In-Silico Docking of Rubia cordifolia Phytocompounds as Potential MMP-2 Inhibitors for Varicose Vein Management

Open Access

Year : 2025 | Volume : 03 | Issue : 02 | Page : 31 42
    By

    K. Anusree,

  1. Student, Department of Chemistry and Biochemistry, School of Sciences, Jain (Deemed-to-be) University, Bangalore, Karnataka, India

Abstract

Varicose veins are one of the most common disorders, affecting the vein structure and function of lower limbs, yet there has been no absolute cure found yet. One of the underlying causes for worsening of the condition is the proteolytic activity of MMPs which are a group of enzymes that affect the extracellular matrix (ECM) surrounding the affected veins. Phytocompounds of Rubia cordifolia (Manjishta) were docked against the MMP-2 protein to check presence of protein-ligand interaction that can predict the possibility of using the best suited ligand as an inhibitor against MMP-2 protein.
Out of a total of 37 phytochemicals 17 were found to have the most drug-like properties. The ligands were retrieved after in-silico pharmacology studies and docked against the MMP-2 protein. 6 P-L were found to have lowest BI (less than or equal to -0.9) and RMSD value of 0, which corresponds to highly stable bonding between the molecules. This study gives a possibility of using the screened ligands, Munjistine, Rubiadin, 1,5-Dihydroxy-2-Methylanthraquinone, Purpuroxanthins, Alizarin and 1-Hydroxy-2-Methoxy Anthraquinone, to study their effects on reducing the activity of MMP-2, which can reduce the progression of varicose veins into chronic venous disease.

Keywords: Rubia cordifolia; MMP-2; Molecular docking; Varicose veins; Munjistine.

[This article belongs to International Journal of Biochemistry and Biomolecule Research ]

How to cite this article:
K. Anusree. In-Silico Docking of Rubia cordifolia Phytocompounds as Potential MMP-2 Inhibitors for Varicose Vein Management. International Journal of Biochemistry and Biomolecule Research. 2025; 03(02):31-42.
How to cite this URL:
K. Anusree. In-Silico Docking of Rubia cordifolia Phytocompounds as Potential MMP-2 Inhibitors for Varicose Vein Management. International Journal of Biochemistry and Biomolecule Research. 2025; 03(02):31-42. Available from: https://journals.stmjournals.com/ijbbr/article=2025/view=216187


References

1. Nicolaides AN. The most severe stage of chronic venous disease: an update on the management of patients with venous leg ulcers. Adv Ther. 2020;37(Suppl 1):19–24. doi:10.1007/s12325-020-01219-y.
2. Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld D. The epidemiology of chronic venous insufficiency and varicose veins. Ann Epidemiol. 2005;15(3):175–84. doi:10.1016/j.annepidem.2004.05.015.
3. Fayyaz F, Vaghani V, Ekhator C, Abdullah M, Alsubari RA, Daher OA, et al. Advancements in varicose vein treatment: anatomy, pathophysiology, minimally invasive techniques, sclerotherapy, patient satisfaction, and future directions. Cureus. 2024;16(3):e51990. doi:10.7759/cureus.51990.
4. Raffetto JD, Khalil RA. Mechanisms of lower extremity vein dysfunction in chronic venous disease and implications in management of varicose veins. Vessel Plus. 2021;5:36. doi:10.20517/2574-1209.2021.16
5. Kowalewski R, Sobolewski K, Wolanska M, Gacko M. Matrix metalloproteinases in the vein wall. Int Angiol. 2004;23(2):164–9.
6. Johansson N, Ahonen M, Kähäri VM. Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci. 2000;57(1):5–15. doi:10.1007/s000180050008

7. Wågsäter D, Zhu CZ, Björkegren J, Skogsberg J, Eriksson P. MMP-2 and MMP-9 are prominent matrix metalloproteinases during atherosclerosis development in the Ldlr−/−Apob100/100 mouse. Int J Mol Med. 2011;28(2):247–53. doi:10.3892/ijmm.2011.693

