Antiviral effects and possible mechanisms of action of constituents from Brazilian propolis and related compounds

Propolis is a well-known medicinal bee hive product amongst others due to its antiviral properties. Human rhinoviruses (HRVs) are recognized to be responsible for more than 50% of common colds worldwide. This study was performed to determine if kaempferol (KF) and p-coumaric acid (p-CA) extracted from Brazilian propolis and another eight previously known compounds of propolis had antiviral activity toward human rhinovirus (HRV)-2, HRV-3, and HRV-4 in HeLa cells and to determine their mechanism of action using sulforhodamine B assay and real-time reverse transcription polymerase chain reaction. Results were compared with those of a positive control ribavirin. Based on IC50 values, KF, quercetin, chrysin, and luteolin were more pronounced in antiviral activity toward HRV-2 (7.3-37.4 mu M), HRV-3 (11.9-20.4 mu M), and HRV-4 (12.9-24.4 mu M) than a drug reference ribavirin (270.1-323.9 mu M). The 35 mu M KF and 610 mu M p-CA did not interact with the HRV-3 particles. KF and p-CA inhibited HRV-3 infection when added during the early stages (0-4 h) after virus inoculation. These constituents remarkably reduced the RNA replication levels of HRV-3 in the HeLa cell cultures. These findings suggest that KF and p-CA may block or reduce the entrance of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play a crucial role in interfering with expressions of intercellular adhesion molecule-1 and interleukin-6. Further studies about the possible applications of propolis-derived materials as potential products to prevent or treat HRV infection are warranted.