Astragaloside IV Enhances Melanogenesis via the AhR-Dependent AKT/GSK-3β/β-Catenin Pathway in Normal Human Epidermal Melanocytes.

Baoyi Liu,Yongyi Xie,Zhouwei Wu,Francesca Mancianti

doi:10.1155/2020/8838656

Abstract

Astragalus membranaceus root has been widely used for repigmentation treatment in vitiligo, but its mechanism is poorly understood. We sought to investigate the effect of astragaloside IV (AS-IV), a main active extract of the Astragalus membranaceus root, on melanin synthesis in normal human epidermal melanocytes (NHEMs) and to elucidate its underlying mechanisms. Melanin content, tyrosinase activity, qPCR, western blot, and immunofluorescence were employed. Specific inhibitors and small interfering RNA were used to investigate the possible pathway. AS-IV stimulated melanin synthesis and upregulated the expression of melanogenesis-related genes in a concentration-dependent manner in NHEMs. AS-IV could activate the aryl hydrocarbon receptor (AhR), and AS-IV-induced melanogenesis was inhibited in si-AhR-transfected NHEMs. In addition, we showed that AS-IV enhanced the phosphorylation of AKT and GSK-3β and nuclear translocation of β-catenin. AS-IV-induced MITF expression upregulation and melanin synthesis were decreased in the presence of β-catenin inhibitor FH353. Furthermore, AhR antagonist CH223191 inhibited the activation of AKT/GSK-3β/β-catenin signaling, whereas the expression of CYP1A1 (marker of AhR activation) was not affected by the AKT inhibitor in AS-IV-exposed NHEMs. Our findings show that AS-IV induces melanogenesis through AhR-dependent AKT/GSK-3β/β-catenin pathway activation and could be beneficial in the therapy for depigmented skin disorders.

Highlights

Vitiligo is a kind of depigmentation disease with about 0.1–2% prevalence in the world [1], characterized by patchy depigmentation of the skin due to the loss of functional epidermal melanocytes
Epidermal melanocytes are responsible for the melanin synthesis which is driven by three key enzymes: tyrosinase (TYR), tyrosinase-related protein-1 (TYRP-1), and TYRP-2 in mammals [2]. e expression and activity of these three enzymes are regulated by the microphthalmia-associated transcription factor (MITF) [2]. e expression of the MITF gene can be modulated by many transcriptional factors in response to various environmental stimuli [3]
normal human epidermal melanocytes (NHEMs) were treated with various concentrations of astragaloside IV (AS-IV) (0, 1, 10, and 100 μM) for 24 h, and our results revealed that the melanin synthesis was increased by 15%, 35%, and 72% respectively

Summary

Introduction

Vitiligo is a kind of depigmentation disease with about 0.1–2% prevalence in the world [1], characterized by patchy depigmentation of the skin due to the loss of functional epidermal melanocytes. Epidermal melanocytes are responsible for the melanin synthesis which is driven by three key enzymes: tyrosinase (TYR), tyrosinase-related protein-1 (TYRP-1), and TYRP-2 in mammals [2]. E expression and activity of these three enzymes are regulated by the microphthalmia-associated transcription factor (MITF) [2]. E expression of the MITF gene can be modulated by many transcriptional factors in response to various environmental stimuli [3]. Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that resides in the cytoplasm of various types of cells, including normal human epidermal melanocytes (NHEMs) [4]. AhR can control the expression of other genes by interacting with various signaling pathways or regulating the half-life of other transcription factors [5]. AhR has been reported to modulate pigment synthesis via interacting with

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