Abstract
BACKGROUND: Oral submucous fibrosis (OSMF) is a precancerous condition primarily associated with betel nut chewing. Naringenin, a flavonoid found in citrus fruits, has been demonstrated to show antifibrotic effects in various fibrosis models. The present study was conducted to investigate the potential antifibrotic properties of naringenin in Human gingival fibroblasts (HGFs) exposed to arecoline. MATERIALS AND METHODS: Naringenin was extracted from grapefruit peel using methanol and characterized via Gas Chromatography-Mass Spectrometry (GC-MS). HGFs were cultured in Dulbecco's Modified Eagle Medium and treated with arecoline to induce fibrosis. The cells were then exposed to naringenin at varying concentrations. Cytotoxicity was assessed using the MTT assay, while the expression of fibrotic markers was quantified using real-time polymerase chain reaction (PCR). Additionally, Masson's trichrome staining was performed to evaluate the collagen deposition aided by An in-silico pharmacological network analysis. RESULTS: GC-MS confirmed the presence of naringenin as a major bioactive compound in grapefruit peel extract. Naringenin significantly improved cell viability in arecoline-treated HGFs. It was found that naringenin markedly downregulated the expression of fibrotic markers, as compared to the arecoline-only group. Histopathological analysis demonstrated a reduction in collagen deposition following naringenin treatment. Pharmacological network analysis identified potential pathways targeted by naringenin, including TGF-β, PI3K-Akt, and MAPK signaling, with hub genes such as MMP9 and TGFB1 playing central roles. CONCLUSION: Naringenin exhibits promising antifibrotic activity in arecoline-induced fibrosis in HGFs, potentially through modulation of key fibrotic signaling pathways. These findings highlight its potential role as a therapeutic agent for OSMF management.