Tang Jingyi, Hu Yingnan, Fang Jintao, Zhu Weihan, Xu Wenjun, Yu Dian, Zheng Zhipeng, Zhou Qiujing, Fu Huiying, Zhang Wei
The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.
Lanxi Hospital of Traditional Chinese Medicine, Jinhua, 321100, People's Republic of China.
Drug Des Devel Ther. 2025 Jan 17;19:303-324. doi: 10.2147/DDDT.S468608. eCollection 2025.
Huanglian-ejiao decoction (HED) is a Chinese traditional medicinal formula evolved from the Shanghan Lun (Treatise on Febrile Diseases). However, HED ultimate mechanism of action remained indistinct. Therefore, this study aimed to investigate whether HED could exert anti-inflammatory effects on 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis (UC) model through the regulation of CD4T subsets and gut microbiota.
Fifty-eight major compounds in HED were identified by UPLC-Q-TOF/MS. The therapeutic efficacy of HED on UC was assessed by evaluating survival rate and so on. Flow cytometry was employed to assay the percentages of CD4T cell. RT-PCR and Western blot took advantage of detecting transcription factors, inflammatory factors, and tight junction proteins. Transcriptome sequencing was performed on colon tissue and 16S rRNA gene sequencing was enforced on intestinal contents.
The administration of HED enhanced the survival rate of colitis mice, significantly restored body weight, DAI score, colon weight and index, spleen weight and index. HED effectively reshaped intestinal barrier dysfunction, inhibited the ratio of Th1 to Th2 cells, and preserved Th2/Th1 and Tregs/Th17 balance. Moreover, HED notably decreased the secretion of transcription factors and related cytokines. Interestingly, HED also exerts regulatory effects on gut dysbiosis by cumulative the plenteous of beneficial probiotics like Lactobacillus and Bacteroides, while inhibiting the overgrowth of opportunistic pathogens such as Helicobacter.
The regulation of Th2/Th1 and Tregs/Th17 cell balance, as well as the modulation of gut microbiota by HED, provides further experimental evidence for the feasibility of its treatment of UC.
黄连阿胶汤(HED)是源自《伤寒论》的一种中药方剂。然而,HED的最终作用机制仍不明确。因此,本研究旨在探讨HED是否能通过调节CD4T亚群和肠道微生物群对2,4,6-三硝基苯磺酸(TNBS)诱导的结肠炎(UC)模型发挥抗炎作用。
采用超高效液相色谱-四极杆飞行时间串联质谱(UPLC-Q-TOF/MS)鉴定HED中的58种主要化合物。通过评估存活率等指标来评价HED对UC的治疗效果。采用流式细胞术检测CD4T细胞的百分比。利用逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹法检测转录因子、炎症因子和紧密连接蛋白。对结肠组织进行转录组测序,并对肠道内容物进行16S rRNA基因测序。
给予HED可提高结肠炎小鼠的存活率,显著恢复体重、疾病活动指数(DAI)评分、结肠重量和指数、脾脏重量和指数。HED有效改善肠道屏障功能障碍,抑制Th1与Th2细胞的比例,维持Th2/Th1和调节性T细胞(Tregs)/辅助性T细胞17(Th17)的平衡。此外,HED显著降低转录因子和相关细胞因子的分泌。有趣的是,HED还通过富集大量有益益生菌如乳酸杆菌和拟杆菌,同时抑制机会致病菌如幽门螺杆菌的过度生长,对肠道菌群失调发挥调节作用。
HED对Th2/Th1和Tregs/Th17细胞平衡的调节以及对肠道微生物群的调节,为其治疗UC的可行性提供了进一步的实验证据。