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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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The effect of PCA on the percentage of monocytes (A), neutrophils (B) and lymphocytes (C) in bronchial alveolar fluid (BALF) on day 7 following infection.A. ## Indicates a statistically significant difference (P<0.01) in monocytes percentage when the untreated group was compared with the PCA- or amantadine-treated groups on day 7. ** Indicates a statistically significant difference (P<0.01) in monocytes percentage when the control group was compared with the virus-treated groups on day 7. B. ## Indicates a statistically significant difference (P<0.01) in neutrophils percentage when the untreated control group was compared with the PCA- or amantadine-treated groups on day 7. ** Indicates a statistically significant difference (P<0.01) in neutrophils percentage when the control group was compared with the virus-treated groups on day 7. C. ## Indicates a statistically significant difference (P<0.01) in lymphocytes percentage when the untreated group was compared with 10 mg/kg PCA-treated group on day 7. ** Indicates a statistically significant difference (P<0.01) in lymphocytes percentage when the control group was compared with the 10 or 20 mg/kg PCA-treated groups on day 7. *or# Indicates a statistically significant difference (P<0.05) in lymphocytes or neutrophils percentage when the untreated group was compared with the control group on day 7.
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pone-0111004-g003: The effect of PCA on the percentage of monocytes (A), neutrophils (B) and lymphocytes (C) in bronchial alveolar fluid (BALF) on day 7 following infection.A. ## Indicates a statistically significant difference (P<0.01) in monocytes percentage when the untreated group was compared with the PCA- or amantadine-treated groups on day 7. ** Indicates a statistically significant difference (P<0.01) in monocytes percentage when the control group was compared with the virus-treated groups on day 7. B. ## Indicates a statistically significant difference (P<0.01) in neutrophils percentage when the untreated control group was compared with the PCA- or amantadine-treated groups on day 7. ** Indicates a statistically significant difference (P<0.01) in neutrophils percentage when the control group was compared with the virus-treated groups on day 7. C. ## Indicates a statistically significant difference (P<0.01) in lymphocytes percentage when the untreated group was compared with 10 mg/kg PCA-treated group on day 7. ** Indicates a statistically significant difference (P<0.01) in lymphocytes percentage when the control group was compared with the 10 or 20 mg/kg PCA-treated groups on day 7. *or# Indicates a statistically significant difference (P<0.05) in lymphocytes or neutrophils percentage when the untreated group was compared with the control group on day 7.

Mentions: As shown in Fig. 3A, the proportions of monocytes in PCA- or amantadine-treated groups were significantly higher than those of the untreated and control groups (P<0.01) while neutrophil percentages in PCA- or amantadine-treated groups largely decreased on day 7 (Fig. 3B). Only lymphocyte percentage of the control group was a little higher (P<0.05) while the 10 mg/kg PCA group was significantly (P<0.01) lower than that of the untreated group. Meanwhile, the 20 mg/kg PCA group was also largely lower than that of the control group in the lymphocyte percentage in BALF (Fig. 3C).


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 percentage of monocytes (A), neutrophils (B) and lymphocytes (C) in bronchial alveolar fluid (BALF) on day 7 following infection.A. ## Indicates a statistically significant difference (P<0.01) in monocytes percentage when the untreated group was compared with the PCA- or amantadine-treated groups on day 7. ** Indicates a statistically significant difference (P<0.01) in monocytes percentage when the control group was compared with the virus-treated groups on day 7. B. ## Indicates a statistically significant difference (P<0.01) in neutrophils percentage when the untreated control group was compared with the PCA- or amantadine-treated groups on day 7. ** Indicates a statistically significant difference (P<0.01) in neutrophils percentage when the control group was compared with the virus-treated groups on day 7. C. ## Indicates a statistically significant difference (P<0.01) in lymphocytes percentage when the untreated group was compared with 10 mg/kg PCA-treated group on day 7. ** Indicates a statistically significant difference (P<0.01) in lymphocytes percentage when the control group was compared with the 10 or 20 mg/kg PCA-treated groups on day 7. *or# Indicates a statistically significant difference (P<0.05) in lymphocytes or neutrophils percentage when the untreated group was compared with the control group on day 7.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111004-g003: The effect of PCA on the percentage of monocytes (A), neutrophils (B) and lymphocytes (C) in bronchial alveolar fluid (BALF) on day 7 following infection.A. ## Indicates a statistically significant difference (P<0.01) in monocytes percentage when the untreated group was compared with the PCA- or amantadine-treated groups on day 7. ** Indicates a statistically significant difference (P<0.01) in monocytes percentage when the control group was compared with the virus-treated groups on day 7. B. ## Indicates a statistically significant difference (P<0.01) in neutrophils percentage when the untreated control group was compared with the PCA- or amantadine-treated groups on day 7. ** Indicates a statistically significant difference (P<0.01) in neutrophils percentage when the control group was compared with the virus-treated groups on day 7. C. ## Indicates a statistically significant difference (P<0.01) in lymphocytes percentage when the untreated group was compared with 10 mg/kg PCA-treated group on day 7. ** Indicates a statistically significant difference (P<0.01) in lymphocytes percentage when the control group was compared with the 10 or 20 mg/kg PCA-treated groups on day 7. *or# Indicates a statistically significant difference (P<0.05) in lymphocytes or neutrophils percentage when the untreated group was compared with the control group on day 7.
Mentions: As shown in Fig. 3A, the proportions of monocytes in PCA- or amantadine-treated groups were significantly higher than those of the untreated and control groups (P<0.01) while neutrophil percentages in PCA- or amantadine-treated groups largely decreased on day 7 (Fig. 3B). Only lymphocyte percentage of the control group was a little higher (P<0.05) while the 10 mg/kg PCA group was significantly (P<0.01) lower than that of the untreated group. Meanwhile, the 20 mg/kg PCA group was also largely lower than that of the control group in the lymphocyte percentage in BALF (Fig. 3C).

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