Planta Med 2019; 85(17): 1292-1303
DOI: 10.1055/a-0947-5712
Biological and Pharmacological Activity
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Neuroprotective Potential of Ginkgo biloba in Retinal Diseases

Isabel Martínez-Solís
1   Biomedical Sciences Institute, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
2   Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
3   Botanical Garden, University of Valencia, Valencia, Spain
,
Nuria Acero
4   Department of Pharmaceutical and Health Sciences, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain
,
Francisco Bosch-Morell
1   Biomedical Sciences Institute, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
5   Department of Biomedical Sciences, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
,
Encarna Castillo
2   Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
,
María Eugenia González-Rosende
2   Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
,
Dolores Muñoz-Mingarro
6   Department of Chemistry and Biochemistry, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain
,
Teresa Ortega
7   Department of Pharmacology and Botany. Universidad Complutense de Madrid, Madrid, Spain
,
María Amparo Sanahuja
2   Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
,
Victoria Villagrasa
2   Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
› Author Affiliations
Further Information

Publication History

received 22 March 2019
revised 22 May 2019

accepted 02 June 2019

Publication Date:
02 July 2019 (online)

Abstract

Like other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.

 
  • References

  • 1 Carelli V, La Morgia C, Ross-Cisneros FN, Sadun AA. Optic neuropathies: the tip of the neurodegeneration iceberg. Hum Mol Genet 2017; 26: 139-150
  • 2 Schmidt KG, Bergert H, Funk RHW. Neurodegenerative diseases of the retina and potential for protection and recovery. Curr Neuropharmacol 2008; 6: 164-178
  • 3 Chhunchha B, Singh P, Singh DP, Kubo E. Ginkgolic acid rescues lens epithelial cells from injury caused by redox regulated-aberrant sumoylation signaling by reviving Prdx6 and Sp1 expression and activities. Int J Mol Sci 2018; 19: E3520
  • 4 Kortuem K, Geiger LK, Levin LA. Differential susceptibility of retinal ganglion cells to reactive oxygen species. Invest Ophthalmol Vis Sci 2000; 41: 3176-3182
  • 5 Rohowetz LJ, Kraus JG, Koulen P. Reactive oxygen species-mediated damage of retinal neurons: drug development targets for therapies of chronic neurodegeneration of the retina. Int J Mol Sci 2018; 19: 3362
  • 6 Vasudevan SK, Gupta V, Crowston JG. Neuroprotection in glaucoma. Indian J Ophtalmol 2011; 59: S102-S113
  • 7 He Y, Leung KW, Zhang YH, Duan S, Zhong XF, Jiang RZ, Peng Z, Tombran-Tink J, Ge J. Mitochondrial complex I defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: protection by antioxidants. Invest Ophthalmol Vis Sci 2008; 49: 1447-1458
  • 8 Li C, Miao X, Li F, Wang S, Liu Q, Wang Y, Sun J. Oxidative stress-related mechanisms and antioxidant therapy in diabetic retinopathy. Oxid Med Cell Longev 2017; 2010: 9702820
  • 9 Castilho Á, Aveleira CA, Leal EC, Simões NF, Fernandes CR, Meirinhos RI, Baptista FI, Ambrósio AF. Heme oxigenase-1 protects retinal endothelial cells against high glucose and oxidative/nitrosative stress-induced toxicity. PLoS One 2012; 7: e42428
