• Sharon Jessica Fandy Food Technology Department, Faculty of Engineering, Bina Nusantara University, Jakarta, Indonesia



Grape seed extract, Parkinson’s disease, neuroprotective, systematic review


Parkinson’s disease (PD) is the most common neurological disease globally, only second to Alzheimer’s disease. One of the emerging treatments for PD is nutraceuticals. Grape seed extract (GSE) has a high concentration of polyphenolic compounds possessing antioxidant and neuroprotective capacity that may be valuable for neurodegenerative diseases. So far, there is no review summarizing the neuroprotective effect of GSE on PD, even though it is crucial to provide an insight into GSE as a potential natural treatment for PD. This systematic review aims to summarize the neuroprotective effect of grape seed extract (GSE) in Parkinson’s Disease in vivo and in vitro and their mechanism. The author performed a literature search using PubMed, Science Direct, Scopus, Sinta, and Garuda databases with keywords comprising “Neuroprotective”, “Grape Seed,” and “Parkinson’s disease.” Out of 1611 studies retrieved, 20 articles fit the inclusion criteria and became the basis for this review. The author analyzed and extracted the records regarding the neuroprotective effect and potential anti-PD properties from the studies. The analysis summarized that GSE could significantly improve the biological hallmarks of PD with numerous mechanisms, including antioxidant, anti-inflammation, protection of dopaminergic neurons, anti-amyloid effect, anti-apoptotic, neurogenesis, and synaptogenesis. Although the precise mechanism underlying PD is still elusive, treatment should target not only a single cause of PD but instead several pathways that could lead to the disease. In conclusion, GSE should be considered a potential nutraceutical in clinical trials to prevent and alleviate Parkinson’s disease by multiple mechanisms.


Feigin VL, Abajobir AA, Abate KH, Abd-Allah F, Abdulle AM, Abera SF, et al. Global, regional, and national burden of neurological disorders during 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol [Internet]; 2017. 16(11):877–97. Available from:

DeMaagd G, Philip A. Parkinson’s disease and its management: Part 1: Disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. Pharm Ther [Internet]; 2015. Aug 1;40(8):504.

Dorsey ER, Elbaz A, Nichols E, Abd-Allah F, Abdelalim A, Geleto M, et al. Global, regional, and national burden of Parkinson’s disease, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol [Internet]; 2018. 17(11):939–53.

Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis [Internet]; 2013. 3(4):461.

Rizek P, Kumar N, Jog MS. An update on the diagnosis and treatment of Parkinson disease. CMAJ [Internet]; 2016 Nov 1;188(16):1157–65.

Borovac JA. Focus: The aging brain: Side effects of a dopamine agonist therapy for Parkinson’s disease: A mini-review of clinical pharmacology. Yale J Biol Med [Internet]; 2016. 89(1):37–47.

Hang L, Basil AH, Lim KL. Nutraceuticals in Parkinson’s Disease. Neuromolecular Med [Internet]; 2016. 18(31):306–21.

Ren X, Chen JF. Caffeine and Parkinson’s disease: Multiple benefits and emerging mechanisms. Front Neurosci [Internet]; 2020. 14:602697. Available from:

Subash S, Essa MM, Al-Adawi S, Memon MA, Manivasagam T, Akbar M. Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regen Res [Internet]; 2014. 9(16):1557.

Ong WY, Farooqui T, Koh HL, Farooqui AA, Ling EA. Protective effects of ginseng on neurological disorders. Front Aging Neurosci [Internet]; 2015. 7:129. Available from: saponins%2C the main constituents,neuroprotective effects in Parkinson%27s disease.

