Antioxidant effect of grape seed extract corrects experimental autoimmune encephalomyelitis behavioral dysfunctions, demyelination, and glial activation.

Background and purpose: Multiple sclerosis (MS), a multifactorial autoimmune disease of the central nervous system (CNS), is characterized by demyelination and chronic inflammation, as well as axonal and neuronal loss. There is no cure for MS, and despite a significant improvement in the therapeutic management of patients during the last 20 years, some symptoms are still resistant to treatment, and the evolution of the disease to progressive form seems still ineluctable. The etiology of MS is complex and still not fully understood. However, inflammation is a major driver of physiopathology and oxidative stress contributes to CNS lesions and promotes existing inflammatory response. Plant polyphenols are endowed with many therapeutic benefits through alleviating oxidative stress and inflammation, thus providing neuroprotection in MS. We presently evaluated the curative effect of grape seed extract (GSE) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Experimental approach: Six-week-old C57Bl/6J females were subjected to the EAE paradigm (using myelin oligodendrocyte glycoprotein peptide fragment (35-55), complete Freund's adjuvant, and pertussis toxin) and then chronically treated with GSE from day 10 to day 30 post-induction. Clinical score and body weight were monitored daily, while evaluation of sensitive, motor, cognitive, and anxiety-related behaviors was performed weekly. Then, the GSE effect was evaluated on whole brain and spinal cord samples through the evaluation of oxidative stress damage, antioxidant capacities, myelin alteration, astroglial and microglial proliferation, and sirtuin expression. Key results: Grape seed extract curative chronic treatment corrected the clinical course of EAE, as well as the mechanical hypersensitivity, and avoided the development of EAE mouse thermal cold allodynia. The neuropathological evaluation showed that GSE reduced oxidative stress in the brain and spinal cord by decreasing the lipid and protein oxidation through correction of the three main antioxidant enzyme activities, namely, superoxide dismutase, catalase, and glutathione peroxidase, as well as restoring normal myelin protein expression and correcting microglial and astroglial protein overexpression and sirtuin downregulation. Conclusion and implications: These data strongly support GSE as an effective therapeutic approach in MS treatment.

Characterization, anti-oxidative effect of grape seed powder and in silico affinity profiling of polyphenolic and extra-phenolic compounds for calpain inhibition.

Vitis vinifera grape is a highly cultivated crop and solid wastes generated by the wine industry are largely under exploited. Plentiful studies have intended analyzing the polyphenolic content of grape seeds but characterization of non phenolic compounds is rather scarce. The present study aimed at the selective extraction of lipid, phenolic and aqueous phases from grape seed powder (GSP) in order to establish their intimate composition, as well as their antioxidant and chelating properties underlying partly their biological effects. Major non phenolic compounds identified in the lipid phase were glyceryl-monostearate and 2-monostearin whereas fructofuranose and sucrose were the most abundant in the aqueous phase. Among the most abundant compounds detected in the various phases, the polyphenol quercetin exhibited the best affinity and free binding energy towards the active site of the calcium-dependent protease calpain. Polyphenols likely constitute the bioactive part of GSP that should be exploited as safe modulators of intracellular signaling which is likely at the basis of their health beneficial effects. Nevertheless other compounds as lipids or sugars should be valorized along with polyphenols to improve their bioavailability into highly protected organs as brain or eye.

Protective effect of grape seed and skin extract against high-fat diet-induced dyshomeostasis of energetic metabolism in rat lung.

BACKGROUND: Obesity is currently one of the major epidemics of this millennium and affects poeples throughout the world. It causes multiple systemic complications as it significantly interferes with respiratory function. OBJECTIVE: We aimed in the present work to study the effect of high fat diet (HFD) on lung oxidative stress and energy metabolism alterations, as well as the putative protection afforded by grape seed and skin extract (GSSE). METHODS: We started by characterizing the GSSE and its composition using gas chromatography coupled to mass spectrometry (GC-MS). We used a rat model of high-fat-diet and we evaluated the effect of GSSE on oxidative stress and energetic disturbances induced by HFD. We analyzed the effect of HFD on lung oxidative status by assessing lipid oxidation level, non-protein thiols (NPSH) and superoxide anion level… We also evaluated the effect of HFD on creatine kinase (CK), malate dehydrogenase (MDH) and mitochondrial complex IV. RESULTS: HFD induced body weight gain, increased lung weight and lipid content without affecting insulinemia and dropped adiponectemia. HFD also provoked on lung oxidative stress characterized by increased carbonylation (+ 95%; p = 0.0045), decreased of NPSH (- 32%; p = 0.0291) and inhibition of antioxidant enzyme activities such as glutathione peroxidase (- 25%; p = 0.0074). HFD also altered lung intracellular mediators as superoxide anion O2¯ (+ 59%; p = 0.0027) and increased lung xanthine oxidase activity (+ 27%; p = 0.0122). HFD induced copper depletion (- 24%; p = 0.0498) and lead (- 51%: p = 0.0490) from the lung. Correlatively HFD decreased the copper associated enzyme tyrosinase (- 29%; p = 0.0500) and decreased glutamine synthetase activity (- 31%; p = 0.0027). HFD altered also lung energy metabolism by increasing CK activity (+ 22%; p = 0.0108) and decreasing MDH and mitochondrial complex IV activities (- 28%; p = 0.0120, - 31%; p = 0.0086 respectively). Importantly all these alterations were efficiently corrected with GSSE treatment. CONCLUSION: In conclusion, GSSE has the potential to alleviate the deleterious lipotoxic effect of HFD on lung and it could find potential application in the protection against HFD-induced lung complications.