  • 10 Whiteside CI. Cellular mechanisms and treatment of diabetes vascular complications converge on reactive oxygen species. Curr Hypertens Rep 2005; 7: 148-154
  • 11 Droy-Lefaix MT. Effect of the antioxidant action of Ginkgo biloba extract (EGb 761) on aging and oxidative stress. Age 1997; 20: 141-149
  • 12 Datta S, Cano M, Ebrahimi K, Wanh L, Handa JT. The impact of oxidative stress and inflammation on the RPE degeneration on non-neovascular AMD. Prog Retin Eye Res 2017; 60: 201-218
  • 13 Osborne NN, Casson RJ, Wood JP, Chidlow G, Graham M, Melena J. Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res 2004; 23: 91-147
  • 14 Roh MI, Murakami Y, Thanos A, Vavvas DG, Miller JW. Edaravone, an ROS scavenger, ameliorates photoreceptor cell death after experimental retinal detachment. Invest Ophthalmol Vis Sci 2011; 52: 3825-3831
  • 15 Montes P, Ruiz-Sánchez E, Rojas C, Rojas P. Ginkgo biloba extract 761: a review of basic studies and potential clinical use in psychiatric disorders. CNS Neurol Disord Drug Targets 2015; 14: 132-149
  • 16 Yin B, Xu Y, Wei R, Luo B. Ginkgo biloba on focal cerebral ischemia: a systematic review and meta-analysis. Am J Chin Med 2014; 42: 769-783
  • 17 Cybulska-Heinrich AK, Mozaffarieh M, Flammer J. Ginkgo biloba: an adjuvant therapy for progressive normal and high tension glaucoma. Mol Vis 2012; 18: 390-402
  • 18 Beck S, Stengel J. Mass spectrometric imaging of flavonoid glycosides and biflavonoids in Ginkgo biloba L. Phytochemistry 2016; 130: 201-206
  • 19 Ahlemeyer B, Krieglstein J. Neuroprotective effects of Ginkgo biloba extracts. CMLS Cell Mol Life Sci 2003; 60: 1779-1792
  • 20 Ahlemeyer B, Selke D, Schaper C, Klumpp S, Krieglstein J. Ginkgolic acids induce neuronal death and activate protein phosphatase type-2C. Eur J Pharmacol 2001; 430: 1-7
  • 21 Mojaverrostami S, Bojnordi MN, Ghasemi-Kasman M, Ebrahimzadeh MA, Hamidabadi HG. A review of herbal therapy in multiple sclerosis. Adv Pharm Bull 2018; 8: 575-590
  • 22 Bachinskaya N, Hoerr R, Ihl R. Alleviating neuropsychiatric symptoms in dementia: the effects of Ginkgo biloba extract EGb 761. Findings from a randomized controlled trial. Neuropsychiatr Dis Treat 2011; 7: 209-215
  • 23 Yuan Q, Wang CW, Shi J, Lin ZX. Effects of Ginkgo biloba on dementia: An overview of systematic reviews. J Ethnopharmacol 2017; 195: 1-9
  • 24 Wu Y, Li S, Cui W, Zu X, Du J, Wang F. Ginkgo biloba extract improves coronary blood flow in healthy elderly adults: role of endothelium-dependent vasodilation. Phytomedicine 2008; 15: 164-169
  • 25 Kubota Y, Tanaka N, Kagota S, Nakamura K, Kunitomo M, Umegaki K, Shinozuka K. Effects of Ginkgo biloba extract on blood pressure and vascular endothelial response by acetylcholine in spontaneously hypertensive rats. J Pharm Pharmacol 2006; 58: 243-249
  • 26 McKenna DJ, Jones K, Highes K. Efficacy, safety, and use of Ginkgo biloba in clinical and preclinical applications. Altern Ther Health Med 2001; 7: 70-86
  • 27 García-Layana A, Cabrera-López F, García-Arumí J, Arias-Barquet L, Ruiz-Moreno J. Early and intermediate age-related macular degeneration: update and clinical review. Clin Interv Aging 2017; 12: 1579-1587
  • 28 Ratnapriya R, Chew EY. Age-related macular degeneration-clinical review and genetics update. Clin Genet 2013; 84: 160-166
  • 29 Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med 2008; 358: 2606-2617
