Abstract

Asthma is a chronic inflammatory disorder of the airway and is characterized by airway remodeling, hyperresponsiveness, and shortness of breath. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicines (TCM), has been demonstrated to have good therapeutic effects on experimental allergic asthma. However, its anti-asthma mechanism remains currently unknown. In the present work, metabolomics studies of biochemical changes in the lung tissue and plasma of ovalbumin (OVA)-induced allergic asthma mice with mKG treatment were performed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Partial least squares–discriminate analysis (PLS−DA) indicated that the metabolic perturbation induced by OVA was reduced after mKG treatment. A total of twenty-four metabolites involved in seven metabolic pathways were identified as potential biomarkers in the development of allergic asthma. Among them, myristic acid (L3 or P2), sphinganine (L6 or P4), and lysoPC(15:0) (L12 or P16) were detected both in lung tissue and plasma. Additionally, l-acetylcarnitine (L1), thromboxane B2 (L2), 10-HDoHE (L10), and 5-HETE (L11) were first reported to be potential biomarkers associated with allergic asthma. The treatment of mKG mediated all of those potential biomarkers except lysoPC(15:0) (P16). The anti-asthma mechanism of mKG can be achieved through the comprehensive regulation of multiple perturbed biomarkers and metabolic pathways.

Highlights

  • Asthma is a chronic inflammatory disorder of the airway characterized by airway remodeling, hyperresponsiveness, and shortness of breath [1,2]

  • The base peak intensity (BPI) chromatograms of Modified Kushen Gancao Formula (mKG), Kushen, and Gancao extracts in positive ion electrospray ionization (ESI) mode are shown in Figures 1A and S1

  • The protective effect of mKG was evaluated in OVA-induced allergic asthma mice using a metabolomic approach

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Summary

Introduction

Asthma is a chronic inflammatory disorder of the airway characterized by airway remodeling, hyperresponsiveness, and shortness of breath [1,2]. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicines (TCM), has been demonstrated to show prominent anti-inflammatory effects and good therapeutic effects on pulmonary fibrosis in our previous study [6]. It contains three herbs: viz., the roots of Sophora flavescens Ait. Ku-Shen and Gan-Cao are the major herbs in ASHMITM (Anti-asthma the Herbal Medicine Intervention), which can prevent allergic asthma airway hyper-reactivity in mice and inhibits acetylcholine (ACh) induced airway smooth muscle (ASM) contraction in tracheal rings from allergic asthmatic mice [15]. More research is needed to investigate the effectiveness and the mechanism of the herbal formula

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