Ginkgo biloba belongs to the botanical family of Ginkgoceae consisting of approximately 15 genera. The ginkgo tree, known to be among the oldest living species on this planet, has flourished in forests for more than 200 million years, hence it is called a “living fossil”. The modern-day Ginkgo biloba has a very distinct appearance characterized by its fan-shaped leaves. They also live a very, very long time. A single Ginkgo biloba tree might drop its distinct fan-shaped leaves every year for centuries, if not millennia. As a ginkgo ages, it does not just survive, it thrives. Though 600-year-old ginkgos grow thinner annual rings, they are likely to pump out just as much defensive and immune-supporting chemicals as their younger relatives.
This tree having survived millions of years has developed a unique adaptability to thrive in even extremely polluted environments. This attribute has made the male ginkgos very popular in air polluted cities. Its resistance, adaptability, and regenerative strength is unsurpassed in the plant kingdom and it imparts this adaptogen quality to its user. Thus, it is medicinally considered an adaptogen remedy. It is a dioecious tree with the male and female reproductive organs on separate trees. The name ginkgo comes from the Chinese words sankyo or yinkuo, which means a hill apricot or silver fruit, due to their apricot shaped mature fruits and yellow color.
It is cultivated around the world for its medicinal properties and aesthetic value.
Both the leaves and the nuts of this tree have been in use for the past several centuries in traditional Chinese medicine. In fact, the nuts are known to have a longer history of usage, being first mentioned in herbals in the Yuan dynasty [1280 to 1368 AD], published in 1350 AD.1 Thus, for over 5000 years, the seeds (nuts) have been used to treat pulmonary disorders (like asthma, cough, and enuresis), and bladder inflammation, while the leaves have been mainly used to treat heart and lung dysfunctions and skin infections. However, it was only in the last 30 to 50 years that the use of the ginkgo leaf and its standardized extracts have been used for cognitive ailments.
According to The German Commission E (a scientific advisory board of the Federal Institute for Drugs and Medical Devices), Ginkgo B. has three primary uses or indications:
(1) For symptomatic treatment of disturbed performance in organic brain syndrome within the regimen of a therapeutic concept in cases of dementia syndromes with the following principal symptoms: memory deficits, disturbances in concentration, depressive emotional condition, dizziness, tinnitus, and headache. The primary target groups are dementia syndromes, including primary degenerative dementia, vascular dementia, and mixed forms of both.
(2) Improvement of pain-free walking distance in peripheral arterial occlusive disease in Stage II of Fontaine (intermittent claudication) and in a regimen of physical therapeutic measures, particularly walking.
(3) Vertigo and tinnitus (ringing in the ear) of vascular and involutional origin.
Studies have also shown positive results from the use of ginkgo for the following conditions: sexual dysfunction secondary to the use of selective serotonin reuptake inhibitors, mountain sickness and decreasing vasoactive response to cold, macular degeneration, asthma, and hypoxia.
The World Health Organization reiterated The Commission E approved uses noted above adding the following specific conditions to peripheral arterial occlusive disease: Raynaud’s disease, acrocyanosis, and post phlebitis syndrome.
Ginkgo contains many different substances. Most of them fall into two categories Flavonoids and Terpenoids or Terpene lactones. Flavonoids are naturally occurring substances that function as antioxidants (scavenge free radicals-damaging compounds in the body that alter cell membranes, tamper with DNA, and even cause cell death) also found in fruits and vegetables. They enhance the immune system in the body and interfere with tumor formation. The type of flavonoid in Ginkgo is called Ginkgolide. Ginkgolides are unique compounds exclusive to Ginkgo and are broken down into separate ginkgolides A, B, C, J, and M. Each Ginkgolide has a different degree of potency. Ginkgolide B is considered the most active. Other flavonoids present are quercetin (which is one of the most studied flavonoids and is a stronger antioxidant than vitamin E), and kaempferol. Terpene lactones are the active constituents that give ginkgo a bitter strong flavor and helps increase blood circulation.