  • 30 Lawrenson JG, Evans JR. Advice about diet and smoking for people with or at risk of age-related macular degeneration: a cross-sectional survey of eye care professionals in the UK. BMC Public Health 2013; 13: 564
  • 31 National Eye Institute (NEI), National Institutes of Health (NIH). Research today…vision tomorrow. Age-related macular degeneration (AMD). Available at: https://nei.nih.gov/eyedata/amd Accessed December 27, 2018
  • 32 Wong WL, Su X, Li X, Cheung CMG, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet 2014; 2: e106-e116
  • 33 National Eye Institute (NEI), National Institutes of Health (NIH). Research today … vision tomorrow. Facts about age-related macular degeneration. Available at: https://nei.nih.gov/health/maculardegen/armd_facts Accessed December 28, 2018
  • 34 World Health Organization. Blindness and vision impairment prevention. Priority eye diseases. Available at: https://www.who.int/blindness/causes/priority/en/index7.html Accessed December 28, 2018
  • 35 Athanasiou D, Aguila M, Bevilacqua D, Novoselov SS, Parfitt DA, Cheetham MEM. The cell stress machinery and retinal degeneration. FEBS Lett 2013; 587: 2008-2017
  • 36 Gorusupudi A, Nelson K, Bernstein PS. The eye-related eye disease 2 study: micronutrients in the treatment of macular degeneration. Adv Nutr 2017; 8: 40-53
  • 37 Zhou YY, Chen CZ, Su Y, Li L, Yi ZH, Qi H, Weng M, Xing YQ. Effect of EGb761 on light-damaged retinal pigment epithelial cells. Int J Ophthalmol 2014; 7: 8-13
  • 38 Yoon SM, Lee BL, Guo YR, Choung SY. Preventive effect of Vaccinium uliginosum L. extract and its fractions on age-related macular degeneration and its action mechanisms. Arch Pharm Res 2016; 39: 21-32
  • 39 Nagineni CN, Raju R, Nagineni KK, Kommineni VK, Cherukuri A, Kutty RK, Hooks JJ, Detrick B. Resveratrol suppresses expression of VEGF by human retinal pigment epithelial cells: potential nutraceutical for age-related macular degeneration. Aging Dis 2014; 5: 88-100
  • 40 Englander M, Kaiser PK. Combination therapy for the treatment of neovascular age-related macular degeneration. Curr Opin Ophthalmol 2013; 24: 233-238
  • 41 Kaiser PK, Do DV. Ranibizumab for the treatment of neovascular AMD. Int J Clin Prac 2007; 61: 501-509
  • 42 Bartlett H, Eperjesi F. Nutrition and age-related ocular disease. Curr Top Nutraceutical Res 2005; 3: 231-242
  • 43 Bartlett H, Eperjesi F. An ideal ocular nutritional supplement?. Ophthalmic Physiol Opt 2004; 24: 339-349
  • 44 Pinazo-Durán MD, Gómez-Ulla F, Arias L, Araiz J, Casaroli-Marano R, Gallego-Pinazo R, García-Medina JJ, López-Gálvez MI, Manzanas L, Salas A, Zapata M, Diaz-Llopis M, García-Layana A. Do nutritional supplements have a role in age macular degeneration prevention?. J Ophthalmol 2014; 2014: 901686
  • 45 Krishnadev N, Meleth AD, Chew E. Nutrition supplements for age-related macular degeneration. Curr Opin Ophthalmol 2010; 21: 184-189
  • 46 Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev 2017; (07) CD000254
  • 47 Evans JR, Lawrenson JG. A review of the evidence for dietary interventions in preventing or slowing the progression of age-related macular degeneration. Ophthalmic Physiol Opt 2014; 34: 390-396
  • 48 Wilkinson JT, Fraunfelder FW. Use of herbal medicines and nutritional supplements in ocular disorders: an evidence-based review. Drugs 2011; 71: 2421-2434
