Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Zingiber officinale Roscoe aqueous extract modulates matrixmetalloproteinases and tissue inhibitors of metalloproteinases expressions in dengue virus-infected cells: implications for prevention of vascular permeability

Binita Koirala Sharma^1,2 , David Charles Klinzing^3,4, John Donnie Ramos^1,5

¹The Graduate School, University of Santo Tomas, España, Manila, Philippines; ²Department of Microbiology, Manipal College of Medical Sciences, Pokhara, Nepal; ³St Luke's Medical Center, Research and Biotechnology Division, Quezon City; ⁴AIT Biotech Pte Ltd, Singapore; ⁵Research Center for the Natural and Applied Sciences, and College of Science, University of Santo Tomas, España, Manila, Philippines.

For correspondence:- Binita Sharma Email: binita_keshab@yahoo.com Tel:+977 9856036122

Received: 19 March 2015 Accepted: 22 June 2015 Published: 30 August 2015

Citation: Sharma BK, Klinzing DC, Ramos JD. Zingiber officinale Roscoe aqueous extract modulates matrixmetalloproteinases and tissue inhibitors of metalloproteinases expressions in dengue virus-infected cells: implications for prevention of vascular permeability. Trop J Pharm Res 2015; 14(8):1371-1381 doi: 10.4314/tjpr.v14i8.8

© 2015 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the effect of the aqueous extract of Zingiber officinale Roscoe. (ZOA) rhizome on the activity and expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 using an in vitro model of Dengue virus (DV) infection.

Methods: Z. officinale rhizomes were extracted with water by continuous shaking for 5 days. The total phenolic content in extract was measured by Folin-Ciocalteu method. High performance liquid chromatography (HPLC) was employed to define qualitative and quantitative content of [6]-gingerol in ZOA. The median inhibitory concentration (IC50) value of ZOA for Vero cells was determined by 3-(4,5 dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To induce MMPs production, Vero cells were infected with DV3. The modulatory effect of ZOA on the activity and expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed using gelatin zymography and quantitative Real-time polymerase chain reaction (RTPCR), respectively.

Results: The yield of the ZOA was 7.98%. Total phenolics in ZOA was 68.17 ± 0.28 mg GAE/g of extract and it contained 29.32 ± 1.97 mg 6-gingerol/g of extract.The half-maximal inhibition concentration (IC₅₀) of ZOA was 348.8 µg/mL for Vero cells. DV infection of Vero cells significantly elevated the production of soluble gelatinolytic MMP-2 and to a lesser extent, MMP-9, and their activities were significantly inhibited by ZOA in a dose-dependent manner. A significant down-regulation of MMP-2, MMP-9 mRNA expression and up-regulation of TIMP-1, TIMP-2 mRNA expression were observed in DV-infected Vero cells following treatment with ZOA, and it occurred in a dose-dependent manner.

Conclusion: The findings of this study suggest that ZOA may ameliorate plasma leakage in dengue virus infection and decrease the chances of severe dengue complications, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) by inhibiting the activities and expression of MMP-2 and MMP-9 while upregulating the expression of TIMP-1 and TIMP-2.

Keywords: Zingiber officinale, Dengue virus, Matrix metalloproteinases, Tissue inhibitor, Vascular leakage, 6-Gingerol