These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Hepatitis C virus replication is inhibited by 22beta-methoxyolean-12-ene-3beta, 24(4beta)-diol (ME3738) through enhancing interferon-beta.
    Author: Hiasa Y, Kuzuhara H, Tokumoto Y, Konishi I, Yamashita N, Matsuura B, Michitaka K, Chung RT, Onji M.
    Journal: Hepatology; 2008 Jul; 48(1):59-69. PubMed ID: 18459156.
    Abstract:
    UNLABELLED: A derivative of soyasapogenol, 22beta-methoxyolean-12-ene-3beta, 24(4beta)-diol (ME3738), ameliorates liver injury induced by Concanavalin A in mice. We examined whether ME3738 has independent antiviral effects against hepatitis C virus (HCV) using an established HCV replication model that expresses the full-length genotype 1a HCV complementary DNA plasmid (pT7-flHCV-Rz) under the control of a replication-defective adenoviral vector expressing T7 polymerase. Hepatocellular carcinoma (HepG2) cells, human hepatoma (Huh7) cells, or monkey kidney (CV-1) cells were transfected with pT7-flHCV-Rz, and infected with adenoviral vector expressing T7 polymerase. ME3738 or interferon-alpha (IFN-alpha) was added thereafter and then protein and RNA were harvested from the cells at 9 days after infection. HCV-positive and HCV-negative strands were measured by real-time reverse-transcription polymerase chain reaction and HCV core protein expression was measured using an enzyme-linked immunosorbent assay. The messenger RNA levels of innate antiviral response-related genes were assessed using real-time reverse-transcription polymerase chain reaction. ME3738 dose-dependently reduced HCV-RNA and core protein in hepatocyte-derived cell lines. The antiviral effect was more pronounced in HepG2 than in Huh7 cells. ME3738 increased messenger RNA levels of interferon-beta (IFN-beta) and of IFN-stimulated genes (2'-5' oligoadenylate synthetase, myxovirus resistance protein A [MxA]). Interferon-beta knockdown by small interfering RNA abrogated the anti-HCV effect of ME3738. Moreover, the anti-HCV effects were synergistic when ME3738 was combined with IFN-alpha. CONCLUSION: ME3738 has antiviral effects against HCV. The enhancement of autocrine IFN-beta suggests that ME3738 exerts antiviral action along the type I IFN pathway. This anti-HCV action by ME3738 was synergistically enhanced when combined with IFN-alpha. ME3738 might be a useful anti-HCV drug either with or without IFN-alpha.
    [Abstract] [Full Text] [Related] [New Search]