Network pharmacology and metabolomics reveal the mechanism of Qi Feng Gu Biao Granules against chronic bronchitis-related cough: a core role for the AGEs/RAGE pathway.

چکیده اصلی

Cough is a prominent and often persistent manifestation of chronic bronchitis (CB) that is frequently difficult to resolve. While Qi Feng Gu Biao Granules (QFGBG) is a traditional Chinese medicine commonly used to treat CB, its pharmacological basis for CB-related cough remains unclear.This study characterized the chemical profile of QFGBG by UPLC-Q-TOF/MS, evaluated its antitussive and anti-inflammatory effects in a rat model induced by lipopolysaccharide instillation combined with cigarette smoke exposure, and integrated network pharmacology, molecular docking, Western blotting, and plasma metabolomics to explore the underlying mechanism.QFGBG reduced cough frequency, prolonged cough latency, improved body-weight gain, and decreased the lung index and wet-to-dry ratio. Histological analyses showed attenuation of lung and tracheal inflammatory injury and mucus hypersecretion. QFGBG also decreased the expression of inflammatory and cough-related factors. Network pharmacology identified 215 overlapping QFGBG-CB targets, with enrichment in inflammatory and metabolic pathways, including the AGEs/RAGE signaling pathway. Molecular docking suggested favorable binding of core components, including Formononetin, Acacetin, and Vanillin, to key targets. Western blotting confirmed that QFGBG downregulated AGEs, RAGE, p-STAT1/STAT1、p-STAT3/STAT3. Metabolomics indicated regulation of glycerophospholipid and arachidonic acid metabolism. These findings suggest that the active components of QFGBG may alleviate CB-related cough by inhibiting the AGEs/RAGE signaling pathway and regulating arachidonic acid and glycerophospholipid metabolism, thereby reducing pulmonary and neurogenic inflammation and the release of cough-related mediators.

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