Am J Perinatol 2023; 40(06): 612-618
DOI: 10.1055/s-0041-1730349
Original Article

Evaluation of the Neuroprotective Effect of Pycnogenol in a Hypoxic–Ischemic Brain Injury Model in Newborn Rats

1   Neonatal Intensive Care Unit, Division of Pediatric, Medical Park Bahcelievler Hospital, Altınbas University Medical Faculty, Istanbul, Turkey
2   Department of Laboratory Animal Science, Faculty of Health Sciences, Dokuz Eylül University, Izmir, Turkey
3   Department of Pathology, Medical Faculty, Izmir Democracy University, Izmir, Turkey
4   Neonatal Intensive Care Unit, Dr. Behçet Uz Children's Education and Research Hospital, Izmir, Turkey
2   Department of Laboratory Animal Science, Faculty of Health Sciences, Dokuz Eylül University, Izmir, Turkey
4   Neonatal Intensive Care Unit, Dr. Behçet Uz Children's Education and Research Hospital, Izmir, Turkey
› Author Affiliations


Objective This study aimed to evaluate the efficacy of Pycnogenol (PYC) and its antioxidant and antiapoptotic effect in an experimental hypoxic–ischemic (HI) rat model.

Study Design A total of 24 Wistar albino rats who were on the seventh postnatal day were divided into three groups with developed HI brain injury model under the sevoflurane anesthesia: 40 mg/kg PYC was given to Group A, saline was given to Group B, and the sham group was Group C. Neuronal apoptosis was investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling and immunohistochemically stained manually with primer antibodies of tumor necrosis factor-α and interleukin-1β.

Results The neuronal cell injury was statistically lower in the PYC treatment group.

Conclusion This is the first study that investigates the role of PYC in the HI brain injury model. PYC reduces apoptosis and neuronal injury in the cerebral tissue of the rats. PYC may be a protective agent against hypoxic–ischemic encephalopathy.

Key Points

  • This is the first study that investigates the role of PYC in the HI brain injury model.

  • PYC may be a protective agent against hypoxic–ischemic encephalopathy.

  • Sevoflurane should not be preferred in rat studies where neuronal apoptosis will be investigated.

Authors' Contributions

R.C. designed the study and wrote the manuscript. A.C., S.A.O., and O.Y. designed the experimental model. G.D. evaluated the histopathological analysis. S.C. revised the manuscript.

