Modulatory activities of Zingiber officinale Roscoe methanol extract on the expression and activity of MMPs and TIMPs on dengue virus infected cells

Abstract Objective To evaluate the effect of methanolic extract of Zingiber officinale (ZOM) rhizome on the activity and expression profile of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2 at the mRNA level in dengue virus infected Vero cells. Methods Total phenolic content and [6]-gingerol content in ZOM were determined by utilizing Folin-Ciocalteu reagent and high performance liquid chromatography. IC 50 value of ZOM for Vero cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Vero cells were infected with dengue virus to induce MMPs production. Modulatory effect of ZOM on the activity and expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 were demonstrated by using gelatin zymography and real time RT-PCR respectively. Results Amount of total phenolics in ZOM in terms of mg gallic acid equivalents/g was (252.89 ± 0.56) and it possessed (137.32 ± 2.47) mg [6]-gingerol content per gram of extract. The IC 50 value of ZOM was 221.5 μg/mL for Vero cells. The activities of MMP-2 and to a lesser extent MMP-9 were significantly enhanced in the conditioned media collected from the dengue virus infected Vero cells compared to conditioned media from non-infected cells and their activities were significantly inhibited by ZOM in dose-dependent manner. ZOM significantly downregulated the mRNA expression of MMP-2 and MMP-9 and upregulated the mRNA expression of TIMP-1 and TIMP-2 in dengue virus infected Vero cells in concentration-dependent manner. Conclusions The results of this study suggest that ZOM may be effective in the control of dengue-virus-induced permeability through the reduction of activities and expression of proteases which degrade the adhesion molecules between cells. This may provide the basis for developing new and effective methods in controlling severe dengue complications.