Planta Med 2020; 86(06): 376-386
DOI: 10.1055/a-1109-3405
Biological and Pharmacological Activity
Georg Thieme Verlag KG Stuttgart · New York

Effects of Ginkgo biloba on Diseases Related to Oxidative Stress

Gabriela Achete de Souza
1   Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
Sâmylla Vaz de Marqui
1   Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
Júlia Novaes Matias
1   Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
Elen Landgraf Guiguer
1   Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
2   Department of Biochemistry and Nutrition, Faculty of Food Technology of Marília, (FATEC), Marília, São Paulo, Brazil
Sandra Maria Barbalho
1   Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
2   Department of Biochemistry and Nutrition, Faculty of Food Technology of Marília, (FATEC), Marília, São Paulo, Brazil
› Author Affiliations
Further Information

Publication History

received 15 December 2019
revised 21 January 2020

accepted 29 January 2020

Publication Date:
25 February 2020 (online)


Ginkgo biloba (GB) is one of the most widely used phytotherapeutic products in the world, and its extract has beneficial properties for the treatment of several pathologies, such as diabetic cardiomyopathy, neurodegenerative diseases, cataracts, hearing loss, myocardial lesion, hippocampus neuronal lesions, morphometry testicular changes, and liver damage. This review aims to investigate the effects of GB on diseases related to oxidative stress. Databases such as MEDLINE/PUBMED and EMBASE were consulted, and PRISMA guidelines were used to build the review. This plant has antioxidant properties since it regulates the expression of antioxidant enzymes positively and reduces reactive oxygen and nitrogen species, contributing to the reduction of lipid peroxidation. It also exhibits anti-inflammatory properties, inhibiting the expression of pro-inflammatory cytokines, such as IL-1, IL-6, and TNF-α. In animal models, the use of GB can show positive effects on brain damage, neurodegenerative diseases, myocardial injury, and renal and liver damage. In humans, the positive effects were shown in diabetes, metabolic syndrome, and ischemic colitis. These effects are due to the presence of compounds such as bilobalide, isoramnetina, quercetin, kaempferol, and ginkgolides A, B, and C. For these reasons, GB can be a low-cost alternative to the therapeutic approach of several pathologies since it acts in the prevention, treatment, and inhibition of several complications of common comorbidities.

  • References

  • 1 Huang XF, Zhang SZ, You YY, Zhang N, Lu H, Daugherty A, Xie XJ. Ginkgo biloba extracts prevent aortic rupture in angiotensin II-infused hypercholesterolemic mice. Acta Pharmacol Sin 2019; 40: 192-198
  • 2 Burgos-Moron E, Abad-Jimenez Z, Maranon AM, Iannantuoni F, Escribano-Lopez I, Lopez-Domenech S, Salom C, Jover A, Mora V, Roldan I, Sola E, Rocha M, Victor V. Relationship between oxidative stress, ER stress, and inflammation in type 2 diabetes: the battle continues. J Clin Med 2019; 8: 1385
  • 3 Senoner T, Dichtl W. Oxidative stress in cardiovascular diseases: still a therapeutic target?. Nutrients 2019; 11: 2090
