Coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly infectious viral disease. Clinical observations have shown that Qing-Fei-Da-Yuan (QFDY) granules have good anti-COVID-19 effects, but the underlying molecular mechanisms are unclear. In this study, we explored the potential mechanism of QFDY with regard to its anti-COVID-19 effect. We first screened the active chemical constituents of QFDY based on the pharmacodynamic activity parameters, followed by screening with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The Uniprot database was used for querying the corresponding genes of the target, and Cyoscape 3.6.1 software was used to construct the network of herb-compound-target. Protein interaction analysis, target gene function enrichment analysis, and signal pathway analysis were performed via STRING database, Database for Annotation, Visualization, and Integrated Discovery, and KEGG Pathway database. Molecular docking was used to predict the binding capacity of the core compound with COVID-19 hydrolase 3CL and angiotensin converting enzyme 2 (ACE2). The results showed that a network of herb-compound-target was successfully constructed, with key targets involving PTGS2, HSP90AA1, CAMKK2, NCOA2, and ESR1. Major metabolic pathways affected were those in cancer, procancer, nonsmall cell lung cancer, and apoptosis. The core compounds, such as quercetin, luteolin, and naringenin, showed a strong binding ability with COVID-19 3CL hydrolase; compounds such as anemasaponin C and medicocarpin showed a strong binding ability with ACE2. Thus, it is predicted that QFDY has the characteristics for multicomponent, multitarget, and multichannel overall control. The mechanism of action of QFDY in the treatment of COVID-19 may be associated with the regulation of genes co-expressed with ACE2, the regulation of inflammation and immune-related signaling pathways, and the influence of COVID-19 3CL hydrolase and ACE2 binding ability.

Mesangial proliferative glomerulonephritis (MsPGN) is characterized by mesangial cell proliferation, inflammation, and extracellular matrix deposition in the mesangial area, which develops into glomerulosclerosis and contributes to end-stage renal disease. Justicidin B is a bioactive compound isolated from Justicia procumbens L., a traditional herbal remedy that reduces proteinuria in nephritis. However, the mechanism of Justicidin B’s therapeutic effect on MsPGN remains unclear. This study was aimed to explore the positive effect of Justicidin B on MsPGN. The results showed that Justicidin B attenuated the proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in MCs and blocked cell cycle progression. Likewise, inflammatory factors, including monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor alpha (TNF-α), in MCs were decreased after treatment with Justicidin B. In addition, Justicidin B exhibited antioxidant activity in PDGF-BB-induced MCs, shown by the decreased production of malondialdehyde and T-AOC, and increased the expression of superoxide dismutase. Besides, Justicidin B suppressed extracellular matrix (ECM) deposition by reducing the protein levels of collagen IV and fibronectin. Furthermore, we found that Justicidin B significantly inhibited activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway in MCs induced by PDGF-BB, but enhanced the levels of proteins in the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. Taken together, Justicidin B prevented PDGF-BB-induced proliferation, inflammation, oxidative stress, and ECM accumulation via regulating the activation of the Nrf2/HO-1 pathway and the Akt/mTOR signaling pathway.