清热败火胶囊缓解LPS诱导小鼠急性肺损伤的药理学物质基础及作用机制研究

Abstract

s Ethnopharmacological relevance Qingre Bawei capsules (QRBW), derived from the traditional Mongolian medicine Erhemu-8 (额日赫木-8), have been clinically used to treat respiratory infections associated with lung heat syndrome, including pneumonia, bronchitis, influenza, and acute lung injury (ALI). However, its specific effects and underlying mechanisms in ALI remain unclear. Aim of the study This study aimed to evaluate the therapeutic effects of QRBW on lipopolysaccharide (LPS)-induced ALI and to identify its active constituents and mechanisms using serum pharmacochemistry, transcriptomics, and biological validation. Materials and methods An in vivo LPS-induced acute lung injury (ALI) mouse model was employed to evaluate the ameliorative effects of QRBW after oral administration. The parameters assessed included body weight changes, pulmonary function, total protein concentration in bronchoalveolar lavage fluid (BALF), the lung wet-to-dry (W/D) weight ratio, levels of IL-6, IL-1β, and TNF-α in BALF, and histopathological examination of lung tissue. Subsequently, UHPLC-Q-Exactive HRMS was applied to identify the chemical constituents absorbed into the bloodstream. Network pharmacology was then used to narrow down the candidate compounds, followed by in vitro anti-inflammatory screening to pinpoint the active components. Furthermore, transcriptomic analysis of lung tissue, Western blotting, quantitative real-time PCR (qRT-PCR), and molecular docking were performed to explore and validate the key signaling pathways through which QRBW alleviates ALI-associated inflammatory injury. Results QRBW significantly ameliorated lung function impairment in an LPS-induced ALI mouse model after oral administration at doses of 620 and 1,240 mg/kg. Additionally, QRBW reduced the lung W/D weight ratio and total protein concentration in BALF, markedly suppressed the release of IL-6, IL-1β, and TNF-α into BALF, and attenuated inflammatory cell infiltration in lung tissue. These find