Li Mu-Xia, Li Min-Yao, Lei Jun-Xuan, Wu Yu-Zhu, Li Ze-Hao, Chen Lin-Ming, Zhou Chang-Lin, Su Ji-Yan, Huang Guo-Xin, Huang Xiao-Qi, Zheng Xue-Bao
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China.
Guangzhou Huibiao Testing Technology Center, Guangzhou 510700, P.R. China.
Phytomedicine. 2022 Jun;100:154052. doi: 10.1016/j.phymed.2022.154052. Epub 2022 Mar 14.
The clinical treatment of ulcerative colitis (UC) is limited. A traditional Chinese medicinal formula, Huangqin decoction (HQD), is chronicled in Shang Han Lun and is widely used to ameliorate gastrointestinal disorders, such as UC; however, its mechanism is yet to be clarified.
The present study aimed to investigate the effect of HQD on 7-day colitis induced by 3% dextran sulfate sodium (DSS) in mice and further explore the inhibitory effect of metabolites on DSS-damaged FHC cells.
The therapeutic efficacy of HQD was evaluated in a well-established DSS-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination, metabolomics, metagenomics, and the evaluation of the epithelial barrier function. The mechanism of metabolites regulated by HQD was evaluated in the DSS-induced FHC cell damage model. The samples were collected to detect the physiological functions of the cells.
HQD suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical manifestations, reversed colon length reduction, and reduced histological injury. After HQD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state. In addition, HQD activated the mTOR signaling pathway by upregulating amino acid metabolism. Significant phosphorylation of S6 and 4E-BP1 ameliorated intestinal epithelial barrier dysfunction. Moreover, HQD-regulated metabolites protected the epithelial barrier integrity by inhibiting DSS-induced apoptosis of FHC cells and regulating the proteins affecting apoptosis and cell-cell junction.
These findings indicated that the mechanism of HQD was related to regulating the gut microbiota and amino acid metabolism, activating the mTOR signaling pathway, and protecting the intestinal mucosal barrier integrity.
溃疡性结肠炎（UC）的临床治疗方法有限。中药方剂黄芩汤（HQD）记载于《伤寒论》，被广泛用于改善胃肠道疾病，如UC；然而，其作用机制尚待阐明。
本研究旨在探讨HQD对3%葡聚糖硫酸钠（DSS）诱导的小鼠7天结肠炎的影响，并进一步探索其代谢产物对DSS损伤的FHC细胞的抑制作用。
在已建立的DSS诱导的结肠炎小鼠模型中评估HQD的治疗效果。分析临床症状，收集生物样本进行显微镜检查、代谢组学、宏基因组学以及上皮屏障功能评估。在DSS诱导的FHC细胞损伤模型中评估HQD调节的代谢产物的作用机制。收集样本以检测细胞的生理功能。
HQD在体内抑制了DSS诱导的结肠炎炎症，减轻了DSS诱导的临床表现，逆转了结肠长度缩短，并减少了组织学损伤。HQD治疗后，DSS诱导的肠道菌群失调得到调节，肠道微生物群达到新的平衡状态。此外，HQD通过上调氨基酸代谢激活了mTOR信号通路。S6和4E-BP1的显著磷酸化改善了肠道上皮屏障功能障碍。此外，HQD调节的代谢产物通过抑制DSS诱导的FHC细胞凋亡以及调节影响凋亡和细胞间连接的蛋白质来保护上皮屏障完整性。
这些发现表明，HQD的作用机制与调节肠道微生物群和氨基酸代谢、激活mTOR信号通路以及保护肠黏膜屏障完整性有关。
