ABSTRACT
We predicted the anti-hepatitis B virus (HBV) active components and mechanism of Salvia miltiorrhiza based on network pharmacology. The active components of S. miltiorrhiza were obtained through TCMSP, PubChem database and literature research. The potential targets of the active components and HBV infection were predicted by SwissTargetPrediction and GeneCards databases, respectively. The protein-protein interaction (PPI) network was constructed by String database. Cytoscape software was adopted to construct a visual network of active component-disease target and perform topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID platform. The molecular docking of key components and core targets was carried out by AutoDock Vina software. We screened out a total of 38 active components and 178 disease-component overlapping targets. Enrichment analyses obtained 405 related GO items and 68 signaling pathways, such as T/B cell receptor signaling pathways, PI3K/AKT signaling pathway, and mTOR signaling pathway. According to the results of molecular docking, most characteristic components of S. miltiorrhiza (miltionone Ⅱ, miltirone, protocatechuic acid, lithospermic acid, protocatechualdehyde) showed good affinity with the key targets (PIK3CA, APP, STAT3,AKT1 and mTOR). Furthermore, the anti-HBV activity of lithospermic acid, the representative active component of S. miltiorrhiza, and its regulation on PI3K/AKT and mTOR signaling pathways were investigated in an HBV replicating mouse model. Animal welfare and experimental procedures follow the regulations of the Animal Ethics and Welfare Committee of Hubei University. The results showed that lithospermic acid significantly inhibited HBV DNA replication, reduced serum HBsAg and HBeAg levels, and decreased the phosphorylation protein expression levels of AKT and mTOR in liver, indicating that lithospermic acid might exert the anti-HBV activity by regulating PI3K/AKT and mTOR signaling pathways.
ABSTRACT
OBJECTIVE: To design and synthesize derivatives of Matijin-Su (MTS) containing trifluoromethyl group and investigate their anti-HBV activities in vitro. METHODS: Taking MTS as lead compound, target compounds were prepared by acylation, alkylation and hydrolysis, etc. The cytotoxicities and anti-HBV activities of the target compounds were tested with MTT method.RESULTS Twenty derivatives of MTS containing trifluoromethyl were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR and MS(ESI). The anti-HBV activities of those compounds were evaluated in HepG2 2.2.15 cells. The screening RESULTS: showed that compounds 3b, 6a, 6c, 6d, 6h-6j and 6n had HBV inhibitory effect for HepG2 2.2.15 cells. Compounds 3b, 6d and 6n exhibited significant anti-HBV activity with IC50 values of 11.74, 8.73 and 11.41 μmol•L-1. CONCLUSION: Incorporation of trifluoromethyl into MTS derivatives can lead to profound changes in their anti-HBV activity, and could be worth of further research.
ABSTRACT
Objective: To evaluate the effect of 8-epi-kingiside (8-Epik) derived from the buds of Jasminum officinale var. grandiflorum (JOG) on hepatitis B virus (HBV) replication in HepG2 2.2.15 cell line in vitro and duck hepatitis B virus (DHBV) replication in ducklings in vivo. Methods: The concentration of extracellular hepatitis B e antigen and hepatitis B surface antigen (HBsAg) in cell culture medium was determined by ELISA, respectively. The anti-HBV effects of 8-Epik were also demonstrated in the model of DHBV. 8-Epik was ip given (20, 40, and 80 mg/kg, twice daily) to the DHBV-infected ducklings for 10 d. The isotonic saline liquid diet was ip given as negative control and Lamivudine (50 mg/kg, twice daily) was given as positive control. DHBV DNA was measured at days 0 (T0), 5 (T5), 10 (T10), and day 3 after cessation of treatment (P3) by dot blotting. Results: 8-Epik effectively blocked HBsAg secretion in HepG2 2.2.15 cells in a dose-dependent manner [IC50 = (19.4 ± 1.04) μg/mL]. 8-Epik (40 or 80 mg/kg, ip, twice daily) also reduced viremia in DHBV-infected ducks. Conclusion: Therefore, 8-Epik is warranted as a potential therapeutic agent for HBV infection. © 2013 Tianjin Press of Chinese Herbal Medicines.