Qingfei Huoxue Decoction and Its Active Component Narirutin Alleviate LPS-Induced Acute Lung Injury by Regulating TLR4/NF-[kappa]B Pathway Mediated Inflammation

Background: Acute lung injury (ALI) is a life-threatening clinical syndrome with high mortality. Currently, the safe and effective therapies for ALI patients are still limited. Qingfei Huoxue decoction (QFHXD) is a hospital agreement prescription for treating pulmonary diseases and displays a remarkable efficacy. However, the pharmacological effect of QFHXD on preventing lipopolysac-charide (LPS)-induced ALI has yet to be reported, let alone questions of potential molecular mechanisms and anti-ALI active substances. Methods: To answer the above-mentioned questions, histopathological observation and kit detection were performed to estimate the protective effect of QFHXD pretreatment against LPS-induced ALI. Based on comprehensive chemical profiling of QFHXD, a network pharmacology strategy and experimental validation were integrated to elucidate the underlying functional mechanisms. The potential anti-ALI active components were identified by molecular docking. The anti-ALI activity of narirutin and its antiinflammatory mechanism were further validated using animal and molecular experiments. Results: Pretreatment with different doses of QFHXD effectively mitigated histopathological lesions and systemic inflammation caused by LPS stimulation. A detailed analysis of established compound-target-disease network revealed the strong correlation between anti-ALI action of QFHXD and inflammatory mechanisms. Compared with the model group, QFHXD intervention markedly restrained the abnormally increased transcription and protein levels of pro-inflammatory factors (TLR4, NF-[kappa]B, IL-6, IL-1[beta], and TNF-[alpha]) in lung tissues of ALI mice. The results of molecular docking highlighted the anti-ALI potential of narirutin targeting to TLR4 and NF-[kappa]B p65. In addition to the protective effect of narirutin on suppressing LPS-induced pathological changes, we found that narirutin pretreatment effectively normalized the disordered protein levels of above pro-inflammatory factors of ALI mice. Conclusion: These interesting findings indicate the beneficial effects of QFHXD and its active component narirutin against ALI partly via regulating TLR4/NF-[kappa]B mediated inflammation. This work contributes to the development of novel medications for ALI patients. Keywords: Qingfei Huoxue decoction, narirutin, LPS-induced acute lung injury, network pharmacology, TLR4/NF-[kappa]B pathway, inflammatory response