  • 4 Bjorklund G, Dadar M, Martins N, Chirumbolo S, Goh BH, Smetanina K, Lysiuk R. Brief challenges on medicinal plants: an eye-opening look at ageing-related disorders. Basic Clin Pharmacol Toxicol 2018; 122: 539-558
  • 5 Hirata BKS, Pedroso AP, Machado MMF, Neto NIP, Perestrelo BO, de Sa R, Alonso-Vale MIC, Nogueira FN, Oyama LM, Ribeiro EB, Tashima AK, Telles MM. Ginkgo biloba extract modulates the retroperitoneal fat depot proteome and reduces oxidative stress in diet-induced obese rats. Front Pharmacol 2019; 10: 686
  • 6 Li W, Qinghai S, Kai L, Xue M, Lili N, Jihua R, Zhengxiang L, Xiaoling L, Di G, Qi Y, Mengyun D, Jianfeng F. Oral administration of ginkgolide B alleviates hypoxia-induced neuronal damage in rat hippocampus by inhibiting oxidative stress and apoptosis. Iran J Basic Med Sci 2019; 22: 140-145
  • 7 Martinez-Solis I, Acero N, Bosch-Morell F, Castillo E, Gonzalez-Rosende ME, Munoz-Mingarro D, Ortega T, Sanahuja MA, Villagrasa V. Neuroprotective potential of Ginkgo biloba in retinal diseases. Planta Med 2019; 85: 1292-1303
  • 8 Li H, Sun X, Yu F, Xu L, Miu J, Xiao P. In silico investigation of the pharmacological mechanisms of beneficial effects of Ginkgo biloba l. on Alzheimerʼs disease. Nutrients 2018; 10: e589
  • 9 Khedr MH, Shafaa MW, Abdel-Ghaffar A, Saleh A. Radioprotective efficacy of Ginkgo biloba and Angelica archangelica extract against technetium-99 m-sestamibi induced oxidative stress and lens injury in rats. Int J Radiat Biol 2018; 94: 37-44
  • 10 Wang H, Wu X, Lezmi S, Li Q, Helferich WG, Xu Y, Chen H. Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer Xenograft model. BMC Complement Altern Med 2017; 17: 516
  • 11 Jiang L, Si ZH, Li MH, Zhao H, Fu YH, Xing YX, Hong W, Ruan LY, Li PM, Wang JS. (1)H NMR-based metabolomics study of liver damage induced by ginkgolic acid (15 : 1) in mice. J Pharm Biomed Anal 2017; 136: 44-54
  • 12 Tang Y, Zhou G, Yao L, Xue P, Yu D, Xu R, Shi W, Yao X, Yan Z, Duan JA. Protective effect of Ginkgo biloba leaves extract, EGb761, on myocardium injury in ischemia reperfusion rats via regulation of TLR-4/NF-kappaB signaling pathway. Oncotarget 2017; 8: 86671-86680
  • 13 Kaur S, Sharma N, Nehru B. Anti-inflammatory effects of Ginkgo biloba extract against trimethyltin-induced hippocampal neuronal injury. Inflammopharmacol 2018; 26: 87-104
  • 14 Ekici Gunay N, Muhtaroglu S, Bedirli A. Administration of Ginkgo biloba extract (EGb761) alone and in combination with FK506 promotes liver regeneration in a rat model of partial hepatectomy. Balkan Med J 2018; 35: 174-180
  • 15 Tao Z, Jin W, Ao M, Zhai S, Xu H, Yu L. Evaluation of the anti-inflammatory properties of the active constituents in Ginkgo biloba for the treatment of pulmonary diseases. Food Funct 2019; 10: 2209-2220
  • 16 Abdel-Zaher AO, Farghaly HSM, El-Refaiy AEM, Abd-Eldayem AM. Protective effect of the standardized leaf extract of Ginkgo biloba (EGb761) against hypertension-induced renal injury in rats. Clin Exp Hypertens 2018; 40: 703-714
  • 17 Hu H, Li Y, Xin Z, Zhanga X. Ginkgolide B exerts anti-inflammatory and chondroprotective activity in LPS-induced chondrocytes. Adv Clin Exp Med 2018; 27: 913-920
  • 18 Zhang L, Liu J, Geng T. Ginkgetin aglycone attenuates the apoptosis and inflammation response through nuclear factor-kB signaling pathway in ischemic-reperfusion injury. J Cell Biochem 2018; DOI: 10.1002/jcb.28086.
