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. 2015 Feb 15;8(2):1824-33.
eCollection 2015.

Pycnogenol, a compound isolated from the bark of pinus maritime mill, attenuates ventilator-induced lung injury through inhibiting NF-κB-mediated inflammatory response

Y F Xia  1 , J H Zhang  2 , Z F Xu  3 , X M Deng  4
Affiliations

Pycnogenol, a compound isolated from the bark of pinus maritime mill, attenuates ventilator-induced lung injury through inhibiting NF-κB-mediated inflammatory response

Y F Xia et al. Int J Clin Exp Med. .

Abstract

Background: During mechanical ventilation, high end-inspiratory lung volume results in a permeability type pulmonary oedema, called ventilator-induced lung injury (VILI). The pathophysiology of ventilator-induced lung injury involves multiple mechanisms, such as excessive inflammation. And pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark that have anti-inflammatory activity.

Objective: We investigated the effects of pyncogenol on ventilator-induced lung injury in rats.

Methods: Rats were orally administrated with pycnogenol once (30 mg/kg) 2 days before lung injury induction with mechanical ventilation, then the rats were divided into three groups: lung-protective ventilation (LV group, n = 20), injurious ventilation (HV group, n = 20), HV + pycnogenol group (HV + Pyc group, n = 20). Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for histopathological examinations and biochemical analyses.

Results: Pretreatment with pycnogenol could markedly decrease lung wet/dry ratio, lower myeloperoxidase (MPO) activity and total protein concentration and reduce the production of TNF-α, IL-6, IL-1β and MIP-2 in the BALF in ventilator-induced lung injury rats. Additionally, pycnogenol improved the histology of the lung and significantly inhibited the phosphorylation of NF-κB p65 and the degradation of IκB-α.

Conclusion: Pycnogenol treatment could attenuate ventilator-induced lung injury in rats, at least in part, through its ability to reduce the production of inflammatory cytokines via inhibiting the activation of NF-κB, indicating it as a potential therapeutic candidate for ventilator-induced lung injury.

Keywords: NF-kB pathway; Pycnogenol; flavonoid; inflammation; ventilator-induced ALI.

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Figures

Figure 1
Figure 1
Histopathological index of rats lung. The H&E-staining of lung sections following the different treatments in (A) LV group (healthy control), (B) HV group (vehicle-treated group), and (C) prycogenol-treated group. (D) The lung injury index of the differentially treated ALI rats. (E) The wet/dry ratio in differentially treated ALI rats. (F) The protein concentration in the BALF of differentially treated ALI rats. *P < 0.05 compared with the vehicle-treated HV group rats. ALI: acute lung injury; LV: lung-protective ventilation; HV: injurious ventilation; HV + Pyc, HV + pycnogenol-treated group; BALF: bronchoalveolar lavage fluid.
Figure 2
Figure 2
Pycnogenol treatment reduced the MPO activity and neutrophils infiltration in differentially treated ALI rats. The myeloperoxidase (MPO) activity (A) in the lung tissues and the neutrophils count (B) in BALF of differentially treated ALI rats were determined. Data are expressed as mean + SEM of the values of 10 rats of each group. *P < 0.05 compared with the vehicle-treated group rats (HV group). ALI: acute lung injury; LV: lung-protective ventilation; HV: injurious ventilation; HV + Pyc: HV + pycnogenol-treated group; BALF: bronchoalveolar lavage fluid; MPO: myeloperoxidase.
Figure 3
Figure 3
The production of pro-inflammatory cytokines in BALF of differentially treated ALI rats. A. The level of TNF-α in BALF of rats with indicated treatment was measured by ELISA. B. The level of IL-6 in BALF of rats with indicated treatment was measured by ELISA. C. The level of IL-1β in BALF of rats with indicated treatment was measured by ELISA. D. The level of MIP-2 in BALF of rats with indicated treatment was measured by ELISA. Data are expressed as mean ± SEM of the values of 10 rats of each group. *P < 0.05 compared with the vehicle-treated group rats (HV group). ALI: acute lung injury; LV: lung-protective ventilation; HV: injurious ventilation; HV + Pyc: HV + pycnogenol-treated group; BALF: bronchoalveolar lavage fluid.
Figure 4
Figure 4
Effect of pycnogenol treatment on IκB-α degradation and NF-κB phosphorylation in lung tissues of ventilator-induced ALI rats. Whole tissue extracts were subjected to SDS-PAGE Western blot analysis using antibodies for phosphrylated NF-κB P65, IκB-α and β-actin. The ratio of immunointensity between the phosphorylation of NF-κB P65, IκB-α and β-actin were calculated. Values are expressed as means + SEM (n = 3 in each group). *P < 0.05 compared with the vehicle-treated group rats (HV group). ALI: acute lung injury; LV: lung-protective ventilation; HV: injurious ventilation; HV + Pyc: HV + pycnogenol-treated group; BALF: bronchoalveolar lavage fluid.
Figure 5
Figure 5
The expression of inflammatory cytokines in the lung tissue of differentially treated ALI rats induced by ventilation. A. The mRNA level of IL-1β in the lung tissues of differentially treated ALI rats; B. The mRNA level of IL-6 in the lung tissues of differentially treated ALI rats; C. The mRNA level of TNF-α in the lung tissues of differentially treated ALI rats. Data are expressed as mead + SEM of the values of 10 rats of each group. *P < 0.05 compared with the vehicle-treated group rats (HV group). ALI: acute lung injury; LV: lung-protective ventilation; HV: injurious ventilation; HV + Pyc: HV + pycnogenol-treated group; BALF: bronchoalveolar lavage fluid.
Figure 6
Figure 6
Pycnogenol treatment delayed the death of rats with ventilator-induced lung injury. The Kaplan-Meier survival curves of rats (n = 10) with indicated treatment were determined. Data are expressed as mean ± SEM of the values of 10 rats of each group. *P < 0.05 compared with the vehicle-treated group rats (HV group). ALI: acute lung injury; LV: lung-protective ventilation; HV: injurious ventilation; HV + Pyc: HV + pycnogenol-treated group; BALF: bronchoalveolar lavage fluid.
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