Abstract

Paeoniflorin (PF) possesses multiple biological functions including anti-oxidization. PF is the major bioactive ingredient of total glycosides of paeony (TGP), which could promote re-pigmentation of vitiligo. The study was sought to investigate the effects and potential signaling pathways of PF on hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes. The results showed that pretreatment with 50 µM PF significantly inhibited cell apoptosis, enhanced cell viability, and suppressed reactive oxygen species (ROS) accumulation by enhancing the productions of superoxide dismutase (SOD) and antioxidant enzymes catalase (CAT). Furthermore, PF activated c-Jun amino terminal kinase (JNK) and the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway to counteract H2O2-induced oxidative damage in PIG1 and PIG3V. Taken together, our study firstly demonstrates that PF resists H2O2-induced oxidative stress in melanocytes probably by activating JNK/Nrf2/HO-1 signaling, suggesting a potential therapeutic application of PF on vitiligo.

Highlights

  • Vitiligo is an acquired disorder which characterized by the loss of functional melanocytes in skin and/or mucosa, and affects 0.5% to 2.0% populations all over the world (Ezzedine et al, 2015; Xie et al, 2016)

  • We found that PF resulted in significant increase of endogenous anti-oxidant Jun amino terminal kinase (JNK), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in stressed cells

  • Previous studies have shown that upregulation of Nrf2/HO-1 could increase the capability to cope with H2O2-induced stress damage in PIG3V (Jian et al, 2014)

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Summary

Introduction

Vitiligo is an acquired disorder which characterized by the loss of functional melanocytes in skin and/or mucosa, and affects 0.5% to 2.0% populations all over the world (Ezzedine et al, 2015; Xie et al, 2016). The pathogenic roles of oxidative damage in vitiligo was reflected in impaired activation of nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway, elevated lipid peroxidation, CAT and SOD, etc (Dell'Anna et al, 2007; Liu et al, 2010; Jian et al, 2014; Chang et al, 2017). The transcription factor Nrf plays a key role in the expression of phase II antioxidant enzymes which was mediated by antioxidant response element (ARE), to prevent cell damage caused by oxidative stress (Zhang et al, 2014). Decreased Nrf signaling pathway can lead to the decreased ability of Paeoniflorin Resists Stress in Melanocytes melanocytes to prevent oxidative damage in patients with vitiligo (Jian et al, 2011; Jian et al, 2014). Elevated Nrf expression may be helpful in the treatment of vitiligo

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