Malar DS, Prasanth MI, Brimson JM, Sharika R, Sivamaruthi BS, Chaiyasut C, et al. Neuroprotective properties of green tea (Camellia sinensis) in Parkinson’s disease: A review. Mol [Internet]; 2020. 25(17):3926. Available from:

El Nebrisi E. Neuroprotective activities of curcumin in Parkinson’s disease: A review of the literature. Int J Mol Sci [Internet]; 2021. 22(20). Available from:

Farkhondeh T, Samarghandian S, Shahri AMP, Samini F. The neuroprotective effects of thymoquinone: a review. Dose Response [Internet]; 2018. 16(2). Available from:

Teixeira A, Baenas N, Dominguez-Perles R, Barros A, Rosa E, Moreno DA, et al. Natural bioactive compounds from winery by-products as health promoters: A review. Int J Mol Sci [Internet]; 2014. 15(9):15638–78. Available from:

Datla KP, Zbarsky V, Rai D, Parkar S, Osakabe N, Aruoma OI, et al. Short-term supplementation with plant extracts rich in flavonoids protect nigrostriatal dopaminergic neurons in a rat model of Parkinson’s disease. J Am Coll Nutr [Internet]; 2007. 26(4):341–9. Available from:

Pasinetti GM, Ho L. Role of grape seed polyphenols in Alzheimer’s disease neuropathology. Nutr Diet Suppl [Internet]; 2010. 2010(2):97. Available from: /pmc/articles/PMC3666959/

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ [Internet]; 2021. 372. Available from:

Gray R. Empty systematic reviews: Identifying gaps in knowledge or a waste of time and effort? Nurse Author Ed [Internet]; 2021. 31(2):42–4. Available from:

Vingill S, Connor-Robson N, Wade-Martins R. Are rodent models of Parkinson’s disease behaving as they should? Behav Brain Res [Internet]; 2018. 352:133–41. Available from:

Sarkaki A, Eidypour Z, Motamedi F, Keramati K, Farbood Y. Motor disturbances and thalamic electrical power of frequency bands’ improve by grape seed extract in animal model of Parkinson’s disease. Avicenna J Phytomedicine [Internet]; 2012. 2(4):222–32. Available from:

Gong X, Xu L, Fang X, Zhao X, Du Y, Wu H, et al. Protective effects of grape seed procyanidin on isoflurane-induced cognitive impairment in mice. Pharm Biol [Internet]; 2020. 58(1):200–7. Available from:

Mervat AA, El-Nabarawy SK, Morsy FA, Ahmed HH, Ali NA. New insights on the neuroprotective potential of grape seed extract: Evidences-based on experimental animal study. Der Pharma Chem [Internet]; 2016. 8(18):204–18.

Calabrese V, Santoro A, Monti D, Crupi R, Di Paola R, Latteri S, et al. Aging and Parkinson’s disease: inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis. Free Radic Biol Med [Internet]; 2018. 115:80–91. Available from:

Mhyre TR, Boyd JT, Hamill RW, Maguire-Zeiss KA. Parkinson’s Disease. Subcell Biochem [Internet]; 2012. 65:389. Available from: /pmc/articles/PMC4372387/

Gupta M, Dey S, Marbaniang D, Pal P, Ray S, Mazumder B. Grape seed extract: Having a potential health benefits. J Food Sci Technol [Internet]; 2019. 57(4):1205–15.

Abdel-Rahman M, Ahmed HH, Moniem AEA. Ameliorative effect of grape seed extract against rotenone-induced neurotoxicity in adult male albino rats; 2008. 1–30. Available from:

Balu M, Sangeetha P, Haripriya D, Panneerselvam C. Rejuvenation of antioxidant system in central nervous system of aged rats by grape seed extract. Neurosci Lett [Internet]; 2005. 383(3):295–300. Available from: findings demonstrated that grape,nervous system of aged rats.