  • 49 Chu K, Pang C. Herbal molecules in eye diseases. Taiwan J Ophthalmol 2014; 4: 103-109
  • 50 Rhone M, Basu A. Phytochemicals and age-related eye diseases. Nutr Rev 2008; 66: 465-472
  • 51 Abdel-Aal ESM, Akhtar H, Zaheer K, Ali R. Dietary sources of lutein and zeaxanthin carotenoids and their role in eye health. Nutrients 2013; 5: 1169-1185
  • 52 Evans JR. Ginkgo biloba extract for age-related macular degeneration. Cochrane Database Syst Rev 2013; (01) CD001775
  • 53 Abu-Amero KK, Kondkar AA, Chalam KV. Resveratrol and ophthalmic diseases. Nutrients 2016; 8: 200
  • 54 Ishihara T, Kaidzu S, Kimura H, Koyama Y, Matsuoka Y, Ohira A. Protective effect of highly polymeric A-type proanthocyanidins from seed shells of japanese horse chestnut (Aesculus turbinata Blume) against light-induced oxidative damage in rat retina. Nutrients 2018; 10: 593
  • 55 Chang CH, Chiu HF, Han YC, Chen IH, Shen YC, Venkatakrishnan K, Wang CK. Photoprotective effects of cranberry juice and its various fractions against blue light-induced impairment in human retinal pigment epithelial cells. Pharm Biol 2017; 55: 571-580
  • 56 Osada H, Okamoto T, Kawashima H, Toda E, Miyake S, Nagai N, Kobayashi S, Tsubota K, Ozawa Y. Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina. PLoS One 2017; 12: e0178627
  • 57 Park SI, Lee EH, Kim SR, Jang YP. Anti-apoptotic effects of Curcuma longa L. extract and its curcuminoids against blue light-induced cytotoxicity in A2E-laden human retinal pigment epithelial cells. J Pharm Pharmacol 2017; 69: 334-340
  • 58 Pescosolido N, Giannotti R, Plateroti AM, Pascarella A, Nebbioso M. Curcumin: therapeutical potential in ophthalmology. Planta Med 2014; 80: 249-254
  • 59 Sin HP, Liu DT, Lam DS. Lifestyle modification, nutritional and vitamins supplements for age-related macular degeneration. Acta Ophthalmol 2013; 91: 6-11
  • 60 Mohanta TK, Tamboli Y, Zubaidha PK. Phytochemical and medicinal importance of Ginkgo biloba L. Nat Prod Res 2014; 28: 746-752
  • 61 Diamond BJ, Shiflett SC, Feiwel N, Matheis RJ, Noskin O, Richards JA, Schoenberger NE. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil 2000; 81: 668-678
  • 62 Singh M, Mathur G, Jain CK, Mathur A. Phyto-pharmacological potential of Ginkgo biloba: a review. J Pharm Res 2012; 5: 5028-5030
  • 63 Dubey AK, Shankar PR, Upadhyaya D, Deshpande VY. Ginkgo biloba – an appraisal. Kathmandu Univ Med J (KUMJ) 2003; 2: 225-229
  • 64 Clostre F. Ginkgo biloba extract (EGb 761). State of knowledge in the dawn of the year 2000. Ann Pharm Fr 1999; 57 (Suppl. 01) 1S8-88
  • 65 Droy-Lefaix MT, Cluzel J, Menerath JM, Bonhomme B, Doly M. Antioxidant effect of a Ginkgo biloba extract (EGb 761) on the retina. Int J Tissue React 1995; 17: 93-100
  • 66 Pritz-Hohmeier S, Chao TI, Krenzlin J, Reichenbach A. Effect of in vivo application of the Ginkgo biloba extract EGb 761 (Rökan) on the susceptibility of mammalian retinal cells to proteolytic enzymes. Ophthalmic Res 1994; 26: 80-86
  • 67 Spadiene A, Savickiene N, Jurgeviciene N, Zalinkevicius R, Norkus A, Ostrauskas R, Skesters A, Silova A, Rodovicius H, Francaite-Daugeliene M. Effect of ginkgo extract on eye microcirculation in patients with diabetes. Cent Eur J Med 2013; 8: 736-741
  • 68 MacVie OP, Harney BA. Vitreous haemorrhage associated with Gingko biloba use in a patient with age related macular disease. Br J Ophthalmol 2005; 89: 1368-1387