8. Soini Y, Satta J, Määttä M, Autio-Harmainen H. Expression of MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA in valvular lesions of the heart. J Pathol. 2001;194(2):225–31. doi:10.1002/path.850

9. Wen C, Chen H, Yang N. Developing phytocompounds from medicinal plants as immunomodulators. In: Aggarwal B, editor. Adv Bot Res. 2012;62:197–272. doi:10.1016/b978-0-12-394591-4.00004-0

10. Festa J, Hussain A, Al-Hareth Z, Singh H, Da Boit M. Anthocyanins and vascular health: A matter of metabolites. Foods. 2023;12(1):47. doi:10.3390/foods12010047

11. Kamble SC, Humbare RB, Sarkar J, Kulkarni AA. Assessment of phytochemicals and antioxidant properties of root extracts of Rubia cordifolia L. in different solvent systems. Biol Life Sci Forum. 2021;4:100. doi:10.3390/IECPS2020-08625

12. Ali A, Aslam M, Chaudhary SS. A review on pharmacognostic and therapeutic uses of Rubia cordifolia. J Drug Deliv Ther. 2020;10(6):195–202. doi:10.22270/jddt.v10i6.4514

13. Ahmad R, Fatima Z, Ali S, Dhaneshwar S, Ahmad S. HPTLC method development and validation for simultaneous quantification of purpurin and alizarin in Rubia cordifolia L. roots and their marketed preparations. Pharmacogn Res. 2024;16(3):652–61. doi:10.5530/pres.16.3.76

14. Pinzi L, Rastelli G. Molecular docking: Shifting paradigms in drug discovery. Int J Mol Sci. 2019;20(18):4331. doi:10.3390/ijms20184331

15. RCSB Protein Data Bank. Crystal structure of human MMP-2 catalytic domain in complex with inhibitor. Available from: https://www.rcsb.org/structure/7XJO

16. Kucukguven A, Khalil RA. Matrix metalloproteinases as potential targets in the venous dilation associated with varicose veins. Curr Drug Targets. 2013;14(3):287–324. doi:10.2174/138945013804998972

17. Dr. Duke’s Phytochemical and Ethnobotanical Databases. Rubia cordifolia (Rubiaceae). Available from: https://phytochem.nal.usda.gov/plant-rubia-cordifolia

18. SwissADME. Available from: http://www.swissadme.ch/

19. Dassault Systèmes BIOVIA. Molecular modeling simulation: Discovery Studio visualization. Available from: https://www.3ds.com/products-services/biovia/products/molecular-modeling-simulation/biovia-discovery-studio/visualization

20. Wlodawer A. Stereochemistry and validation of macromolecular structures. In: Mittermaier A, editor. Methods Mol Biol. 2017;1607:595–610. doi:10.1007/978-1-4939-7000-1_24
21. 21. Ramakrishnan C, Ramachandran GN. Stereochemical criteria for polypeptide and protein chain conformations. II Allowed conformation for a pair of peptide units. Biophys J. 1965;5:909–33. doi:10.1016/S0006-3495(65)86759-5

22. EMBL‑EBI PDBsum Procheck. Available from: https://www.ebi.ac.uk/thornton-srv/databases/pdbsum/

23. Dallakyan S, Olson AJ. Small‑molecule library screening by docking with PyRx. In: Hempel JE, Williams CH, Hong CC, editors. Chemical Biology. New York, NY: Springer; 2015. p. 243–50.

24. Onkaramurthy M, Vishwakarma KK, Singh P, Hegde S, Azeemuddin MM, Rafiq M, Babu UV. Herbal formulations ameliorate chronic venous insufficiency, venotonicity, and elastase inhibition in the management of varicose veins: a preclinical study. Indian J Pharm Sci. 2022;84(4). doi:10.36468/pharmaceutical-sciences.1000

25. Gwozdzinski L, Pieniazek A, Gwozdzinski K. Factors influencing venous remodeling in the development of varicose veins of the lower limbs. Int J Mol Sci. 2024;25:1560. doi:10.3390/ijms25031560

26. Korff T, et al. Biomechanical stretch triggers varicose vein remodeling in mice through activation of the transcription factor AP‑1. FASEB J. 2011;25.