  • 19 Tian J, Liu Y, Liu Y, Chen K, Lyu S. Ginkgo biloba leaf extract protects against myocardial injury via attenuation of endoplasmic reticulum stress in streptozotocin-induced diabetic ApoE(-/-) mice. Oxid Med Cell Longev 2018; 2018: 2370617
  • 20 Li Y, Zhang Y, Wen M, Zhang J, Zhao X, Zhao Y, Deng J. Ginkgo biloba extract prevents acute myocardial infarction and suppresses the inflammation and apoptosisregulating p38 mitogenactivated protein kinases, nuclear factorkappaB and Bcell lymphoma 2 signaling pathways. Mol Med Rep 2017; 16: 3657-3663
  • 21 Wang A, Yang Q, Li Q, Wang X, Hao S, Wang J, Ren M. Ginkgo biloba l. extract reduces H2O2-induced bone marrow mesenchymal stem cells cytotoxicity by regulating mitogen-activated protein kinase (MAPK) signaling pathways and oxidative stress. Med Sci Monit 2018; 24: 3159-3167
  • 22 Zhang J, Yang S, Chen F, Li H, Chen B. Ginkgetin aglycone ameliorates LPS-induced acute kidney injury by activating SIRT1 via inhibiting the NF-kappaB signaling pathway. Cell Biosci 2017; 7: 44
  • 23 Wang C, Wang B. Ginkgo biloba extract attenuates oxidative stress and apoptosis in mouse cochlear neural stem cells. Phytother Res 2016; 30: 774-780
  • 24 Cao S, Gao M, Wang N, Liu N, Du G, Lu J. Prevention of selenite-induced cataratogenesis by Ginkgo biloba extract (EGb761) in Wistar rats. Cur Eye Res 2015; 40: 1028-1033
  • 25 Belviranli M, Okudan N. The effects of Ginkgo biloba extract on cognitive functions in aged female rats: the role of oxidative stress and brain-derived neurotrophic factor. Behav Brain Res 2015; 278: 453-461
  • 26 El-Ghazaly MA, Sadik NA, Rashed ER, Abd-El-Fattah AA. Neuroprotective effect of EGb761(R) and low-dose whole-body gamma-irradiation in a rat model of Parkinsonʼs disease. Toxicol Ind Health 2015; 31: 1128-1143
  • 27 Park SY, Back SA, Kim HL, Kim DK, Yeo SW, Park SN. Renexin as a rescue regimen for noise-induced hearing loss. Noise Health 2014; 16: 257-264
  • 28 Gevrek F, Aydin D, Ozsoy S, Aygun H, Bicer C. Inhibition by Egb761 of the effect of cellphone radiation on the male reproductive system. Bratisl Lek Listy 2017; 118: 676-683
  • 29 Sharma M, Fitzpatrick AL, Arnold AM, Chi G, Lopez OL, Jenny NS, DeKosky ST. Inflammatory biomarkers and cognitive decline: the Ginkgo evaluation of memory study. J Am Geriatr Soc 2016; 64: 1171-1177
  • 30 Saini AS, Taliyan R, Sharma PL. Protective effect and mechanism of Ginkgo biloba extract-EGb 761 on STZ-induced diabetic cardiomyopathy in rats. Pharmacogn Mag 2014; 10: 172-178
  • 31 Wu JQ, Kosten TR, Zhang XY. Free radicals, antioxidant defense systems, and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2013; 46: 200-206
  • 32 Lee CY, Yang JJ, Lee SS, Chen CJ, Huang YC, Huang KH, Kuan YH. Protective effect of Ginkgo biloba leaves extract, EGb761, on endotoxin-induced acute lung injury via a JNK- and Akt-dependent NFkappaB pathway. J Agric Food Chem 2014; 62: 6337-6344
  • 33 Aziz TA, Hussain SA, Mahwi TO, Ahmed ZA. Efficacy and safety of Ginkgo biloba extract as an “add-on” treatment to metformin for patients with metabolic syndrome: a pilot clinical study. Ther Clin Risk Mang 2018; 14: 1219-1226
