A Docking and Network Pharmacology Study on the Molecular Mechanisms of Curcumin in Dental Caries and

Overview

Journal Dent J (Basel)

Specialty Dentistry

Date 2024 Jun 26

PMID 38920854

Authors

Juan Manuel Guzman-Flores

Angel Perez-Reyes

Sonia Isela Vazquez-Jimenez

Mario Alberto Isiordia-Espinoza

Fernando Martinez-Esquivias

Affiliations

Soon will be listed here.

Abstract

Background: Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone's quality of life because it can cause tooth loss and make chewing difficult. Dental caries involves various factors, such as and host factors. Currently, adjuvant therapies, such as curcumin, have emerged, but how they work has not been adequately described. Therefore, this work aims to identify the molecular mechanism of curcumin in caries and .

Methods: We obtained differentially expressed genes from a GEO dataset, and curcumin targets were obtained from other databases. The common targets were analyzed according to gene ontology enrichment, key genes were obtained, and binding to curcumin was verified by molecular docking.

Results: Our analysis showed that curcumin presents 134 therapeutic targets in caries. According to the gene ontology analysis, these targets are mainly involved in apoptosis and inflammation. There are seven key proteins involved in the action of curcumin on caries: MAPK1, BCL2, KRAS, CXCL8, TGFB1, MMP9, and IL1B, all of which spontaneously bind curcumin. In addition, curcumin affects metabolic pathways related to lipid, purine, and pyrimidine metabolism in .

Conclusions: Curcumin affects both host carious processes and .

References

Szklarczyk D, Santos A, von Mering C, Jensen L, Bork P, Kuhn M . STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res. 2015; 44(D1):D380-4. PMC: 4702904. DOI: 10.1093/nar/gkv1277. View

Dallakyan S, Olson A . Small-molecule library screening by docking with PyRx. Methods Mol Biol. 2015; 1263:243-50. DOI: 10.1007/978-1-4939-2269-7_19. View

Killcoyne S, Carter G, Smith J, Boyle J . Cytoscape: a community-based framework for network modeling. Methods Mol Biol. 2009; 563:219-39. DOI: 10.1007/978-1-60761-175-2_12. View

Li B, Pan T, Lin H, Zhou Y . The enhancing antibiofilm activity of curcumin on Streptococcus mutans strains from severe early childhood caries. BMC Microbiol. 2020; 20(1):286. PMC: 7493841. DOI: 10.1186/s12866-020-01975-5. View

Sahebkar A, Cicero A, Simental-Mendia L, Aggarwal B, Gupta S . Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacol Res. 2016; 107:234-242. DOI: 10.1016/j.phrs.2016.03.026. View

Jiashuo W, Fangqing Z, Zhuangzhuang L, Weiyi J, Yue S . Integration strategy of network pharmacology in Traditional Chinese Medicine: a narrative review. J Tradit Chin Med. 2022; 42(3):479-486. PMC: 9924699. DOI: 10.19852/j.cnki.jtcm.20220408.003. View

Baker J, Faustoferri R, Quivey Jr R . Acid-adaptive mechanisms of Streptococcus mutans-the more we know, the more we don't. Mol Oral Microbiol. 2016; 32(2):107-117. PMC: 5498100. DOI: 10.1111/omi.12162. View

Sayers E, Bolton E, Brister J, Canese K, Chan J, Comeau D . Database resources of the national center for biotechnology information. Nucleic Acids Res. 2021; 50(D1):D20-D26. PMC: 8728269. DOI: 10.1093/nar/gkab1112. View

Davis A, Wiegers T, Johnson R, Sciaky D, Wiegers J, Mattingly C . Comparative Toxicogenomics Database (CTD): update 2023. Nucleic Acids Res. 2022; 51(D1):D1257-D1262. PMC: 9825590. DOI: 10.1093/nar/gkac833. View

10.

Machiulskiene V, Campus G, Carvalho J, Dige I, Ekstrand K, Jablonski-Momeni A . Terminology of Dental Caries and Dental Caries Management: Consensus Report of a Workshop Organized by ORCA and Cariology Research Group of IADR. Caries Res. 2019; 54(1):7-14. DOI: 10.1159/000503309. View

11.

Bojanich M, Calderon R . Streptococcus mutans membrane lipid composition: Virulence factors and structural parameters. Arch Oral Biol. 2017; 81:74-80. DOI: 10.1016/j.archoralbio.2017.04.023. View

12.

Daina A, Michielin O, Zoete V . SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019; 47(W1):W357-W364. PMC: 6602486. DOI: 10.1093/nar/gkz382. View

13.

Fujiwara N, Whitford G, Bartlett J, Suzuki M . Curcumin suppresses cell growth and attenuates fluoride-mediated Caspase-3 activation in ameloblast-like LS8 cells. Environ Pollut. 2021; 273:116495. PMC: 8272738. DOI: 10.1016/j.envpol.2021.116495. View

14.

Jimenez-Flores L, Lopez-Briones S, Macias-Cervantes M, Ramirez-Emiliano J, Perez-Vazquez V . A PPARγ, NF-κB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver. Molecules. 2014; 19(6):8289-302. PMC: 6271620. DOI: 10.3390/molecules19068289. View

15.

Arellano-Rodriguez N, Alvarez-Quezada O, Zapata Benavides P, Vargas-Alanis G, Franco-Molina M, Zamora-Avila D . Curcumin Sensitizes 4T1 Murine Breast Cancer Cells to Cisplatin Through PAR4 Secretion. In Vivo. 2022; 36(6):2767-2773. PMC: 9677768. DOI: 10.21873/invivo.13013. View

16.

Nogales C, Mamdouh Z, List M, Kiel C, Casas A, Schmidt H . Network pharmacology: curing causal mechanisms instead of treating symptoms. Trends Pharmacol Sci. 2021; 43(2):136-150. DOI: 10.1016/j.tips.2021.11.004. View

17.

Guzman-Flores J, Arevalo-Caro C, Martinez-Esquivias F, Isiordia-Espinoza M, Franco-de la Torre L . Molecular mechanism of curcumin on periodontitis: A pharmacological network study. J Oral Biosci. 2023; 65(4):379-385. DOI: 10.1016/j.job.2023.08.004. View

18.

Hu X, Song T, Zhu Y, Wu L, Zhang X, Zhou J . Association of ENAM, TUFT1, MMP13, IL1B, IL10 and IL1RN gene polymorphism and dental caries susceptibility in Chinese children. J Int Med Res. 2019; 47(4):1696-1704. PMC: 6460591. DOI: 10.1177/0300060519828450. View

19.

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S . PubChem 2023 update. Nucleic Acids Res. 2022; 51(D1):D1373-D1380. PMC: 9825602. DOI: 10.1093/nar/gkac956. View

20.

Ehteshami A, Shirban F, Gharibpour F, Bagherniya M, Sathyapalan T, Sahebkar A . Does Curcumin Have an Anticaries Effect? A Systematic Review of In Vitro Studies. Adv Exp Med Biol. 2021; 1291:213-227. DOI: 10.1007/978-3-030-56153-6_12. View