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Protocatechuic acid, a novel active substance against avian influenza virus H9N2 infection.

Ou C, Shi N, Yang Q, Zhang Y, Wu Z, Wang B, Compans RW, He C - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Animal Science, Henan Institute of Science and Technology, Xinxiang, China; Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.

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 PCA-treated 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.

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Therapeutic efficacy of protocatechuic acid (PCA) in mice infected with influenza virus A/Chicken/Hebei/4/2008(H9N2).(A) The assessment of mouse body weight post administration with PCA or amantadine hydrochloride as compared to the untreated or control animals; (B) The mice survival rate post administration with 10, 20 and 40 mg/kg of PCA or 50 mg/kg of amantadine hydrochloride twice daily by oral gavages at 12 h intervals for 7 days. The untreated group was inoculated with H9N2 virus without any medication.
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pone-0111004-g001: Therapeutic efficacy of protocatechuic acid (PCA) in mice infected with influenza virus A/Chicken/Hebei/4/2008(H9N2).(A) The assessment of mouse body weight post administration with PCA or amantadine hydrochloride as compared to the untreated or control animals; (B) The mice survival rate post administration with 10, 20 and 40 mg/kg of PCA or 50 mg/kg of amantadine hydrochloride twice daily by oral gavages at 12 h intervals for 7 days. The untreated group was inoculated with H9N2 virus without any medication.

Mentions: Within three days post inoculation with avian influenza H9N2 virus mice exhibited a decreased food intake and decreased activity (data not shown). Body weight and mortality of all groups are shown in Fig. 1A and B. The body weight loss in the untreated group was significantly different from all other groups during the observation period. Mice treated with PCA exhibited a decreased body weight within the first week and began to increase their weight on day 8. The mean body weights of PCA-treated groups amounted to the level of the control group and were higher than that of the untreated group (Fig. 1A). Meanwhile, the survival was 94.4%, 100.0% and 95.0%, respectively in the 40 mg/kg, 20 mg/kg and 10.0 mg/kg PCA-treated groups, while the amantadine-treated group survival was 94.4%, while the survival in the untreated group was less than 60% by the end of the observation period (Fig. 1B).


Protocatechuic acid, a novel active substance against avian influenza virus H9N2 infection.

Ou C, Shi N, Yang Q, Zhang Y, Wu Z, Wang B, Compans RW, He C - PLoS ONE (2014)

Therapeutic efficacy of protocatechuic acid (PCA) in mice infected with influenza virus A/Chicken/Hebei/4/2008(H9N2).(A) The assessment of mouse body weight post administration with PCA or amantadine hydrochloride as compared to the untreated or control animals; (B) The mice survival rate post administration with 10, 20 and 40 mg/kg of PCA or 50 mg/kg of amantadine hydrochloride twice daily by oral gavages at 12 h intervals for 7 days. The untreated group was inoculated with H9N2 virus without any medication.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206475&req=5

pone-0111004-g001: Therapeutic efficacy of protocatechuic acid (PCA) in mice infected with influenza virus A/Chicken/Hebei/4/2008(H9N2).(A) The assessment of mouse body weight post administration with PCA or amantadine hydrochloride as compared to the untreated or control animals; (B) The mice survival rate post administration with 10, 20 and 40 mg/kg of PCA or 50 mg/kg of amantadine hydrochloride twice daily by oral gavages at 12 h intervals for 7 days. The untreated group was inoculated with H9N2 virus without any medication.
Mentions: Within three days post inoculation with avian influenza H9N2 virus mice exhibited a decreased food intake and decreased activity (data not shown). Body weight and mortality of all groups are shown in Fig. 1A and B. The body weight loss in the untreated group was significantly different from all other groups during the observation period. Mice treated with PCA exhibited a decreased body weight within the first week and began to increase their weight on day 8. The mean body weights of PCA-treated groups amounted to the level of the control group and were higher than that of the untreated group (Fig. 1A). Meanwhile, the survival was 94.4%, 100.0% and 95.0%, respectively in the 40 mg/kg, 20 mg/kg and 10.0 mg/kg PCA-treated groups, while the amantadine-treated group survival was 94.4%, while the survival in the untreated group was less than 60% by the end of the observation period (Fig. 1B).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Animal Science, Henan Institute of Science and Technology, Xinxiang, China; Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.

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 PCA-treated 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.

Show MeSH
Related in: MedlinePlus