ShaGan QingFei JieDu granules alleviate acute lung injury through inhibition of the TGF-β/Smad signaling pathway.

BACKGROUND

Acute lung injury (ALI) is a severe inflammatory condition marked by an inflammatory response, diffuse alveolar damage, and pulmonary edema. ShaGan QingFei JieDu granules (SGQF) is an established Tibetan medicine formula, commonly used to treat various lung diseases associated with lung heat. However, the role of SGQF in protecting against ALI and its mechanism remains unclear.

PURPOSE: The study objective was to verify the therapeutic effectiveness of SGQF in treating ALI and further investigate its mechanism.

METHODS

In vivo, animal models of ALI were established by inducing lipopolysaccharide (LPS) to investigate the pharmacodynamic effects and molecular mechanisms of SGQF in ALI. HPLC-Q Exactive-Orbitrap-MS was employed to identify the SGQF components, and a 293 T-TGF-β1 cell model was established to screen the bioactivity of major components. The MLE-12 cell injury model was then used to validate the mechanisms through which the key active components exert their effects.

RESULTS

SGQF reduced the pathological signs in the lung tissue of ALI by reducing the levels of pro-inflammatory cytokines. The expression of transforming growth factor (TGF)-β1, Smad2/3, and connective tissue growth factor (CTGF) was also significantly downregulated, while Smad7 was significantly upregulated. A total of 83 compounds, consisting of phenolic acids, flavonoids, flavonoid glycosides, alkaloids, coumarins, terpenoids, and other categories, were successfully characterized. In a 293 T-TGF-β1 cell model and molecular docking, isoliquiritin (ILQ) significantly inhibited TGF-β1 activity. In an MLE-12 cell injury model, ILQ notably reduced the levels of pro-inflammatory cytokines and exerted a protective effect on alveolar epithelial cells by downregulating the expression of Smad2/3 and upregulating the expression of Smad7.

CONCLUSION

These findings suggest that SGQF mitigates LPS-induced ALI in mice by inhibiting the TGF-β/Smad signaling pathway, with ILQ being a key active component responsible for this regulatory effect.