Abstract
Pulmonary fibrosis (PF) is a clinically common disease caused by many factors, which will lead to lung function decline and even respiratory failure. Jingyin granule has been confirmed to have anti-inflammatory and antiviral effects by former studies, and has been recommended for combating H1N1 influenza A virus (H1N1) infection and Coronavirus disease 2019 (COVID-19) in China. At present, studies have shown that patients with severe COVID-19 infection developed lung fibrotic lesions. Although Jingyin granule can improve symptoms in COVID-19 patients, no study has yet reported whether it can attenuate the process of PF. Here, we explored the underlying mechanism of Jingyin granule against PF by network pharmacology combined with in vitro experimental validation. In the present study, the active ingredients as well as the corresponding action targets of Jingyin granule were firstly collected by TCMSP and literature data, and the disease target genes of PF were retrieved by disease database. Then, the common targets were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and then a PPI network and an ingredient–target network were constructed. Next, UPLC-MS was used to isolate and identify selected representative components in Jingyin granule. Finally, LPS was used to induce the A549 cell fibrosis model to verify the anti-PF effect of Jingyin granule in vitro. Our results indicated that STAT3, JUN, RELA, MAPK3, TNF, MAPK1, IL-6, and AKT1 were core targets of action and bound with good affinity to selected components, and Jingyin granule may alleviate PF progression by Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT3), the mammalian nuclear factor-κB (NF-κB), the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), tumor necrosis factor (TNF), and the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathways. Overall, these results provide future therapeutic strategies into the mechanism study of Jingyin granule on PF.
Highlights
Fibrosis, which may occur in any organ, is the outcome of dysregulated tissue repair responses to multiple types of tissue injury, during chronic inflammatory disease processes
Based on the multi-component, multi-target, and multi-channel function of Chinese medicines, this study found the mechanism of the anti-Pulmonary fibrosis (PF) effect of Jingyin granule, which provides a theoretical basis for Jingyin granule in the treatment of PF
The 111 targets of intersection were confirmed by UniProt database, and a lung fibrosis–target network of the main components acting on Jingyin granule was constructed by Cytoscape software (Figure 4)
Summary
Fibrosis, which may occur in any organ, is the outcome of dysregulated tissue repair responses to multiple types of tissue injury, during chronic inflammatory disease processes. Pulmonary fibrosis (PF) is an excessive reparative response to tissue injury characterized by spontaneous, progressive scarring of the lungs in the absence of infectious or autoimmune etiologies (Cui et al, 2020). As a fatal malignant disease of the lung, idiopathic pulmonary fibrosis (IPF) has an unknown etiology, a very poor prognosis, and a very high mortality rate, even worse than several cancers, and lung transplantation is the only curative treatment (Vancheri et al, 2010). The incidence of IPF is high in the elderly, and the condition gradually deteriorates with age, and importantly, the survival rate varies greatly among different patients (Kim et al, 2015), with a median survival of 3–5 years following diagnosis (Raghu et al, 2018), and a 3-year survival rate of only 50% (Cui et al, 2020)
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