Partridgeberry polyphenols protect rat primary cortical neurons from oxygen–glucose deprivation–reperfusion-induced injury via suppression of inflammatory adipokines and regulation of HIF-1α and PPARγ

Abstract

Objectives: The aim of this study was to investigate the neuroprotective ability of partridgeberry polyphenols in rat primary cortical neurons against oxygen-glucose deprivation/reperfusion (OGD/R) injury in vitro and explore the underlying therapeutic mechanism(s).

Methods: The OGD/R injury was induced in rat primary cortical neurons by incubation with deoxygenated glucose-free medium in a hypoxia chamber.

Results: The strongest activity in this regard was exhibited by partridgeberry-derived PPF2 and PPF3, i.e. the flavan-3-ol- and flavonol-rich polyphenol fractions of partridgeberry (P ≤ 0.05). Moreover, partridgeberry polyphenol pre-treatment reduced the membrane damage in primary neurons, as measured by the lactose dehydrogenase (LDH) release assay (P ≤ 0.05). Furthermore, PPF2 and PPF3 pre-treatment (100 µg ml⁻¹) for 24 hours, before OGD/R, resulted in the strongest suppression of interleukin (IL)-6 and tumor necrosis factor-α induction by OGD/R injury, compared with the control group (P ≤ 0.05). Additionally, the protein levels of hypoxia-inducible factor (HIF-1α) and PPARγ, quantified by ELISA presented a significant modulation following PPFs treatment (100 µg ml⁻¹), favorably toward neuroprotection, compared with the respective controls after OGD/R injury in vitro (P ≤ 0.05).

Conclusion: In summary, partridgeberry polyphenols at concentrations of 1–100 µg ml⁻¹, significantly induced a decline in OGD/R injury-triggered apoptosis in vitro, suppressed the inflammatory biomarkers in primary neurons, and modulated the activity of HIF-1α and proliferator-activated receptor gamma (PPARγ) following hypoxic injury.

Keywords:

• Polyphenols
• Stroke
• Hypoxia
• Neurons
• HIF-1α
• TNF-α
• Neuroprotection
• Brain
• Lingonberry

Acknowledgements

The authors acknowledge the funding provided by the Canada Research Chair Program, the Atlantic Innovation Funds Program of the Atlantic Canada Opportunities Agency (ACOA) and the Department of Natural Resources of the Government of Newfoundland and Labrador.

Disclaimer statements

Contributors VR (principal investigator) contributed to designing the experiments, providing all required resources for research, and writing the manuscript. KB: conducted all the experiments, analyzed the data, and wrote the draft manuscript.

Funding None.

Conflicts of interest None.

Ethics approval None.