Anti-asthmatic potential of Rudanti (Capparis moonii Wight): Integrated metabolomics and network pharmacology approach for identifying lead molecule, associated pharmacological mechanisms, and ex-vivo experimental studies

Capparis moonii (CM) Wight, commonly called Rudanti, is recognized for its medicinal value. The CM fruits are used as pickles, culinary, and traditional medicines to treat respiratory ailments such as asthma, common cold, and cough. However, no phytochemicals have been explored to determine their protective action in asthma management. The current study aims to investigate the anti-asthmatic potential of the plant by integrating metabolomics and network pharmacology studies, supported by in-silico findings and ex-vivo experimental analysis. Metabolite profiling of CM fruits was achieved using liquid chromatography-orbitrap-tandem mass spectrometry (LC-Orbitrap-MS/MS) and gas chromatography-mass spectrometry (GC-MS). Network pharmacology analysis predicts CM's active components, hub targets, and potential pharmacological mechanisms against asthma. Computational analysis was performed to assist in validating active components at hub targets. Among 127 putatively identified phytochemicals, quercetin, rosmarinic acid, and naringenin have exhibited the highest binding affinity (−11.0 kcal/mol) with matrix metalloproteinase 9 (MMP9) receptor. Aurantiamide acetate has shown significant binding affinity (−10.6 kcal/mol) with prostaglandin-endoperoxide synthase 2 (PTGS2) and MMP9 (−9.8 kcal/mol) receptors. Additionally, molecular dynamics (MD) simulation experiments have validated the receptor binding affinity of aurantiamide acetate with PTGS2 and MMP9 as potential targets. Further, ex-vivo studies have demonstrated the concentration-dependent bronchodilation potential of CM extract on isolated murine bronchial ring tissue. The present study demonstrates the multi-target complex mechanisms of CM bioactives via the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathway, signifying their role in the management of respiratory disorders.