Grape Seed Flour Extends Longevity by Improving Multi-Organ Dysfunction and Age-Associated Oxidative Stress and Inflammation in Healthy Rat.

According to the free-radical theory of aging, accumulation of reactive oxygen species (ROS) within mitochondria throughout life span leads to impairment of the main biological macromolecules as DNA, lipids, and proteins, which might be at the basis of premature aging. One way to test experimentally such a hypothesis consists in intervention studies using antioxidant nutrients aimed at limiting or inhibiting ROS production that should be able to reduce the aging rate and disease pathogenesis. Grape seed flour (GSF) contains a high level of phytochemicals among which bioactive polyphenols exhibit numerous biological properties and beneficial health effects as antioxidant, anti-inflammatory, anticarcinogenic, multi-organ (heart, liver, kidney, and brain among others) protective. The present study aimed at testing the ability of high dosing GSF (4 g/kg bw) used as a nutritional supplement to slow down aging and prolong life span of Wistar rats when administered from early life (1-month-old animals) till their natural death. Data clearly show that high-dose GSF extends organism longevity and health span by improving multi-organ damages, systemic fueling metabolism declines, and alleviated oxidative stress and inflammation in aging rats. Our data support the extending longevity effect of grape polyphenols especially when used as high dosing nutritional supplement or as natural medicine whose appropriate galenic form as solid lipid nanoformulation is currently under investigation.

Safety evaluation, anti-oxidative and anti-inflammatory effects of subchronically dietary supplemented high dosing grape seed powder (GSP) to healthy rat.

Grape seed powder (GSP) contains high amount of bioactive polyphenols usually used as nutritional supplement or food preservatives due to their antioxidant and scavenging properties. The purpose of the present work was to evaluate the safety of increasing dosage GSP (w/w) of 0.5%, 5%, 10% and 20% corresponding to 0.4, 4, 8 and 16 g/kg bw respectively, when administered sub-chronically to Wistar rats in a 2 month-repeated dosing oral toxicity trial. Overally GSP had no effect on food intake, decreased body weight gain without affecting brain, liver, heart or kidney relative weight. GSP did not alter haematology except an increase in platelets, slightly decreased plasma transaminases, creatinine, urea and xanthine oxidase activity, without affecting uricemia, glycemia, triglyceridemia and cholesterolemia. GSP did not affect intracellular mediators as calcium, free iron or H2O2, but exerted real anti-oxidative properties in the four selected organs as assessed by lower lipoperoxidation and carbonylation, higher non protein thiols and antioxidant enzyme activities as CAT, GPx and SOD. Besides GSP exerted anti-inflammatory properties as supported by lower plasma IL17 A and CRP and higher IL10 and adiponectin. Histopathologically GSP provoked the dilation of heart and kidney arterioles and increased the size of the hippocampal dentate gyrus reflecting higher neurogenesis as assessed by Ki-67 labeling. Under the experimental conditions of the current study, GSP appeared as highly safe even when administered at very high dosage and could find potential applications in a variety of biotic or abiotic stresses-induced multi-organ dysfunction.

Supplementation of grape seed and skin extract to orlistat therapy prevents high-fat diet-induced murine spleen lipotoxicity.

Spleen is the largest lymphoid organ and obesity is related to an elevated risk of immunity dysfunction. The mechanism whereby fat adversely affects the spleen is poorly understood. This study was designed to assess the effectiveness of grape seed and skin extract (GSSE) and orlistat (Xenical, Xe) on high-fat diet (HFD)-induced spleen lipotoxicity. Obese rats were treated either with GSSE (4 g/kg body weight) or Xe (2 mg/kg body weight) or GSSE+Xe and monitored for weight loss for 3 months. Animals were then sacrificed and their spleen used for the evaluation of lipotoxicity-induced oxidative stress and inflammation as well as the putative protection afforded by GSSE and Xe treatment. HFD induced body weight gain and glycogen accumulation into the spleen; ectopic deposition of cholesterol and triglycerides and an oxidative stress characterized by increased lipoperoxidation and carbonylation; inhibition of antioxidant enzyme activities, such as catalase, glutathione peroxidase, and superoxide dismutase; depletion of zinc and copper; and a concomitant increase in calcium. HFD also increased plasma pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17A, tumour necrosis factor alpha, and C-reactive protein, and decreased plasma IL-10 and adiponectin. Importantly, GSSE counteracted all the deleterious effects of HFD on spleen (i.e., lipotoxicity, oxidative stress, and inflammation) and the best protection was obtained when combining Xe+GSSE. Combining GSSE with Xe prevented against fat-induced spleen lipotoxicity, oxidative stress, and inflammation; this combination may be beneficial in other diseases related to the spleen.