关键词: FAK/PI3K/AKT Fructan Hepatic fibrosis Hepatic stellate cells

Mesh : Mice Animals Proto-Oncogene Proteins c-akt / metabolism Inulin / metabolism Phosphatidylinositol 3-Kinases / metabolism Hepatic Stellate Cells Signal Transduction Liver Cirrhosis / chemically induced drug therapy metabolism Carbon Tetrachloride Liver / metabolism

来  源:   DOI:10.1016/j.carbpol.2023.121637

Abstract:
Studies have shown that terrestrial acidic polysaccharides containing carboxyl groups and seaweed sulfated polysaccharides have strong potential in anti-liver fibrosis. However, there is no investigation on the anti-liver fibrosis of fructan, a ubiquitous natural polysaccharide. The present study aimed to understand the effect of fructan in ameliorating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Here, an inulin-like fructan ABWW from Achyranthes bidentata Bl. was characterized by fructose enzymatic hydrolysis, methylation analysis, ESI-MS, and NMR. It was composed of →2)-β-d-Fruf-(1→ and →2)-β-d-Fruf-(1, 6→, terminated with →1)-α-d-Glcp and →2)-β-d-Fruf residues. The biological studies showed that ABWW could improve liver damage and liver fibrosis induced by CCl4in vivo and inhibit hepatic stellate cell (HSC) activation and migration in vitro. We further demonstrated that ABWW inhibited LX2 activation via suppressing the FAK/PI3K/AKT signaling pathway. Hence, ABWW might be a potential novel active compound for anti-fibrosis new drug development.
摘要:
研究表明,含羧基的陆生酸性多糖和海藻硫酸多糖具有很强的抗肝纤维化潜力。然而,目前尚无关于果聚糖抗肝纤维化的研究,一种普遍存在的天然多糖。本研究旨在了解果聚糖改善四氯化碳(CCl4)诱导的小鼠肝纤维化的作用。这里,来自牛膝的菊粉状果聚糖ABWW。以果糖酶水解为特征,甲基化分析,ESI-MS,和NMR。由→2)-β-d-Fruf-(1→和→2)-β-d-Fruf-(1,6→,终止于→1)-α-d-Glcp和→2)-β-d-Fruf残基。生物学研究表明,ABWW在体内能改善CCl4诱导的肝损伤和肝纤维化,体外能抑制肝星状细胞(HSC)的活化和迁移。我们进一步证明ABWW通过抑制FAK/PI3K/AKT信号通路抑制LX2活化。因此,ABWW可能是抗纤维化新药开发的潜在新型活性化合物。
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