Study on the mechanism of Sangbaipi Decoction in treating acute lung injury via the inflammasome NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sangbaipi Decoction (SBPD) has been used as a therapy for lung-related diseases in China for hundreds of years. It is commonly applied in the treatment of pulmonary diseases such as acute exacerbation of chronic obstructive pulmonary disease (COPD) and acute attack of chronic bronchitis. However, the anti-inflammatory mechanism underlying its therapeutic effect on acute lung injury (ALI) remains unclear.

RESEARCH PURPOSE: Under the guidance of traditional Chinese medicine theory, this study aims to explore the therapeutic effect and mechanism of SBPD on ALI, so as to provide a scientific basis for its clinical application.

MATERIALS AND

METHODS

The chemical composition of SBPD was characterized using high-performance liquid chromatography (HPLC). An ALI model was established in mice induced by lipopolysaccharide (LPS), and an inflammatory cell model was constructed using LPS-stimulated RAW264.7 macrophages. The pharmacological effects of SBPD were investigated both at the whole-formula level and the monomer level, while its anti-inflammatory mechanisms were subsequently validated. The effects of SBPD were evaluated through hematoxylin and eosin(H&E) staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and Western blot analysis. Key signaling pathways and targets were verified, and it was demonstrated that SBPD exerts anti-inflammatory and lung-protective effects via the inflammasome pathway. All data were analyzed using GraphPad Prism 9.0 software.

RESULTS

Six characteristic compounds were identified as marker components for quality control of SBPD. In a murine model of ALI, SBPD administration significantly ameliorated pathological conditions, as evidenced by reduced inflammatory cell infiltration and lower inflammatory scores. ELISA results demonstrated decreased tumor necrosis factor-α(TNF-α) levels in lung tissues of SBPD-treated mice. Immunohistochemical analysis revealed markedly downregulated protein expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease-1(Caspase-1), high mobility group box 1(HMGB1), Toll-like receptor 2(TLR2), yeloid differentiation factor 88(MyD88), and nuclear factor-κB(NF-κB) in the treatment group compared with the model group. Consistent with these findings, Western blot analysis confirmed that SBPD significantly suppressed the expression of TNF-α, NLRP3, Caspase-1, HMGB1, TLR2, MyD88, and NF-κB proteins in lung tissues. Both SBPD and its monomer component baicalin significantly inhibited LPS-induced protein expression of p-NF-κB/NF-κB, interleukin-1β(IL-1β), HMGB1, and interleukin-6 (IL-6) in RAW264.7 macrophages. Western blot results further verified that treatment with either SBPD or baicalin effectively reduced the expression levels of these proteins.

CONCLUSION

This study investigated the pharmacodynamics and mechanism of SBPD in treating respiratory inflammation. SBPD protected mice against LPS-induced ALI by alleviating lung tissue damage. Through integrated investigation of the complete formulation and the monomer baicalin, it was collaboratively demonstrated that SBPD exerts anti-inflammatory effects via the NLRP3 inflammasome pathway.