title: Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir.
abstract: Influenza epidemics cause numerous deaths and millions of hospitalizations each year. Because of the alarming emergence of resistance to anti-influenza drugs, there is a need to identify new naturally occurring antiviral molecules. We tested the hypothesis that pomegranate polyphenol extract (PPE) has anti-influenza properties. Using real time PCR, plaque assay, and TCID 50% hemagglutination assay, we have shown that PPE suppresses replication of influenza A virus in MDCK cells. PPE inhibits agglutination of chicken red blood cells (cRBC) by influenza virus and is virucidal. The single-cycle growth conditions indicated that independent of the virucidal effect PPE also inhibits viral RNA replication. PPE did not alter virus ribonucleoprotein (RNP) entry into nucleus or translocation of virus RNP from nucleus to cytoplasm in MDCK cells. We evaluated four major Polyphenols in PPE (ellagic acid, caffeic acid, luteolin, and punicalagin) and demonstrated that punicalagin is the effective, anti-influenza component of PPE. Punicalagin blocked replication of the virus RNA, inhibited agglutination of chicken RBC's by the virus and had virucidal effects. Furthermore, the combination of PPE and oseltamivir synergistically increased the anti-influenza effect of oseltamivir. In conclusion, PPE inhibited the replication of human influenza A/Hong Kong (H3N2) in vitro. Pomegranate extracts should be further studied for therapeutic and prophylactic potential especially for influenza epidemics and pandemics.
authors: University of Texas Health Science Center at Houston, USA.
authors: Mehran
authors: M
authors: Haidari
authors: Muzammil
authors: M
authors: Ali
authors: Samuel
authors: S
authors: Ward Casscells
authors: Mohammad
authors: M
authors: Madjid
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002645:Chickens; D004285:Dogs; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects; D006384:Hemagglutination / Q000187:drug effects; D006801:Humans; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects*; D009981:Influenza B virus / Q000187:drug effects; D007251:Influenza, Human / Q000188:drug therapy*; D029561:Lythraceae / Q000737:chemistry*; D053139:Oseltamivir / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D053139:Oseltamivir; C115642:punicalagin