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

Abstract

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.

Nobiletin promotes the pyroptosis of breast cancer via regulation of miR‐200b/JAZF1 axis

“…In addition, Miyata et al found that upregulation of ASC could significantly inhibit the progression of cancer. 25 Our research found ASC was activated in MCF-7 cells in the presence of nobiletin, which further verified that ASC may play a key role in the pyroptosis and apoptosis of MCF-7 and BT-549 cells.…”

The Protective Effects of Flavonoids in Cataract Formation through the Activation of Nrf2 and the Inhibition of MMP-9

“…At the same time, MAPK inhibitors, specifically for ERK1/2, p38, and JNK, inhibited MMP-9 expression and its subsequent activity in SRA01/04 cells [120]. The PMFs also inhibited phosphorylation of p38 and JNK in SRA01/04 cells, indicating that these flavones regulate MMP-9 mRNA expression via the PKC/p38 and PKC/JNK pathways in LECs [120]. Considering the crucial role of MMP-9 expression in cataract formation such as ASC and PCO, the authors suggested that the dietary intake of PMFs may have a therapeutic potential to prevent or help in the treatment of fibrotic cataracts.…”

“…Considering that MAPK signaling is a crucial mechanism to regulate the expression of MMP, the study showed that PMA increased MAPKs phosphorylation in LECs. At the same time, MAPK inhibitors, specifically for ERK1/2, p38, and JNK, inhibited MMP-9 expression and its subsequent activity in SRA01/04 cells [120]. The PMFs also inhibited phosphorylation of p38 and JNK in SRA01/04 cells, indicating that these flavones regulate MMP-9 mRNA expression via the PKC/p38 and PKC/JNK pathways in LECs [120].…”

The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms

“…It was found to increase MMP-2 production in the aqueous humor, reduce IOP and improve the morphology of the trabecular meshwork and retina in rats with steroid-induced glaucoma [203,204]. Miyata and co-workers showed that individual polymethoxylated flavones isolated from Kaempferia parviflora decreased gelatinase activity and the mRNA expression of MMP-9, and increased the protein production of TIMP-2 in phorbol 12-myristate 13-acetate-stimulated LECs via suppression of p38 MAPK, JNK1/2 and ERK1/2 pathway activation [205]. This finding highlights the efficacy of flavones in the prevention of PCO.…”