Melanocyte‐protective effect of afzelin is mediated by the Nrf2‐ARE signalling pathway via GSK‐3β inactivation

Abstract

Vitiligo is an acquired condition characterized by depigmented, cutaneous lesions that result from the death of pigment-producing cells, melanocytes. The occurrence of oxidative stress has been proposed as a pathogenetic mechanism for melanocyte degeneration in vitiligo. Therefore, in this study, we investigated the cytoprotective effects of afzelin against oxidative stress and its mechanism of action in human epidermal melanocytes. We found that afzelin significantly inhibited hydrogen peroxide-induced cell death, cellular reactive oxygen species production and lipid peroxidation in melanocytes. In an antioxidant response element (ARE)-luciferase reporter assay, afzelin increased ARE-luciferase reporter activity in a concentration-dependent manner. Consistently, the expression of antioxidant genes, including NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1) and catalase, was enhanced by afzelin treatment. Nuclear translocation of Nrf2 also increased in response to afzelin treatment. In addition, the phosphorylation of glycogen synthase kinase-3β (GSK-3β) was induced by afzelin treatment. The enhancement of HO-1 gene expression by afzelin treatment was reduced by Nrf2-siRNA expression. Furthermore, we found that the expression of Nrf2-siRNA significantly attenuated the cytoprotective effect of afzelin against hydrogen peroxide. These data suggest that the cytoprotective effects of afzelin against hydrogen peroxide may be mediated by Nrf2-ARE signalling via GSK-3β inactivation. Our data suggest the novel use of afzelin for the prevention of oxidative stress-induced damage in melanocytes and its potential as a therapeutic agent for vitiligo.

TTB Protects Astrocytes Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury via Activation of Nrf2/HO-1 Signaling Pathway

“…Growing evidence demonstrated that the Nrf2/HO-1 signaling pathway participated in the process of oxidative stress in several brain dysfunctional diseases (Meng et al, 2016; Bellaver et al, 2017; Zhao et al, 2018). Several antioxidant ingredients indicated that they protected cell damage by up-regulating Nrf2 and HO-1 expression in various diseases (Hsu et al, 2012; Yao et al, 2015; Jung et al, 2017). To explore whether TTB-induced cytoprotection was dependent on the presence of Nrf2 by inhibiting oxidative stress, the astrocytes were treated with OGD in different time courses of 6, 12, and 24 h followed by reoxygenation for 24 h. Our results showed that the protein levels of Nrf2 were increased by OGD for 6 h and reoxygenation for 24 h but decreased by OGD for 12 or 24 h and reoxygenation for 24 h compared to the control group.…”

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 .…”

Diuretic and Renal Protective Effect of Kaempferol 3-O-Alpha-l-rhamnoside (Afzelin) in Normotensive and Hypertensive Rats

“…Kaempferol and afzelin are natural flavonoids found in different plant species. Kaempferol is a major flavonoid aglycone found in many plants and displays several promising biological activities, such as antimicrobial, antioxidant, antitumor, cardioprotective, neuroprotective, and antidiabetic, as well as anti-inflammatory. , Studies have also demonstrated the potential of afzelin as an anti-inflammatory, antioxidant, , skin protector, , and hepatic and renal protector agent. , Based on the introduction above and considering that B. forficata preparations and kaempferitrin have already demonstrated diuretic potential in previous studies, and knowing that afzelin and kaempferol are both active compounds from its metabolism, this study aimed to evaluate, for the first time, the acute and prolonged diuretic properties of these compounds, in addition to demonstrating afzelin’s mode of action in promoting diuresis and renal protection.…”