Ji-Chuan decoction ameliorates slow transit constipation via regulation of intestinal glial cell apoptosis  

作　　者：Xiu-Min Wang Li-Xia Lv Yue-Si Qin Yu-Zhu Zhang Ni Yang Shu Wu Xiu-Wen Xia Hong Yang Hong Xu Ying Liu Wei-Jun Ding 

机构地区：[1]Department of Fundamental Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu 610072,Sichuan Province,China [2]Department of Proctology,Chengdu First People’s Hospital,Chengdu 610041,Sichuan Province,China [3]Department of Endocrinology and Metabolism,Chengdu First People’s Hospital,Chengdu 610041,Sichuan Province,China [4]Department of Dermatology,Chengdu First People’s Hospital,Chengdu 610041,Sichuan Province,China [5]Department of Preventive Medicine,Shantou University Medical College,Shantou 515063,Guangdong Province,China

出　　处：《World Journal of Gastroenterology》2022年第34期5007-5022,共16页世界胃肠病学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China,No. 82074151;the Experimental Formulary Sichuan Youth Science and Technology Innovation Research Team,No. 2020JDTD0022

摘　　要：BACKGROUND Slow transit constipation(STC)is a common intestinal disease with increasing incidence.STC results from various factors,such as the enteric nervous system and metabolic changes.As a classical formula of traditional Chinese medicine,Ji-Chuan decoction(JCD)has been extensively and effectively used in STC treatment,yet its pharmacological mechanism remains unclear.AIM To explore the integrated regulatory pattern of JCD against STC through hyphenated techniques from metabolism,network pharmacology and molecular methods.METHODS STC model mice were generated by intragastric administration of compound diphenoxylate(10 mg/kg/d)for 14 d.The STC mice in the low dose of JCD(3.04 g/kg),middle dose of JCD(6.08 g/kg)and high dose of JCD(12.16 g/kg)groups were orally administered JCD solution once a day for 2 wk.The acetylcholine(ACH)level was examined by enzyme-linked immunosorbent assay.The pathological features of colon tissue were observed by hematoxylin and eosin staining.The differentially expressed metabolites and metabolic pathways were tested by nontargeted metabolomics.The main targets and core ingredients of JCD were identified by network pharmacology,and the expression of AKT was confirmed by immunohistochemistry.Finally,the pathways involved in JCD treatment were predicted using a combination of differentially expressed metabolites and targets,and intestinal glial cell apoptosis was demonstrated by immunofluorescence.RESULTS JCD significantly promoted intestinal motility,increased the levels of the excitatory neurotransmitter ACH and reduced intestinal inflammation in STC mice.Untargeted metabolomics results showed that JCD significantly restored metabolic dysfunction and significantly affected taurine and hypotaurine metabolism.Network pharmacology and molecular experiments showed that JCD regulates AKT protein expression,and the core component is quercetin.Combined analysis demonstrated that apoptosis may be an important mechanism by which JCD relieves constipation.Further experiments showed that JCD r

关 键 词：Slow-transit constipation Ji-Chuan decoction Taurine and hypotaurine metabolism AKT Enteric glial cell APOPTOSIS 

分 类 号：R285.5[医药卫生—中药学]