The Protective Effects of Modified Dachaihu Decoction against LPS-induced Acute Lung Injury via Modulating PI3K/Akt Signalling Pathway

Abstract

Background: Modified Dachaihu decoction (MDD) is a herbal prescription that has shown promising therapeutic benefits in ameliorating pulmonary diseases in clinical practice. However, the detailed mechanisms remain unclear. Objective: This study aimed to elucidate the lung-protective effects of MDD against acute lung injury (ALI) and the involvement of underlying mechanisms. Methods: High-performance liquid chromatography (HPLC) was performed to identify the main active ingredients of MDD. Network pharmacological method was adapted to explore the potential mechanisms. Mice were orally administered MDD (11.25, 22.5, and 45 g/kg) once daily for 7 days. H&E staining was performed to evaluate histological changes in the lungs. Levels of inflammatory cytokines and oxidative stress markers were measured to determine the extent of lung injury. Total protein content in bronchoalveolar lavage fluid (BALF) and lung wet/dry weight ratio were measured to assess the severity of pulmonary edema. TUNEL staining and immunohistochemistry analysis were performed to detect apoptosis. RT-qPCR and western blotting were performed to validate the mechanisms involved. Results: About 10 main active ingredients of MDD were identified. Notably, treatment with MDD resulted in a remarkable reduction in total protein content in BALF and lung W/D weight ratio, as well as substantial mitigation of the inflammatory response and oxidative stress. Mechanistically, the PI3K/Akt signalling pathway was activated. Moreover, MDD pretreatment downregulated p53 and caspase-9 mRNA expression and decreased the Bax/Bcl-2 ratio to ameliorate lung apoptosis. Conclusions: MDD exhibited pronounced therapeutic effects via attenuating inflammatory response, oxidative stress, and apoptosis. These therapeutic effects could be attributed to the synergistic effect of the main active ingredients and are believed to be associated with the activation of the PI3K/Akt pathway.