1. Academic Validation
  2. Lucidone suppresses hepatitis C virus replication by Nrf2-mediated heme oxygenase-1 induction

Lucidone suppresses hepatitis C virus replication by Nrf2-mediated heme oxygenase-1 induction

  • Antimicrob Agents Chemother. 2013 Mar;57(3):1180-91. doi: 10.1128/AAC.02053-12.
Wei-Chun Chen 1 Sheng-Yang Wang Chien-Chih Chiu Chin-Kai Tseng Chun-Kuang Lin Hui-Chun Wang Jin-Ching Lee
Affiliations

Affiliation

  • 1 Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract

Upon screening of plant-derived Natural Products against hepatitis C virus (HCV) in the replicon system, we demonstrate that lucidone, a phytocompound, isolated from the fruits of Lindera erythrocarpa Makino, significantly suppressed HCV RNA levels with 50% effective concentrations of 15 ± 0.5 μM and 20 ± 1.1 μM in HCV replicon and JFH-1 infectious assays, respectively. There was no significant cytotoxicity observed at high concentrations, with a 50% cytotoxic concentration of 620 ± 5 μM. In addition, lucidone significantly induced heme oxygenase-1 (HO-1) production and led to the increase of its product biliverdin for inducing Antiviral interferon response and inhibiting HCV NS3/4A Protease activity. Conversely, the anti-HCV activity of lucidone was abrogated by blocking HO-1 activity or silencing gene expression of HO-1 or NF-E2-related factor 2 (Nrf2) in the presence of lucidone, indicating that the anti-HCV action of lucidone was due to the stimulation of Nrf-2-mediated HO-1 expression. Moreover, the combination of lucidone and alpha interferon, the Protease inhibitor telaprevir, the NS5A inhibitor BMS-790052, or the NS5B polymerase inhibitor PSI-7977, synergistically suppressed HCV RNA replication. These findings suggest that lucidone could be a potential lead or supplement for the development of new anti-HCV agent in the future.

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