  • 34 Hirata BK, Banin RM, Dornellas AP, de Andrade IS, Zemdegs JC, Caperuto LC, Oyama LM, Ribeiro EB, Telles MM. Ginkgo biloba extract improves insulin signaling and attenuates inflammation in retroperitoneal adipose tissue depot of obese rats. Mediators Inflamm 2015; 2015: 419106
  • 35 Siegel G, Ermilov E, Knes O, Rodriguez M. Combined lowering of low grade systemic inflammation and insulin resistance in metabolic syndrome patients treated with Ginkgo biloba . Atherosclerosis 2014; 237: 584-588
  • 36 Fang H, Zhang C, Wang J, Xu Z, Qian C, Zhang L. Therapeutic effects of Ginkgo biloba extract against acute ischemic colitis. Medicine (Baltimore) 2018; 97: e12166
  • 37 Lebda MA, Sadek KM, Tohamy HG, Abouzed TK, Shukry M, Umezawa M, El-Sayed YS. Potential role of alpha-lipoic acid and Ginkgo biloba against silver nanoparticles-induced neuronal apoptosis and blood-brain barrier impairments in rats. Life Sci 2018; 212: 251-260
  • 38 Zayed AE, Saleh A, Gomaa AMS, Abd-Elkareem M, Anwar MM, Hassanein KMA, Elsherbiny MM, Kotb AM. Protective effect of Ginkgo biloba and magnetized water on nephropathy in induced type 2 diabetes in rat. Oxid Med Cell Longev 2018; 2018: 1785614
  • 39 Rhee KJ, Lee CG, Kim SW, Gim DH, Kim HC, Jung BD. Extract of Ginkgo biloba ameliorates streptozotocin-induced type 1 diabetes mellitus and high-fat diet-induced type 2 diabetes mellitus in mice. Int J Med Sci 2015; 12: 987-994
  • 40 Ahmed HH, El-Abhar HS, Hassanin EAK, Abdelkader NF, Shalaby MB. Ginkgo biloba L. leaf extract offers multiple mechanisms in bridling N-methylnitrosourea-mediated experimental colorectal cancer. Biomed Pharmacother 2017; 95: 387-393
  • 41 Liang Z, Bai S, Shen P, Hu Q, Wang X, Dong M, Wang W, Li J, Cheng K, Zhang S, Zou D, Han Y, Wang H, Xie P. GC-MS-based metabolomic study on the antidepressant-like effects of diterpene ginkgolides in mouse hippocampus. Behav Brain Res 2016; 314: 116-124
  • 42 Badem S, Ugurlucan M, El H, Sahin M, Uysal M, Sayin OA, Gurel B, Basaran M, Bayinder C, Alpagut U, Dayioglu E. Effects of Ginkgo biloba extract on spinal cord ischemia-reperfusion injury in rats. Ann Vas Surg 2014; 28: 1296-1305
  • 43 Trebaticka J, Durackova Z. Psychiatric disorders and polyphenols: can they be helpful in therapy?. Oxid Med Cell Longev 2015; 2015: 248529
  • 44 Mi XS, Zhong JX, Chang RC, So KF. Research advances on the usage of traditional Chinese medicine for neuroprotection in glaucoma. J Integr Med 2013; 11: 233-240
  • 45 Zhang J, Wang J, Zhou GS, Tan YJ, Tao HJ, Chen JQ, Pu ZJ, Ma JY, She W, Kang A, Zhu Y, Liu P, Zhu ZH, Shi XQ, Tang YP, Duan JA. Studies of the anti-amnesic effects and mechanisms of single and combined use of donepezil and Ginkgo ketoester tablet on scopolamine-induced memory impairment in mice. Oxid Med Cell Longev 2019; 2019: 8636835
  • 46 Qin Y, Zhang Y, Tomic I, Hao W, Menger MD, Liu C, Fassbender K, Liu Y. Ginkgo biloba extract EGb 761 and its specific components elicit protective protein clearance through the autophagy-lysosomal pathway in tau-transgenic mice and cultured neurons. J Alzheimers Dis 2018; 65: 243-263
  • 47 El Tabaa MM, Sokkar SS, Ramadan ES, Abd El Salam IZ, Zaid A. Neuroprotective role of Ginkgo biloba against cognitive deficits associated with bisphenol A exposure: An animal model study. Neurochem Int 2017; 108: 199-212
