Kaempferol Blocks the Skin Fibroblastic Interleukin 1β Expression and Cytotoxicity Induced by 12-O-tetradecanoylphorbol-13-acetate by Suppressing c-Jun N-terminal Kinase

Kaempferol, a bioflavonoid present in fruits and vegetables, has a variety of antioxidant and anti-inflammatory capacities, but the functional role of kaempferol in oxidative skin dermal damage has yet to be well studied. In this study, we examine the role of kaempferol during the inflammation and cell death caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) in normal human dermal fibroblasts (NHDF). TPA (5 mu M) significantly induced cytotoxicity of NHDF, where a robust increase in the interleukin (IL)-1 beta mRNA among the various pro-inflammatory cytokines. The skin fibroblastic cytotoxicity and IL-1 beta expression induced by TPA were significantly ameliorated by a treatment with 100 nM of kaempferol. Kaempferol blocked the production of the intracellular reactive oxygen species (ROS) responsible for the phosphorylation of c-Jun N-terminal kinase (JNK) induced by TPA. Interestingly, we found that kaempferol inhibited the phosphorylation of nuclear factor-kappa B (NF-kappa B) and the inhibitor NF-kappa B (I kappa B alpha), which are necessary for the expression of cleaved caspase-3 and the IL-1 beta secretion in TPA-treated NHDF. These results suggest that kaempferol is a functional agent that blocks the signaling cascade of the skin fibroblastic inflammatory response and cytotoxicity triggered by TPA.

Automated summary

The study showed that Kaempferol can inhibit the cytotoxicity and inflammatory response induced by TPA, by preventing the generation of ROS and JNK phosphorylation, as well as inhibiting the phosphorylation of NF-kappa B and I kappa B alpha, to reduce the expression of cleaved caspase-3 and IL-1 beta.