Daxiefei Decoction (Dunhuang Formula) ameliorates acute exacerbation of chronic obstructive pulmonary disease in rats: involvement of the PI3K/AKT/MMP9/TIMP1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) features severe airway inflammation and massive release of inflammatory factors, with highly complex and interrelated pathogenic processes. Daxiefei Decoction (DXFD) is recorded in Fuxingjue Zangfu Yongyao Fayao (abbreviated as Fuxingjue), a classic Dunhuang medical prescription, has demonstrated clinical efficacy in AECOPD treatment. However, the pharmacological roles and potential mechanisms of DXFD in treating AECOPD remain unclear. AIM OF STUDY: To investigate the therapeutic effects and potential molecular mechanisms of DXFD in the treatment of AECOPD, with particular attention to PI3K/AKT/MMP9/TIMP1 signaling pathway. MATERIALS AND METHODS: Chemical constituents and blood-absorbed components were analyzed using UPLC-Q-TOF-MS/MS. AECOPD rat models were constructed by cigarette smoke exposure plus intratracheal LPS instillation to evaluate the therapeutic effects of DXFD and Ti-Yong-Hua compatibility. Network pharmacology was further applied to screen core targets and key signaling pathways, and Western Blotting assay was used for experimental verification. RESULTS: DXFD markedly improved pulmonary function and alleviated lung tissue injury in AECOPD rats, elevated SOD activity and GSH content, and reduced the levels of MDA, TNF-α, IL-6, IL-1β, SAA and CRP significantly. The Ti group, Ti-Yong group and Ti-Hua group exhibited superior therapeutic effects. These findings are consistent with the therapeutic principle of prioritizing purging visceral substance (Ti) and supplementarily tonifying visceral function (Yong) recorded in Fuxingjue. Combined network pharmacology and western blotting analyses showed that DXFD significantly downregulated p-Akt, upregulated total Akt, decreased Mmp9 expression, and increased Timp1 levels in lung tissue. These findings suggest that the effects of DXFD are associated with changes in Akt phosphorylation and Mmp9/Timp1 expression. The five blood-absorbed constituents of emodin, baicalein, liquiritin, sinapic acid, and wogonin may be the active components responsible for the efficacy of DXFD in improving AECOPD. CONCLUSION: DXFD ameliorates AECOPD progression by modulating the PI3K/AKT/MMP9/TIMP1 pathway to suppress inflammation and extracellular matrix degradation, alleviating airway remodeling and lung injury.