activity are reported. This study evaluated the protective effect of APs on liver fibrosis using LPS-treated activated HSC-T6 cells and alcohol-treated liver fibrosis (ALF) mice. The results indicated that APs inhibited HSC-T6 cells activation in vitro and reduced the level of serum hyaluronic acid (HA) (p < 0.05), decreased fibrogenesis marker expression (p < 0.05), thereby alleviating ALF. In addition, APs (800 mg/kg b.w.) decreased the Firmicutes/Bacteroidetes ratio (p < 0.05) in ALF mice, inhibited LPS accumulation in the liver tissue and serum (p < 0.05), and significantly inhibited the TLR4/NF-κB/TGF-β signaling in mice liver. In conclusion, APs markedly ameliorated ALF, possibly by improving gut microbiota homeostasis, decreasing the translocation of bacterial endotoxins to the blood, and suppressing the TLR4/NF-κB/TGF-β signaling pathway, indicating its potential as lead compounds for functional foods and/or drugs against ALF.

摘要

苹果多酚(APs)因其多种生物活性而受到关注,而目前尚无关于其抗肝纤维化活性的研究。本研究采用 LPS 处理的活化 HSC-T6 细胞和酒精处理的肝纤维化(ALF)小鼠模型,评估了 APs 对肝纤维化的保护作用。结果表明,APs 可抑制体外 HSC-T6 细胞的活化,并降低血清透明质酸(HA)水平(p<0.05),降低纤维化标志物的表达(p<0.05),从而减轻 ALF。此外,APs(800mg/kg b.w.)可降低 ALF 小鼠厚壁菌门/拟杆菌门比值(p<0.05),抑制肝组织和血清中 LPS 的积累(p<0.05),并显著抑制小鼠肝脏中 TLR4/NF-κB/TGF-β 信号通路。总之,APs 显著改善了 ALF,可能是通过改善肠道微生物组稳态、减少细菌内毒素向血液的易位以及抑制 TLR4/NF-κB/TGF-β 信号通路来实现的,这表明其有潜力作为防治 ALF 的功能性食品和/或药物的先导化合物。

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