Mechanism of mangiferin in the treatment of oral submucous fibrosis based on Gene Expression Omnibus database chip mining combined with network pharmacology and molecular docking

doi:10.7518/hxkq.2024.2024050

Abstract

Abstract:

Objective This study aims to investigate the primary target and potential mechanism of mangiferin (MF) in treating oral submucous fibrosis (OSF) through Gene Expression Omnibus (GEO) database chip mining, network pharmacology, and molecular docking techniques. Methods Potential therapeutic targets for OSF were identified using GEO chip data. The potential targets of MF were predicted, and disease-related targets for OSF were collected from databases. A Venn diagram was created using the EVenn platform to identify overlapping targets. The protein-protein interaction (PPI) network was constructed using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID platform. Cytoscape 3.10.1 software was used to visualize a drug-target-pathway-disease network, while AutoDocktools 1.5.6 software was employed for molecular docking analysis. Results A total of 356 potential targets for MF and 360 disease-related targets for OSF were obtained from multiple databases. The top 15 key target proteins in the PPI network were selected as significant candidates. GO function and KEGG pathway enrichment analyses revealed that MF treatment primarily involved advanced glycation end products-receptor (AGE-RAGE), epidermal growth factor receptor (EGFR), and other signaling pathways associated with OSF pathogenesis. Molecular docking analysis demonstrated that MF exhibited a strong binding activity toward AKT serine kinase 1 (AKT1), tumor necrosis factor (TNF), and other core targets. Conclusion These findings suggest that MF may exert its therapeutic effects on OSF through a multitarget approach involving various signaling pathways.

Key words: oral submucous fibrosis, mangiferin, Gene Expression Omnibus database, network pharmacology, molecular docking

CLC Number:

R781.5

Song Ziyi, Yang Chao, Zhang Yunlong, Zhang Zhujiang, Ren Tianjiao, Zhang Xinyue, Li Xue. Mechanism of mangiferin in the treatment of oral submucous fibrosis based on Gene Expression Omnibus database chip mining combined with network pharmacology and molecular docking[J]. West China Journal of Stomatology, 2024, 42(4): 444-451.

