Codonopsis pilosula Extract Protects Melanocytes against H2O2-Induced Oxidative Stress by Activating Autophagy

Abstract

Recently, as the anti-aging role of melanin in the skin and the inhibition of melanin production has been identified, the development of materials capable of maintaining skin homeostasis has been attracting attention. In this study, we further investigated the anti-melanogenic effect of Codonopsis pilosula extract (CPE) and, under oxidative stress, the cytoprotective effect in Melan-a melanocytes exposed to H2O2. First, CPE treatment significantly reduced melanin production by inhibiting melanogenesis-associated proteins, including microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 2 (TRP 2), as a result of the phosphorylation of MAPK/JNK in Melan-a cells. Next, to investigate the protective effects of the CPE on oxidative-stress-induced skin injury and its molecular mechanism, we determined the effect of CPE after inducing oxidative stress by exposing melanocytes to H2O2. CPE protected cells from H2O2-induced cytotoxicity by reducing the expression of the gene encoding the Bax pro-apoptotic protein, whereas it induced the genes encoding the B-cell lymphoma 3 (Bcl2) family and MITF, which is a transcriptional regulator that promotes melanocyte differentiation. Furthermore, our results show that CPE enhanced the production of autophagy-related proteins such as Beclin-1 and light chain 3 (LC3) II; this was substantially reversed by 3-methyladenin (MA, an autophagy inhibitor) pretreatment. Collectively, our findings demonstrate that CPE treatment exhibits not only an anti-melanogenic effect in normal melanocytes, but also a cytoprotective effect in melanocytes subjected to oxidative stress by inducing autophagy and MITF expression. Therefore, we believe that CPE is a potent candidate for cell maintenance in melanocytes.