Effects of and mechanisms underlying qingwen baidu decoction in sepsis-associated acute kidney injury

Ethnopharmacological relevance: Despite advances in critical care, sepsis-associated acute kidney injury (SA-AKI) remains a serious illness that has limited treatment options. Qingwen Baidu Decoction (QWBD) is a prominent traditional Chinese medicine (TCM) formulation; it is widely used in infectious disease management. Nevertheless, its therapeutic impact on SA-AKI and the underlying mechanisms of action are markedly unexplored.

Objective: This study seeks to integrate molecular docking along with network pharmacology and both cellular and animal experiments to explore the therapeutic utility of QWBD in SA-AKI and provide additional information on its mechanisms.

Materials and methods: Renoprotective actions of QWBD were investigated in a cecal ligation and puncture (CLP)-induced SA-AKI mice model. Outcomes consisted of mouse status, survival rate, serum creatinine (SCr) levels, renal tubular histopathology, blood urea nitrogen (BUN) levels, and Apoptosis. Renal inflammation and Pyroptosis were evaluated through immunohistochemistry, western blotting, and reverse transcription quantitative polymerase chain reaction. QWBD elements and possible targets were determined through ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Furthermore, enrichment analyses elucidated the potential mechanisms. In vitro as well as in vivo tests affirmed the involved pathways. Additionally, molecular docking was conducted to identify key active monomeric compounds within QWBD that may exert protective effects.

Results: In SA-AKI mice, QWBD lowered mortality, decreased both BUN and SCr levels, mitigated tubular damage and inflammatory response, and alleviated Pyroptosis. Network pharmacology suggested 894 TCM components, 555 potential targets, 221 Kyoto Encyclopedia of Genes and Genomes pathways, and 3395 Gene Ontology biological processes. Results from the experiments confirmed that QWBD exerts its renoprotective effects by inhibiting the TLR4/MyD88/NF-κB cascade. Of the QWBD compounds, 2,3-dihydrodauriporphine, homochelidonine, and baicalin were present in high content. They were identified as the key monomeric constituents via molecular docking.

Conclusions: QWBD reduces inflammatory response and Pyroptosis in SA-AKI, likely by suppressing the TLR4/MyD88/NF-κB cascade. The monomeric constituents 2,3-Dihydrodauriporphine, homochelidonine, and baicalin may play important roles in regulating these renoprotective effects.

Inflammation; Pyroptosis; Qingwen baidu decoction; Sepsis-associated acute kidney injury.