  • 69 Lebuisson DA, Leroy L, Rigal G. Treatment of senile macular degeneration with Ginkgo biloba extract. A preliminary double-blind drug vs. placebo study. Presse Med 1986; 15: 1556-1558
  • 70 Fies P, Dienel A. Ginkgo extract in impaired vision-treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration. Wien Med Wochenschr 2002; 152: 423-426
  • 71 Jalali S. Retinal detachment. Comm Eye Health 2003; 16: 25-26
  • 72 Dunaief JL, Dentchev T, Ying GS, Milam AH. The role of apoptosis in age-related macular degeneration. Arch Ophthalmol 2002; 120: 1435-1442
  • 73 Barber AJ, Lieth E, Khin SA, Antonetti D, Buchanan AG, Gardner TW. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 1998; 102: 783-791
  • 74 Huynh TP, Mann SN, Mandal NA. Botanical compounds: effects on major eye diseases. Evid Based Complement Alternat Med 2013; 2013: 549174
  • 75 Fernández-Sánchez L, Lax P, Noailles A, Angulo A, Maneu V, Cuenca N. Natural compounds from saffron and bear bile prevent vision loss and retinal degeneration. Molecules 2015; 20: 13875-13893
  • 76 Marcocci L, Maguire JJ, Droy-Lefaix MT, Packer L. The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761. Biochem Biophys Res Commun 1994; 201: 748-755
  • 77 Maclennan KM, Darlington CL, Smith PF. The CNS effects of Ginkgo biloba extracts and ginkgolide B. Prog Neurobiol 2002; 67: 235-257
  • 78 Ma K, Xu L, Zhang H, Zhang S, Pu M, Jonas B. The effect of Ginkgo biloba on the rat retinal ganglion cell survival in the optic nerve crush mode. Acta Ophthalmol 2010; 88: 553-557
  • 79 Falsini B, Piccardi M, Minnella A, Savastano C, Capoluongo E, Fadda A, Balestrazzi E, Maccarone R, Bisti S. Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Invest Ophthalmol Vis Sci 2010; 51: 6118-6124
  • 80 Ramassamy C, Clostre F, Christen Y, Costentin J. Prevention by a Ginkgo biloba extract (GBE 761) of the dopaminergic neurotoxicity of MPTP. J Pharm Pharmacol 1990; 42: 785-789
  • 81 Sastre J, Millán A, de la Asunción JG, Plá R, Juan G, Pallardo FV, OʼConnor E, Martin JA, Droy-Lefaix MT, Viña J. A Ginkgo biloba extract (EGb-761) prevents mitochondrial aging by protecting against oxidative stress. Free Radic Biol Med 1998; 24: 298-330
  • 82 Baudouin C, Ettaiche M, Imbert F, Droy-Lefaix MT, Gastaud P, Lapalus P. Inhibition of preretinal proliferation by free radical scavengers in an experimental model of tractional retinal detachment. Exp Eye Res 1994; 59: 697-706
  • 83 Qiu QH, Xie ZG, Xu X, Liang SX, Gao Y. EGb 761 on retinal light injury in rats. Chin Med J 2012; 125: 2306-2309
  • 84 Paasche G, Gärtner U, Germer A, Grosche J, Reichenbach A. Mitochondria of retinal Müller (glial) cells: the effects of aging and of application of free radical scavengers. Ophthalmic Res 2000; 32: 229-236
  • 85 Huckfeldt RM, Vavvas DG. Neuroprotection for retinal detachment. Int Ophthalmol Clin 2013; 53: 105-117
  • 86 Murakami Y, Notomi S, Hisatomi T, Nakazawa T, Ishibashi T, Miller JW, Vavvas DG. Photoreceptor cell death and rescue in retinal detachment and degenerations. Prog Retin Eye Res 2013; 37: 114-140
  • 87 Li T, Yang S, She X, Yan Q, Zhang P, Zhu H, Wang F, Luo X, Sun X. Pharmacological interference of adrenergic receptor signaling preserve photoreceptors after retinal detachment through inhibition of oxidative stress and inflammation. Br J Pharmacol 2019; DOI: 10.1111/bph.14565.
