Integration of metabolomics and transcriptomics reveals the therapeutic mechanism underlying Chelidonium majus L. in the treatment of allergic asthma

Abstract

Background Chelidonium majus L. (C. majus) belongs to the Papaveridae family and is the dried whole grass of C. majus. It is usually used in clinical practice of traditional Chinese medicine and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. This research aimed to illuminate the therapeutic effect of C. majus in the inhibition of allergic asthma. Methods Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, lung histopathological analysis (HE, Masson, PAS) and inflammatory cytokines assay (IL-4, IL-17, IL-6) were implemented to evaluate the protective effects of C. majus on asthma. Then, the effects of C. majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. Results After administration with C. majus, the histological injury of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after C. majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC(10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs are mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. Conclusion C. majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation.