Protocatechuic Acid, a Novel Active Substance against Avian Influenza Virus H9N2 Infection

• Authors: Changbo Ou, Henan Institute of Science and Technology; Ningning Shi, Agricultural University of Hebei; Qunhui Yang, China Agricultural University; Yu Zhang, China Agricultural University; Zongxue Wu, China Agricultural University; Baozhong Wang, Emory University; Richard Compans, Emory University; Cheng He, China Agricultural University
• Journal Title: PLoS ONE
• Volume: Volume 9, Number 10
• Publisher: Public Library of Science | 2014-10-22, Pages e111004-e111004
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0111004
• Subjects: Health Sciences, Epidemiology; Biology, Virology; Health Sciences, Immunology
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; ACUTE LUNG INJURY; A H5N1 VIRUS; IN-VITRO; MICE; CELLS; OSELTAMIVIR; PATHOGENESIS; COMBINATION; RESISTANCE; CHICKENS; Mouse models; Avian influenza; Inflammation; Body weight; Cytokines; Influenza viruses; Respiratory infections; Neutrophils

Abstract

Influenza virus H9N2 subtype has triggered co-infection with other infectious agents, resulting in huge economical losses in the poultry industry. Our current study aims to evaluate the antiviral activity of protocatechuic acid (PCA) against a virulent H9N2 strain in a mouse model. 120 BALB/c mice were divided into one control group, one untreated group, one 50 mg/kg amantadine hydrochloride-treated group and three PCA groups treated 12 hours post-inoculation with 40, 20 or 10 mg/kg PCA for 7 days. All the infected animals were inoculated intranasally with 0.2 ml of a A/Chicken/Hebei/4/2008(H9N2) inoculum. A significant body weight loss was found in the 20 mg/kg and 40 mg/kg PCA-treated and amantadine groups as compared to the control group. The 14 day survivals were 94.4%, 100% and 95% in the PCA-treated groups and 94.4% in the amantadine hydrochloride group, compared to less than 60% in the untreated group. Virus loads were less in the PCAtreated groups compared to the amantadine-treated or the untreated groups. Neutrophil cells in BALF were significantly decreased while IFN-γ, IL-2, TNF-α and IL-6 decreased significantly at days 7 in the PCA-treated groups compared to the untreated group. Furthermore, a significantly decreased CD4+/CD8+ ratio and an increased proportion of CD19 cells were observed in the PCA-treated groups and amantadine-treated group compared to the untreated group. Mice administered with PCA exhibited a higher survival rate and greater viral clearance associated with an inhibition of inflammatory cytokines and activation of CD8+ T cell subsets. PCA is a promising novel agent against bird flu infection in the poultry industry.