  • 88 Behl T, Kotwani A. Chinese herbal drugs for the treatment of diabetic retinopathy. J Pharm Pharmacol 2017; 69: 223-235
  • 89 Bucolo C, Marrazzo G, Platania CBM, Drago F, Leggio M, Salomone S. Fortified extract of red berry, Ginkgo biloba and white bark in experimental early diabetic retinopathy. J Diabetes Res 2013; 2013: 432695
  • 90 Gupta N, Mansoor S, Sharma A, Sapkal A, Sheth J, Falatoonzadeh P, Kuppermann BD, Kenney MC. Diabetic retinopathy and VEGF. Open Ophthalmol J 2013; 7: 4-10
  • 91 Zhao Y, An X, Liu J, Liu S, Xu W, Yu X, Yu J. The improvement of oxidative stress by two proprietary herbal medicines in type 2 diabetes. Complement Ther Med 2018; 40: 120-125
  • 92 Zhao Y, Yu J, Liu J, An X. The role of Liuwei Dihuang pills and Ginkgo leaf tablets in treating diabetic complications. Evid Based Complement Alternat Med 2016; 2016: 7931314
  • 93 Zhao M, Wang XX, Wan WH. Effects of the Ginkgo biloba extract on the superoxide dismutase activity and apoptosis of endothelial progenitor cells from diabetic peripheral blood. Genet Mol Res 2014; 13: 220-227
  • 94 Nuhu AA. Ginkgo biloba: A “living fossil” with modern day phytomedicinal applications. J Appl Pharm Sci 2014; 4: 96-103
  • 95 IMO (Instituto de Microcirugía Ocular). Nd. Glaucoma IMO. Available at: https://www.imo.es/es/glaucoma Accessed November 15, 2018
  • 96 Pinazo-Duran MD, Shoaie-Nia K, Zanon-Moreno V, Sanz-Gonzalez SM, del Castillo JB, Garcia-Medina JJ. Strategies to reduce oxidative stress in glaucoma patients. Curr Neuropharmacol 2018; 16: 903-918
  • 97 Loskutova E, OʼBrien C, Loskutov I, Loughman J. Nutritional supplementation in the treatment of glaucoma: A systematic review. Surv Ophthalmol 2019; 64: 195-216
  • 98 Shim SH, Kim JM, Choi CY, Kim CY, Park KH. Ginkgo biloba extract and bilberry anthocyanins improve visual function in patients with normal tension glaucoma. J Med Food 2012; 15: 818-823
  • 99 Kang JM, Lin S. Ginkgo biloba and its potential role in glaucoma. Curr Opin Ophthalmol 2018; 29: 116-120
  • 100 González Aguaviva B. Monográfico del Ginkgo biloba. . Med Natur 2011; 5: 93-99
  • 101 Chan KKW, Tang F, Tham CCY, Young AL, Cheung CY. Retinal vasculature in glaucoma: a review. BMJ Open Ophthalmol 2017; 1: e000032
  • 102 Lesk MR, Wajszilber M, Deschenes MC. The effects of systemic medications on ocular blood flow. Can J Ophthalmol 2008; 43: 351-355
  • 103 Kim SY, Kwak JS, Shin JP, Lee SH. The protection of the retina from ischemic injury by the free radical scavenger EGb 761 and zinc in the cat retina. Ophthalmologica 1998; 212: 268-274
  • 104 Menerath JM, Cluzel J, Droy-Lefaix MT, Doly M. Experimental electroretinographic exploration of retinal ischemia: preventive use of free radical scavengers and anti-PAF agents. J Ocul Pharmacol Ther 1997; 13: 81-88
  • 105 Droy-Lefaix MT, Menerath JM, Szabo-Tosaki E, Guillaumin D, Doly M. Protective effect of EGb 761 on ischemia-reperfusion damage in the rat retina. Transplant Proc 1995; 27: 2861-2862
  • 106 Szabo ME, Droy-Lefaix MT, Doly M, Braquet P. Free radical-mediated effects in reperfusion injury: a histologic study with superoxide dismutase and EGb 761 in rat retina. Ophthalmic Res 1991; 23: 225-234
  • 107 Szabo ME, Droy-Lefaix MT, Doly M. EGb 761 and the recovery of ion imbalance in ischemic reperfused diabetic rat retina. Ophthalmic Res 1995; 27: 102-109
  • 108 Szabo ME, Droy-Lefaix MT, Doly M. Direct measurement of free radicals in ischemic/reperfused diabetic rat retina. Clin Neurosci 1997; 4: 240-245
  • 109 Clostre F. Protective effects of a Ginkgo biloba extract (EGb 761) on ischemia-reperfusion injury. Therapie 2001; 56: 595-600
