Review Blessings in disguise: Bio-functional benefits of grape seed extracts Javaid Ashraf Nowshehri, Zulfiqar Ali Bhat ⁎, Mohammad Yaseen Shah Department of Pharmaceutical Sciences, University of Kashmir, Srinagar 190006, Jammu and Kashmir, India abstract article info Article history: Received 7 April 2015 Received in revised form 1 August 2015 Accepted 17 August 2015 Available online 29 August 2015 Keywords: Grape seed extract Polyphenol Proanthocyanidin By-product Food industry Bioactivity Grapes (Vitis vinifera) are one of the largest fruit crops in the world, with an annual production of 69 million metric tons. They are a good source of polyphenolic compounds and 60–70% of these polyphenols, especially phenolic acids, ellagitannins, flavonols, flavan-3-ols such as catechins and their isomers, anthocyanins, proanthocyanidins and the stilbene derivative resveratrol exist in grape seeds. Grape seeds comprise 5% by-mass of grapes and are the major industrial by-products from grape processing industries such as grape juice and wine industries. Nowadays, grape seed extracts (GSEs) are receiving increased interest from scientists, nutritionists and consumers as a result of their reported potential health benefits for a variety of disorders. They are widely being con- sumed as a dietary supplement on the basis of their potent anti-oxidant, anti-cancer, antimicrobial, anti-aging, anti- hepatotoxic and anti-inflammatory activities and also have generally recognized as safe status approved by Food and Drug Administration. The beneficial activities of the grape seeds give them the possibility to be used in pharma- ceutical and food industries, for medical treatments and health supplements. The review summarizes current knowledge on the bioactivities of grape seeds and provides tools for those intending to conduct research in this field as large quantities of grape seeds are discarded as waste from the wine making industry. Therefore, this by- product resulting from the grape industry could be utilized through results of diverse studies on their bioactivities. © 2015 Elsevier Ltd. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 2. Chemistry of grape seeds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 3. Extraction of GSPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 4. Bioavilability of GSPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 5. Biological activities of grape seeds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 5.1. Antioxidative activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 5.2. Antidiabetic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 5.3. Anticancer activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 5.4. Cardiovascular protective action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 5.5. Hepatoprotective activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 5.6. Antimicrobial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 5.7. Neuroprotective and anti-aging activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 5.8. Skin protective activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 5.9. Anti-inflammation activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 6. Grape seed extract & other diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 7. Toxicological studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 8. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Food Research International 77 (2015) 333–348 Abbreviations: GSE, Grape seed extract; GSEs, Grape seed extracts; GSPS, Grape seed polyphenols; GSPE, Grape seed proanthocyanidin extract; GSP, Grape seed proanthocyanidin; GSPs, Grape seed proanthocyanidins; DP, Degree of polymerization; SW, Subcritical water; PA, Proanthocyanidin; PAs, Proanthocyanidins; LDL, Low density lipoprotein; GSH, Glutathione; ROS, Reactive oxygen species; MDA, Malondialdehyde; STZ, Streptozotocin; HF, High fructose; AGEs, Advanced glycation end products; PCA, Prostate carcinoma; NF-κB, Nuclear factor kappa B; CRC, Colo-rectal cancer; NO, Nitric oxide; TG, Triglyceride; AST, Aminotransferase; ALT, Alanine aminotransferase; LDH, Lactate dehydrogenase. ⁎ Corresponding author. E-mail addresses: nowshehrija1123@gmail.com (J.A. Nowshehri), zabhat2000@gmail.com (Z.A. Bhat), shahmy1954@gmail.com (M.Y. Shah). 334 335 335 336 336 336 337 338 340 340 341 342 342 342 343 343 344 344 344 http://dx.doi.org/10.1016/j.foodres.2015.08.026 0963-9969/© 2015 Elsevier Ltd. All rights reserved. Contents lists available at ScienceDirect Food Research International journal homepage: www.elsevier.com/locate/foodres