Figures/Tables 10

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References 29

1	Gayathri K, Malathi N, Gayathri V, et al. Molecular pathways of oral submucous fibrosis and its progression to malignancy[J]. Arch Oral Biol, 2023, 148: 105644.
2	Liu B, Shen M, Xiong J, et al. Synergistic effects of betel quid chewing, tobacco use (in the form of cigarette smo-king), and alcohol consumption on the risk of malignant transformation of oral submucous fibrosis (OSF): a case-control study in Hunan Province, China[J]. Oral Surg O-ral Med Oral Pathol Oral Radiol, 2015, 120(3): 337-345.
3	Das A, Giri S. A review on role of arecoline and its metabolites in the molecular pathogenesis of oral lesions with an insight into current status of its metabolomics[J]. Prague Med Rep, 2020, 121(4): 209-235.
4	Arakeri G, Rai KK, Hunasgi S, et al. Oral submucous fibrosis: an update on current theories of pathogenesis[J]. J Oral Pathol Med, 2017, 46(6): 406-412.
5	Tom A, Baghirath V, Krishna B, et al. Ultrastructural changes of collagen in different histopathological grades of oral submucous fibrosis[J]. J Pharm Bioallied Sci, 2019, 11(): S309-S313.
6	Shen YW, Shih YH, Fuh LJ, et al. Oral submucous fibrosis: a review on biomarkers, pathogenic mechanisms, and treatments[J]. Int J Mol Sci, 2020, 21(19): 7231.
7	郭锦材, 谢辉. 中医药治疗口腔黏膜下纤维化的临床研究进展[J]. 口腔医学研究, 2019, 35(5): 423-426.
	Guo JC, Xie H. Research progress of traditional chinese medicine in treatment of oral submucous fibrosis[J]. J Oral Sci Res, 2019, 35(5): 423-426.
8	Dutta T, Das T, Gopalakrishnan AV, et al. Mangiferin: the miraculous xanthone with diverse pharmacological properties[J].Naunyn Schmiedebergs Arch Pharmacol, 2023, 396(5): 851-863.
9	Zhang L, Huang C, Fan S. Mangiferin and organ fibrosis: a mini review[J]. Biofactors, 2021, 47(1): 59-68.
10	Zhang L, Liu C, Yin L, et al. Mangiferin relieves CCl4-induced liver fibrosis in mice[J]. Sci Rep, 2023, 13(1): 4172.
11	Chen J, Liu B, Xie X, et al. Comparative molecular analy-sis of oral submucous fibrosis and other organ fibrosis ba-sed on weighted gene co-expression network analysis[J]. J Cent South Univ (Med Sci), 2022, 47(12): 1663-1672.
12	Wang X, Wang ZY, Zheng JH, et al. TCM network pharmacology: a new trend towards combining computatio-nal, experimental and clinical approaches[J]. Chin J Nat Med, 2021, 19(1): 1-11.
13	Dong Y, Zhao Q, Wang Y. Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy[J]. Sci Rep, 2021, 11(1): 19496.
14	Wang N, Li Q. Simultaneous extraction and analysis of seven major saikosaponins from bupleuri radix and the exploration of antioxidant activity and its mechanism[J]. Molecules, 2023, 28(15): 5872.
15	Song J, Meng Y, Wang M, et al. Mangiferin activates Nrf2 to attenuate cardiac fibrosis via redistributing glutaminolysis-derived glutamate[J]. Pharmacol Res, 2020, 157: 104845.
16	Song Y, Liu W, Tang K, et al. Mangiferin alleviates renal interstitial fibrosis in streptozotocin-induced diabetic mice through regulating the PTEN/PI3K/Akt signaling pathway[J]. J Diabetes Res, 2020, 2020: 9481720.
17	Lan A, Du J. Potential role of Akt signaling in chronic kidney disease[J]. Nephrol Dial Transplant, 2015, 30(3): 385-394.
18	Lin Y, Jiang Y, Xian H, et al. Expression and correlation of the Pi3k/Akt pathway and VEGF in oral submucous fibrosis[J]. Cell Prolif, 2023, 56(11): e13491.
19	Siegmund D, Wajant H. TNF and TNF receptors as the-rapeutic targets for rheumatic diseases and beyond[J]. Nat Rev Rheumatol, 2023, 19(9): 576-591
20	Gupta S, Nigam K, Srivastav RK, et al. Genetic polymorphism of tumor necrosis factor alpha (TNF-α) and tumor necrosis factor beta (TNF-β) genes and risk of oral pre-cancer and cancer in North Indian population[J]. Oral Maxillofac Surg, 2022, 26(1): 33-43.
21	Guo ZX, Zhang Z, Yan JF, et al. A biomaterial-based therapy using a sodium hyaluronate/bioglass composite hydrogel for the treatment of oral submucous fibrosis[J]. Acta Biomater, 2023, 157: 639-654.
22	Wu L, Cheng Y, Geng D, et al. O-GlcNAcylation regulates epidermal growth factor receptor intracellular trafficking and signaling[J]. Proc Natl Acad Sci U S A, 2022, 119(10): e2107453119.
23	郭锦材, 谢辉, 吴昊, 等. 姜黄素治疗口腔黏膜下纤维性变有效性的Meta分析[J]. 华西口腔医学杂志, 2021, 39(2): 195-202.
	Guo JC, Xie H, Wu H, et al. Efficacy of curcumin in the treatment of oral submucous fibrosis: a Meta-analysis[J]. West China J Stomatol, 2021, 39 (2): 195-202.
24	Parwani K, Patel F, Bhagwat P, et al. Swertiamarin mitigates nephropathy in high-fat diet/streptozotocin-induced diabetic rats by inhibiting the formation of advanced glycation end products[J]. Arch Physiol Biochem, 2024, 130(2): 136-154.
25	Chang MC, Chan CP, Chen YJ, et al. Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling[J]. Oncotarget, 2016, 7(13): 16879-16894.
26	Zhou S, Zhu Y, He Z, et al. Long non-coding RNA expression profile associated with malignant progression of oral submucous fibrosis[J]. J Oncol, 2019, 2019: 6835176.
27	Ho YC, Yang SF, Lee SS, et al. Regulation of hypoxia-inducible factor-1α in human buccal mucosal fibroblasts stimulated with arecoline[J]. J Formos Med Assoc, 2017, 116(6): 484-487.
28	Tsai CH, Lee SS, Chang YC. Hypoxic regulation of plasminogen activator inhibitor-1 expression in human buccal mucosa fibroblasts stimulated with arecoline[J]. J O-ral Pathol Med, 2015, 44(9): 669-673.
29	Fu TL, Li GR, Li DH, et al. Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis[J]. Acta Pharmacol Sin, 2024, 45(5): 1002-1018.

序号	蛋白名称	度值	接近中心性	中介中心性
1	AKT1	20	0.71	0.21
2	TNF	20	0.70	0.19
3	EGFR	16	0.66	0.09
4	SRC	16	0.65	0.08
5	BCL2	15	0.62	0.05
6	MMP9	14	0.60	0.03
7	HIF1A	13	0.59	0.09
8	PTGS2	12	0.58	0.02
9	IGF1	12	0.58	0.03
10	MMP2	11	0.58	0.02
11	ALB	9	0.55	0.04
12	ITGB1	9	0.55	0.09
13	AR	8	0.52	0.03
14	PGR	8	0.51	0.03
15	MAPK8	7	0.52	0.00

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[6]	Bo Yang,Mengfan Fu,Zhangui Tang. Rat model with oral submucous fibrosis induced by arecoline and mechanical stimulation [J]. West China Journal of Stomatology, 2019, 37(3): 260-264.
[7]	LI Ning1, JIAN Xin-chun1，XU Chun-jiao2. Expression of loricrin and cytochrome P450 3A5 in oral submucous fibrosis and their significance [J]. West China Journal of Stomatology, 2009, 27(01): 29-33.
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