Exploration in the Mechanism of Zhisou San for the Treatment of Cough Variant Asthma Based on Network Pharmacology

Abstract

Background. Cough variant asthma (CVA) has no definitive diagnosis or pathogenic causes, and there is currently no effective and safe treatment. Methods. The network pharmacology was employed to investigate possible targets of Zhisou San (ZSS) in CVA treatment. The main chemical constituents of seven herbs in ZSS were collected based on the TCMSP. To explain the main mechanism, we sequentially screened the targets of each active ingredient and constructed the network of “herb-ingredient-target-disease.” The core targets of ZSS were further confirmed by the molecular docking analysis. Furthermore, pulmonary function, histopathology, and biochemical assays in mice were used to investigate the effect of ZSS on the treatment of CVA. Results. A total of 137 active ingredients and 86 potential targets for the ZSS in the treatment of CVA were screened, which were connected with the regulation of inflammatory response and immune balance, such as IL-17 signaling pathway, Th17 cell differentiation, TNF signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, T-cell receptor signaling pathway, Th1 and Th2 cell differentiation, and other signaling pathways closely related to the pathogenesis of CVA. Thereinto, 29 core targets contained 8 of the highest scores and could evidently bind to components such as stigmasterol, quercetin, stemoninine B, luteolin, and β-sitosterol predicted by molecular docking. Furthermore, experiments in vivo were conducted for further validation that ZSS had essential effects on lung function and histopathology as well as the inflammatory state in CVA mice, which was significantly related to regulating the Th17/Treg immune balance to reduce inflammation as the important pharmacological mechanism. Conclusion. This study revealed that ZSS has multicomponent and multipathway characteristics of ZSS in the treatment of CVA, which was primarily associated with inflammation and Th17/Treg immune balance. This study provides a scientific foundation for systematically elaborating the pharmacological activities and mechanism of ZSS, as well as explaining the reliability of the TCM compatibility theory.

Herbal medicine for the treatment of chronic cough: a systematic review and meta-analysis

“…The therapeutic mechanism of HM on chronic cough has been proposed in various ways. Among the included studies, Zhisou-san, or its modified form, was used most frequently, which was reported to be related to inflammation and Th17/Treg immune balance regulation for the treatment of CVA ( Guo et al, 2022 ). In addition, the pulmonary protective effect and antitussive effect of P. grandiflorus (Jacq.)…”