  • 48 Ribeiro ML, Moreira LM, Arcari DP, Dos Santos LF, Marques AC, Pedrazzoli jr. J, Cerutti SM. Protective effects of chronic treatment with a standardized extract of Ginkgo biloba l. in the prefrontal cortex and dorsal hippocampus of middle-aged rats. Behav Brain Res 2016; 313: 144-150
  • 49 Zeng YQ, Wang YJ, Zhou XF. Ginkgetin ameliorates neuropathological changes in app/ps1 transgenical mice model. J Prev Alzheimers Dis 2016; 3: 24-29
  • 50 Wan W, Zhang C, Danielsen M, Li Q, Chen W, Chan Y, Li Y. EGb761 improves cognitive function and regulates inflammatory responses in the APP/PS1 mouse. Exp Gerontol 2016; 81: 92-100
  • 51 Liu X, Hao W, Qin Y, Decker Y, Wang X, Burkart M, Schotz K, Menger MD, Fassbender K, Liu Y. Long-term treatment with Ginkgo biloba extract EGb 761 improves symptoms and pathology in a transgenic mouse model of Alzheimerʼs disease. Brain Behav Immun 2015; 46: 121-131
  • 52 Wang YQ, Wang MY, Fu XR, Peng Y, Gao GF, Fan YM, Duan XL, Zhao BL, Chang YZ, Shi ZH. Neuroprotective effects of ginkgetin against neuroinjury in Parkinsonʼs disease model induced by MPTP via chelating iron. Free Radic Res 2015; 49: 1069-1080
  • 53 Harada S, Tsujita T, Ono A, Miyagi K, Mori T, Tokuyama S. Stachys sieboldii (Labiatae, Chorogi) protects against learning and memory dysfunction associated with ischemic brain injury. J Nutr Sci Vitaminol 2015; 61: 167-174
  • 54 Liu Q, Jin Z, Xu Z, Yang H, Li L, Li G, Li F, Gu S, Zong S, Zhou J, Cao L, Wang Z, Xiao W. Antioxidant effects of ginkgolides and bilobalide against cerebral ischemia injury by activating the Akt/Nrf2 pathway in vitro and in vivo . Cell Stress Chaperones 2019; 24: 441-452
  • 55 Chen M, Zou W, Chen M, Cao L, Ding J, Xiao W, Hu G. Ginkgolide K promotes angiogenesis in a middle cerebral artery occlusion mouse model via activating JAK2/STAT3 pathway. Eur J Pharmacol 2018; 833: 221-229
  • 56 Aydin D, Peker EG, Karakurt MD, Gurel A, Ayyildiz M, Cevher SC, Agar E, Dane S. Effects of Ginkgo biloba extract on brain oxidative condition after cisplatin exposure. Clin Invest Med 2016; 39: 27511
  • 57 Vaghef L, Bafandeh Gharamaleki H. Effects of physical activity and Ginkgo biloba on cognitive function and oxidative stress modulation in ischemic rats. Int J Angio 2017; 26: 158-164
  • 58 Yallapragada PR, Velaga MK. Effect of Ginkgo biloba extract on lead-induced oxidative stress in different regions of rat brain. J Environ Pathol Toxicol Oncol 2015; 34: 161-173
  • 59 Chen XJ, Ren SM, Dong JZ, Qiu CG, Chen YW, Tao HL. Ginkgo biloba extract-761 protects myocardium by regulating Akt/Nrf2 signal pathway. Drug Des Devel Ther 2019; 13: 647-655
  • 60 Wang Z, Zhang J, Ren T, Dong Z. Targeted metabolomic profiling of cardioprotective effect of Ginkgo biloba L. extract on myocardial ischemia in rats. Phytomedicine 2016; 23: 621-631
  • 61 Wu F, Shi W, Zhou G, Yao H, Xu C, Xiao W, Wu J, Wu X. Ginkgolide B functions as a determinant constituent of ginkgolides in alleviating lipopolysaccharide-induced lung injury. Biomed Pharmacother 2016; 81: 71-78
  • 62 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
  • 63 Jeong HS, Kim KH, Lee IS, Park JY, Kim Y, Kim KS, Jang HJ. Ginkgolide A ameliorates non-alcoholic fatty liver diseases on high fat diet mice. Biomed Pharmacother 2017; 88: 625-634
