Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism

• Published in: International journal of molecular sciences Vol. 20; no. 17; p. 4216
• Main Authors: Pang, Zhiqiang, Ran, Nan, Yuan, Yuze, Wang, Cuizhu, Wang, Guoqiang, Lin, Hongqiang, Hsu, Alan Chen-Yu, Liu, Jinping, Wang, Fang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-08-2019; MDPI
• Subjects: Animal models; Animals; Asthma; Asthma - drug therapy; Asthma - pathology; Cytokines - genetics; Cytokines - metabolism; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Drug Resistance; Drug Therapy, Combination; Female; Genotype & phenotype; Glucocorticoids - administration & dosage; Glucocorticoids - pharmacology; Glucocorticoids - therapeutic use; High performance liquid chromatography; Inflammation; Leukocytes (eosinophilic); Lung - drug effects; Lung - microbiology; Lymphocyte Subsets - drug effects; MAP kinase; Metabolism; Metabolites; Mice; Mice, Inbred BALB C; Microbiota - drug effects; multiomics; Neutrophils; Organic chemistry; Ovalbumin; Pathogenesis; Pharmacology; Phenotype; Phenotypes; Phosphorylation; Plant Extracts - administration & dosage; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Quality assessment; Quality control; Regulation; Respiratory tract; Respiratory tract diseases; Rhodiola - chemistry; Rhodiola wallichiana var. cholaensis; Salidroside; Signal transduction; Steroids; Tyrosol; Rhodiola wallichiana var. cholaensis; dexamethasone; phenotype; asthma; multiomics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20174216

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.
var.
(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.