ABSTRACT
Objective: To reveal the molecular mechanism of Chaiyin Granules in treatment of coronavirus infection based on network pharmacology and molecular docking. Methods: The chemical constituents of Chaiyin Granules were collected by TCMSP database. SwissTargetPrediction database and GeneCards database were used to predict the potential targets of active ingredients and coronavirus. The potential active ingredients and its targets of Chaiyin Granules in the treatment of coronavirus infection were found through Venn diagram. The potential active compounds-targets network and the PPI network were visualized by Cytoscape 3.7.0. GO-enriched analysis and KEGG pathways analysis were constructed on STRING database. The molecular docking of potential active compounds and key targets was achieved by autodock vina 1.1.2. Results: Fifty-one potential active ingredients and 14 potential targets for Chaiyin Granules on treatment of coronavirus infection were obtained. KEGG pathways analysis showed that 44 metabolic pathways were involved to Chaiyin Granules effect on coronavirus infection, including MAPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, Fc epsilon RI signaling pathway and IL-17 signaling pathway. The results of molecular docking showed that baicalin, cubebin, coptisine, daidzein-4,7-diglucoside, linarin, liquiritin, luteolin and wogonin in Chaiyin Granules had strong affinity with NTRK2, PRKCα, TNF, VEGFA, GSK3β. Conclusion: This study elaborated that baicalin, cubebin and coptisine in Chaiyin Granules interacted with NTRK2, PRKCα, TNF, VEGFA, GSK3β and regulated PI3K-Akt/mTOR, ErbB/Ras and IL-17 signaling pathways to inhibit the invasion and replication of coronavirus and enhance immunity to battle against coronavirus infection. This study provides a research basis and theoretical basis for the application of Chaiyin Granules in the treatment of anti-coronavirus infection.
ABSTRACT
Abstract Recent publications have highlighted the numerous biological activities attributed to the lignan (-)-cubebin (1), Piper cubeba L. f., Piperaceae, and ongoing studies have focused on its structural optimization, in order to obtain derivatives with greater pharmacological potential. The aim of this study was the obtainment of (1), its semisynthetic derivatives and evaluation of antibacterial activity. The extract of the seeds of P. cubeba was chromatographed, subjected to recrystallization and was analyzed by HPLC and spectrometric techniques. It was used for the synthesis of: (-)-O-methylcubebin (2), (-)-O-benzylcubebin (3), (-)-O-acetylcubebin (4), (-)-O-(N, N-dimethylamino-ethyl)-cubebin (5), (-)-hinokinin (6) and (-)-6.6'-dinitrohinokinin (7). The evaluation of the antibacterial activity has been done by broth microdilution technique for determination of the minimum inhibitory concentration and the minimum bactericidal concentration against Porphyromonas gingivalis, Prevotella nigrescens, Actinomyces naeslundii, Bacteroides fragilis and Fusobacterium nucleatum. It was possible to make an analysis regarding the relationship between structure and antimicrobial activity of derivatives against microorganisms that cause endodontic infections. The most promising were minimum inhibitory concentration =50 µg/ml against P. gingivalis by (2) and (3), and minimum inhibitory concentration =100 µg/ml against B. fragilis by (6). Cytotoxicity assays demonstrated that (1) and its derivatives do not display toxicity.