Anti-Infectivity against Herpes Simplex Virus and Selected Microbes and Anti-Inflammatory Activities of Compounds Isolated from Eucalyptus globulus Labill.
Viliam BrezániVeronika LelákováSherif T S HassanKateřina Berchová-BímováPavel NovýPavel KloučekPetr MaršíkAbdolmajid FataJan HošekKarel ŠmejkalPublished in: Viruses (2018)
Herpes simplex virus (HSV) causes numerous mild-to-serious human diseases, including mucocutaneous herpes infections and life-threatening herpes encephalitis. Moreover, herpes viral lesions can be complicated by inflammation and secondary bacterial infections. The development of resistance to antiviral drugs along with the undesirable side effects of these drugs are relevant argue for the development of new anti-HSV drugs with diverse mechanisms of action. Eucalyptus extracts have been used for decades to combat various infectious diseases. We isolated and studied 12 pure compounds and one mixture of two constitutional isomers from the leaves and twigs of E. globulus. The structures were identified by spectroscopic methods (NMR, HR-MS, IR) and all of them were tested for antiherpetic activity against the replication of antigen types HSV-1 and HSV-2. Tereticornate A (12) (IC50: 0.96 μg/mL; selectivity index CC50/IC50: 218.8) showed the strongest activity in the anti-HSV-1 assay, even greater than acyclovir (IC50: 1.92 μg/mL; selectivity index CC50/IC50: 109.4), a standard antiviral drug. Cypellocarpin C (5) (EC50: 0.73 μg/mL; selectivity index CC50/EC50: 287.7) showed the most potent anti-HSV-2 activity, also more intensive than acyclovir (EC50: 1.75 μg/mL; selectivity index CC50/EC50: 120.0). The antimicrobial activity of the isolated compounds was also evaluated against the bacteria Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa and the yeast Candida albicans. The anti-inflammatory potential was examined using LPS-stimulated THP-1-XBlue™-MD2-CD14 and THP-1 macrophages and focusing on the influences of the NF-κB/AP-1 activity and the secretion of pro-inflammatory cytokines IL-1β and TNF-α.
Keyphrases
- herpes simplex virus
- anti inflammatory
- candida albicans
- biofilm formation
- pseudomonas aeruginosa
- escherichia coli
- staphylococcus aureus
- infectious diseases
- high resolution
- oxidative stress
- magnetic resonance
- rheumatoid arthritis
- mass spectrometry
- endothelial cells
- high throughput
- drug induced
- inflammatory response
- sars cov
- cystic fibrosis
- signaling pathway
- emergency department
- immune response
- cell proliferation
- multidrug resistant
- molecular dynamics
- lps induced
- solid state
- drug resistant
- essential oil