Published online Sep 14, 2022. doi: 10.3748/wjg.v28.i34.5007
Peer-review started: May 20, 2022
First decision: July 13, 2022
Revised: July 19, 2022
Accepted: August 21, 2022
Article in press: August 21, 2022
Published online: September 14, 2022
Slow transit constipation (STC) is a common intestinal disorder without an effective therapeutic regimen. Ji-Chuan Decoction (JCD) is an established formula for STC. However, its pharmacological mechanism is still unclear.
To determine the ingredients and mechanism of JCD for STC treatment.
To explore the integrated regulatory pattern of JCD against STC through hyphenated techniques from metabolism, network pharmacology and molecular methods.
STC model mice were generated by gavage of diphenoxylate for 14 d. STC mice in the low- (3.04 g/kg), medium- (6.08 g/kg) and high-dosage (12.16 g/kg) JCD groups were orally administered. The acetylcholine (ACH) level was detected by enzyme-linked immunosorbent assay. AKT expression and enteric glial cell (EGC) apoptosis were demonstrated by immunofluorescence. The differentially expressed metabolites were tested by nontargeted metabolomics. The targets and core ingredients were identified by network pharmacology.
JCD significantly promotes intestinal motility, increases colonic ACH content and reduces inflammation in STC mice. It markedly restores the misaligned metabolites, including taurine/hypotaurine, and rescues AKT expression with quercetin. Inhibition of EGC apoptosis is a potential mechanism by which JCD relieves constipation.
Regulating gut metabolites and reducing EGC apoptosis in STC mice may be the key mechanism of JCD for STC treatment.
Further investigation into the molecular interactions among the JCD ingredients and metabolites, intestinal microbiota and host response in STC mice is necessary.