The in vitro and in vivo depigmenting activity of pterostilbene through induction of autophagy in melanocytes and inhibition of UVA-irradiated α-MSH in keratinocytes via Nrf2-mediated antioxidant pathways

• DOI: 10.1016/j.redox.2021.102007
• Publication Date: 2021-05-19T07:39:52Z
• Authors: You-Cheng Hseu; Yugandhar Vudhya ...; Li-Wei Wang; Yan-Zhen Zhang; Xuan-Zao Chen; Pei-Jane Huang; Hung-Rong Yen; Hsin-Ling Yang
• Keywords: Pterostilbene; Melanocyte

Pterostilbene (Pt) is a natural polyphenol found in blueberries and several grape varieties. Pt's pharmacological importance was well documented. Nevertheless, the depigmenting effects are not demonstrated. We evaluated through autophagy induction B16F10 cells inhibition of UVA (3 J/cm2)-irradiated α-MSH keratinocyte HaCaT via Nrf2-mediated antioxidant pathways. Pt (2.5-5μM) attenuated ROS production downregulated POMC/α-MSH pathway cells. The conditioned medium-derived from UVA-irradiated pretreated with suppressed melanogenesis MITF-CREB-tyrosinase downregulation. Interestingly, Pt-induced revealed by enhanced LC3-II accumulation, p62/SQSTM1 activation, AVO formation. significantly decreased melanosome gp100 but increased levels exposed to B16F10-derived melanin. activated facilitated Nrf2 leading HO-1, γ-GCLC, NQO-1 protein expression. ERK, AMPK, pathways mediate activation. However, knockdown ability uncontrolled after UVA-irradiation suggested essentiality pathway. Moreover, α-MSH-stimulated cells, (10-30 μM) MC1R, MITF, tyrosinase, TRP-1/-2, melanin Further, showed potent anti-melanogenic mechanism verified LC3-II/p62 levels, formation, Beclin-1/Bcl-2 ratio, ATG4B PI3K/AKT/mTOR Transmission electron microscopy provided direct evidence showing autophagosomes engulfing melanosomes following treatment activity downregulation CREB-MITF pathway-mediated tyrosinase expressions, synthesis substantially reversed due 3-MA (autophagy inhibitor) pretreatment or LC3 silencing In vivo results also confirmed that Pt-inhibited expression/activity endogenous pigmentation zebrafish model. Therefore, pterostilbene skin-whitening agent could be used formulations as topical applicant.