Other components present are Amino Acid-6hydrozykynurenic acid, Dimeric flavones (bilobetin, ginkgetin, isoginkgetin, scieadopitysin), Proanthocyanidins, ginkgolic acid, ascorbic acid, carotenoids, and Bilobalide.
The nuts contain essential oil, fatty acid, tannin, and resin.
Data suggest that ginkgo biloba exhibits protective effects in ischemic stroke. Li et. al showed that ginkgo in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischemic stroke without increasing the incidence of vascular events. Therefore, the administration of G biloba is recommended after acute ischemic stroke.
Several animal studies have shown that ginkgo improves memory. However, human studies have been mixed in demonstrating that ginkgo improves memory and reduces cognitive decline. Some results confirm that the effects of gingko b. on aspects of cognition in asymptomatic volunteers are more pronounced for memory, particularly working memory. Wesnes et. al. showed a ginkgo/ginseng combination to significantly improve an Index of Memory Quality and demonstrated improvements to the memory of healthy middle-aged volunteers. Additionally, it has been shown to reduce tinnitus.
Some of the more promising studies of Ginkgo involve its positive effect in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.
Shakibaei et. al. has shown ginkgo biloba to be an effective complementary treatment for ADHD.
Moraga et. al, showed evidence supporting the use of ginkgo in the prevention of acute mountain sickness (AMS), thus demonstrating that 24 hours of pretreatment with ginkgo.
Ginkgo biloba and subsequent maintenance during exposure to high altitude are sufficient to reduce the incidence of AMS in participants with no previous high-altitude experience.
Ye et. al have shown data to suggest ginkgo may reduce ovarian cancer risk.
The mechanism of action of ginkgo is produced by its functions as a neuroprotective agent, an antioxidant, a free-radical scavenger, a membrane stabilizer, and an inhibitor of platelet-activating factor via the terpene ginkgolide B. Other pharmacologic effects include the following: endothelium relaxation mediated by inhibition of 3',5'-cyclic GMP (guanosine monophosphate) phosphodiesterase; inhibition of age-related loss of muscarinergic cholinoceptors and α-adrenoceptors; and stimulation of choline uptake in the hippocampus. Ginkgo extract also has been shown to inhibit beta-amyloid deposition, thus suggested in Alzheimer’s disease.
Ginkgo interacts with several cytochrome P450 enzymes. Pretreatment with G. biloba extract induces expression of CYP3A proteins and mRNA and increases CYP3A activity. It also inhibits CYP2B6 catalytic activity and bupropion hydroxylation. Ginkgo may play a role in decreasing high-glucose-induced endothelial inflammation via inhibition of interleukin-6 activation, and repeated intake of ginkgo enhanced cell proliferation and neuroblast differentiation. Flavonoids present in ginkgo extracts inhibited estrogen biosynthesis via aromatase inhibition, decreased CYP19 mRNA, and induced transcriptional suppression.
Chemopreventive properties of bilobalide, a terpene trilactone, may occur via alterations in cryptal cell proliferation and drug-metabolizing enzyme activities. Exocarp polysaccharides from ginkgo affected expression of c-myc, bcl-2 and c-fos genes, which can inhibit proliferation and induce apoptosis and differentiation of human gastric tumor cells.
