Asiatic acid inhibits NF-κB signaling and ameliorates experimental acute and chronic colitis in mice.

OBJECTIVE

This study aimed to elucidate the anti-inflammatory mechanisms of asiatic acid (AA) by focusing on its modulation of the nuclear factor-κB (NF-κB) signaling pathway and to evaluate its therapeutic effects in murine models of both acute and chronic colitis.

INTRODUCTION

AA, a naturally occurring triterpenoid compound derived from Centella asiatica, is known for its anti-inflammatory activity. However, its comprehensive effects on both acute and chronic intestinal inflammation, particularly through detailed modulation of the NF-κB pathway, have not been fully elucidated.

METHODS

Human intestinal epithelial cells COLO 205 and murine macrophage cells RAW 264.7 were pretreated with AA, followed by stimulation with tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS), respectively. The mRNA expression of pro-inflammatory cytokines, including interleukin (IL)-8, TNF-α, and IL-6, was quantified using real-time RT-PCR. Western blotting was performed to assess the phosphorylation and degradation of the NF-κB inhibitor IκBα, and NF-κB DNA-binding activity was assessed via electrophoretic mobility shift assay (EMSA). In vivo, acute colitis was induced using dextran sulfate sodium (DSS) in wild-type mice, and chronic colitis was established by piroxicam administration in IL-10⁻/⁻ mice. Following AA treatment, colon length, body weight, histology (H&E) with histologic scoring, and colonic NF-κB p65 immunohistochemistry (IHC) were evaluated.

RESULTS

AA significantly downregulated cytokine expression in both cell lines. It inhibited IκBα phosphorylation and degradation, and EMSA demonstrated a marked reduction in NF-κB DNA-binding activity. In mice, AA attenuated body weight loss, colonic shortening, and histologic inflammation in both DSS and IL-10⁻/⁻ models. Concomitantly, colonic IHC showed reduced nuclear NF-κB p65.

CONCLUSIONS

AA alleviates intestinal inflammation by suppressing NF-κB signaling in vitro and exhibits therapeutic efficacy in both acute and chronic colitis models, suggesting its potential as a therapeutic candidate for inflammatory bowel disease.