ABSTRACT
The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.
ABSTRACT
OBJECTIVE@#To investigate the antibacterial activity of SHH extracted with either water or ethanol against methicillin-resistant Staphylococcus aureus (MRSA) and combinatory antimicrobial effect with ciprofloxacin (CIP) by time kill assay and checkerboard dilution test.@*METHODS@#The antibacterial activity determined by broth dilution method indicated that the antibacterial activity of Sami-Hyanglyun-Hwan (SHH) water extract (SHHW) and SHH ethanol extract (SHHE) ranged from 250 to 2000 μg/mL and 125 to 1000 μg/mL against MRSA, respectively.@*RESULTS@#In the checkerboard method, the combinations of SHHE with CIP had a partial synergistic or synergistic effect against MRSA. The time-kill curves showed that a combined SHHE and CIP treatment reduced the bacterial counts dramatically after 24 h.@*CONCLUSIONS@#The present study demonstrates the therapeutic ability of SHHE against MRSA infections.
ABSTRACT
Objective: To investigate the antibacterial activity of SHH extracted with either water or ethanol against methicillin-resistant Staphylococcus aureus (MRSA) and combinatory antimicrobial effect with ciprofloxacin (CIP) by time kill assay and checkerboard dilution test. Methods: The antibacterial activity determined by broth dilution method indicated that the antibacterial activity of Sami-Hyanglyun-Hwan (SHH) water extract (SHHW) and SHH ethanol extract (SHHE) ranged from 250 to 2. 000 μg/mL and 125 to 1. 000 μg/mL against MRSA, respectively. Results: In the checkerboard method, the combinations of SHHE with CIP had a partial synergistic or synergistic effect against MRSA. The time-kill curves showed that a combined SHHE and CIP treatment reduced the bacterial counts dramatically after 24 h. Conclusions: The present study demonstrates the therapeutic ability of SHHE against MRSA infections.