State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Biomed Pharmacother. 2022 Jul;151:113185. doi: 10.1016/j.biopha.2022.113185. Epub 2022 May 24.
Liver fibrosis is a chronic and progressive disease with complex pathogenesis related to bile acids (BAs) and gut microbiota. Forsythiaside A (FTA), isolated from the traditional Chinese medicine Forsythiae Fructus (Lian Qiao), is a natural hepatoprotective agent. The purpose of this study was to investigate the protective effect of FTA on carbon tetrachloride (CCl)-induced liver fibrosis in mice. Liver fibrosis was induced in mice by intraperitoneal injection of 2 mL/kg CCl three times a week for 4 weeks. FTA attenuated CCl-induced liver fibrosis in mice, which was proved by the results of Masson and Sirius red staining, liver hydroxyproline, hyaluronic acid, laminin, type III procollagen, and type IV collagen assays. FTA inhibited hepatic stellate cell activation, and reduced hepatic inflammation and oxidative stress in mice treated with CCl. What's more, FTA ameliorated CCl-induced gut dysbiosis, maintained intestinal barrier function, increased the production of short-chain fatty acids (SCFAs), and improved endotoxemia, as manifested by decreased serum lipopolysaccharide levels and increased expression of ileal tight junction proteins. Besides, FTA can modulate the genes related to bile acid metabolism to alter the distribution of fecal BAs in fibrotic mice. In a word, FTA can improve liver fibrosis by inhibiting inflammation and oxidative stress, regulating gut microbiota and BA metabolism, and increasing the content of SCFAs. The results of this study provided an important reference for the study on the mechanisms by which natural products prevent liver fibrosis.
肝纤维化是一种慢性进行性疾病，其发病机制复杂，与胆汁酸（BAs）和肠道微生物群有关。连翘酯苷 A（FTA）是从传统中药连翘中分离出来的一种天然肝保护剂。本研究旨在探讨 FTA 对四氯化碳（CCl）诱导的小鼠肝纤维化的保护作用。通过每周腹腔注射 2 mL/kg CCl 三次，共 4 周，在小鼠中诱导肝纤维化。结果表明，FTA 减轻了 CCl 诱导的小鼠肝纤维化，Masson 和天狼猩红染色、肝羟脯氨酸、透明质酸、层粘连蛋白、III 型前胶原和 IV 型胶原测定结果均证实了这一点。FTA 抑制肝星状细胞激活，并减少 CCl 处理小鼠的肝炎症和氧化应激。此外，FTA 改善了 CCl 诱导的肠道菌群失调，维持了肠道屏障功能，增加了短链脂肪酸（SCFAs）的产生，并改善了内毒素血症，表现为血清脂多糖水平降低和回肠紧密连接蛋白表达增加。此外，FTA 可以调节与胆汁酸代谢相关的基因，改变纤维化小鼠粪便中 BAs 的分布。总之，FTA 通过抑制炎症和氧化应激、调节肠道微生物群和 BA 代谢以及增加 SCFAs 的含量来改善肝纤维化。本研究结果为研究天然产物预防肝纤维化的机制提供了重要参考。