27. Zeng W, Fang Y, Mo S, Shen C, Yang H, Luo G, et al. The underlying mechanisms exploration of Rubia cordifolia L. extract against rheumatoid arthritis by integrating network pharmacology and metabolomics. Drug Des Devel Ther. 2023;17:439–57. doi:10.2147/DDDT.S388932

28. PubChem. Available from: https://pubchem.ncbi.nlm.nih.gov/

29. Ahmad A, Sayed A, Ginnebaugh KR, Sharma V, Suri A, Saraph A, Padhye S, Sarkar FH. Molecular docking and inhibition of matrix metalloproteinase‑2 by novel difluorinated‑benzylidene curcumin analog. Am J Transl Res. 2015;7(2):298–308. PMID:25785001

30. Khan A, Sorour AA, Anton GE, et al. Venous Insufficiency: Endovascular and Surgical Treatment. Curr Cardiol Rep. 2025;27:67. doi:10.1007/s11886-024-02155-x

31. Costa D, Andreucci M, Ielapi N, Serraino GF, Mastroroberto P, Bracale UM, Serra R. Molecular determinants of chronic venous disease: a comprehensive review. Int J Mol Sci. 2023;24(3):1928. doi:10.3390/ijms24031928

32. Roomi MW, Monterrey JC, Kalinovsky T, Niedzwiecki A, Rath M. Modulation of MMP‑2 and MMP‑9 by cytokines, mitogens and inhibitors in lung cancer and malignant mesothelioma cell lines. Oncol Rep. 2009;22(6):1283–91. doi:10.3892/or_00000566

33. Raffetto JD, Ligi D, Maniscalco R, Khalil RA, Mannello F. Why venous leg ulcers have difficulty healing: overview on pathophysiology, clinical consequences, and treatment. J Clin Med. 2021;10(1):29. doi:10.3390/jcm10010029

34. Smetanina MA, Shevela AI, Gavrilov KA, Filipenko ML. The genetic constituent of varicose vein pathogenesis as a key for future treatment option development. Vessel Plus. 2021;5:19. doi:10.20517/2574-1209.2021.17

35. Chiu SC, Tsao SW, Hwang PI, et al. Differential functional genomic effects of anti‑inflammatory phytocompounds on immune signaling. BMC Genomics. 2010;11:513. doi:10.1186/1471-2164-11-513

36. Hoffmann J, Wölfle U, Schempp CM, Casetti F. Tannins from Potentilla officinalis display antiinflammatory effects in the UV erythema test and on atopic skin. J Dtsch Dermatol Ges. 2016;14(9):917–22. doi:10.1111/ddg.12792

37. Wu J‑H, Tung Y‑T, Chien S‑C, Wang S‑Y, Kuo Y‑H, Shyur L‑F, Chang S‑T. Effect of phytocompounds from the heartwood of Acacia confusa on inflammatory mediator production. J Agric Food Chem. 2008;56(5):1567–73. doi:10.1021/jf072959u

38. Liang D, Liu L, Zhao Y, Luo Z, He Y, Li Y, Tang S, Tang J, Chen N. Targeting extracellular matrix through phytochemicals: a promising approach of multi-step actions on the treatment and prevention of cancer. Front Pharmacol. 2023;14:1186712. doi:10.3389/fphar.2023.1186712

39. Patil R, Mohan M, Kasture V, Kasture S. Rubia cordifolia: a review. Orient Pharm Exp Med. 2009;9(1):1–13. doi:10.3742/opem.2009.9.1.001

Regular Issue Open Access Original Research
Volume 03
Issue 02
Received 21/05/2025
Accepted 12/06/2025
Published 07/07/2025
Publication Time 47 Days
204

Login


My IP

PlumX Metrics