Puji Zhichuang suppositories alleviate acetic acid-induced hemorrhoid-like anorectal inflammation model may involve reduced the PI3K-Akt signaling pathway.

Abstract

Hemorrhoids are commonly associated with inflammatory manifestations. Puji Zhichuang suppositories (PJZC) have been widely applied in the treatment of hemorrhoids; however, their underlying therapeutic mechanisms remain insufficiently understood. Therefore, this study investigated the mechanisms of PJZC in inflammatory hemorrhoids using network pharmacology, 16 S rDNA sequencing, and fecal metabolomics analyses. First, the anti-inflammatory effects of PJZC were validated by evaluating perianal diameter, anorectal coefficient, TNF-α and IL-6 levels, intestinal barrier integrity, and damage-associated molecular patterns (DAMPs). Subsequent multi-omics analyses demonstrated that PJZC exert anti-inflammatory effects may involve reduced PI3K-Akt signaling pathway, gut microbiota composition and metabolic profiles. Finally, molecular docking analysis predicted that the core targets and active ingredients may be closely related to ITGB1, EGFR, and bile acids.