中文摘要：炎症性肠病（IBD）是一种慢性复发性胃肠道炎症疾病，包括溃疡性结肠炎（UC）和克罗恩病（CD）。肠道菌群及其代谢产物可能是IBD，尤其是UC的病原体中发挥重要作用。清肠化湿方（QHF）是一种传统的中药方剂，其在临床中对UC有治疗作用，但治疗机理尚不明确。本研究旨在探索QHF及其含有的白头翁（PBR）和白芷（ADR）等成分对UC的治疗作用。结果表明，QHF能显著抑制结肠炎，ADR和PBR对葡聚糖硫酸钠（DSS）诱导的结肠炎有较强的抑制作用。研究证实，虽然ADR是QHF维持肠道菌群内稳态和代谢的主要原因，但PBR在保持隐窝干细胞增殖和结肠杯状细胞功能方面更为突出；另外，QHF对结肠炎的缓解作用与其恢复肠道微生物代谢稳态、保护肠上皮屏障和调节NLRP3/IL-1β信号通路有关。
外文摘要：Ethnopharmacological relevance: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disease of the gastrointestinal tract, consisting of ulcerative colitis (UC) and Crohn's disease (CD). Gut microbiota and their metabolites may play a role in the pathogen of IBD, especially of the UC. Qingchang Huashi Formula (QHF), a traditional Chinese medicine formula, has shown therapeutic effect on treating UC based on the clinical practice without clear pharmacological mechanism.
   Aim of the study: The aim of this study was to clearly define the effect of QHF and its components, Baitouweng (PBR) and Baizhi (ADR) on treating UC.
   Materials and Methods: Pharmacodynamic effects of QHF and single herb were evaluated in dextran sulfate sodium (DSS) induced acute or chronic colitis mice. Body weight loss, disease activity index (DAI) and colon length were estimated. Histological changes were observed by H&E staining. The number and abundance of gut microbiota were measured with 16S rRNA sequencing. LC-MS and GC-MS were used to detect the concentration of metabolites (e.g., bile acids (BAs) and short chain fatty acids (SCFAs)). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining and the crypt stem cell was estimated by immunohistochemical analyses. The colorectal tissues were used to detect levels of IL-1 beta, IL-6 and TNF-alpha by ELISA or qRT-PCR. The expression of NLRP3, Caspase 1 and IL-1 beta were examined by western blotting.
   Results: QHF significantly inhibited colitis, protected mice from the loss of body weight and colon shorten. Comparatively, ADR and PBR showed strong efficacy in inhibiting DSS-induced colitis. We verified that while ADR was responsible for QHF's effect on maintaining gut microbiota homeostasis and metabolism, PBR was more prominent in keeping crypt stem cells proliferation and colonic goblet cells function. Moreover, we demonstrated that the alleviation of colitis by QHF was associated with the restoration of gut microbiota-metabolism homeostasis, protection of intestinal epithelial barrier and regulation of NLRP3/IL-1 beta pathway.
   Conclusions: The finding of the present study suggested that QHF is curative in DSS-induced colitis by restoring gut microbiota-metabolism homeostasis and goblet cells function. An optimized QHF was constituted by ADR and PBR, which showed comparable efficacy on colitis to that of QHF. Our work probed out the active constitutes as well as the relevant pharmacological mechanisms of QHF, shedding light on potential new drug combination for the treatment of IBD.
 
外文关键词：Qingchang Huashi formula; Ulcerative colitis; Gut microbiota; Goblet Cell
作者：Hu, JY；Huang, H；Che, Y；Ding, CJ；Zhang, L；Wang, Y；Hao, HP；Shen, H；Cao, LJ
作者单位：Nanjing Univ Chinese Med；China Pharmaceut Univ
期刊名称：JOURNAL OF ETHNOPHARMACOLOGY
期刊影响因子：3.69
出版年份：2021
出版刊次：266
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