Balu M, Sangeetha P, Murali G, Panneerselvam C. Age-related oxidative protein damages in central nervous system of rats: modulatory role of grape seed extract. Int J Dev Neurosci [Internet]; 2005. 23(6):501–7. Available from:

Balu M, Sangeetha P, Murali G, Panneerselvam C. Modulatory role of grape seed extract on age-related oxidative dna damage in central nervous system of rats. Brain Res Bull [Internet]; 2006. 68(6):469–73. Available from:

Fujishita K, Ozawa T, Shibata K, Tanabe S, Sato Y, Hisamoto M, et al. Grape seed extract acting on astrocytes reveals neuronal protection against oxidative stress via interleukin-6-mediated mechanisms. Cell Mol Neurobiol [Internet]; 2009. 29(8):1121–9. Available from:

Hassan SN, Hassan SMA, Saleh N, Maarof NNN. Neuro-glial modulatory roles of black and red grape seed extract-derived polyphenols (Vitis vinifera) in normal aged albino mice’s brain. Pak Vet J [Internet]; 2022. 8318(2):1–9. Available from:

Liu Y, Pukala TL, Musgrave IF, Williams DM, Dehle FC, Carver JA. Gallic Acid is the major component of grape seed extract that inhibits amyloid fibril formation. Bioorganic Med Chem Lett [Internet]; 2013. 23(23):6336–40. Available from: the components of grape,κ-CN to pheochromocytoma12 cells.

Ma J, Gao SS, Yang HJ, Wang M, Cheng BF, Feng ZW, et al. Neuroprotective effects of proanthocyanidins, natural flavonoids derived from plants, on rotenone-induced oxidative stress and apoptotic cell death in human neuroblastoma SH-SY5Y cells. Front Neurosci [Internet]; 2018. 12(369):1–10. Available from:

Rastegar-moghaddam SH, Bigham M, Hosseini M, Ebrahimzadeh-bideskan A, Malvandi AM, Mohammadipour A. Grape seed extract effects on hippocampal neurogenesis, synaptogenesis and dark neurons production in old mice. can this extract improve learning and memory in aged animals? Nutr Neurosci [Internet]; 2021. 1–11. Available from: tests showed that GSE,and increase memory and learning.

Rodrigues P de A, Maia de Morais S, Fernandes Pereira J, Costa de Assis AL, Aragão Alves A, Benjamin SR, et al. Neuroprotective effects of proanthocyanidins of grape seed extracts against oxidative stress and apoptosis induced by 6-hydroxydopamine in PC12 cells. Conjecturas [Internet]; 2021. 21(2):68–86. Available from:

Sarkaki A, Farbood Y, Badavi M. The effect of grape seed extract (GSE) on spatial memory in aged male rats. Pakistan J Med Sci [Internet]; 2007. 23(4):561–5. Available from:

Strathearn KE, Yousef GG, Grace MH, Roy SL, Tambe MA, Ferruzzi MG, et al. Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinson’s Disease. Brain Res [Internet]; 2014. 1555:60–77. Available from:

Tikhonova MA, Tikhonova NG, Tenditnik MV, Ovsyukova MV, Akopyan AA, Dubrovina NI, et al. Effects of grape polyphenols on the life span and neuroinflammatory alterations related to neurodegenerative Parkinson disease-like disturbances in mice. Molecules [Internet]; 2020. Nov 16. 25(22):5339. Available from:

Trapani A, Guerra L, Corbo F, Castellani S, Sanna E, Capobianco L, et al. Cyto/biocompatibility of dopamine combined with the antioxidant grape seed-derived polyphenol compounds in solid lipid nanoparticles. Molecules [Internet]; 2021. 26(4):916. Available from:

Wu TH, Liao JH, Hsu FL, Wu HR, Shen CK, Yuann JMP, et al. Grape seed proanthocyanidin extract chelates iron and attenuates the toxic effects of 6-hydroxydopamine: implications for Parkinson’s disease. J Food Biochem [Internet]; 2010. 34(2):244–62. Available from:

Youssef S Ben, Brisson G, Doucet-Beaupré H, Castonguay AM, Gora C, Amri M, et al. Neuroprotective benefits of grape seed and skin extract in a mouse model of Parkinson’s disease. Nutr Neurosci [Internet]; 2021. 24(3):197–211. Available from: we found that GSSE,in a model of PD.

Pieper D, Puljak L. Language restrictions in systematic reviews should not be imposed in the search strategy but in the eligibility criteria if necessary. J Clin Epidemiol [Internet]; 2021. 132:146–7. Available from:




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