Mucoadhesive chitosan-coated boswellic acids nanoparticles as promising gastroprotective nanoagents via modulation of the RAS/ERK signaling pathway

Abstract

Chitosan, a natural biological macromolecule, was employed to coat boswellic acids extract nanoparticles (CT/BA NPs) to enhance their gastroprotective potential. This study evaluated the therapeutic effects of CT/BA NPs compared to free boswellic acids (BA) in a murine model of ethanol-induced gastric ulcers. Histological analysis showed that CT/BA NPs preserved gastric gland integrity and minimized inflammatory infiltration, achieving a ~ 97% reduction in ulcer index compared to the ulcer group, whereas BA alone achieved ~ 80% protection. CT/BA NPs treatment markedly modulated key growth factors, with TGF-α and TGF-β1 increased by more than 100% relative to the ulcer group, while VEGF expression was suppressed by ~ 74%, indicating more controlled angiogenesis. In addition, CT/BA NPs significantly reduced RAS and ERK levels (by ~ 1.6- and 1.2-fold, respectively) and lowered TNF-α compared to BA, highlighting their role in regulating the RAS-ERK signaling pathway. The superior mucoadhesive properties of CT/BA NPs (76.4% vs. 15.8% for BA NPs) improved gastric mucosal retention, contributing to localized therapeutic effects. Collectively, these findings demonstrate that CT/BA NPs provide promising gastroprotection by promoting epithelial healing, modulating growth factors and signaling pathways, and mitigating ulcer severity.