[Mechanism of Keke Tablets in treating post-infection cough based on network pharmacology and metabolomics]

This study aimed to evaluate the therapeutic effect of Keke Tablets(KKP) on post-infectious cough(PIC) in rat models and to explore its potential mechanism of action. PIC models were established through exposure to cigarette smoke, capsaicin atomization, and nasal instillation of lipopolysaccharide. Hematoxylin-eosin(HE) staining was used to evaluate the morphological changes in the trachea and lung tissue, while enzyme-linked immunosorbent assay(ELISA) kits were used to determine the cytokine levels in serum and lung tissue. The expressions of nerve growth factor(NGF), TrkA(tyrosine receptor kinase-A), and transient receptor potential vanilloid 1(TRPV1) in lung tissue were observed via immunofluorescence. The potential mechanism of action of KKP was explored through network pharmacology and non-targeted metabolomics analysis, and the expression levels of key pathway-related proteins were verified by Western blot. The results show that KKP alleviated the cough symptoms in PIC model rats, significantly improved the pathological injury of trachea and lung tissue, and enhanced lung function. KKP treatment can effectively regulate the inflammatory balance and inhibit tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-13(IL-13). It may also reduce lung nerve sensitivity in the PIC model rats by modulating the NGF-TrkA-TRPV1 signaling axis. Network pharmacology and metabolomics analyses suggest that KKP may exert therapeutic effects by regulating inflammation-related signaling pathways, such as the mitogen-activated protein kinase(MAPK) signaling pathway and arginine metabolism. Western blot analysis further confirmed that KKP can effectively downregulate the expression of cytochrome P450 family 1 subfamily A member 1(CYP1A1), nitric oxide synthase 2(NOS2) and monoamine oxidase A(MAOA), arachidonate 5-lipoxygenase(ALOX5), prostaglandin-endoperoxide synthase 1(PTGS1), and p38 mitogen-activated protein kinase(p38 MAPK). In summary, the study reveals the clinical potential of KKP in the treatment of PIC and confirms that KKP alleviates inflammation and improves cough symptoms through multi-target and multi-pathway regulation, with the mechanism of action likely related to MAPK signaling pathway, arginine metabolism, and other inflammation-related pathways.