Anti-asthma components and mechanism of Kechuanting acupoint application therapy: based on serum metabolomics and network pharmacology

Abstract

This study aims to explore the anti-asthma components and mechanism of Kechuanting acupoint application therapy(KAAT) based on serum metabolomics and network pharmacology. A total of 60 asthma patients who had used low-dose inhaled corticosteroids-formoterol(ICS-formoterol) for a long time were randomized into the western medicine group(low-dose ICS-formoterol) and western medicine+Kechuanting group(KAAT+low-dose ICS-Formoterol), 30 in either group. In addition, 30 healthy people were included as the control(no intervention). The asthma control test(ACT) score, forced expiratory volume in 1 second(FEV1), and peak expiratory flow(PEF) were measured in the western medicine group and western medicine+Kechuanting group before and after treatment. The potential biomarkers of KAAT in the treatment of asthma were screened by gas chromatography-mass spectrometry combined with multivariate analysis, and the related metabolic pathways were further analyzed. UPLC/LTQ-Orbitrap-MS, together with network pharmacology, was employed to construct the component-target-pathway network. Thereby, the effective components and me-chanism of KAAT in the treatment of asthma were clarified. According to the ACT score, FEV1, and PEF, KAAT was effective in the treatment of asthma. A total of 10 endogenous biomarkers of KAAT in the treatment of asthma were screened by serum metabolomics, and the pathways of the metabolism of glycine, serine and threonine, and the metabolism of glyoxylic acid and dicarboxylic acid were obtained. UPLC/LTQ-Orbitrap-MS identified 51 chemical components of KAAT: 24 flavonoids, 11 alkaloids, 8 phenols, 2 diterpenoids, 2 triterpenoids, 2 glycosides, and 2 aldehydes. Network pharmacology analysis suggested that KAAT mainly acted on serum crea-tinine(SRC), matrix metalloproteinase 9(MMP-9), and other target proteins. The treatment was closely related to metabolic pathway, phosphatidylinositol 3-kinase-protein kinase B(PI3 K-Akt), mitogen-activated protein kinase(MAPK), and calcium signaling pathway. Sinapine thiocyanate, corydaline, dihydroberberine, stylopine, leonticine, N-methyl tetrahydroberberine, kaempferide, erio-dictyol, quercetin, catechin, 6-gingerol, 6-shogaol, ingenol, and luteolin may be potential effective compounds of KAAT in the treatment of asthma. This study preliminarily revealed that the effective components and mechanism of KAAT in treatment of asthma based on serum metabolomics and network pharmacology. It lays a theoretical foundation for in-depth study of the mechanism and clinical development and application.