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.
OBJECTIVE
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).


CONCLUSIONS
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.
a Department of Environmental Sciences, Faculty of Agriculture , Dalhousie University , Truro , Nova Scotia , Canada B2N 5E3.
Khushwant S
KS
Bhullar
a Department of Environmental Sciences, Faculty of Agriculture , Dalhousie University , Truro , Nova Scotia , Canada B2N 5E3.|b Department of Pathology, Faculty of Medicine, Dalhousie University , Halifax , Nova Scotia , Canada B3H 4R2.
H P Vasantha
HP
Rupasinghe
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005638:Fruit / Q000737:chemistry*; D007003:Hypoglycemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D059808:Polyphenols / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D029801:Vaccinium vitis-idaea / Q000737:chemistry*; D000093242:Interleukin-6 Inhibitors
D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D047495:PPAR gamma; D010936:Plant Extracts; D059808:Polyphenols; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C497444:Hif1a protein, rat; C000613696:PPAR gamma, rat
Brain; HIF-1α; Hypoxia; Lingonberry; Neurons; Neuroprotection; Polyphenols; Stroke; TNF-α