Bastianetto, Stéphane, Charles Ramassamy, Sylvain Doré, Yves Christen, Judes Poirier, and Rémi Quirion. "The ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by β‐amyloid." European Journal of Neuroscience 12, no. 6 (2000): 1882-1890. https://d1wqtxts1xzle7.cloudfront.net/40044694/0deec517a8579ccac1000000.pdf20151115-68247-1pdtt4j-with-cover-page-v2.pdf?Expires=1645563391&Signature=aIt8r6bfr-8R7iRQsI3xz4RP45POBJwAGhpEcGUoCSJkLw1P0k~DNXZN46cKovegYvzTEjN~YicdLb-nFW~HuvVAFPbnDw38KxymeC3lp2nd5EBRMtPxQeWbFj7ogoNGGMLKbANDzzrSUDDB3UkuxpOgcSR2rH8Aes6kQP7EWE9Ayha4Ffey5jiPJT6ks~PPFnipT2HYQsEDGROOQrZnruD14j50F7f6T~hlA5QtSk8tyO1Wx-TUakfYv9ahLAjXE8G-NNy5m6Uj7EM1PwNEGAYq-l7OcZ3W2va2sqAl67EgOQLHQU1bND9KhRxlQPW7BD0wBVRePZwZeA2klci1dA__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA
Bastianetto, Stéphane, Wen‐Hua Zheng, and Rémi Quirion. "The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide‐induced toxicity: involvement of its flavonoid constituents and protein kinase C." Journal of neurochemistry 74, no. 6 (2000): 2268-2277. https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1471-4159.2000.0742268.x
Chen JS, Chen YH, Huang PH, et al. Ginkgo biloba extract reduces high-glucose-induced endothelial adhesion by inhibiting the redox-dependent interleukin-6 pathways. Cardiovasc Diabetol. May 3 2012;11:49.
Cohen, Alan J., and Barbara Bartlik. "Ginkgo biloba for antidepressant-induced sexual dysfunction." Journal of sex & marital therapy 24, no. 2 (1998): 139-143. https://www.tandfonline.com/doi/abs/10.1080/00926239808404927
DeFeudis, F. V., and K. Drieu. "Ginkgo biloba extract (EGb 761) and CNS functions basic studies and clinical applications." Current drug targets 1, no. 1 (2000): 25-58. https://web.archive.org/web/20170829174853id_/http://www.comilac.com.tr/uploads/pdf/Kaynak16x.pdf
Goh, Lena M., and Philip J. Barlow. "Antioxidant capacity in Ginkgo biloba." Food Research International 35, no. 9 (2002): 815-820. https://www.sciencedirect.com/science/article/abs/pii/S0963996902000844
Hauns B, Haring B, Kohler S, et al. Phase II study of combined 5-fluorouracil/Ginkgo biloba extract (GBE 761 ONC) therapy in 5-fluorouracil pretreated patients with advanced colorectal cancer. Phytother Res. Feb 2001;15(1):34-38.
Hoenerhoff MJ, Pandiri AR, Snyder SA, et al. Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways. Toxicol Pathol. Aug 2013;41(6):826-841.
Ji H, Zhou X, Wei W, et al. Ginkgol biloba extract as an adjunctive treatment for ischemic stroke: A systematic review and meta-analysis of randomized clinical trials. Medicine (Baltimore). Jan 2020;99(2):e18568.
Kleijnen, Jos, and Paul Knipschild. "Ginkgo biloba for cerebral insufficiency." British journal of clinical pharmacology 34, no. 4 (1992): 352-358. https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.1992.tb05642.x
Kudolo GB. The effect of 3-month ingestion of Ginkgo biloba extract on pancreatic beta-cell function in response to glucose loading in normal glucose tolerant individuals. J Clin Pharmacol. Jun 2000;40(6):647-654.
Li, Ming-hua, Ben-ying Yang, Hong Yu, and Hong-liang Zhang. "Clinical observation of the therapeutic effect of ginkgo leaf concentrated oral liquor on bronchial asthma." Chinese Journal of Integrated Traditional and Western Medicine 3, no. 4 (1997): 264-267. https://link.springer.com/article/10.1007/BF02934827
Li S, Zhang X, Fang Q, et al. Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial. Stroke Vasc Neurol. Dec 2017;2(4):189-197.
