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Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism
The heterogeneity of asthma involves complex pathogenesis leading to confusion regarding the choice of therapeutic strategy. In the clinic, asthma is commonly classified as having either eosinophilic asthma (EA) or non-eosinophilic asthma (NEA) phenotypes. Microbiota colonizing in airways has been d...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747379/ https://www.ncbi.nlm.nih.gov/pubmed/31466312 http://dx.doi.org/10.3390/ijms20174216 |
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author | Pang, Zhiqiang Ran, Nan Yuan, Yuze Wang, Cuizhu Wang, Guoqiang Lin, Hongqiang Hsu, Alan Chen-Yu Liu, Jinping Wang, Fang |
author_facet | Pang, Zhiqiang Ran, Nan Yuan, Yuze Wang, Cuizhu Wang, Guoqiang Lin, Hongqiang Hsu, Alan Chen-Yu Liu, Jinping Wang, Fang |
author_sort | Pang, Zhiqiang |
collection | PubMed |
description | The heterogeneity of asthma involves complex pathogenesis leading to confusion regarding the choice of therapeutic strategy. In the clinic, asthma is commonly classified as having either eosinophilic asthma (EA) or non-eosinophilic asthma (NEA) phenotypes. Microbiota colonizing in airways has been demonstrated to induce distinct phenotypes of asthma and the resistance to steroids. Rhodiola wallichiana var. cholaensis (RWC) has the potential to alleviate asthmatic inflammation according to recent studies, but its pharmacological mechanisms remain unclarified. In our study, murine asthmatic phenotypes were established and treated with RWC and/or dexamethasone (DEX). Combined treatment with RWC and DEX could improve spirometry and airway hyperresponsiveness (AHR) in asthmatic phenotypes, alleviate steroid resistance in NEA, and reduce the inflammatory infiltration of the both phenotypes. The combined treatment increased Th1, regulated the imbalance of Th2/Th1, and decreased the related cytokines in EA. As for NEA, the combined treatment reduced Th17 and promoted the accumulation of regulatory T cells (Tregs) in lung. A microbiome study based on 16S rDNA sequencing technique revealed the significantly changed structure of the lower airway microbiota after combined treatment in NEA, with 4 distinct genera and 2 species identified. OPLS-DA models of metabolomics analysis based on UPLC-Q/TOF-MS technique identified 34 differentiated metabolites and 8 perturbed metabolic pathways. A joint multiomics study predicted that the colonized microbiota in airways might be associated with susceptibility of asthma and steroid resistance, which involved systematic and pulmonary metabolic perturbation. In summary, the pharmacological network of RWC included the complicated interaction mechanisms of immune regulation, microbiota change, and metabolic perturbation. |
format | Online Article Text |
id | pubmed-6747379 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67473792019-09-27 Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism Pang, Zhiqiang Ran, Nan Yuan, Yuze Wang, Cuizhu Wang, Guoqiang Lin, Hongqiang Hsu, Alan Chen-Yu Liu, Jinping Wang, Fang Int J Mol Sci Article The heterogeneity of asthma involves complex pathogenesis leading to confusion regarding the choice of therapeutic strategy. In the clinic, asthma is commonly classified as having either eosinophilic asthma (EA) or non-eosinophilic asthma (NEA) phenotypes. Microbiota colonizing in airways has been demonstrated to induce distinct phenotypes of asthma and the resistance to steroids. Rhodiola wallichiana var. cholaensis (RWC) has the potential to alleviate asthmatic inflammation according to recent studies, but its pharmacological mechanisms remain unclarified. In our study, murine asthmatic phenotypes were established and treated with RWC and/or dexamethasone (DEX). Combined treatment with RWC and DEX could improve spirometry and airway hyperresponsiveness (AHR) in asthmatic phenotypes, alleviate steroid resistance in NEA, and reduce the inflammatory infiltration of the both phenotypes. The combined treatment increased Th1, regulated the imbalance of Th2/Th1, and decreased the related cytokines in EA. As for NEA, the combined treatment reduced Th17 and promoted the accumulation of regulatory T cells (Tregs) in lung. A microbiome study based on 16S rDNA sequencing technique revealed the significantly changed structure of the lower airway microbiota after combined treatment in NEA, with 4 distinct genera and 2 species identified. OPLS-DA models of metabolomics analysis based on UPLC-Q/TOF-MS technique identified 34 differentiated metabolites and 8 perturbed metabolic pathways. A joint multiomics study predicted that the colonized microbiota in airways might be associated with susceptibility of asthma and steroid resistance, which involved systematic and pulmonary metabolic perturbation. In summary, the pharmacological network of RWC included the complicated interaction mechanisms of immune regulation, microbiota change, and metabolic perturbation. MDPI 2019-08-28 /pmc/articles/PMC6747379/ /pubmed/31466312 http://dx.doi.org/10.3390/ijms20174216 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pang, Zhiqiang Ran, Nan Yuan, Yuze Wang, Cuizhu Wang, Guoqiang Lin, Hongqiang Hsu, Alan Chen-Yu Liu, Jinping Wang, Fang Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism |
title | Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism |
title_full | Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism |
title_fullStr | Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism |
title_full_unstemmed | Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism |
title_short | Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism |
title_sort | phenotype-specific therapeutic effect of rhodiola wallichiana var. cholaensis combined with dexamethasone on experimental murine asthma and its comprehensive pharmacological mechanism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747379/ https://www.ncbi.nlm.nih.gov/pubmed/31466312 http://dx.doi.org/10.3390/ijms20174216 |
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