State Key Laboratory for Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street 1, Xicheng District, Beijing 100050, China.
Experimental Research Center, China Academy of Chinese Medical Sciences, Nan Xiao Street 16, Dong Zhi Men Nei, Dongcheng District, Beijing 100700, China.
Pharmacol Res. 2022 Apr;178:106191. doi: 10.1016/j.phrs.2022.106191. Epub 2022 Mar 25.
Metabolic inflammation is a crucial factor in the pathogenesis of obesity and promotes related complications. Accumulating evidence has indicated that regulating intestinal integrity and the gut microbiota may be new treatment strategies for metabolic inflammation and obesity. Cordycepin has been reported to improve obesity, but the mechanism is not yet clear. Here, we showed that cordycepin considerably alleviated systemic inflammation while reducing body weight gain and metabolic disorders in Western diet (WD)-fed mice. Further investigations showed that cordycepin significantly ameliorated WD-induced damage to the intestinal barrier and decreased the leakage of lipopolysaccharide (LPS) into the blood in mice by suppressing intestinal inflammation, oxidative stress damage, and decreasing intestinal epithelial cell apoptosis and pyroptosis. In addition, by using metagenomic sequencing, we found that cordycepin could also regulate the homeostasis of intestinal flora, including selectively increasing the abundance of Akkermansia muciniphila and reducing the production of fecal LPS. Besides, we demonstrated that the intestinal flora partially mediated the beneficial effects of cordycepin on improving intestinal barrier function, and obesity-related symptoms in WD-fed mice by a fecal microbiota transplantation experiment. Hence, our findings provided new insights into the role of cordycepin in improving metabolic inflammation and obesity from the perspective of regulating the intestinal barrier function and intestinal flora, and further provided data support for the utility of cordycepin in the treatment of obesity and its complications.
代谢性炎症是肥胖症发病机制中的一个关键因素，并促进相关并发症的发生。越来越多的证据表明，调节肠道完整性和肠道微生物群可能是治疗代谢性炎症和肥胖的新策略。蛹虫草素已被报道可改善肥胖，但机制尚不清楚。在这里，我们表明蛹虫草素可显著减轻系统性炎症，同时减轻西方饮食（WD）喂养小鼠的体重增加和代谢紊乱。进一步的研究表明，蛹虫草素通过抑制肠道炎症、氧化应激损伤、减少肠道上皮细胞凋亡和焦亡，显著改善 WD 诱导的肠道屏障损伤，并降低小鼠血液中脂多糖（LPS）的渗漏。此外，通过使用宏基因组测序，我们发现蛹虫草素还可以调节肠道菌群的平衡，包括选择性增加阿克曼氏菌的丰度和减少粪便 LPS 的产生。此外，通过粪便微生物群移植实验，我们证明肠道菌群部分介导了蛹虫草素改善 WD 喂养小鼠肠道屏障功能和肥胖相关症状的有益作用。因此，我们的研究结果从调节肠道屏障功能和肠道菌群的角度提供了蛹虫草素改善代谢性炎症和肥胖的作用的新见解，并为蛹虫草素在肥胖及其并发症治疗中的应用提供了数据支持。
