Runchangningshen paste activates NLRP6 inflammasome-mediated autophagy to stimulate colonic mucin-2 secretion and modulates mucosal microbiota in functional constipation  

作　　者：Xue-Jiao Liu Ye-li-ya Ye-er-tai Yue-Bo Jia Chen-Heng Wu Xiang-Xiang Wang Ke-Ming Yang Xuan Yao Jiang-Hong Ling 

机构地区：[1]Department of Gastroenterology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200021,China [2]School of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [3]Department of Gastroenterology,Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518033,Guangdong Province,China [4]Guangdong Shaxi Pharmaceutical Co.,Ltd,Zhongshan 528471,Guangdong Province,China

出　　处：《World Journal of Gastroenterology》2025年第9期100-134,共35页世界胃肠病学杂志(英文)

基　　金：Supported by National Natural Science Foundation of China,No.82174309;and Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Siming Fund Special Project for Scientific Research,No.SGKJ-202304.

摘　　要：BACKGROUND Runchangningshen paste(RCNSP)is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey.It is known for its ability to nourish yin and blood as well as to loosen the bowel to relieve constipation.The pathophysiology of functional constipation(FC)is associated with a reduction in mucin-2(MUC2)secretion and microbial dysbiosis.AIM To investigate the underlying mechanism of RCNSP against FC through MUC2 and the gut mucosal microbiota.METHODS Ultra-performance liquid chromatography tandem mass spectrometry characterized RCNSP composition to elucidate the material basis of action.FC model was induced via loperamide gavage(16 mg/kg)twice daily for 7 days.Applying defecation function and gastrointestinal motility to assess constipation severity.Hematoxylin and eosin and Alcian blue-periodic acid-schiff staining analyzed colonic mucosal morphology.Transmission electron microscope was used to observe the ultrastructure of goblet cells(GCs).Immunofluorescence colocalization,quantitative PCR,and western blot assessed the impact of RCNSP on gene and protein expression within the NLRP6/autophagy pathway.16S rDNA was employed to sequence the gut mucosal microbiota.RESULTS RCNSP contained 12 components with potential laxative effects.It enhanced defecation function,accelerated gastrointestinal motility,and maintained colonic mucosal integrity.RCNSP treatment significantly increased GC abundance and MUC2 production while preserving GC ultrastructure.At the molecular level,RCNSP enhanced the colocalized expression of key regulatory proteins and modulated mRNA and protein expressions in the NLRP6/autophagy pathway.Through 16S rDNA sequencing analysis,RCNSP significantly altered the mucosal microbiota composition.Specifically,it increased beneficial bacterial strains while reducing harmful ones.Simultaneously,RCNSP reduced butyrate-producing bacteria like Proteobacteria,Enterobacteriaceae,Blautia,and Eubacterium and decreased hydrogen sulfide-producing species,such as Prevotellaceae.It also

关 键 词：Traditional Chinese medicine Functional constipation NLRP6 AUTOPHAGY Mucosal microbiota MUCIN Goblet cells 

分 类 号：R57[医药卫生—消化系统]