Liebgott, Thibaut, Malvina Miollan, Yves Berchadsky, Katy Drieu, Marcel Culcasi, and Sylvia Pietri. "Complementary cardioprotective effects of flavonoid metabolites and terpenoid constituents of Ginkgo biloba extract (EGb 761) during ischemia and reperfusion." Basic research in cardiology 95, no. 5 (2000): 368-377. https://www.researchgate.net/profile/Sylvia-Pietri/publication/12229106_Complementary_cardioprotective_effects_of_flavonoid_metabolites_and_terpenoid_constituents_of_Ginkgo_biloba_extract_EGb_761_during_ischemia_and_reperfusion/links/5a9401bb45851535bcd98aa9/Complementary-cardioprotective-effects-of-flavonoid-metabolites-and-terpenoid-constituents-of-Ginkgo-biloba-extract-EGb-761-during-ischemia-and-reperfusion.pdf
Luo, Yuan, Julie V. Smith, Vijaykumar Paramasivam, Adam Burdick, Kenneth J. Curry, Justin P. Buford, Ikhlas Khan, William J. Netzer, Huaxi Xu, and Peter Butko. "Inhibition of amyloid-β aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761." Proceedings of the national academy of sciences 99, no. 19 (2002): 12197-12202. https://www.pnas.org/content/pnas/99/19/12197.full.pdf
Mahady, Gail B. "Ginkgo biloba for the prevention and treatment of cardiovascular disease: a review of the literature." Journal of Cardiovascular Nursing 16, no. 4 (2002): 21-32. https://www.researchgate.net/profile/Gail-Mahady/publication/10891572_Ginkgo_Biloba_for_the_Prevention_and_Treatment_of_Cardiovascular_Disease_A_Review_of_the_Literature/links/59b020a80f7e9b3743465c86/Ginkgo-Biloba-for-the-Prevention-and-Treatment-of-Cardiovascular-Disease-A-Review-of-the-Literature.pdf
McKenna, Dennis J., Kenneth Jones, and Kerry Hughes. "Efficacy, safety, and use of ginkgo biloba in clinical and preclinical applications." Alternative therapies in health and medicine 7, no. 5 (2001): 70. https://www.proquest.com/openview/7a27773d0094456d47e0f4ace442ec04/1?pq-origsite=gscholar&cbl=32528
Moraga FA, Flores A, Serra J, et al. Ginkgo biloba decreases acute mountain sickness in people ascending to high altitude at Ollague (3696 m) in northern Chile. Wilderness Environ Med. Winter 2007;18(4):251-257.
Oken, Barry S., Daniel M. Storzbach, and Jeffrey A. Kaye. "The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease." Archives of neurology 55, no. 11 (1998): 1409-1415. https://jamanetwork.com/journals/jamaneurology/fullarticle/774397
Oskouei DS, Rikhtegar R, Hashemilar M, et al. The effect of Ginkgo biloba on functional outcome of patients with acute ischemic stroke: a double-blind, placebo-controlled, randomized clinical trial. J Stroke Cerebrovasc Dis. Nov 2013;22(8):e557-563.
Park YJ, Choo WH, Kim HR, et al. Inhibitory Aromatase Effects of Flavonoids from Ginkgo biloba Extracts on Estrogen Biosynthesis. Asian Pac J Cancer Prev. 2015;16(15):6317-6325.
Pietri, Sylvia, Eziana Maurelli, Katy Drieu, and Marcel Culcasi. "Cardioprotective and Anti-oxidant Effects of the Terpenoid Constituents ofGinkgo bilobaExtract (EGb 761)." Journal of molecular and cellular cardiology 29, no. 2 (1997): 733-742. https://www.researchgate.net/profile/Sylvia-Pietri/publication/14077269_Cardioprotective_and_Anti-oxidant_Effects_of_the_Terpenoid_Constituents_ofGinkgo_bilobaExtract_EGb_761/links/5b82c0b84585151fd133f92c/Cardioprotective-and-Anti-oxidant-Effects-of-the-Terpenoid-Constituents-ofGinkgo-bilobaExtract-EGb-761.pdf
Ponto, Laura L. Boles, and Susan K. Schultz. "Ginkgo biloba extract: review of CNS effects." Annals of Clinical Psychiatry 15, no. 2 (2003): 109-119. http://webspace.pugetsound.edu/facultypages/bdasher/Chem361/Review_Articles_files/Ginko%20Biloba.pdf
Printer E, Amri H, Li W, et al. Cancer-related overexpression of the peripheral-type benzodiazepine receptor and cytostatic anticancer effects of Ginkgo biloba extract (EGb 761). Anticancer Res. Jan-Feb 2006;26(1a):9-22.
