Investigation of the Pharmacological Effect and Mechanism of Jinbei Oral Liquid in the Treatment of Idiopathic Pulmonary Fibrosis Using Network Pharmacology and Experimental Validation

Overview: Idiopathic pulmonary fibrosis (IPF) is a disease caused by many factors, eventually resulting in lung function failure. Jinbei oral liquid (JBOL) is a traditional Chinese clinical medicine used to treat pulmonary diseases. However, the pharmacological effects and mechanism of the action of JBOL on IPF remain unclear. This study investigated the protective effects and mechanism of the action of JBOL on IPF using network pharmacology analysis, followed by in vivo and in vitro experimental validation.

Methods: The components of JBOL and their targets were screened using the TCMSP database. IPF-associated genes were obtained using DisGeNET and Drugbank. The common targets of JBOL and IPF were identified with the STRING database, and a protein–protein interaction (PPI) network was constructed. GO and KEGG analyses were performed. Sprague–Dawley rats were injected with bleomycin (BLM) to establish an IPF model and treated orally with JBOL at doses of 5.4, 10.8, and 21.6 ml/kg. A dose of 54 mg/kg of pirfenidone was used as a control. All rats were treated for 28 successive days. Dynamic pulmonary compliance (Cdyn), minute ventilation volume (MVV), vital capacity (VC), and lung resistance (LR) were used to evaluate the efficacy of JBOL. TGF-β–treated A549 cells were exposed to JBOL, and epithelial-to-mesenchymal transition (EMT) changes were assessed. Western blots were performed.

Results: Two hundred seventy-eight compounds and 374 targets were screened, and 103 targets related to IPF were identified. Core targets, including MAPK1 (ERK2), MAPK14 (p38), JUN, IL-6, AKT, and others, were identified by constructing a PPI network. Several pathways were involved, including the MAPK pathway. Experimentally, JBOL increased the levels of the pulmonary function indices (Cdyn, MVV, and VC) in a dose-dependent manner and reduced the RL level in the BLM-treated rats. JBOL increased the epithelial marker E-cadherin and suppressed the mesenchymal marker vimentin expression in the TGF-β–treated A549 cells. The suppression of ERK1/2, JNK, and p38 phosphorylation by JBOL was validated.

Conclusion: JBOL had therapeutic effects against IPF by regulating pulmonary function and EMT through a systemic network mechanism, thus supporting the need for future clinical trials of JBOL.