Anti-DHAV-1 reproduction and immuno-regulatory effects of a flavonoid prescription on duck virus hepatitis

Pharm Biol. 2017 Dec;55(1):1545-1552. doi: 10.1080/13880209.2017.1309554.

Abstract

Context: The flavonoid prescription baicalin-linarin-icariin-notoginsenoside R1 (BLIN) has a curative effect on duck virus hepatitis (DVH) caused by duck hepatitis A virus type 1 (DHAV-1). However, the mechanism of this curative effect is not understood.

Objective: This study investigates the mechanism of the curative effect of BLIN on DVH caused by DHAV-1. We analyzed the anti-DHAV-1 reproduction mechanism and immuno-regulatory effect of BLIN.

Materials and methods: The anti-DHAV-1 reproduction effects of BLIN at 20, 10, 5 and 2.5 μg/mL in vitro, as well as the influence of BLIN at 20 μg/mL on DHAV-1 adsorption, replication and release were tested using the qRT-PCR method. The promotion abilities of BLIN at 20, 10, 5 and 2.5 μg/mL on T- and B-lymphocyte proliferation were investigated by the MTT method. IL-2 and IFN-γ levels and total anti-DHAV-1 antibody secretion after treatment with DHAV-1 for 4, 8 and 54 h were determined by ELISA.

Results: BLIN showed a dose-dependent DHAV-1 reproduction inhibitory effect. The inhibitory effect was highest at 20 μg/mL, where DHAV-1 adsorption and release were significantly lower. Meanwhile, BLIN at 5 μg/mL significantly increased T and B lymphocyte proliferation. BLIN stimulated total anti-DHAV-1 antibody secretion in ducklings at the dosage of 4 mg per duckling, but did not stimulate IL-2 and IFN-γ secretion significantly.

Conclusions: BLIN inhibits DHAV-1 reproduction by suppressing its adsorption and release. Additionally, BLIN promoted the duckling antiviral response.

Keywords: Duck hepatitis A virus type 1; baicalin-linarin-icariin-notoginsenoside R1; virus adsorption; virus release; virus replication.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Ducks
  • Flavonoids / pharmacology*
  • Ginsenosides / pharmacology*
  • Glycosides / pharmacology*
  • Hepatitis Virus, Duck / drug effects*
  • Hepatitis Virus, Duck / growth & development
  • Hepatitis Virus, Duck / immunology
  • Hepatocytes / drug effects*
  • Hepatocytes / immunology
  • Hepatocytes / virology
  • Immunologic Factors / pharmacology*
  • Lymphocyte Activation / drug effects
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Cytokines
  • Drug Combinations
  • Flavonoids
  • Ginsenosides
  • Glycosides
  • Immunologic Factors
  • baicalin
  • linarin
  • icariin
  • notoginsenoside R1

Grants and funding

The project was supported by National Natural Science Foundation of China [Grant No. 31172355, 31572557], the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Special Fund for Agro-scientific Research in the Public Interest [201303040, 201403051]. We are grateful to all other staff in the Institute of Traditional Chinese Veterinary Medicine of Nanjing Agricultural University for their assistances in the experiments.