Abstract Background Acute lung injury (ALI) is a severe respiratory inflammatory disorder with high morbidity and mortality. Huangqin Qingfei Decoction (HQQFD), a classic traditional Chinese medicine formulation composed of Scutellaria baicalensis Georgi (Scutellariae Radix, SR) and Gardenica jasminoides Ellis (Gardeniae Fructus, GF), is clinically used for treating respiratory inflammation including ALI. However, the pharmacodynamic basis of HQQFD and the optimal combination of raw and processed forms of SR and GF remain unclear. Purpose of the research This study aimed to evaluate the therapeutic differences among four clinical variants of HQQFD and identify key bioactive components using a lipopolysaccharide (LPS)-induced ALI rat model. Methods ALI rats were induced by LPS and treated with four HQQFD combinations (different raw/processed forms of SR and GF) at low or high doses. Therapeutic effects were assessed by lung histopathological observation, injury scoring, determination of inflammatory cytokine levels, lung wet/dry (W/D) ratio, and bronchoalveolar lavage fluid (BALF) analysis. Ultra-high performance liquid chromatography-Orbitrap high-resolution mass spectrometry (UHPLC-Orbitrap HRMS) was used to characterize the chemical profiles of different HQQFD variants. Pearson correlation analysis, gray relational analysis (GRA), and Orthogonal partial least squares (OPLS) spectrum-effect relationship analyses were performed to identify efficacy-oriented components. Results A total of 113 compounds were identified in HQQFD, among which 49 showed significant differences between raw and processed combinations. High-dose HQQFD groups exhibited superior therapeutic effects compared to low-dose groups, with the combination of wine Scutellariae Radix (WSR) and Gardeniae Fructus Praeparatus (GFP) being the most effective variant. This optimal combination significantly alleviated lung tissue damage, reduced inflammatory cytokine levels, improved lung W/D ratio, and attenuated BALF abnormalities in ALI rats. Spectrum-effect relationship analysis revealed 20 key bioactive components correlated with pharmacodynamic effects, in which 8 compounds include: geniposidic acid, genipin 1-gentiobioside, geniposide, baicalin, glychionide A, wogonoside, oroxylin A and crocetin was detected in lung tissues, these components are more closely related and may synergise more targets in the treatment of ALI. Conclusion These findings demonstrate that HQQFD ameliorates LPS-induced ALI in rats by regulating the inflammatory response. The combination of WSR and GFP at high dose shows the best therapeutic effect, and the 20 identified compounds are potential pharmacodynamic substances of HQQFD. This study provides experimental evidence for the clinical optimization and quality control of HQQFD in the treatment of ALI.
Liu et al. (2026) studied this question.