546 Kaempferol and Isorhamnetin isolated from the Inula britannica prevents heat-induced MMP-1 expression by inhibiting MAPKs and AP-1 signaling in HaCaT cells

Abstract

The skin aging process can be divided into intrinsic aging and extrinsic aging like photo-aging. However, recent studies have shown that heat also can cause skin aging, called thermal skin aging, by fragmentation of collagen fibrils, which is initiated by matrix metalloproteinase 1 (MMP-1). In this study, we investigated the influence of Kaempferol and Isorhamnetin isolated from the Inula Britannica on heat-exposed HaCaT cells (immortalized human keratinocytes) and the relationship among MMP-1 expression, c-Jun and MAP kinases. Kaempferol and Isorhamnetin showed very good reactive oxygen species (ROS) activity in DPPH assay and increased the viability of heat-exposed HaCaT cells. Especially, Pre-treatment of HaCat cells with Kaempferol and Isorhamnetin declined MMP-1 level, which is over expressed by heat. We studied the influence of heat on c-Jun, MAP Kinases, and AP-1 by Western blotting and enzymic activity assay with and without Kaempferol and Isorhamnetin treatment. They suppressed c-Jun and the phosphorylation of MAP Kinases, upstream modulators of AP-1 after heat exposure condition. These results indicate that Kaempferol and Isorhamnetin can inhibit heat-induced MMP-1 expression by interfering with MAP Kanases and AP-1 signaling. Our studies demonstrate that Kaempferol and Isorhamnetin isolated from the Inula Britannica may be potentially useful in the prevention and treatment of thermal skin aging.