Abstract:
Chlorogenic acid (CGA) is a functional phenolic acid widely used in food and medicine-related fields. It has been proved to be effective in the treatment of alcoholic liver disease (ALD). However, the exact mechanism by which CGA prevents ALD, especially from the crosstalk between gut and liver, has not been previously reported. This work was aimed to explore the protective effects of CGA against ALD and its relationships to gut-liver axis abnormalities. Experimental results showed the increased (p < 0.05) serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), low density lipoprotein (LDL), total cholesterol (TC) and triglyceride (TG) levels of mice fed with ethanol were ameliorated by supplementing with CGA. Moreover, CGA promoted the production of n-butyric acid by nearly 3 times (1.78 vs 0.62 nM, p < 0.01), a short-chain fatty acid that helps maintain the integrity of the intestinal barrier. Furthermore, CGA alleviated microbial dysbiosis, evidenced by the increased relative abundances of beneficial bacteria Muribaculaceae, Bacteroides, Alloprevotella, and Parabacteroides, and decreased that of opportunistic pathogens Eubacterium_nodatum, Eubacterium_ruminantium, and Anaerotruncus. Correlation analysis further elucidated the microbiota altered after CGA intervention was positively correlated with short-chain fatty acids and antioxidant indexes, while negatively correlated with inflammatory cytokines. In summary, these findings suggested the hepatoprotective effect of CGA was ascribed to the modulation of gut-liver axis homeostasis.
摘要:
绿原酸(CGA)是一种广泛用于食品和医药相关领域的功能性酚酸。它已被证明是有效的治疗酒精性肝病(ALD)。然而,CGA预防ALD的确切机制,尤其是肠道和肝脏之间的串扰,以前没有报道过。这项工作旨在探讨CGA对ALD的保护作用及其与肠-肝轴异常的关系。实验结果显示血清谷丙转氨酶(ALT)升高(p<0.05),天冬氨酸转氨酶(AST),低密度脂蛋白(LDL),补充CGA可改善乙醇喂养小鼠的总胆固醇(TC)和甘油三酯(TG)水平。此外,CGA将正丁酸的生产提高了近3倍(1.78vs0.62nM,p<0.01),一种短链脂肪酸,有助于维持肠屏障的完整性。此外,CGA缓解微生物菌群失调,有益菌Muribaculaceae的相对丰度增加,拟杆菌,Alloprevotella,和副杆菌属,并降低了机会致病菌的数量,真细菌_反刍动物,还有Anaerotruncus.相关分析进一步阐明CGA干预后微生物区系改变与短链脂肪酸和抗氧化指标呈正相关,而与炎性细胞因子呈负相关。总之,这些发现表明CGA的保肝作用归因于肠-肝轴稳态的调节。