Regulation of wound strength by Ocimum sanctum: in silico and in vivo evidences

Authors

  • Amit Singh Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India
  • Abha Mishra School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi-221005, India
  • Sharad Verma School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi-221005, India
  • Vinay Purohit Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India
  • Raj Kumar Goel Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India

Keywords:

Eugenol, MMP, Collagenase, Gelatinase, Elastase, Stromelysin, Wound healing

Abstract

Background: The present work has been an attempt to facilitate the scientific understanding of the wound strength by Ocimum sanctum (OS, holy basil) a traditional knowledge practiced since ancient times in India.

Methods: The in vivo Incision (wound strength) and Dead space wound models (biochemical estimation of components of ECM) in rats and  In silico method, where one of the target proteins from each class of MMPs involved in wound strength was selected for molecular docking with eugenol (one of the flavonoid present in OS).

Results: Molecular docking showed that eugenol was able to inhibit all selected MMPs, i.e. collagenase (-6.37 Kcal/mol), gelatinase (-5.99 Kcal/mol), elastase (-6.31 Kcal/mol) and stromelysin (-5.79 Kcal/mol). Ethanolic extract of Ocimum sanctum (OSE, 200-800 mg/kg) when administered as suspension showed dose-dependent increase in wound breaking strength in in vivo Incision wound rat model. OSE 400 mg/kg produced a significant increase in protein and collagen constituents like hydroxyproline, hexuronic acid and hexosamine in the connective tissue content of extracellular matrix when studied in Dead space wound model in rat.

Conclusions: The present study is an attempt to correlate the in vivo findings on wound strength promoting activity by Ocimum sanctum with in silico tools.

References

Lu W, Zhu J, Zou S, Li X, Huang J. The efficient expression of human fibroblast collagenase in Escherichia coli and the discovery of flavonoid inhibitors. J Enzyme Inhib Med Chem. 2013Aug;28(4):741-6.

Klein T, Bischoff R. Physiology and pathophysiology of matrix metalloproteases. Amino Acids. 2011;41(2):271–90.

Patruno A, Pesce M, Marrone A, Speranza L, Grilli A, De Lutiis MA, Felaco M, Reale M. Activity of matrix metallo proteinases (MMPs) and the tissue inhibitor of MMP (TIMP)-1 in electromagnetic field-exposed THP-1 cells. J Cell Physiol. 2012;227(6):2767-74.

Wang X, Li KF, Adams E, Schepdael AV. Matrix Metalloproteinase Inhibitors: A Review on Bioanalytical Methods, Pharmacokinetics and Metabolism. Current Drug Metabolism. 2011;12:395-410.

Muller M, Trocme C, Lardy B, Morel F, Halimi S, Benhamou PY. Matrix metalloproteinases and diabetic foot ulcers: the ratio of MMP-1 to TIMP-1 is a predictor of wound healing. Diabet Med. 2008;25:419–26.

Singh E, Sheel S, Dwivedi J and Sharma S: Diversified potentials of Ocimum sanctum Linn (Tulsi). An exhaustive survey; J Nat Prod Plant Resour. 2012;2(1):39-48.

Agarwal PK, Singh A, Goel S, Khanna HD & Goel RK. Evaluation of wound healing activity of extract of plantain banana (Musa sapientum var. paradisiaca) in rats. Indian journal of experimental biology. 2009;47:32-40.

Verma S, Singh A, Mishra A. Dual inhibition of chaperoning process by taxifolin: Molecular dynamics simulation study. J Mol Graphics and Modelling. 2012;37:27-38.

Rother K. Introduction to PyMOL, 2005. Available at: http://www.jhu.edu/pfleming/bioinform/files/PyMOL_Tutorial.pdf. Accessed Oct 2005.

Gillian M, Hideaki N. Progress in matrix metalloproteinase research. Mol Aspects Med. 2008;29(5):290–308.

Hall MC, Young D A, Waters JG, Rowan AD, Chantry A, Edwards DR, Clark IM. The comparative role of activator protein 1 and Smad factors in the regulation of Timp-1 and MMP-1 gene expression by transforming growth factor-beta 1. J of Biol Chem. 2003;278:10304-13.

Han YP, Yan C, Garner WL: Proteolytic Activation of Matrix Metalloproteinase-9 in Skin Wound Healing Is Inhibited by α-1-Antichymotrypsin. J Invest Dermatol. 2008;128(9):2334–42.

Chakrabarti S, Patel KD. Matrix metalloproteinase-2 (MMP-2) and MMP-9 in pulmonary pathology. Experimental Lung Res. 2005;31:599–621.

Shapiro S, Khodalev O, Bitterman H, Auslender R, Lahat N. Different activation forms of MMP-2 oppositely affect the fate of endothelial cells. Am J Physiol - Cell Physiol. 2010;298:C942–51.

Meilang X, Nghia TV Le, Jackson CJ. Targeting matrix metalloproteases to improve cutaneous wound healing. Opinion on Therapeutic Targets 2006;10(1):143-55.

Hunninghake GM, Cho MH, Tesfaigzi Y, Soto-Quiros ME, Avila L, Lasky-Su J, Stidley C, Melen E, Soderhall C, Hallberg J, Kull I, Kere J, Svartengren M, Pershagen G, Wickman M, Lange C, Demeo DL, Hersh CP, Klanderman BJ, Raby BA, Sparrow D, Shapiro SD, Silverman EK, Litonjua AA, Weiss ST, Celedon JC. MMP12, lung function, and COPD in high-risk populations. N Engl J Med. 2009;361:2599–2608.

Demedts IK, Morel-Montero A, Lebecque S, Pacheco Y, Cataldo D, Joos GF, Pauwels RA, Brusselle GG. Elevated MMP-12 protein levels in induced sputum from patients with COPD. Thorax. 2006;61:196–201.

Jin X, Yagi M, Akiyama N, Hirosaki T, Higashi S, Lin CY, Dickson RB, Kitamura H, Miyazaki K. Matriptase activates stromelysin (MMP-3) and promotes tumor growth and angiogenesis. Cancer Sci. 2006;97:1327–34.

Fray MJ, Dickinson RP, Huggins JP, Occleston NL. A potent, selective inhibitor of matrix metalloproteinase-3 for the topical treatment of chronic dermal ulcers. J of Med Chem. 2003;46:3514–25.

Yager DR, Nwomeh BC. The proteolytic environment of chronic wounds. Wound Repair Regen. 1999;7:433-41.

Downloads

Published

2017-01-23

How to Cite

Singh, A., Mishra, A., Verma, S., Purohit, V., & Goel, R. K. (2017). Regulation of wound strength by Ocimum sanctum: in silico and in vivo evidences. International Journal of Basic & Clinical Pharmacology, 3(1), 179–185. Retrieved from https://www.ijbcp.com/index.php/ijbcp/article/view/974

Issue

Section

Original Research Articles