Extract of Polygala tenuifolia Alleviates Stress-Exacerbated Atopy-Like Skin Dermatitis through the Modulation of Protein Kinase A and p38 Mitogen-Activated Protein Kinase Signaling Pathway

Bongjun Sur,Insop Shim,Dae-Hyun Hahm,Riwon Hong,Ye Yoon,Bombi Lee,Mijung Yeom,Hyejung Lee,Hyang Lee,Young Jang,Pooreum Lim,Hijoon Park

doi:10.3390/ijms18010190

Bongjun Sur, Insop Shim + Show 10 more

Open Access

https://doi.org/10.3390/ijms18010190

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Abstract

Atopic dermatitis (AD) and stress create a vicious cycle: stress exacerbates atopic symptoms, and atopic disease elicits stress and anxiety. Targeting multiple pathways including stress and allergic inflammation is, therefore, important for treating AD. In this study, we investigated the remedial value of Polygala tenuifolia Willd. (PTW) for treating immobilization (IMO) stress-exacerbated atopy-like skin dermatitis and its underlying mechanism. Trimellitic anhydride (TMA) was applied to dorsal skin for sensitization and subsequently both ears for eliciting T-cell-dependent contact hypersensitivity in mice, which underwent 2 h-IMO stress and PTW administration for the latter 6 and 9 days in the ear exposure period of TMA, respectively. To elicit in vitro degranulation of human mast cell line-1 (HMC-1), 10 µM substance P (SP) and 200 nM corticotrophin-releasing factor (CRF) were sequentially added with 48 h-interval. PTW extract (500 µg/mL) was added 30 min before CRF treatment. IMO stress exacerbated TMA-induced scratching behavior by 252%, and increased their blood corticosterone levels by two-fold. Treatment with 250 mg/kg PTW significantly restored IMO stress-exacerbated scratching behavior and other indicators such as skin inflammation and water content, lymph node weights, and serum histamine and immunoglobulin E (lgE) levels. Furthermore, it also reversed TMA-stimulated expression of tumor necrosis factor (TNF)-α and interleukin (IL)-4 mRNAs in ear tissues. PTW significantly inhibited SP/CRF-stimulated degranulation of HMC-1 cells, subsequent tryptase secretion, and protein kinase A (PKA) activity. PTW also selectively inhibited p38 mitogen-activated protein kinase (MAPK) phosphorylation in SP/CRF-treated HMC-1 cells. PTW significantly inhibited HMC-1 cell degranulation and alleviated IMO stress-exacerbated atopic dermatitis symptoms by modulating the PKA/p38 MAPK signaling pathway.

Highlights

The incidence of atopic dermatitis (AD) is increasing worldwide, with a current prevalence rate of 20%–30% [1]
Atopic dermatitis (AD) is most common in infants and children; the condition persists into adulthood in a minority of cases, affecting approximately 10% of the adult population, and its prevalence has increased in urbanized societies over recent decades [2]
By virtue of the high resolution and high speed of Ultra Performance Liquid Chromatography (UPLC), and accurate mass measurement by time-of-flight (TOF)-Mass Spectrometry (MS), a total of 21 compounds were identified from the Polygala tenuifolia Willd. (PTW) extract [15]

Summary

Introduction

The incidence of atopic dermatitis (AD) is increasing worldwide, with a current prevalence rate of 20%–30% [1]. AD is most common in infants and children; the condition persists into adulthood in a minority of cases, affecting approximately 10% of the adult population, and its prevalence has increased in urbanized societies over recent decades [2]. In 95% of pediatric cases, AD symptoms occur before five years of age. Adult onset of AD symptoms occurs in 15% of adult cases [3]. Adult AD generally has a more complex pathogenesis than does pediatric AD [4], and its causes include work-related stress, industrialization, urbanization, and pollution. Adult AD symptoms are exacerbated by a vicious cycle involving scratching, inflammation and stress

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