Investigating the Synergistic Effects of Chitosan and Dexamethasone in the Management of Periapical Inflammation: A Computational Perspective

Abstract

Chitosan, a natural biopolymer, is known for its biocompatibility and anti-inflammatory properties, positioning it as a promising alternative to conventional anti-inflammatory agents. This study aims to evaluate and compare the anti-inflammatory efficacy of chitosan with that of dexamethasone, focusing on molecular docking analysis and in-vitro assays. The anti-inflammatory effects of chitosan and dexamethasone were assessed using cultured RAW 264.7 macrophages treated at various concentrations after LPS-induced inflammation. Inflammatory markers TNF-α, IL-6, and nitric oxide (NO) were quantified via ELISA and Griess assays. Additionally, molecular docking studies targeting iNOS, ALOX5, MAPK, PKC, ERK, and TNF-α were performed to compare binding affinities. In vitro, dexamethasone exhibited a stronger anti-inflammatory effect than chitosan, with a lower IC50 (22.7 µg/mL versus 40.3 µg/mL for chitosan). At maximum concentration, dexamethasone inhibited inflammation by 90%, compared to 80% for chitosan. Docking studies further demonstrated that dexamethasone had consistently stronger binding affinities with all targets, particularly iNOS and ALOX5. While dexamethasone's potency surpasses that of chitosan, chitosan’s moderate anti-inflammatory efficacy and natural origin make it a promising complementary agent. The findings suggest potential applications of chitosan in cases where synthetic drugs may cause side effects or are unsuitable for long-term use.