An in-vitro exploration of the antifibrotic activity of Naringenin: A potential therapeutic agent for oral submucous fibrosis management

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 potent...

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Main Authors: S. Samyuktha Aarthi, Deepak Pandiar, Raghunandhakumar Subramanian, Reshma Poothakulath Krishnan
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Journal of Oral Biology and Craniofacial Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2212426825001186
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author S. Samyuktha Aarthi
Deepak Pandiar
Raghunandhakumar Subramanian
Reshma Poothakulath Krishnan
author_facet S. Samyuktha Aarthi
Deepak Pandiar
Raghunandhakumar Subramanian
Reshma Poothakulath Krishnan
author_sort S. Samyuktha Aarthi
collection DOAJ
description 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.
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spelling doaj-art-4ec409525ade4083bd269c19a54e97bc2025-08-20T03:02:10ZengElsevierJournal of Oral Biology and Craniofacial Research2212-42682025-07-0115484985710.1016/j.jobcr.2025.06.006An in-vitro exploration of the antifibrotic activity of Naringenin: A potential therapeutic agent for oral submucous fibrosis managementS. Samyuktha Aarthi0Deepak Pandiar1Raghunandhakumar Subramanian2Reshma Poothakulath Krishnan3Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, IndiaDepartment of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India; Corresponding author.Cancer and Stem Cell Research Lab, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, IndiaDepartment of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, IndiaBackground: 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.http://www.sciencedirect.com/science/article/pii/S2212426825001186NaringeninOral submucous fibrosisArecolineHuman gingival fibroblastsTGF-βFibrosis
spellingShingle S. Samyuktha Aarthi
Deepak Pandiar
Raghunandhakumar Subramanian
Reshma Poothakulath Krishnan
An in-vitro exploration of the antifibrotic activity of Naringenin: A potential therapeutic agent for oral submucous fibrosis management
Journal of Oral Biology and Craniofacial Research
Naringenin
Oral submucous fibrosis
Arecoline
Human gingival fibroblasts
TGF-β
Fibrosis
title An in-vitro exploration of the antifibrotic activity of Naringenin: A potential therapeutic agent for oral submucous fibrosis management
title_full An in-vitro exploration of the antifibrotic activity of Naringenin: A potential therapeutic agent for oral submucous fibrosis management
title_fullStr An in-vitro exploration of the antifibrotic activity of Naringenin: A potential therapeutic agent for oral submucous fibrosis management
title_full_unstemmed An in-vitro exploration of the antifibrotic activity of Naringenin: A potential therapeutic agent for oral submucous fibrosis management
title_short An in-vitro exploration of the antifibrotic activity of Naringenin: A potential therapeutic agent for oral submucous fibrosis management
title_sort in vitro exploration of the antifibrotic activity of naringenin a potential therapeutic agent for oral submucous fibrosis management
topic Naringenin
Oral submucous fibrosis
Arecoline
Human gingival fibroblasts
TGF-β
Fibrosis
url http://www.sciencedirect.com/science/article/pii/S2212426825001186
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