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The use of bee venom (Apis mellifera L., BV) occasionally causes side effects such asinflammation and allergic reactions in the recipients. Several case reports also suggested thetreatment of BV has some limitations in its clinical uses, due to the occurrence of dermalnecrosis and anaphylatic reactions. It is generally understood that bee venom allergy is mainlythe result of its allergic component, phospholipase A2 (PLA2). The present study was aimed togenerate PLA2-free bee venom (PBV) and evaluate its efficacy as skin care and cosmeticpreparation, comparing with original bee venom (BV). Our results showed that both BV andPBV exhibited significant protective effects in UVB-irradiated human keratinocyte (HaCaT) andhuman dermal fibroblast (HDF) cells and they also induced type I collagen synthesis inUVB-irradiated HDF cells except BV at 3 μg/ml. Furthermore, BV and PBV showed theinhibition of UVB-stimulated matrix metalloproteinase-1 (MMP-1), a major collagen degradingenzyme in skin. However, BV, unlike PBV, exhibited strong cytotoxicities in skin cells (bothHaCaT and HDF) at its working concentrations of anti-wrinkle effect. The underlying cellsignaling mechanisms of anti-wrinkle effects of BV and PBV were demonstrated by theactivation of ERK1/2, and p38. Conclusively, PBV appears to be the bee venom of choice withless cytotoxicity and higher efficacy on UVB-irradiated skin cells in comparison with originalbee venom (BV). Therefore, PBV can better be used as a cosmetic ingredient exhibitingexcellent anti-wrinkle effect against photoaging than original BV.