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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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Related in: MedlinePlus

The effect of PCA on the levels of the inflammatory cytokines and antiviral cytokines (TNF-α, IFN-γ, IL-2, and IL-6) and IL-10 in BALF by ELISA assay on days 7 and 14 post infection.A. ** ## Indicates a statistically significant difference (P<0.01) in the IFN-γ concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). B. ** ## Indicates a statistically significant difference (P<0.01) in the TNF-α concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). C. ** ## Indicates a statistically significant difference (P<0.01) in the IL-6 concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). D. ## Indicates a statistically significant difference (P<0.01) in the IL-2 concentration when the untreated group samples were compared with the 20 mg/kg PCA-treated group and amantadine-treated group on day 14. E. # Indicates a statistically significant difference (P<0.05) in the IL-10 concentration when the untreated group samples were compared with 20 mg/kg PCA-treated group on day 14.
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pone-0111004-g004: The effect of PCA on the levels of the inflammatory cytokines and antiviral cytokines (TNF-α, IFN-γ, IL-2, and IL-6) and IL-10 in BALF by ELISA assay on days 7 and 14 post infection.A. ** ## Indicates a statistically significant difference (P<0.01) in the IFN-γ concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). B. ** ## Indicates a statistically significant difference (P<0.01) in the TNF-α concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). C. ** ## Indicates a statistically significant difference (P<0.01) in the IL-6 concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). D. ## Indicates a statistically significant difference (P<0.01) in the IL-2 concentration when the untreated group samples were compared with the 20 mg/kg PCA-treated group and amantadine-treated group on day 14. E. # Indicates a statistically significant difference (P<0.05) in the IL-10 concentration when the untreated group samples were compared with 20 mg/kg PCA-treated group on day 14.

Mentions: Low levels of secretion of the inflammatory cytokines, IFN-γ, TNF-α and IL-6, were observed in the control group and in all drug-treated groups when compared with the untreated group on day 7 or 14 (P<0.01) (Fig. 4A–C). No significant difference was found between the PCA-treated groups and the amantadine group. In the case of IL-6 secretion, the mean values for all drug-treated groups were reduced to the levels seen in the healthy animals (Fig. 4C). By day 7 post-infection the mean IL-2 levels had increased in the all virus-infected groups compared with the control group, while on day 14 the mean IL-2 levels in the 20 mg/kg PCA- and amantadine-treated groups were significantly higher than that of the untreated group (P<0.01). Finally, there were no significant differences in the mean IL-10 concentration among the various groups, except in the case of the PCA20 group IL-10 mean value which was significantly greater than the untreated group and control group on day 14 (Fig. 4E).


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)

The effect of PCA on the levels of the inflammatory cytokines and antiviral cytokines (TNF-α, IFN-γ, IL-2, and IL-6) and IL-10 in BALF by ELISA assay on days 7 and 14 post infection.A. ** ## Indicates a statistically significant difference (P<0.01) in the IFN-γ concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). B. ** ## Indicates a statistically significant difference (P<0.01) in the TNF-α concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). C. ** ## Indicates a statistically significant difference (P<0.01) in the IL-6 concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). D. ## Indicates a statistically significant difference (P<0.01) in the IL-2 concentration when the untreated group samples were compared with the 20 mg/kg PCA-treated group and amantadine-treated group on day 14. E. # Indicates a statistically significant difference (P<0.05) in the IL-10 concentration when the untreated group samples were compared with 20 mg/kg PCA-treated group on day 14.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111004-g004: The effect of PCA on the levels of the inflammatory cytokines and antiviral cytokines (TNF-α, IFN-γ, IL-2, and IL-6) and IL-10 in BALF by ELISA assay on days 7 and 14 post infection.A. ** ## Indicates a statistically significant difference (P<0.01) in the IFN-γ concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). B. ** ## Indicates a statistically significant difference (P<0.01) in the TNF-α concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). C. ** ## Indicates a statistically significant difference (P<0.01) in the IL-6 concentration when the untreated group samples were compared with all other groups on day 7 (**) or day 14 (##). D. ## Indicates a statistically significant difference (P<0.01) in the IL-2 concentration when the untreated group samples were compared with the 20 mg/kg PCA-treated group and amantadine-treated group on day 14. E. # Indicates a statistically significant difference (P<0.05) in the IL-10 concentration when the untreated group samples were compared with 20 mg/kg PCA-treated group on day 14.
Mentions: Low levels of secretion of the inflammatory cytokines, IFN-γ, TNF-α and IL-6, were observed in the control group and in all drug-treated groups when compared with the untreated group on day 7 or 14 (P<0.01) (Fig. 4A–C). No significant difference was found between the PCA-treated groups and the amantadine group. In the case of IL-6 secretion, the mean values for all drug-treated groups were reduced to the levels seen in the healthy animals (Fig. 4C). By day 7 post-infection the mean IL-2 levels had increased in the all virus-infected groups compared with the control group, while on day 14 the mean IL-2 levels in the 20 mg/kg PCA- and amantadine-treated groups were significantly higher than that of the untreated group (P<0.01). Finally, there were no significant differences in the mean IL-10 concentration among the various groups, except in the case of the PCA20 group IL-10 mean value which was significantly greater than the untreated group and control group on day 14 (Fig. 4E).

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