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Antifibrotic effect of silymarin on arecoline-induced fibrosis in primary human buccal fibroblasts: an in silico and in vitro analysis
被引:2
作者:
Venugopal, Divyambika Catakapatri
[1
]
Viswanathan, Paramesh
[2
]
Ravindran, Soundharya
[3
]
Punnoose, Alan Mathew
[2
]
Yasasve, Madhavan
[1
]
Dicky John, Davis G.
[4
]
Prabhakar, Lavanya
[4
]
Ramanathan, Gnanasambandan
[5
]
Sankarapandian, Sathasivasubramanian
[1
]
Ramshankar, Vijayalakshmi
[3
]
机构:
[1] Sri Ramachandra Inst Higher Educ & Res DU, Sri Ramachandra Dent Coll & Hosp, Dept Oral Med & Radiol, Chennai, India
[2] Sri Ramachandra Inst Higher Educ & Res DU, Fac Clin Res, Stem Cell & Regenerat Biol Lab, Chennai 600116, India
[3] Canc Inst WIA, Dept Prevent Oncol Res, Chennai 600020, India
[4] Sri Ramachandra Inst Higher Educ & Res DU, Dept Bioinformat, Chennai 600116, India
[5] Vellore Inst Technol, Sch Biosci & Technol, Dept Biomed Sci, Vellore 632014, India
关键词:
OSMF;
Silymarin;
Arecoline;
Fibrosis;
Cell culture;
Gene expression;
ORAL SUBMUCOUS FIBROSIS;
EXPRESSION;
D O I:
10.1007/s11033-023-09177-8
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
BackgroundThis study aimed to assess silymarin's anticancer and antifibrotic potential through in silico analysis and investigate its impact on in vitro arecoline-induced fibrosis in primary human buccal fibroblasts (HBF).Methods & resultsThe study utilized iGEMDOCK for molecular docking, evaluating nine bioflavonoids, and identified silymarin and baicalein as the top two compounds with the highest target affinity, followed by subsequent validation through a 100ns Molecular Dynamic Simulation demonstrating silymarin's stable behavior with Transforming Growth Factor Beta. HBF cell lines were developed from tissue samples obtained from patients undergoing third molar extraction. Arecoline, a known etiological factor in oral submucous fibrosis (OSMF), was employed to induce fibrogenesis in these HBFs. The inhibitory concentration (IC50) of arecoline was determined using the MTT assay, revealing dose-dependent cytotoxicity of HBFs to arecoline, with notable cytotoxicity observed at concentrations exceeding 50 mu M. Subsequently, the cytotoxicity of silymarin was assessed at 24 and 72 h, spanning concentrations from 5 mu M to 200 mu M, and an IC50 value of 143 mu M was determined. Real-time polymerase chain reaction (qPCR) was used to analyze the significant downregulation of key markers including collagen, epithelial-mesenchymal transition (EMT), stem cell, hypoxia, angiogenesis and stress markers in silymarin-treated arecoline-induced primary buccal fibroblast cells.ConclusionSilymarin effectively inhibited fibroblast proliferation and downregulated genes associated with cancer progression and EMT pathway, both of which are implicated in malignant transformation. To our knowledge, this study represents the first exploration of silymarin's potential as a novel therapeutic agent in an in vitro model of OSMF.
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