Study on the Molecular Basis of Huanglian Jiedu Decoction Against Atopic Dermatitis Integrating Chemistry, Biochemistry, and Metabolomics Strategies.

Jinguang Chen,Saizhen Chen,Bixin Shen,Zhengli Jiang,Yubin Xu,Jing Chen

doi:10.3389/fphar.2021.770524

Jinguang Chen, Saizhen Chen + Show 4 more

Open Access

https://doi.org/10.3389/fphar.2021.770524

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Abstract

Atopic dermatitis (AD) is a common chronic relapsing skin inflammation, which severely affect the quality of life of patients. Inhibiting itching and enhancing immunity to mitigate scratching are key elements in the fight against AD. Huanglian Jiedu decoction (HLJDD) has multiple pharmacological effects in the treatment of AD. However, the effective ingredients and underlying molecular mechanisms have not yet been fully explored. Thus, this study integrates chemistry, biochemistry, and metabolomics strategies to evaluate the active substance basis of HLJDD against AD. First, HLJDD was split to five fractions (CPF, 40AEF, 90AEF, PEF and WEF) and 72 chemical components were identified. NSD (Non-similarity degree) among the different fractions showed significant chemical differences (>81%). Interleukin IL-13, IL-17A, IL-3, IL-31, IL-33, IL4, IL-5, TSLP, IgE, and histamine in the serum, and IL-4Rα, JAK1, and HRH4 levels in skin, participating in inhibiting itching and regulating immunity signaling, were found to be restored to varying degrees in AD treating with HLJDD and its fractions, especially 40AEF and CPF. Untargeted metabolomics analysis demonstrated that forty metabolites were differential metabolites in plasma between the HLJDD-treated group and the AD group, involving in histidine metabolism, arginine biosynthesis, pyrimidine metabolism, and so on. Further, targeted metabolomics analysis revealed that eleven differential metabolites, associating with physiological and biochemical indices, were significant improved in the HLJDD and its fractions groups. In conclusion, HLJDD exhibited anti-AD effects by inhibiting itching and enhancing immunity, which in turn regulating the levels of relative metabolites, and CPF and 40AEF were considered the most important components of HLJDD.

Highlights

Atopic dermatitis (AD), known as atopic eczema, is a common chronic relapsing skin inflammation (Serrano et al, 2019)
Recent studies have shown that eosinophils and mast cells are the most important effector cells in AD, releasing inflammatory mediators, such as histamine, leukotrienes, and cytokines (IL-3, IL-4, IL-5, and IL-13), which leads to itching and skin lesions, which are characteristic of AD (Raap et al, 2006; Lam, 2010)
Huanglian Jiedu decoction (HLJDD) was split into five fractions: crude polysaccharide fraction (CPF), petroleum ether fraction (PEF), 40% ethanol eluted fraction (40AEF), 90% ethanol eluted fraction (90AEF), and water eluted fraction (WEF)

Summary

Introduction

Atopic dermatitis (AD), known as atopic eczema, is a common chronic relapsing skin inflammation (Serrano et al, 2019). Recent studies have shown that eosinophils and mast cells are the most important effector cells in AD, releasing inflammatory mediators, such as histamine, leukotrienes, and cytokines (IL-3, IL-4, IL-5, and IL-13), which leads to itching and skin lesions, which are characteristic of AD (Raap et al, 2006; Lam, 2010). CD4+ T cells exhibit a variety of biological functions, including secretion of cytokines for immune regulation and effector function, which are divided into Th1 and Th2 subsets (Sur et al, 2016). A vast variety of treatments, including emollient, anti-inflammatory, and antimicrobial therapies, have been prescribed for AD. Even though these treatments seem optimal in many patients, their long-term use carries the risk of severe systemic and cutaneous adverse effects. A cure for AD requires a new treatment strategy to improve the efficacy and reduce the toxicity of short- and long-term therapeutic regimens

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