  • 64 Ye N, Wang H, Hong J, Zhang T, Lin C, Meng C. PXR mediated protection against liver inflammation by ginkgolide a in tetrachloromethane treated mice. Biomol There (Seoul) 2016; 24: 40-48
  • 65 Wang Y, Wang R, Wang Y, Peng R, Wu Y, Yuan Y. Ginkgo biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF-kappaB/IkappaBalpha, and Bcl-2/Bax signaling. Drug Des Devel Ther 2015; 9: 6303-6317
  • 66 Li H, Qiu P, Wang J, Niu C, Pan S. Effects of compound Ginkgo biloba on intestinal permeability in rats with alcohol-induced liver injury. Food Funct 2015; 6: 470-478
  • 67 Ahmed AI, Lasheen NN, El-Zawahry KM. Ginkgo biloba ameliorates subfertility induced by testicular ischemia/reperfusion injury in adult wistar rats: a possible new mitochondrial mechanism. Oxid Med Cell Longev 2016; 2016: 6959274
  • 68 Mohamed NE, Abd El-Moneim AE. Ginkgo biloba extract alleviates oxidative stress and some neurotransmitters changes induced by aluminum chloride in rats. Nutrition 2017; 35: 93-99
  • 69 Lu Q, Hao M, Wu W, Zhang N, Isaac AT, Yin J, Zhu X, Du L, Yin X. Antidiabetic cataract effects of GbE, rutin and quercetin are mediated by the inhibition of oxidative stress and polyol pathway. Acta Biochim Pol 2018; 65: 35-41
  • 70 Sjostrand AP, Dogan R, Kocyigit A, Karatas E, Budak BB, Ozturan O. Therapeutic efficacy of Ginkgo biloba for early-period noise-induced hearing loss: an experimental animal study. Am J Otolaryngol 2016; 37: 416-424
  • 71 Kaur N, Dhiman M, Perez-Polo JR, Mantha AK. Ginkgolide B revamps neuroprotective role of apurinic/apyrimidinic endonuclease 1 and mitochondrial oxidative phosphorylation against Abeta25-35-induced neurotoxicity in human neuroblastoma cells. J Neurosci Res 2015; 93: 938-947
  • 72 Lin H, Guo X, Zhang S, Dial SL, Guo L, Manjanatha MG, Moore MM, Mei N. Mechanistic evaluation of Ginkgo biloba leaf extract-induced genotoxicity in L5178Y cells. Toxicol Sci 2014; 139: 338-349
  • 73 Parimoo HA, Sharma R, Patil RD, Sharma OP, Kumar P, Kumar N. Hepatoprotective effect of Ginkgo biloba leaf extract on lantadenes-induced hepatotoxicity in guinea pigs. Toxicon 2014; 81: 1-12
  • 74 Serrano-Garcia N, Pedraza-Chaverri J, Mares-Samano JJ, Orozco-Ibarra M, Cruz-Salgado A, Jimenez-Anguiano A, Sotelo J, Trejo-Solis C. Antiapoptotic effects of EGb 761. Evid Based Complement Alternat Med 2013; 2013: 495703
  • 75 Choudhary S, Kumar P, Malik J. Plants and phytochemicals for Huntingtonʼs disease. Pharmacogn Rev 2013; 7: 81-91
  • 76 Wang J, Zhang L, Zhang Y, Luo M, Wu Q, Yu L, Chu H. Transcriptional upregulation centra of HO-1 by EGB via the MAPKs/Nrf2 pathway in mouse C2C12 myoblasts. Toxicol In Vitro 2015; 29: 380-388
  • 77 Wang L, Bai Y, Wang B, Cui H, Wu H, Lv JR, Mei Y, Zhang JS, Liu S, Qi LW, Chen Y. Suppression of experimental abdominal aortic aneurysms in the mice by treatment with Ginkgo biloba extract (EGb 761). J Ethnopharmacol 2013; 150: 308-315
  • 78 Lu L, Wang S, Fu L, Liu D, Zhu Y, Xu A. Bilobalide protection of normal human melanocytes from hydrogen peroxide-induced oxidative damage via promotion of antioxidase expression and inhibition of endoplasmic reticulum stress. Clin Exp Dermatol 2016; 41: 64-73