Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian
Capsule (SHTB) is a
traditional Chinese medicine (TCM) which effectively improve the symptoms of
constipation. However, the mechanism has not been fully evaluated. The purpose of this study was to evaluate the effect of SHTB on the symptoms and intestinal barrier of mice with
constipation. Our data showed that SHTB effectively improved the
constipation induced by
diphenoxylate, which was confirmed by shorter first defecation time, higher internal propulsion rate and fecal water content. Additionally, SHTB improved the intestinal barrier function, which was manifested by inhibiting the leakage of
Evans blue in intestinal tissues and increasing the expression of
occludin and ZO-1. SHTB inhibited NLRP3
inflammasome signaling pathway and TLR4/NF-κB signaling pathway, reduced the number of proinflammatory cell subsets and increased the number of immunosuppressive cell subsets to relieve
inflammation. The photochemically induced reaction coupling system combined with cellular thermal shift assay and central
carbon metabolomics technology confirmed that SHTB activated AMPKα through targeted binding to Prkaa1 to regulate Glycolysis/Gluconeogenesis and Pentose Phosphate Pathway, and finally inhibited intestinal
inflammation. Finally, no obvious toxicity related to SHTB was found in a repeated
drug administration toxicity test for consecutive 13 weeks. Collectively, we reported SHTB as a TCM targeting Prkaa1 for anti-
inflammation to improve intestinal barrier in mice with
constipation. These findings broaden our knowledge of Prkaa1 as a druggable target
protein for
inflammation inhibition, and open a new avenue to novel
therapy strategy for
constipation injury.