ABSTRACT
Influenza viruses are one of the most important respiratory pathogens worldwide, causing both epidemic and pandemic infections. The aim of the study was to evaluate the effect of FPR2 antagonists PBP10 and BOC2 on influenza virus replication. We determined that these molecules exhibit antiviral effects against influenza A (H1N1, H3N2, H6N2) and B viruses. FPR2 antagonists used in combination with oseltamivir showed additive antiviral effects. Mechanistically, the antiviral effect of PBP10 and BOC2 is mediated through early inhibition of virus-induced ERK activation. Finally, our preclinical studies showed that FPR2 antagonists protected mice from lethal infections induced by influenza, both in a prophylactic and therapeutic manner. Thus, FPR2 antagonists might be explored for novel treatments against influenza.
Subject(s)
Antiviral Agents/pharmacology , Gelsolin/antagonists & inhibitors , Influenza A virus/drug effects , Oligopeptides/antagonists & inhibitors , Peptide Fragments/antagonists & inhibitors , Receptors, Formyl Peptide/antagonists & inhibitors , Receptors, Lipoxin/antagonists & inhibitors , Virus Replication/drug effects , A549 Cells/drug effects , Animals , Antiviral Agents/administration & dosage , Cell Survival , Dogs , Drug Combinations , Female , Gelsolin/administration & dosage , Haplorhini , Humans , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H3N2 Subtype/drug effects , Influenza B virus/drug effects , Influenza, Human/drug therapy , Influenza, Human/virology , MAP Kinase Signaling System/drug effects , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred C57BL , Oligopeptides/administration & dosage , Oseltamivir/pharmacology , Peptide Fragments/administration & dosage , Sequence AlignmentABSTRACT
Bidens pilosa is an Asteraceae widely used in traditional medicine for the treatment of various ailments including pain and inflammation. The present work was undertaken to assess the analgesic and antiinflammatory properties of the ethyl acetate fraction of methylene chloride/methanol (1:1) extract of leaves of Bidens pilosa at the gradual doses of 50, 100 and 200 mg/kg in mice and rats, respectively. The analgesic properties of Bidens pilosa were investigated using the acetic acid writhing, hot plate, capsaicin and formalin-induced pain models. This was followed by a study of the antiinflammatory properties using carrageenan, dextran, histamine and serotonin to induce acute inflammation in rat hind paw. The extract provided a significant (p < 0.01) reduction in pain induced by all four models of nociception. It also presented significant (p < 0.05) antiinflammatory activity in all four models of acute inflammation. These results show that the ethyl acetate fraction of methylene chloride/methanol (1:1) of Bidens pilosa has both analgesic and antiinflammatory properties. The qualitative analysis of the fraction by the high-performance liquid chromatography (HPLC) fingerprint revealed the presence of two flavonoids, namely quercetin and iso-okanin, known to have antiinflammatory and antinociceptive properties, which could be responsible for the analgesic and antiinflammatory effects observed.
