Network Pharmacological Analysis on the Herbal Combinations for Mitigating Inflammation in Respiratory Tracts and Experimental Evaluation

Abstract

The regulation of inflammatory mediators, such as TNF-alpha, IL-6, IL-1 beta, and leukotriene B4, could play a crucial role in suppressing inflammatory diseases such as COVID-19. In this study, we investigated the potential mechanisms of drug combinations comprising Ephedrae Herba, Schisandra Fructus, Platycodonis Radix, and Ginseng Radix; validated the anti-inflammatory effects of these drugs; and determined the optimal dose of the drug combinations. By constructing a herb-compound-target network, associations were identified between the herbs and tissues (such as bronchial epithelial cells and lung) and pathways (such as the TNF, NF-kappa B, and calcium signaling pathways). The drug combinations exerted anti-inflammatory effects in the RAW264.7 cell line treated with lipopolysaccharide by inhibiting the production of nitric oxide and inflammatory mediators, including TNF-alpha, IL-6, IL-1 beta, and leukotriene B4. Notably, the drug combinations inhibited PMA-induced MUC5AC mRNA expression in NCI-H292 cells. A design space analysis was carried out to determine the optimal herbal medicine combinations using the design of experiments and synergy score calculation. Consequently, a combination study of the herbal preparations confirmed their mitigating effect on inflammation in COVID-19.