Protective Effects of the Wenfei Buqi Tongluo Formula on the Inflammation in Idiopathic Pulmonary Fibrosis through Inhibiting the TLR4/MyD88/NF-κB Pathway.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and poor prognosis. The prognostic signatures related to conventional therapy response remain limited. The Wenfei Buqi Tongluo (WBT) formula, a traditional Chinese medicine (TCM) formula, has been widely utilized to treat respiratory diseases in China, which is particularly effective in promoting inflammatory absorption. In this study, we aim to explore the mechanism of the WBT formula in the inhibition of inflammatory response during IPF, based on network pharmacology and in vivo experiments. METHODS: Network pharmacology was applied to predict the changes of biological processes and potential pathways for the WBT formula against IPF. Histopathological changes, inflammatory factors (IL-6, IL-1ß, and TNF-α), and the proteins of the TLR4/MyD88/NF-κB pathway in bleomycin- (BLM-) induced mice model were examined by hematoxylin-eosin (H&E), Masson or immunohistochemistry staining, Western blot, and enzyme-linked immunosorbent assay analysis. RESULTS: A total of 163 possible components and 167 potential targets between the WBT formula and IPF were obtained. The enrichments of network pharmacology showed that inflammation response, TNF, and NF-κB pathways were involved in the treatment of WBT against IPF. The in vivo experiments indicated that the WBT formula could ameliorate inflammatory exudation and collagen deposition at a histopathology level in the BLM-induced mice model. The levels of IL-6, IL-1ß, and TNF-α were reduced after the WBT formula treatment. Moreover, the expressions of phosphorylated-NF-κB p65, TLR4, and MyD88 were significantly downregulated by the WBT formula, compared with the BLM-induced group. CONCLUSION: These results indicated that the WBT formula can suppress BLM-induced IPF in a mouse model by inhibiting the inflammation via the TLR4/MyD88/NF-κB pathway. This study provides a new insight into the molecular mechanisms of the WBT formula in the application at the clinic.