Angong niuhuang wan attenuates LPS-induced acute lung injury by inhibiting PIK3CG/p65/MMP9 signaling in mice based on proteomics

Abstract

Acute lung injury (ALI) is a serious pulmonary complication that often arises from pneumonia, respiratory tract infections caused by bacteria or viruses, and other factors. It is characterized by acute onset and high mortality. Angong Niuhuang Wan (AGNHW) is a renowned emergency medicine in traditional Chinese medicine, known as the "cool open (febrile disease) three treasures" and regarded as the first of the "three treasures". Previously studies have confirmed that AGNHW has anti-inflammatory effects, improves cerebral circulation, reduces brain edema, and protects vascular endothelium. However, the active components and pharmacological mechanisms of AGNHW in treating ALI remain unclear. In this study, we confirmed that AGNHW can inhibit cytokine storm activity and reduce inflammation induced by LPS in ALI mice. We then analyzed differential proteins using proteomic technology and identified 741 differential proteins. By combining network pharmacological analysis, we deeply discussed the key active components and mechanism of AGNHW in treating ALI. By constructing the interaction network between disease and drug, we identified 21 key active components (such as Quercetin, Kaempferol, and Crocetin) and 25 potential core targets (such as PIK3CG, p65, and MMP9). These candidate targets play an important role in anti-inflammation and immune regulation. Through enrichment analysis of core targets, we found several pathways related to ALI, such as the NF-κB signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. This indicates that AGNHW plays a therapeutic role in ALI through multi-components, multi-targets, and multi-pathways.