Tuo-Min-Ding-Chuan Decoction Alleviate Ovalbumin-Induced Allergic Asthma by Inhibiting Mast Cell Degranulation and Down-Regulating the Differential Expression Proteins.

Jingbo Qin,Zeqiang Jiang,Ji Wang,Xianghe Meng,Yi Wang,Mingsheng Lv,Jiarui Cui,Qi Wang

doi:10.3389/fphar.2021.725953

Abstract

Allergic asthma is a stubborn chronic inflammatory disease, and is considered a co-result of various immune cells, especially mast cells, eosinophils and T lymphocytes. At present, the treatment methods of allergic asthma are limited and the side effects are obvious. Traditional Chinese medicine has been used to treat diseases for thousands of years in China. One such example is the treatment of allergic asthma, which take the characteristics of less adverse reactions and obvious curative effect. Tuo-Min-Ding-Chuan Decoction (TMDCD) is a traditional Chinese medicine compound for the treatment of allergic asthma optimized from Ma-Xing-Gan-Shi Decoction (MXGSD), which was put forward in Treatise on Febrile Diseases by Zhang Zhongjing in the Eastern Han Dynasty. The compound shows a significant clinical effect, but the mechanism of its influence on the immune system is still unclear. The purpose of this study was to observe whether TMDCD could alleviate the symptoms of ovalbumin (OVA) challenged allergic asthma mice, and to explore its immune regulatory mechanism, especially on mast cell (MC) degranulation. The results showed TMDCD could not only reduce the airway hyperresponsiveness (AHR), inflammatory cell infiltration and mucus secretion in the lung tissue of OVA challenged mice, but also decrease the levels of total IgE, OVA-specific IgE, histamine and LTC4 in serum. We found that TMDCD can downregulate the expression of Fractalkine, Tryptase ε, IL-25, CCL19, MCP-1, OX40L, Axl, CCL22, CD30, G-CSF, E-selectin, OPN, CCL5, P-selectin, Gas6, TSLP in OVA challenged mice serum by using mouse cytokines antibody array. It has been reported in some literatures that these differentially expressed proteins are related to the occurrence of allergic asthma, such as tryptase ε, MCP-1, CCL5, etc. can be released by MC. And the results of in vitro experiments showed that TMDCD inhibited the degranulation of RBL-2H3 cells stimulated by DNP-IgE/BSA. Taken together, we made the conclusion that TMDCD could reduce the infiltration of inflammatory cells in lung tissue and alleviate airway remodeling in mice with allergic asthma, showed the effects of anti-inflammatory and antiasthmatic. TMDCD could also reduce the levels of IgE, histamine, LTC4, Tryptase ε, and other MC related proteins in the serum of allergic asthma mice, and the in vitro experiments showed that TMDCD could inhibit IgE mediated degranulation and histamine release of RBL-2H3 cells, proved its anti allergic effect.

Highlights

Allergic asthma is a chronic inflammatory disease, which is known as the result of hypersensitivity to inhaled antigens and is driven by aberrant innate and adaptive immune responses, the cardinal features include mucus hypersecretion, pulmonary eosinophilic infiltration, and Airway Hyperresponsiveness (AHR) (Thio et al, 2018)
We investigated the inhibitory effect of TMDCD on degranulation of mast cells sensitized by DNPIgE/BSA via measuring the release level of β-hexosaminase
TMDCD can reduce the content of total IgE and OVA-specific IgE in serum of mice with allergic asthma

Summary

Introduction

Allergic asthma is a chronic inflammatory disease, which is known as the result of hypersensitivity to inhaled antigens and is driven by aberrant innate and adaptive immune responses, the cardinal features include mucus hypersecretion, pulmonary eosinophilic infiltration, and AHR (Thio et al, 2018). According to the (The Global Asthma Report 2018, 2018), over 339 million people worldwide suffer from asthma (E, 2018). The increase of asthma patients is associated with increasing air pollution by rapid urbanization and industrialization, and adds a serious burden on the health system and patients’ quality of life (Dhar et al, 2020). The 2019 Global Initiative for Asthma (GINA) guidelines suggested adult asthma patients be treated with corticosteroids inhaling daily, or as needed, and reduced asthma triggers as much as possible (Mauer and Taliercio, 2020). Some researchers have found that long-term or repeated short-term use of corticosteroids may lead to certain side effects on systemic health (Price et al, 2018; Matsunaga et al, 2020). It’s an urgent problem for researchers to find some safe and effective drugs for asthma, alternatively

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