  • 110 Tian J, Liu Y, Chen K. Ginkgo biloba Extract in vascular protection: molecular mechanisms and clinical applications. Curr Vasc Pharmacol 2017; 15: 532-548
  • 111 Varga E, Bodi A, Ferdinandy P, Droy-Lefaix MT, Blasig IE, Tosaki A. The protective effect of EGb 761 in isolated ischemic/reperfused rat hearts: a link between cardiac function and nitric oxide production. J Cardiovasc Pharmacol 1999; 34: 711-717
  • 112 Chung HS, Harris A, Kristinsson JK, Ciulla TA, Kagemann C, Ritch R. Ginkgo biloba extract increases ocular blood flow velocity. J Ocul Pharmacol Ther 1999; 5: 233-240
  • 113 Chung SY, Cheng FC, Lee MS, Lin JY, Lin MC, Wang MF. Ginkgo biloba leaf extract (EGb761) combined with neuroprotective agents reduces the infarct volumes of gerbil ischemic brain. Am J Chin Med 2006; 34: 803-817
  • 114 Thiagarajan G, Chandani S, Harinarayana Rao S, Samuni AM, Chandrasekaran K, Balasubramanian D. Molecular and cellular assessment of Ginkgo biloba extract as a possible ophthalmic drug. Exp Eye Res 2002; 75: 421-430
  • 115 Park YH, Chiou GC. Structure-activity relationship (SAR) between some natural flavonoids and ocular blood flow in the rabbit. J Ocul Pharmacol Ther 2004; 20: 35-42
  • 116 Park JW, Kwon HJ, Chung WS, Kim CY, Seong GJ. Short-term effects of Ginkgo biloba extract on peripapillary retinal blood flow in normal tension glaucoma. Korean J Ophthalmol 2011; 25: 323-328
  • 117 Wimpissinger B, Berisha F, Garhoefer G, Polak K, Schmetterer L. Influence of Ginkgo biloba on ocular blood flow. Acta Ophthalmol Scand 2007; 85: 445-449
  • 118 Harris A, Gross J, Moore N, Do T, Huang A, Gama W, Siesky B. The effects of antioxidants on ocular blood flow in patients with glaucoma. Acta Ophthalmol 2018; 96: e237-e241
  • 119 Lerman S. Effects of Sunlight on the Eye. In: Ben Hur E, Rosenthal I. eds. Photomedicine. Boca Raton: CRC Press; 1985: 79-121
  • 120 Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging 2007; 2: 219-226
  • 121 Boulton M, Rózanowska M, Rózanowski B. Retinal photodamage. J Photochem Photobiol B 2001; 64: 144-161
  • 122 Ranchon I, Gorrand JM, Cluzel J, Droy-Lefaix MT, Doly M. Functional protection of photoreceptors from light-induced damage by dimethylthiourea and Ginkgo biloba extract. Invest Ophthalmol Vis Sci 1999; 40: 1191-1199
  • 123 Xie Z, Wu X, Gong Y, Song Y, Qiu Q, Li C. Intraperitoneal injection of Ginkgo biloba extract enhances antioxidation ability of retina and protects photoreceptors after light-induced retinal damage in rats. Curr Eye Res 2007; 32: 471-479
  • 124 Grosche J, Grimm D, Clemens N, Reichenbach A. Retinal light damage vs. normal aging of rats: altered morphology, intermediate filament expression, and nuclear organization of Müller (glial) cells. J Hirnforsch 1997; 38: 459-470
  • 125 Bauduin C, Pisella PJ, Ettaiche M, Goldschild M, Becquet F, Gastaud P, Droy-Lefaix MT. Effects of EGb 761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical. Graefes Arch Clin Exp Ophthalmol 1999; 237: 58-66
  • 126 Kose K, Dogan P, Ascioglu M, Ascioglu O. In vitro antioxidant effect of Ginkgo biloba extract (EGb 761) on lipoperoxidation induced by hydrogen peroxide in erythrocytes of Behcetʼs patients. Jpn J Pharmacol 1997; 75: 253-258
  • 127 Bilgihan A, Aricioğlu A, Bilgihan K, Onol M, Hasanreisoğlu B, Türközkan N. The effect of EGb 761 on retinal lipid peroxidation and glutathione peroxidase level in experimental lens induced uveitis. Int Ophthalmol 1994; 18: 21-24
  • 128 Ilieva I, Ohgami K, Shiratori K, Koyama Y, Yoshida K, Kase S, Kitamei H, Takemoto Y, Yazawa K, Ohno S. The effects of Ginkgo biloba extract on lipopolysaccharide-induced inflammation in vitro and in vivo . Exp Eye Res 2004; 79: 181-187
