Teresa Pollicino1, Cristina Musolino2, Natasha Irrera3, Alessandra Bitto3, Daniele Lombardo3, Martina Timmoneri3, Letteria Minutoli3, Giovanni Raimondo3, Giovanni Squadrito2, Francesco Squadrito4, Domenica Altavilla5. 1. Division of Clinical and Molecular Hepatology, Department of Human Pathology, University Hospital of Messina, Via Consolare Valeria, 98125, Messina, Italy. tpollicino@unime.it. 2. Division of Clinical and Molecular Hepatology, Department of Human Pathology, University Hospital of Messina, Via Consolare Valeria, 98125, Messina, Italy. 3. Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Via Consolare Valeria, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125, Messina, Italy. 4. Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Via Consolare Valeria, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125, Messina, Italy. fsquadrito@unime.it. 5. Department of Biomedical and Dental Sciences and Morphological and Functional Sciences, University of Messina, Via Consolare Valeria, 98125, Messina, Italy.
Abstract
INTRODUCTION: Flavocoxid is a proprietary blend of two flavonoids, baicalin and catechin, and recent evidence has shown that bioflavonoids may exert antiviral activities. The potential antiviral activity of Flavocoxid against hepatitis B virus (HBV) was evaluated. Additionally, it was investigated if Flavocoxid used in combination with Entecavir could potentiate its anti-HBV activity. MATERIALS AND METHODS: Hepatoma cells replicating HBV were treated with Flavocoxid, or Entecavir alone or in combination for up to 5 days. Viral replicative intermediates, transcripts, and cccDNA levels were evaluated in HBV-replicating cells by real-time PCR, Southern and Northern blotting. Expression profiling was performed using TaqMan low-density arrays. RESULTS: Flavocoxid treatment induced a reduction of HBV replicative intermediates, the amount of transcripts, and HBsAg levels. Flavocoxid and Entecavir combination therapy further decreased the amount of HBV replicative intermediates, compared to Flavocoxid alone. Importantly, Flavocoxid alone or in combination with Entecavir also induced a reduction of cccDNA. Gene-expression analysis showed that Flavocoxid activates type I IFNs-signaling and dampens the HBV-induced inflammatory response. CONCLUSIONS: Flavocoxid inhibits HBV replication by targeting multiple steps of viral life cycle. These results indicate that the antiviral activity of Entecavir is potentiated by Flavocoxid, suggesting that this medical food might be considered as an adjuvant for anti-HBV therapy.
INTRODUCTION:Flavocoxid is a proprietary blend of two flavonoids, baicalin and catechin, and recent evidence has shown that bioflavonoids may exert antiviral activities. The potential antiviral activity of Flavocoxid against hepatitis B virus (HBV) was evaluated. Additionally, it was investigated if Flavocoxid used in combination with Entecavir could potentiate its anti-HBV activity. MATERIALS AND METHODS:Hepatoma cells replicating HBV were treated with Flavocoxid, or Entecavir alone or in combination for up to 5 days. Viral replicative intermediates, transcripts, and cccDNA levels were evaluated in HBV-replicating cells by real-time PCR, Southern and Northern blotting. Expression profiling was performed using TaqMan low-density arrays. RESULTS:Flavocoxid treatment induced a reduction of HBV replicative intermediates, the amount of transcripts, and HBsAg levels. Flavocoxid and Entecavir combination therapy further decreased the amount of HBV replicative intermediates, compared to Flavocoxid alone. Importantly, Flavocoxid alone or in combination with Entecavir also induced a reduction of cccDNA. Gene-expression analysis showed that Flavocoxid activates type I IFNs-signaling and dampens the HBV-induced inflammatory response. CONCLUSIONS:Flavocoxid inhibits HBV replication by targeting multiple steps of viral life cycle. These results indicate that the antiviral activity of Entecavir is potentiated by Flavocoxid, suggesting that this medical food might be considered as an adjuvant for anti-HBV therapy.
Authors: Susan L Uprichard; Stefan F Wieland; Alana Althage; Francis V Chisari Journal: Proc Natl Acad Sci U S A Date: 2003-01-27 Impact factor: 11.205