Assessing the Anti-inflammatory Mechanism of Reduning Injection by Network Pharmacology

Reduning Injection (RDNI) is a traditional Chinese medicine formula indicated for the treatment of inflammatory diseases. However, the molecular mechanism of RDNI is unclear. The information of RDNI ingredients was collected from previous studies. Targets of them were obtained by data mining and molecular docking. The information of targets and related pathways was collected in UniProt and KEGG. Networks were constructed and analyzed by Cytoscape to identify key compounds, targets, and pathways. Data mining and molecular docking identified 11 compounds, 84 targets, and 201 pathways that are related to the anti-inflammatory activity of RDNI. Network analysis identified two key compounds (caffeic acid and ferulic acid), five key targets (Bcl-2, eNOS, PTGS2, PPARA, and MMPs), and four key pathways (estrogen signaling pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and calcium signaling pathway) which would play critical roles in the treatment of inflammatory diseases by RDNI. The cross-talks among pathways provided a deeper understanding of anti-inflammatory effect of RDNI. RDNI is capable of regulating multiple biological processes and treating inflammation at a systems level. Network pharmacology is a practical approach to explore the therapeutic mechanism of TCM for complex disease.

Oseltamivir, Lopinavir/ritonavir and Reduning May Improve Survival of COVID-19 Patients With High-risk

Background No therapeutics have demonstrated specific efficacy for patients with COVID-19. Methods We retrospectively evaluated 351 patients with COVID-19 admitted to the Third People's Hospital of Yichang from 9 January to 25 March, 2020.Univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were employed to identify risk factors associated with progression, which were then incorporated into the nomogram. Survival of patients between high-risk and low-risk groups was compared by kaplan-Meier analysis. Moreover, we assessed the effects of existing common drugs on survival of patients with high-risk. Results Based on the LASSO, four variables (white blood cell, C-reactive protein, whether lymphocyte ≥ 0.8 × 109/L, and whether lactate dehydrogenase ≥ 400 U/L) were selected for construction of the nomogram. Patients in the total cohort were stratified into low-risk group (total point < 160) and high-risk group (total point ≥ 160). Kaplan-Meier analysis demonstrated that there was significant difference in survival of patients between high-risk and low-risk groups (8-week survival rate: 71.41% vs 100%, P < 0.0001). Among the common drugs, we found that patients with high-risk received oseltamivir, lopinavir/ritonavir or Reduning injection exhibited better survival. The combination of these three drugs showed the effect of improving survival, although single drug may have no effect in different grouping analysis. Conclusions The combination of oseltamivir, lopinavir/ritonavir and Reduning injection may improve survival of COVID-19 patients with high-risk identified by our simple-to-use nomogram.

Network analysis of the pharmacological mechanism of Reduning injection in the treatment of novel coronavirus pneumonia

Background: Pneumonia caused by novel coronavirus (COVID-19) is spreading worldwide. Traditional Chinese medicines (TCM) have played an important role in COVID-19 treatment in China. This study explores the specific mechanisms of action of Reduning injection (RDN) as a novel clinical treatment for COVID-19. Material and Methods: We collected RDN chemical components and targets, COVID-19-related targets, and predictions of potential targets of RDN treatment for COVID-19 and performed network topology, Gene Ontology (GO) functional enrichment analysis and WikiPathways enrichment analysis of these potential targets. Results: This study identified 14 chemical components and 200 targets of RDN; 3,558 COVID-19-related targets; 54 potential targets of RDN treatment for COVID-19. GO functional enrichment analysis identified 83 entries in biological process, including regulation of vasoconstriction、arachidonic acid secretion, and 17 entries in molecular function, including oxidoreductase activity, acting on the aldehyde or oxo group of donors. WikiPathways enrichment analysis identified 16 entries including the interleukin-12 signaling pathway. Conclusion: In brief, RDN may be involved in the core anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) action and also in the reduction of the resulting inflammatory response, oxidative stress, and lung tissue damage, and the regulation of apoptosis, providing evidence for the characteristics of TCM in COVID-19 treatment involving multiple components, targets, and pathways.