Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation

Abstract

Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear.Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology.Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology.Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05).Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.

Network pharmacology combined with GEO database identifying the mechanisms and molecular targets of Polygoni Cuspidati Rhizoma on Peri-implants

“…Molecular docking refers to process in which two or more molecules identify each other through geometric matching and energy matching, including electrostatic interaction, hydrogen bonding, van der Waals interaction and hydrophobic interaction. In the field of drug design, the purpose of molecular docking was to find the best binding position and binding conformation between small molecule and target enzyme protein 36 . In order to assess the credibility of the association between the target and the compound and to identify the new ingredient candidates for the treatment of Peri-implants, we performed molecular docking between the core compound and the core target.…”

Exploring the active ingredients and pharmacological mechanisms of the oral intake formula Huoxiang Suling Shuanghua Decoction on influenza virus type A based on network pharmacology and experimental exploration

“…Based on the above ingredients analysis results of HSSD by the methods of HPLC and UPLC/Q-TOF MS, combined with their oral bioavailability [OB ≥ 30%, drug likeness (DL) ≥ 0.14] in TCMSP database ( Ru et al, 2014 ; Lai et al, 2020 ), as well as the pharmacodynamic components information with definite anti-influenza virus effects in the published researches, the candidate components of HSSD were supplemented and collected. Subsequently, the potential targets of the identified ingredients of HSSD were obtained mainly from PubChem ( Wang et al, 2012 ), Swiss Target Prediction ( Daina et al, 2019 ), and BATMAN-TCM ( Liu et al, 2016 ).…”

Influenza A virus infects pulmonary microvascular endothelial cells leading to microvascular leakage and release of pro-inflammatory cytokines

“…The PCR system comprised of, 25 µl reaction buffer (RNA17 µl RNA template, 5 µl M-MLV 5 × reaction buffer, primer 50p molar buffer, 0.1mMd nucleotide, 25 units ribonuclease inhibitor and 200 units M-MLVRT polymerase). 18s rRNA was regarded as a house-keeping gene ( Armstrong et al, 2012 ; Chunlian et al, 2014 ; Lai et al, 2020 ; Plotnikova, Klotchenko & Vasin, 2016 ; Yang et al, 2015 ).…”