Procházková K, Šejna I, Skutil J, et al. Ginkgo biloba extract EGb 761(®) versus pentoxifylline in chronic tinnitus: a randomized, double-blind clinical trial. Int J Clin Pharm. Oct 2018;40(5):1335-1341.
Rigney, U., S. Kimber, and I. Hindmarch. "The effects of acute doses of standardized Ginkgo biloba extract on memory and psychomotor performance in volunteers." Phytotherapy Research 13, no. 5 (1999): 408-415. https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1099-1573(199908/09)13:5%3C408::AID-PTR530%3E3.0.CO;2-C
Sastre, Juan, Arantxa Millan, Jose Garcia de la Asuncion, Rosa Pla, Gloria Juan, Federico V. Pallardo, Enrique O’Connor, Jose A. Martin, Marie-Therese Droy-Lefaix, and José Viña. "A Ginkgo biloba extract (EGb 761) prevents mitochondrial aging by protecting against oxidative stress." Free Radical Biology and Medicine 24, no. 2 (1998): 298-304. https://www.sciencedirect.com/science/article/abs/pii/S0891584997002281
Shakibaei F, Radmanesh M, Salari E, et al. Ginkgo biloba in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. A randomized, placebo-controlled, trial. Complement Ther Clin Pract. May 2015;21(2):61-67.
Shi, Chun, Jun Liu, Fengming Wu, and David T. Yew. "Ginkgo biloba extract in Alzheimer’s disease: from action mechanisms to medical practice." International Journal of Molecular Sciences 11, no. 1 (2010): 107-123. https://www.mdpi.com/1422-0067/11/1/107
Smith, J. V., and Yuan Luo. "Studies on molecular mechanisms of Ginkgo biloba extract." Applied microbiology and biotechnology 64, no. 4 (2004): 465-472. https://link.springer.com/article/10.1007/s00253-003-1527-9
Smith, Julie Vining, and Yuan Luo. "Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761." Journal of Alzheimer's Disease 5, no. 4 (2003): 287-300. https://www.researchgate.net/profile/Yuan-Luo-15/publication/9003295_Elevation_of_Oxidative_Free_Radicals_in_Alzheimer%27s_Disease_Models_Can_Be_Attenuated_by_Ginkgo_biloba_Extract_EGb_761/links/004635168089b3e3da000000/Elevation-of-Oxidative-Free-Radicals-in-Alzheimers-Disease-Models-Can-Be-Attenuated-by-Ginkgo-biloba-Extract-EGb-761.pdf
Spiegel R, Kalla R, Mantokoudis G, et al. Ginkgo biloba extract EGb 761(®) alleviates neurosensory symptoms in patients with dementia: a meta-analysis of treatment effects on tinnitus and dizziness in randomized, placebo-controlled trials. Clin Interv Aging. 2018;13:1121-1127.
