Antioxidant Polyphenols of Antirhea borbonica Medicinal Plant and Caffeic Acid Reduce Cerebrovascular, Inflammatory and Metabolic Disorders Aggravated by High-Fat Diet-Induced Obesity in a Mouse Model of Stroke.

Metabolic disorders related to obesity and type 2 diabetes are associated with aggravated cerebrovascular damages during stroke. In particular, hyperglycemia alters redox and inflammatory status, leading to cerebral endothelial cell dysfunction, blood-brain barrier (BBB) disruption and brain homeostasis loss. Polyphenols constitute the most abundant dietary antioxidants and exert anti-inflammatory effects that may improve cerebrovascular complications in stroke. This study evaluated the effects of the characterized polyphenol-rich extract of Antirhea borbonica medicinal plant and its major constituent caffeic acid on a high-fat diet (HFD)-induced obesity mouse model during ischemic stroke, and murine bEnd3 cerebral endothelial cells in high glucose condition. In vivo, polyphenols administered by oral gavage for 12 weeks attenuated insulin resistance, hyperglycemia, hyperinsulinemia and dyslipidemia caused by HFD-induced obesity. Polyphenols limited brain infarct, hemorrhagic transformation and BBB disruption aggravated by obesity during stroke. Polyphenols exhibited anti-inflammatory and antioxidant properties by reducing IL-1ß, IL-6, MCP-1, TNF-α and Nrf2 overproduction as well as total SOD activity elevation at the cerebral or peripheral levels in obese mice. In vitro, polyphenols decreased MMP-2 activity that correlated with MCP-1 secretion and ROS intracellular levels in hyperglycemic condition. Protective effects of polyphenols were linked to their bioavailability with evidence for circulating metabolites including caffeic acid, quercetin and hippuric acid. Altogether, these findings show that antioxidant polyphenols reduced cerebrovascular, inflammatory and metabolic disorders aggravated by obesity in a mouse model of stroke. It will be relevant to assess polyphenol-based strategies to improve the clinical consequences of stroke in the context of obesity and diabetes.

Protective Effects of Antioxidant Polyphenols against Hyperglycemia-Mediated Alterations in Cerebral Endothelial Cells and a Mouse Stroke Model.

SCOPE: Hyperglycemia alters cerebral endothelial cell and blood-brain barrier functions, aggravating cerebrovascular complications such as stroke during diabetes. Redox and inflammatory changes play a causal role. This study evaluates polyphenol protective effects in cerebral endothelial cells and a mouse stroke model during hyperglycemia. METHODS AND RESULTS: Murine bEnd.3 cerebral endothelial cells and a mouse stroke model are exposed to a characterized, polyphenol-rich extract of Antirhea borbonica or its predominant constituent caffeic acid, during hyperglycemia. Polyphenol effects on redox, inflammatory and vasoactive markers, infarct volume, and hemorrhagic transformation are determined. In vitro, polyphenols improve reactive oxygen species levels, Cu/Zn superoxide dismutase activity, and both NAPDH oxidase 4 and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression deregulated by high glucose. Polyphenols reduce Nrf2 nuclear translocation and counteract nuclear factor-ĸappa B activation, interleukin-6 secretion, and the altered production of vasoactive markers mediated by high glucose. In vivo, polyphenols reduce cerebral infarct volume and hemorrhagic transformation aggravated by hyperglycemia. Polyphenols attenuate redox changes, increase vascular endothelial-Cadherin production, and decrease neuro-inflammation in the infarcted hemisphere. CONCLUSION: Polyphenols protect against hyperglycemia-mediated alterations in cerebral endothelial cells and a mouse stroke model. It is relevant to assess polyphenol benefits to improve cerebrovascular damages during diabetes.

Maternal stress during late gestation has moderate but long-lasting effects on the immune system of the piglets.

Events acting prenatally on developing foetuses are important determinants for disorders later in life. Prenatal stress (PNS) is one of these events. The purpose of this study was to determine the consequences of a repeated social stress applied during late gestation of the pregnant gilt on the immune system and hypothalamo-pituitary-adrenal (HPA) axis activity of the piglets from birth to two months of age. Pregnant gilts were submitted to repeated social stress which was induced by housing unfamiliar gilts in pairs modified twice a week during 4 weeks between days 77 and 105 of gestation (S group, n=18). Control gilts were housed in stable pairs during the same period (C group, n=18). Blood cortisol, haptoglobin and IgG levels, immune cell counts, mitogen-induced whole-blood proliferation and TNF-alpha production were evaluated in piglets at 4 days of age (D4), before and after weaning (D26 and 28) and before and after relocation to a new building (D60 and 62). We found that PNS did not affect growth rate of the progeny. It decreased the relative weight of adrenal glands on D4 (P<0.05) but plasma cortisol levels were similar in both groups at all ages. IgG levels in colostrum and in the serum of piglets were not affected. PNS decreased the total numbers of white blood cells, lymphocytes and granulocytes from D26 to D60 (P<0.05), the CD4(+)/CD8(+) T cell ratio on D4 (P<0.05), and LPS induced-TNF-alpha production on D60 (P<0.05). PNS increased the ConA-induced lymphocyte proliferation on D4 and D60 and the PWM-induced proliferation on D60 (P<0.05). Our results demonstrate that a repeated social stress applied to pregnant sows during late gestation can induce long-lasting effects on several parameters of the immune function of the offspring. These effects are not due to modifications of the HPA axis activity and may impair the abilities of the piglets to efficiently react against infections during the suckling period and around weaning.