1. Academic Validation
  2. Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells

Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells

  • Br J Pharmacol. 2014 Jan;171(1):237-52. doi: 10.1111/bph.12440.
Jin-Ching Lee 1 Chin-Kai Tseng Kung-Chia Young Hung-Yu Sun Shainn-Wei Wang Wei-Chun Chen Chun-Kuang Lin Yu-Hsuan Wu
Affiliations

Affiliation

  • 1 Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract

Background and purpose: This study aimed to evaluate the anti-hepatitis C virus (HCV) activity of andrographolide, a diterpenoid lactone extracted from Andrographis paniculata, and to identify the signalling pathway involved in its Antiviral action.

Experimental approach: Using HCV replicon and HCVcc infectious systems, we identified anti-HCV activity of andrographolide by measuring protein and RNA levels. A reporter activity assay was used to determine transcriptional regulation of anti-HCV agents. A specific inhibitor and short hairpin RNAs were used to investigate the mechanism responsible for the effect of andrographolide on HCV replication.

Key results: In HCV replicon and HCVcc infectious systems, andrographolide time- and dose-dependently suppressed HCV replication. When combined with IFN-α, an inhibitor targeting HCV NS3/4A Protease (telaprevir), or NS5B polymerase (PSI-7977), andrographolide exhibited a significant synergistic effect. Andrographolide up-regulated the expression of haeme oxygenase-1 (HO-1), leading to increased amounts of its metabolite biliverdin, which was found to suppress HCV replication by promoting the Antiviral IFN responses and inhibiting NS3/4A Protease activity. Significantly, these Antiviral effects were attenuated by an HO-1-specific inhibitor or HO-1 gene knockdown, indicating that HO-1 contributed to the anti-HCV activity of andrographolide. Andrographolide activated p38 MAPK phosphorylation, which stimulated nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated HO-1 expression, and this was found to be associated with its anti-HCV activity.

Conclusions and implications: Our results demonstrate that andrographolide has the potential to control HCV replication and suggest that targeting the Nrf2-HO-1 signalling pathway might be a promising strategy for drug development.

Keywords

HCV; andrographolide; heme oxygenase-1; nuclear factor erythroid 2-related factor 2; p38 MAPK.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15005
    99.99%, HCV 抑制剂
    HCV