Stackman, Robert W., Felix Eckenstein, Balz Frei, Doris Kulhanek, Jessica Nowlin, and Joseph F. Quinn. "Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment." Experimental neurology 184, no. 1 (2003): 510-520. https://d1wqtxts1xzle7.cloudfront.net/42921227/Prevention_of_age-related_spatial_memory20160221-15236-vnqg90-libre.pdf?1456118206=&response-content-disposition=inline%3B+filename%3DPrevention_of_age_related_spatial_memory.pdf&Expires=1645563805&Signature=HDbrPmY7GKfyHkfiEBtjYEqnlrwjuh500anOGXtvt4DruY-cdR4b-S4BnHDdaOjhtRI~YczamfdOTKnZb6X08qPEevoKjT-3b4A4WrtLEesr7q1ZTodUX~1ytBlaeNAKsk5cfLpnhKtQBXKwTrkYktNvCbcu2N9bqvUhVyaBNPhagsI3RFH6rz0dsrXkXpUKjlg8M8gvQmsBh9o2F1gmJYdPE3WIKMZv9JwmAzVUYA8q7rdN8S8Pt0FGBpked5ZyrMkcae4vK4jeVp~gMmXEnMsX63UrffNe7sPrXxTOW0IatghpBemMP0ChJzhQtVa0aIOoZdS2uXKWaEo2VAZcjA__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA
Stromgaard, K. "Medicinal chemistry of Ginkgolides from Ginko biloba." Medicinal Chemistry of Bioactive Natural Products. New Jersey: John Wiley & Sons (2006): 301-323. https://www.webpal.org/SAFE/aaarecovery/7_medicine/Medicine%20-%20Herbal/Medicine%20Herbal%20Pharmacology.pdf#page=317
Suzuki R, Kohno H, Sugie S, et al. Preventive effects of extract of leaves of ginkgo (Ginkgo biloba) and its component bilobalide on azoxymethane-induced colonic aberrant crypt foci in rats. Cancer Lett. Jul 16 2004;210(2):159-169.
Watanabe, Coran MH, Siegfried Wolffram, Peter Ader, Gerald Rimbach, Lester Packer, John J. Maguire, Peter G. Schultz, and Kishorchandra Gohil. "The in vivo neuromodulatory effects of the herbal medicine ginkgo biloba." Proceedings of the National Academy of Sciences 98, no. 12 (2001): 6577-6580. https://www.pnas.org/content/pnas/98/12/6577.full.pdf
Wesnes, K. A., T. Ward, A. McGinty, and O. Petrini. "The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers." Psychopharmacology 152, no. 4 (2000): 353-361. https://www.researchgate.net/profile/Orlando-Petrini/publication/12189551_The_memory_enhancing_effects_of_a_Ginko_bilobaPanax_ginseng_combination_in_healthy_middle-aged_volunteers/links/547ad4d60cf2a961e487b7db/The-memory-enhancing-effects-of-a-Ginko-biloba-Panax-ginseng-combination-in-healthy-middle-aged-volunteers.pdf
Xu AH, Chen HS, Sun BC, et al. Therapeutic mechanism of Ginkgo biloba exocarp polysaccharides on gastric cancer. World J Gastroenterol. Nov 2003;9(11):2424-2427.
Yao, Ping, Fangfang Song, Ke Li, Shaoliang Zhou, Shuang Liu, Xiufa Sun, Andreas K. Nussler, and Liegang Liu. "Ginkgo biloba extract prevents ethanol induced dyslipidemia." The American journal of Chinese medicine 35, no. 04 (2007): 643-652. http://www.encognitive.com/files/Ginkgo%20biloba%20Extract%20Prevents%20Ethanol%20Induced%20Dyslipidemia.pdf
Ye B, Aponte M, Dai Y, et al. Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence. Cancer Lett. Jun 18 2007;251(1):43-52.
Yoo DY, Nam Y, Kim W, et al. Effects of Ginkgo biloba extract on promotion of neurogenesis in the hippocampal dentate gyrus in C57BL/6 mice. J Vet Med Sci. Jan 2011;73(1):71-76.
Yu, Dingyi, Pengli Zhang, Junying Li, Ting Liu, Yaodan Zhang, Qingqing Wang, Jianbing Zhang, Xiaoyan Lu, and Xiaohui Fan. "Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson’s disease." Journal of pharmaceutical analysis 11, no. 2 (2021): 220-231. https://www.sciencedirect.com/science/article/pii/S2095177919309876
Zhou, Wei, Hong Chai, Peter H. Lin, Alan B. Lumsden, Qizhi Yao, and Changyi Chen. "Clinical use and molecular mechanisms of action of extract of Ginkgo biloba leaves in cardiovascular diseases." Cardiovascular Drug Reviews 22, no. 4 (2004): 309-319. https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1527-3466.2004.tb00148.x