Potential Therapeutic Agents, Polymethoxylated Flavones Isolated from Kaempferia parviflora for Cataract Prevention through Inhibition of Matrix Metalloproteinase-9 in Lens Epithelial Cells

Natural flavonoids have powerful antioxidant activity and have been reported to show promising protective effects against cataracts. The plant Kaempferia parviflora (K. parviflora) is indigenous to southeast Asia, including Thailand, and typically contains polymethoxylated flavones. The flavones in K. parviflora are reported to have various biological properties. Recently, polymethoxylated flavones of K. parviflora (KPMFs) were shown to have potent Sirtuin 1 enzyme-stimulating and anti-glycation activities that led to the suppression of cataract formation. Matrix metalloproteinases (MMPs) are upregulated in several pathologic ocular diseases, including cataracts, and have been established as an attractive target for the prevention and/or treatment of specific cataract phenotypes, such as anterior subcapsular cataract (ASC) and posterior capsular opacification (PCO). In the present study, we investigated the effect of KPMFs on MMP (gelatinase) activity in the human lens epithelial cell line, SRA01/04. We demonstrated that KPMFs inhibited the phorbol ester-induced MMP-9 activity and the mRNA expression through the suppression of mitogen-activated protein kinases (MAPKs) phosphorylation in human lens epithelial cells; 5,7-dimethoxyflavone was found to exert the most potent inhibition, but 3,5,7,4'-tetramethoxyflavone and 3,5,7,3',4'-pentamethoxyflavone also resulted in considerable inhibition. Our results suggested that the consumption of PMFs isolated from K. parviflora, may be an effective strategy to delay the development of cataracts, such as ASC and PCO.