Exploring the Regulatory Mechanism of Total Alkaloids from Portulaca oleracea L. in UC Treatment Based on Network Pharmacology

This study aimed to investigate the potential mechanisms of action of total alkaloids from <i>Portulaca oleracea</i> L. (POL) on ulcerative colitis (UC) using a network pharmacology approach. Network pharmacology analysis identified two bioactive alkaloids within POL as primary anti-UC constituents, targeting 16 core therapeutic proteins and 113 UC-associated signaling pathways. To further explore the therapeutic effects, in vitro cell assays and in vivo animal experiments were conducted. In vitro, high concentrations of <i>Portulaca oleracea</i> total alkaloids (POAs) demonstrated dose-dependent cytotoxicity, significantly reducing Caco-2 cell viability and impairing migration. In a murine model of UC, disease induction led to substantial weight loss, elevated disease activity index (DAI) scores, colon shortening, and severe colonic tissue damage compared to controls. Furthermore, the UC group displayed significantly upregulated serum levels of pro-inflammatory cytokines, TNF-α and IL-1β, as well as increased protein and mRNA expression of TLR4 and NF-κB in colon tissues. Crucially, POAs treatment effectively ameliorated UC symptoms in mice, significantly reducing DAI scores, mitigating colon shortening, and markedly suppressing TLR4/NF-κB pathway activation. These findings strongly suggest that the therapeutic effects of POAs in UC are, at least in part, mediated by the inhibition of the TLR4/NF-κB signaling pathway, leading to a reduction in colonic inflammation.