{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T04:35:38Z","timestamp":1774154138603,"version":"3.50.1"},"reference-count":41,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>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 <jats:italic>Centella asiatica<\/jats:italic>, has demonstrated pharmacological properties, including anti-inflammatory and antioxidant effects, making it a potential candidate for mitigating LPS-induced pulp inflammation. This <jats:italic>in vivo<\/jats:italic> study aims to investigate the impact of Asiatic acid on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in <jats:italic>Rattus norvegicus<\/jats:italic> with LPS-induced pulp inflammation.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>This quasi-laboratory experimental <jats:italic>in vivo<\/jats:italic> 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, <jats:italic>n<\/jats:italic> = 5). The negative control group (NCG, <jats:italic>n<\/jats:italic> = 5) received only glass ionomer cement. The positive control group (PCG, <jats:italic>n<\/jats:italic> = 5) received Eugenol with glass ionomer cement. Intervention groups 1, 2, and 3 (IG1, IG2, IG3; <jats:italic>n<\/jats:italic> = 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-\u03b1) 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).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>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 \u00b1 1.092 ng\/mL; <jats:italic>p<\/jats:italic> = 0.047), 1.0% (IG2) (9.132 \u00b1 1.285 ng\/mL; <jats:italic>p<\/jats:italic> = 0.020), and 2.0% (IG3) (11.972 \u00b1 1.888 ng\/mL; <jats:italic>p<\/jats:italic> = 0.000) Asiatic acid compared to NCG (7.146 \u00b1 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 \u00b1 0.888 ng\/mL; <jats:italic>p<\/jats:italic> = 0.001), as well as IG1 (<jats:italic>p<\/jats:italic> = 0.001) and IG2 (<jats:italic>p<\/jats:italic> = 0.002). However, no significant difference was observed between administering 0.5% Asiatic acid (IG1), 1.0% Asiatic acid (IG2), and Eugenol (PCG).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.18004","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T07:10:32Z","timestamp":1725606632000},"page":"e18004","source":"Crossref","is-referenced-by-count":5,"title":["Asiatic acid reduces lipopolysaccharides-induced pulp inflammation through activation of nuclear factor erythroid 2-related factor 2 in rats"],"prefix":"10.7717","volume":"12","author":[{"given":"Risya","family":"Cilmiaty","sequence":"first","affiliation":[{"name":"Doctoral Program of Medical Sciences, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Central Java, Indonesia"},{"name":"Department of Oral Diseases, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Central Java, 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