6-Shogaol Protects Human Melanocytes against Oxidative Stress through Activation of the Nrf2-Antioxidant Response Element Signaling Pathway

Abstract

Skin is a major target of oxidative stress. Increasing evidence suggests that oxidative stress is the cause of melanocyte disappearance in vitiligo, which is an acquired pigmentary skin disorder characterized by patches of skin that have lost pigmentation. New herbal extracts with antioxidant activity are therefore being studied. 6-Shogaol (6-SG), an active compound from ginger, is capable of attenuating oxidative stress-induced ageing and neurotoxicity. Subsequently, to investigate whether 6-SG could protect melanocytes from oxidative stress, cultured human primary epidermal melanocytes (HEMn-MPs) were treated with hydrogen peroxide (H2O2) in the presence or absence of 6-SG. The 6-SG exhibited protective effects against H2O2-induced cell death by reducing oxidative stress. In addition, the 6-SG treatment activated the Nrf2-antioxidant response element signaling pathway by upregulating the mRNA expression of the antioxidant enzyme heme oxygenase 1 (HO-1), and protein expression of Nrf2, NAD(P)H: quinine oxidoreductase 1 (Nqo1), and HO-1. Furthermore, the 6-SG also displayed protective effects on melanocytes against Rhododendrol-induced oxidative stress. We concluded that 6-SG protects melanocytes against oxidative stress in vitro, and its protective effect is associated with the activation of the Nrf2-antioxidant response element signaling pathway. 6-SG, therefore, has potential for use in the prevention of melanocyte loss in the early stages of vitiligo or other pigmentary disorders.

Transcriptome and Differential Methylation Integration Analysis Identified Important Differential Methylation Annotation Genes and Functional Epigenetic Modules Related to Vitiligo

“…GO enrichment analyses of the oxidation-reduction process, response to oxidative stress, and oxidoreductase activity have been partially studied in vitiligo (20)(21)(22)(23). Inflammation-related processes such as positive regulation of T cell proliferation, regulation of acute inflammatory response, and melanogenesisrelated processes such as cellular pigmentation, melanocyte differentiation, melanosome transport were also widely studied in vitiligo (24)(25)(26).…”

Mechanisms of melanocyte death in vitiligo

“…Quercetin also possesses anti‐inflammatory and antioxidative capacity, albeit not studied in vitiligo treatment 96 . Apart from polyphenols, an array of organics, such as glycyrrhizin, afzelin, 6‐Shogaol, simvastatin, aspirin, also demonstrated their antioxidative ability by targeting Nrf2 pathways 97–101 . Vitamin D can ameliorate ROS in melanocytes and restore their viability in oxidative stress through activating Wnt/β‐catenin pathway 102 .…”

Natural Nrf2 Modulators for Skin Protection

“…In vivo, the topical application of an extract of Paeonia suffruticosa and paeonol attenuated UVB-induced MMP-1 expression and promoted procollagen type I production in hairless mice. 6-Shogaol, a bioactive compound from ginger, attenuated H 2 O 2 - or rhododendrol-induced cell death and oxidative stress of human epidermal melanocytes through the induction of Nrf2-mediated expression of HO-1 and NQO-1 [ 120 ].…”

“… Various natural products modulating the Nrf2-mediated pathway [ 87 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]. Gallic acid inhibits the Nrf2-mediated pathway and all other compounds activate this pathway.…”