Asiatic acid reduces lipopolysaccharides-induced pulp inflammation through activation of nuclear factor erythroid 2-related factor 2 in rats

Abstract

Background Dental pulp inflammation, often initiated by Gram-negative microorganisms and lipopolysaccharides (LPS), can lead to pulpitis and, subsequently, dental pulp necrosis, compromising tooth structure and increasing susceptibility to fracture. Asiatic acid, derived from Centella asiatica, has demonstrated pharmacological properties, including anti-inflammatory and antioxidant effects, making it a potential candidate for mitigating LPS-induced pulp inflammation. This in vivo study aims to investigate the impact of Asiatic acid on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in Rattus norvegicus with LPS-induced pulp inflammation. Methods This quasi-laboratory experimental in vivo study employed a post-test-only control group design to investigate the effects of Asiatic acid on LPS-induced pulp inflammation in Wistar rats. Thirty rats were randomly divided into six groups subjected to various interventions. LPS was administered to all groups for 6 h except the standard control group (CG, n = 5). The negative control group (NCG, n = 5) received only glass ionomer cement. The positive control group (PCG, n = 5) received Eugenol with glass ionomer cement. Intervention groups 1, 2, and 3 (IG1, IG2, IG3; n = 5 each) received Asiatic acid at concentrations of 0.5%, 1%, and 2%, respectively, with glass ionomer cement. Dental pulp inflammation was confirmed through immunological (tumor necrosis factor alpha (TNF-α) levels), histopathological (inflammatory parameters), and physiological (pain assessment using the rat grimace scale) analyses. Additionally, Nrf2 levels were examined using enzyme-linked immunosorbent assay (ELISA). Results Asiatic acid administration significantly influenced Nrf2 levels in rats with LPS-induced pulp inflammation. Nrf2 levels were significantly higher in groups treated with 0.5% (IG1) (8.810 ± 1.092 ng/mL; p = 0.047), 1.0% (IG2) (9.132 ± 1.285 ng/mL; p = 0.020), and 2.0% (IG3) (11.972 ± 1.888 ng/mL; p = 0.000) Asiatic acid compared to NCG (7.146 ± 0.706). Notably, Nrf2 levels were also significantly higher in the 2.0% Asiatic acid group (IG3) compared to the PCG treated with Eugenol (8.846 ± 0.888 ng/mL; p = 0.001), as well as IG1 (p = 0.001) and IG2 (p = 0.002). However, no significant difference was observed between administering 0.5% Asiatic acid (IG1), 1.0% Asiatic acid (IG2), and Eugenol (PCG). Conclusion This research showed that Asiatic acid significantly impacted the Nrf2 levels in rats with LPS-induced pulp inflammation. This suggests that it has the potential to be used as a therapeutic agent for reducing dental pulp inflammation. These findings support the need to further explore Asiatic acid as a promising intervention for maintaining dental pulp health.