In traditional Korean/Asian medicine, Salvia plebeia R.Br. (S. plebeia) leaves are used to treat inflammatory diseases, including dermatitis, cough, asthma and toothache. Recently, S. plebeia leaves have been applied in skin care, as they promote skin lightening and elasticity. Therefore, the present study investigated the anti-aging effects of S. plebeia leaf methanolic extract and its fractions (dichloromethane, ethylacetate and n-butanol). The results of a whole-cell patch clamp analysis indicated that the methanolic extract mediated ultraviolet (UV)-induced photoaging-associated ion channels, transient receptor potential vanilloid 1 (TRPV1) and calcium release-activated calcium channel protein 1 (ORAI1) channel activity in HEK293T cells overexpressing TRPV1 or ORAI1 and STIM1. Electrophysiological analysis revealed that the butanol fraction inhibited capsaicin-induced TRPV1 (84 +/- 8% at -60 mV/86 +/- 1% at 100 mV at 100 mu g/ml) and ORAI1 (87 +/- 2% at -120 mV at 100 mu g/ml) currents. Furthermore, the dichloromethane and hexane fractions inhibited tyrosinase activity by 32.4 +/- 0.69 and 22.6 +/- 0.96% at 330 mu g/ml, respectively. Furthermore, the ethylacetate and butanol fractions inhibited elastase activity by 65.2 +/- 1.30 and 31.7 +/- 1.23% at 330 mu g/ml, respectively. Tyrosinase and elastase, which are UV-induced photoaging-associated enzymes, regulate skin pigmentation and wrinkle formation, respectively. The results of the present study indicated that S. plebeia leaves may be a novel treatment for UV-induced photoaging.