  • 129 Liu XP, Luan JJ, Goldring CE. Comparison of the antioxidant activity amongst Gingko biloba extract and its main components. Zhong Yao Cai 2009; 32: 736-740
  • 130 Wang J, Zheng M, Chen L, Liu Z, Zhang Y, Liu CM, Liu S. Rapid screening, separation, and detection of hydroxyl radical scavengers from total flavonoids of Ginkgo biloba leaves by chromatography combined with molecular devices. J Sep Sci 2016; 39: 4158-4165
  • 131 Rojas C, Rojas-Castañeda J, Ruiz-Sánchez E, Montes P, Rojas P. Antioxidant properties of a Ginkgo biloba leaf extract (EGb 761) in animal models of Alzheimerʼs and Parkinsonʼs diseases. Curr Top Nutraceutical Res 2015; 3: 105-120
  • 132 Mahadevan S, Park Y. Multifaceted therapeutic benefits of Ginkgo biloba L.: chemistry, efficacy, safety, and uses. J Food Sci 2008; 73: R14-R19
  • 133 Rojas P, Montes S, Serrano-García N, Rojas-Castañeda J. Effect of EGb 761 supplementation on the content of copper in mouse brain in an animal model of Parkinsonʼs disease. Nutrition 2009; 25: 482-485
  • 134 Rojas C, Montes S, Rojas O. EGb 761 supplementation increases manganese content in mouse brain in an animal model of Parkinsonʼs disease. Curr Top Nutraceutical Res 2014; 12: 57-64
  • 135 Kaur S, Sharma N, Nehru B. Anti-inflammatory effects of Ginkgo biloba extract against trimethyltin-induced hippocampal neuronal injury. Inflammopharmacology 2018; 26: 87-104
  • 136 Dumont E, DʼArbigny P, Nouvelot A. Protection of polyunsaturated fatty acids against iron-dependent lipid peroxidation by a Ginkgo biloba extract (EGb 761). Methods Find Exp Clin Pharmacol 1995; 17: 83-88
  • 137 Drieu K, Vranckx R, Benassayad C, Haourigi M, Hassid J, Yoa RG, Rapin JR, Nunez EA. Effect of the extract of Ginkgo biloba (EGb 761) on the circulating and cellular profiles of polyunsaturated fatty acids: correlation with the anti-oxidant properties of the extract. Prostaglandins Leukot Essent Fatty Acids 2000; 63: 293-300
  • 138 Tachikawa M, Akanuma SI, Imai T, Okayasu S, Tomohiro T, Hatanaka Y, Hoso KI. Multiple cellular transport and binding processes of unesterified docosahexaenoic acid in outer blood-retinal barrier retinal pigment epithelial cells. Biol Pharm Bull 2018; 41: 1384-1392
  • 139 Ibarra M, Moreno L, Vera R, Cogolludo A, Duarte J, Tamargo J, Perez-Vizcaino F. Effects of the flavonoid quercetin and its methylated metabolite isorhamnetin in isolated arteries from spontaneously hypertensive rats. Planta Med 2003; 69: 995-1000
  • 140 Lin H, Wang H, Chen D, Gu Y. A dose-effect relationship of Ginkgo biloba extract to nerve regeneration in a rat model. Microsurgery 2007; 27: 673-677
  • 141 Zhu Z, Zhou X, He B, Dai T, Zheng C, Yang C, Zhu S, Zhu J, Zhu Q, Liu X. Ginkgo biloba extract (EGb 761) promotes peripheral nerve regeneration and neovascularization after acellular nerve allografts in a rat model. Cell Mol Neurobiol 2015; 35: 273-282
  • 142 Sun BL, Hu DM, Yuan H, Ye WJ, Wang XC, Xia ZL, Zhang SM, Wang LX. Extract of Ginkgo biloba promotes the expression of VEGF following subarachnoid hemorrhage in rats. Int J Neurosci 2009; 119: 995-1005
  • 143 Oh JH, Oh J, Togloom A, Kim SW, Huh K. Effects of Ginkgo biloba extract on cultured human retinal pigment epithelial cells under chemical hypoxia. Curr Eye Res 2013; 38: 1072-1082
  • 144 Juárez CP, Muiño JC, Guglielmone H, Sambuelli R, Echenique JR, Hernández M, Luna JD. Experimental retinopathy of prematurity: angiostatic inhibition by nimodipine, ginkgo-biloba, and dipyridamole, and response to different growth factors. Eur J Ophthalmol 2000; 10: 51-59