Publication History

Received: 07 February 2021

Accepted: 05 April 2021

Article published online:
27 May 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Papazian O. Encefalopatía hipóxica-isquémica neonatal. Medicina (B Aires) 2018; 78 (02, suppl 2): 36-41
  • 2 Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 2010; 86 (06) 329-338
  • 3 Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med 2012; 166 (06) 558-566
  • 4 Papile LA, Baley JE, Benitz W. et al; Committee on Fetus and Newborn. Hypothermia and neonatal encephalopathy. Pediatrics 2014; 133 (06) 1146-1150
  • 5 D'Andrea G. Pycnogenol: a blend of procyanidins with multifaceted therapeutic applications?. Fitoterapia 2010; 81 (07) 724-736
  • 6 Ozoner B, Yuceli S, Aydin S. et al. Effects of Pycnogenol on ischemia/reperfusion-induced inflammatory and oxidative brain injury in rats. Neurosci Lett 2019; 704: 169-175
  • 7 Paarmann K, Prakash SR, Krohn M. et al. French maritime pine bark treatment decelerates plaque development and improves spatial memory in Alzheimer's disease mice. Phytomedicine 2019; 57: 39-48
  • 8 Vannucci RC, Connor JR, Mauger DT. et al. Rat model of perinatal hypoxic-ischemic brain damage. J Neurosci Res 1999; 55 (02) 158-163
  • 9 Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther 2002; 40 (04) 158-168
  • 10 Nikpayam O, Rouhani MH, Pourmasoumi M, Roshanravan N, Ghaedi E, Mohammadi H. The effect of Pycnogenol supplementation on plasma C-reactive protein concentration: a systematic review and meta-analysis. Clin Nutr Res 2018; 7 (02) 117-125
  • 11 Sahebkar A. A systematic review and meta-analysis of the effects of Pycnogenol on plasma lipids. J Cardiovasc Pharmacol Ther 2014; 19 (03) 244-255
  • 12 Schoonees A, Visser J, Musekiwa A, Volmink J. Pycnogenol for the treatment of chronic disorders. Cochrane Database Syst Rev 2012; (02) CD008294
  • 13 Dogan E, Yanmaz L, Gedikli S, Ersoz U, Okumus Z. The effect of Pycnogenol on wound healing in diabetic rats. Ostomy Wound Manage 2017; 63 (04) 41-47
  • 14 Zhang Z, Tong X, Wei YL, Zhao L, Xu JY, Qin LQ. Effect of Pycnogenol supplementation on blood pressure: a systematic review and meta-analysis. Iran J Public Health 2018; 47 (06) 779-787
  • 15 Lau BH, Riesen SK, Truong KP, Lau EW, Rohdewald P, Barreta RA. Pycnogenol as an adjunct in the management of childhood asthma. J Asthma 2004; 41 (08) 825-832
  • 16 Cesarone MR, Belcaro G, Agus GB. et al. Chronic venous insufficiency and venous microangiopathy: management with compression and Pycnogenol. Minerva Cardioangiol 2019; 67 (04) 280-287
  • 17 Perrone S, Stazzoni G, Tataranno ML, Buonocore G. New pharmacologic and therapeutic approaches for hypoxic-ischemic encephalopathy in the newborn. J Matern Fetal Neonatal Med 2012; 25 (Suppl. 01) 83-88
  • 18 Akisu M, Kumral A, Canpolat FE. Turkish Neonatal Society Guideline on neonatal encephalopathy. Turk Pediatri Ars 2018; 53 (01, suppl 1): S32-S44
  • 19 Hannun YA, Obeid LM. Ceramide: an intracellular signal for apoptosis. Trends Biochem Sci 1995; 20 (02) 73-77
  • 20 Oygür N, Sönmez O, Saka O, Yeğin O. Predictive value of plasma and cerebrospinal fluid tumour necrosis factor-alpha and interleukin-1 beta concentrations on outcome of full term infants with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 1998; 79 (03) F190-F193
  • 21 Aly H, Khashaba MT, El-Ayouty M, El-Sayed O, Hasanein BM. IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy. Brain Dev 2006; 28 (03) 178-182
  • 22 Peng Q, Wei Z, Lau BH. Pycnogenol inhibits tumor necrosis factor-α-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothelial cells. Cell Mol Life Sci 2000; 57 (05) 834-841
  • 23 Xia R, Ji C, Zhang L. Neuroprotective effects of Pycnogenol against oxygen-glucose deprivation/reoxygenation-induced injury in primary rat astrocytes via NF-κB and ERK1/2 MAPK pathways. Cell Physiol Biochem 2017; 42 (03) 987-998
  • 24 Unsal AIA, Kocaturk T, Gunel C. et al. Effect of Pycnogenol on an experimental rat model of allergic conjunctivitis. Graefes Arch Clin Exp Ophthalmol 2018; 256 (07) 1299-1304
  • 25 David IMB, de Souza Fernandes F, Dos Santos Silva Ferreira JB. et al. Dietary supplementation with procyanidin-rich Pinus pinaster extract is associated with attenuated Ehrlich tumor development in mice. Nutr Res 2019; 62: 41-50
  • 26 Shi CX, Jin J, Wang XQ. et al. Sevoflurane attenuates brain damage through inhibiting autophagy and apoptosis in cerebral ischemia–reperfusion rats. Mol Med Rep 2020; 21 (01) 123-130
  • 27 Ozdemir SA, Ozdemir N, Aksan O. et al. Effect of humic acid on oxidative stress and neuroprotection in hypoxic-ischemic brain injury: part 1. J Matern Fetal Neonatal Med 2020; DOI: 10.1080/14767058.2020.1856809.
  • 28 Sun MY, Cui KJ, Yu MM, Zhang H, Peng XL, Jiang H. Bax inhibiting peptide reduces apoptosis in neonatal rat hypoxic-ischemic brain damage. Int J Clin Exp Pathol 2015; 8 (11) 14701-14708
  • 29 Piao M, Wang Y, Liu N. et al. Sevoflurane exposure induces neuronal cell parthanatos initiated by DNA damage in the developing brain via an increase of intracellular reactive oxygen species. Front Cell Neurosci 2020; 14: 583782