Antioxidant and anti-inflammatory effects of piperine on UV-B-irradiated human HaCaT keratinocyte cells.

The increase in intracellular reactive oxygen and nitrogen species plays a key role in ultraviolet B (UV-B)-induced inflammatory responses in the human skin. Piperine exhibits many pharmacological benefits. In the present study, the photoprotective effects and the possible underlying mechanisms of the anti-inflammatory effects of piperine on UV-B-irradiated keratinocytes were investigated. Piperine exerted strong, direct scavenging effects on DPPH radicals and exhibited free radical scavenging capabilities as demonstrated by the DCFH-DA and Griess assays. Consistent with these results, 10, 20, and 40 μM piperine pretreatments attenuated UV-B irradiation-induced keratinocyte cytotoxicity as reported by the resazurin assay. The highest concentration of piperine inhibited UV-B irradiation-induced cell apoptosis, as revealed by Hoechst 33342 staining. Moreover, we demonstrated the anti-inflammatory effects of piperine using western blot analysis, real-time PCR, and ELISA. Pretreatment with piperine suppressed the activation of phosphorylated p38, JNK, and AP-1 as well as the levels of COX-2/PGE and iNOS synthesis, while UV-B-irradiated cells triggered the induction of these signaling molecules. These results indicated that the inhibition of these inflammatory signaling pathways might play a key role in the regulation of the anti-inflammatory effects of piperine. In addition, piperine showed stronger anti-inflammatory effects than celecoxib which served as a positive control at the same concentration. All these results suggested that the anti-inflammatory properties of piperine protected keratinocytes from UV-B-induced damage, which might be due to its antioxidant properties. Therefore, piperine may be an effective therapeutic candidate compound for the treatment of UV irradiation-induced skin inflammation.