Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, PR China.
J Ethnopharmacol. 2023 Jan 10;300:115741. doi: 10.1016/j.jep.2022.115741. Epub 2022 Sep 24.
Pulsatilla decoction (PD), is an herbal formula commonly used for the treatment of ulcerative colitis (UC) in clinical practice, but the mechanism of PD alters the colitis remains elusive.
To evaluate the intervention effect of PD on Dextran Sodium Sulfate (DSS)-induced UC based on gut microbiota and intestinal short-chain fatty acid (SCFAs) metabolism, and to investigate the mechanism of action of PD in treating UC.
A 3% (wt/vol) DSS-induced ulcerative colitis model in C57BL/6 male mice was used to evaluate the effect of oral PD in treating UC. The changes in gut microbiota in mice were analyzed by 16SrDNA gene sequencing, and the content of SCFAs in the intestinal contents of mice was determined by gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was applied to analyze the expression of inflammatory cytokines in serum and colonic tissues, and western blotting (WB) was applied to analyze the expression of tight junction proteins in colonic tissues.
PD can alleviate the symptoms of UC mice, Pulsatilla Decoction high dose treatment group (PDHT) shows the best effect. Compared with the DSS group, the PDHT had significantly lower body mass, disease activity index (DAI) score, colonic macroscopic damage index (CMDI) score, and pathological damage score, at the phylum level, the relative abundance of Bacteroidetes increased while that of Firmicutes and Proteobacteria decreased, at the Genus level, the abundance of Bacteroides and Lachnospiraceae.NK4A136.group increased while that of Clostridium. sensu.stricto。, Escherichia. shigella and Turicibacter decreased. Compared with the DSS group, acetate, propionate, and total SCFAs in the PDHT with significantly higher levels. The concentrations of interleukin-1β (L-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17) decreased whereby the concentration of interleukin-10 (IL-10) increased in the PDHT group. The expression levels of Occludin, zonula occludens-1 (ZO-1), Claudin1, Claudin5, G protein-coupled receptor43 (GPR43) protein, and the relative expression of ZO-1 and Occludin mRNA were significantly increased PDHT group.
PD has a good therapeutic effect on UC mice. The pharmacological mechanism is probably maintaining the homeostasis and diversity of gut microbiota, increasing the content of SCFAs, and repairing the colonic mucosal barrier.
白头翁汤（PD）是一种常用于临床治疗溃疡性结肠炎（UC）的草药配方，但 PD 改变结肠炎的机制仍不清楚。
基于肠道微生物群和肠道短链脂肪酸（SCFA）代谢，评估 PD 对葡聚糖硫酸钠（DSS）诱导的 UC 的干预作用，并探讨 PD 治疗 UC 的作用机制。
采用 3%（wt/vol）DSS 诱导的 C57BL/6 雄性小鼠溃疡性结肠炎模型，评价 PD 口服治疗 UC 的效果。通过 16SrDNA 基因测序分析小鼠肠道微生物群的变化，通过气相色谱-质谱联用（GC-MS）测定小鼠肠内容物中 SCFA 的含量。酶联免疫吸附试验（ELISA）分析血清和结肠组织中炎症细胞因子的表达，Western blot（WB）分析结肠组织中紧密连接蛋白的表达。
PD 可缓解 UC 小鼠的症状，高剂量 PD 治疗组（PDHT）效果最佳。与 DSS 组相比，PDHT 组的体重、疾病活动指数（DAI）评分、结肠大体损伤指数（CMDI）评分和病理损伤评分均显著降低，在门水平上，厚壁菌门的相对丰度增加，而 Firmicutes 和 Proteobacteria 的相对丰度降低，在属水平上，拟杆菌属和lachnospiraceae.NK4A136.group 的丰度增加，而梭菌。sensu.stricto。、大肠杆菌。志贺氏菌和 Turicibacter 的丰度降低。与 DSS 组相比，PDHT 组的乙酸盐、丙酸盐和总 SCFA 水平显著升高。IL-1β（L-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-17（IL-17）的浓度降低，IL-10（IL-10）的浓度升高。PDHT 组的 Occludin、zonula occludens-1（ZO-1）、Claudin1、Claudin5、G 蛋白偶联受体 43（GPR43）蛋白表达水平以及 ZO-1 和 Occludin mRNA 的相对表达水平均显著升高。
PD 对 UC 小鼠有较好的治疗作用。其药理机制可能是维持肠道微生物群的平衡和多样性，增加 SCFA 的含量，修复结肠黏膜屏障。
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