Xia Xinhua, He Xueling, Huang Jinzhou, Hou Xuyang, Lin Chen, Liu Yaxiong, Liu Mei
TCM Department, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Institute of Integrated Chinese and Western Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China.
Front Pharmacol. 2024 Dec 24;15:1516272. doi: 10.3389/fphar.2024.1516272. eCollection 2024.
The aim of this study is to examine the physiological effects of emodin on intestinal microorganisms and the liver in the BALb/c mice.
Following an 8-week administration of emodin at doses of 25, 50, and 100 mg/kg/day,pathological analyses revealed that emodin significantly reduced the colon length, induced colonic crypt inflammation,diminished the colonic mucus layer,and decreased the fluorescence intensity of colonic tight junction proteins ZO-1 and Occludin. Concurrently, 16S rDNA gene sequencing corroborated that emodin altered the diversity and composition of the intestinal microbiota by increasing the to ratio. Simultaneously, the non-targeted metabolomics analyses exhibited significant alternations in both short chain fatty acids and free fatty acids between the emodin-treated and the normal groups, indicating emodin-induced disturbance in intestinal metabolic disorder. Furthermore, emodin exhibited a significant elevation in LPS levels in colon, serum and liver as well an marked increase in the levels of TC, TG, AST, and ALT in serum. Additionally, histological examination employing by HE and oil-red O staining furtherly verified that the administration of varying doses emodin induced hepatic inflammation and lipid accumulation. Whereas qRT-PCR and Western blot analyses demonstrated that the administering of varying doses of emodin upregulated the mRNA levels of TNF-α, IL-1β, IL-6, and IL-18 as well as the expression of TLR4, Myd88, and P-65. Following the combined administration of probiotics, the high-dose emodin did not significantly influence ALT and AST levels in mice. However, the faeces of the high-dose emodin transplanted in mice and induced a significant increase in AST levels and in the relative abundance of and .
These findings further corroborate that emodin induces liver injury via the intestinal dysfunction. These findings suggested that emodin may disrupt intestinal microbiota and resulted in significant alternations in endogenous metabolites in mice, thereby facilitating the entry of LPS and FFAs into the liver, potentially leading to hepatic injury.
本研究旨在探讨大黄素对BALb/c小鼠肠道微生物群和肝脏的生理影响。
以25、50和100mg/kg/天的剂量对大黄素进行8周给药后，病理分析显示大黄素显著缩短结肠长度，诱发结肠隐窝炎症，减少结肠黏液层，并降低结肠紧密连接蛋白ZO-1和闭合蛋白的荧光强度。同时，16S rDNA基因测序证实大黄素通过增加 与 的比例改变了肠道微生物群的多样性和组成。同时，非靶向代谢组学分析显示，大黄素处理组和正常组之间的短链脂肪酸和游离脂肪酸均有显著变化，表明大黄素诱导肠道代谢紊乱。此外，大黄素使结肠、血清和肝脏中的LPS水平显著升高，血清中的TC、TG、AST和ALT水平也显著增加。此外，采用HE和油红O染色的组织学检查进一步证实，不同剂量大黄素的给药均诱发肝脏炎症和脂质积累。而qRT-PCR和蛋白质免疫印迹分析表明，不同剂量大黄素的给药上调了TNF-α、IL-1β、IL-6和IL-18的mRNA水平以及TLR4、Myd88和P-65的表达。联合使用益生菌后，高剂量大黄素对小鼠的ALT和AST水平没有显著影响。然而，高剂量大黄素移植到小鼠体内的粪便导致AST水平以及 和 的相对丰度显著增加。
这些发现进一步证实大黄素通过肠道功能障碍诱导肝损伤。这些发现表明，大黄素可能破坏肠道微生物群，导致小鼠体内内源性代谢产物发生显著变化，从而促进LPS和FFA进入肝脏，可能导致肝损伤。
