Abstract
Problem statement: Atherosclerosis is associated with chronic inflammation triggered by bacterial infection that activates the breakdown of extracellular matrix protein by matrix Metalloproteinases (MMPs). Zingiberaceae, a group of tropical food crops grown in Indonesia and other Southeast Asia regions, has been traditionally used for food coloring, seasoning, culinary and medicinal purposes. However, its efficacy as natural vascular protection has not been explored. Approach: The research was aimed to investigate the effects of 10 Indonesian Zingiberaceae rhizome extracts on inhibition of MMP-9 expression in human vascular endothelial cells treated with Lipopolysaccharide (LPS) in vitro by conducting gelatin zymogram, Western blotting and RT-PCR assays. Results: LPS (2 μg mL−1) significantly elevated the expression of MMP-9 secretion, protein and mRNA in the vascular endothelial cells. Selected Zingiberaceae exctracts (5 μg mL−1), i.e., Curcuma xanthorrhiza, C. aeruginosa, C. mangga, C. longa, Kaempferia galanga, Alpinia galanga and Zingiberaceae officinale, effectively attenuated the expression of MMP-9 secretion, protein and mRNA in LPS-induced vascular endothelial cells. Furthermore, MMP-9 expression was specifically blocked by MAPK inhibitors, i.e., PD98059 (ERK1/2 inhibitor), SB203580 (p38 inhibitor), SP600125 (JNK inhibitor) and PI3K inhibitor (LY294002), indicating that MAPK and PI3K signaling pathways are involved in regulation of MMP-9 gene expression in LPS-induced vascular endothelial cells. Conclusion: These results suggest that selected Indonesian Zingiberaceae rhizomes with potent MMP- 9 inhibitory activity may scientifically offer the promising therapeutic target in vascular diseases, particularly atherosclerosis.
Highlights
ECM solution which is mediated by MMP-2 and MMP-9 (Galis and Khatri, 2002).Matrix Metalloproteinases (MMPs) are a group ofThe use of synthetic inhibitors of MMPs and zinc- and calcium-dependent endopeptidases that play a antibiotics were effectively found to reduce the vascular key role in degradation of Extracellular Matrix (ECM) expression of MMPs, in particular MMP-2 and MMP-9 proteins
The human oligonucleotide inhibition of matrix metalloproteinase-9 secretion, primers for MMP-9, TIMP-1 and glyceraldehyde 3- protein and mRNA in lipopolysaccharide-induced phosphate dehydrogenase (GAPDH) were designed human vascular endothelial cells: We further according to a PCR primer selection program at the determined if Zingiberaceae rhizome extracts possess website of the Virtual Genomic Center from the anti-atherosclerotic potential on the expression of GenBank database
Mediated the expression of MMP-9 in LPS-induced the broad spectrum MMP inhibitor, vascular endothelial cells, we examined the effect of GM6001, was tested to verify its potential on the various mitogen-activated protein kinase (MAPK) expression of MMP-9 in LPS-induced vascular inhibitors (PD98059, SB203580 and SP600125) and endothelial cells
Summary
The use of synthetic inhibitors of MMPs and zinc- and calcium-dependent endopeptidases that play a antibiotics were effectively found to reduce the vascular key role in degradation of Extracellular Matrix (ECM) expression of MMPs, in particular MMP-2 and MMP-9 proteins. These enzymes have been associated with and delay the progression of atherosclerotic plaque several major cellular physiological and pathological (Rodriguez et al, 2007). The treatment groups included Zingiberaceae rhizome extract (5 μg mL−1), MMP inhibitors (doxycycline (Sigma-Aldrich) at 5 μg mL−1 and appropriate dose of potential agents
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