The purpose of this review is to assess all the aspects of Ginkgo biloba L. for traditional medicines practitioners in Pakistan and abroad. It is a large tree with fan-shaped leaves. The leaves are commonly included in supplements and taken by mouth for memory problems. The ginkgo tree is thought to be one of the oldest living trees, dating back more than 200 million years. It is native to China, Japan, and Korea, but is also now grown in Europe and the United States. It seems to improve blood circulation, and might also act as an antioxidant to slow down changes in the brain.

Keywords: Gingko biloba L., morphology, phytochemistry, Maidenhair, pharmacological effects

The fossil species must be ancient in relation to the current clade's time of genesis in order to qualify as a living fossil. Although they don't have to, living fossils typically come from lineages with few species. A living fossil's body plan may not change significantly from its distant relatives, but it is never the same species since genetic drift will always alter a fossil's chromosomal makeup. Stasis is observed in living fossils across extended geological timescales. It is a common misconception in popular literature that a "living fossil" has not changed much since the time of the fossil record, essentially lacking any morphological or molecular evolution. Scientific studies have consistently refuted these assertions.^1-3 Although the slightest outward alterations to extant fossils are incorrectly interpreted as proof against evolution, they actually represent stabilizing selection, an evolutionary process and may be the main driver of morphological evolution.⁴

One of these living fossils is Ginko bilioba linn. (GBL), which is commonly known as maidenhair. It is a native Chinese tree species. In the order Ginkgoales, which made its initial appearance more than 290 million years ago, it is the only surviving species. Very identical fossils to the extant species may be found in the Middle Jurassic, about 170 million years ago, and they belong to the genus Ginkgo.⁵ Early human history saw the cultivation of this tree, which is still widely grown today (Table 1). The purpose of present study was to assess the various aspects of GBL that may help in prescribing practices of traditional medicines practitioners in Pakistan and abroad.

Various electronic databases such as PubMed, Embase, Scopus, and Google Scholar were searched for keywords “Ginkgo biloba” or “ginkgo” in combination with “phytochemistry”, “ethnobotany”, “pharmacology” etc. to collect the relevant articles. There was no language restriction.

GBL and other species in the genus were formerly found all over the planet, but two million years ago, their range narrowed to include only a small portion of China. It was believed to be extinct in the wild for centuries, but it is currently confirmed to grow in the Tianmushan Reserve in Zhejiang province, eastern China, in at least two small locations.⁷

Morphology: Large trees, ginkgos typically grow to a height of 20–35 meters⁸ however some specimens in China reach as high as 50 meters. The tree is typically deeply rooted, has an angular crown, long, rather erratic branches, and is resistant to extreme cold and windy weather. As a tree ages, its crown widens; young trees are frequently tall, slender, and sparsely branched. Ginkgos are woody; some have been reported to be over 2,500 years old. Their resistance to disease, their insect-resistant wood, and their capacity to produce aerial roots and sprouts all contribute to their longevity. Among seed plants, the leaves are distinct in that they have a fan-like morphology with veins that extend into the leaf blade, occasionally bifurcating (splitting), but never forming an anastomosing network. Dichotomous venation occurs when two veins continually split into two at the base of the leaf blade. Usually ranging from 5 to 10 cm (2 to 4 in), the leaves can occasionally reach a length of 15 cm (6 in). The leaves of the maidenhair fern, Adiantum capillus-veneris, have a pinnae-like appearance, which is whence the ancient popular name "maidenhair tree" originated. Ginkgos are highly valued for their rich saffron-colored autumn leaves.⁹ Long shoot leaves are typically lobed or notch between veins, but only on the outer surface. They are borne on short, stubby spur shoots, where they are grouped at the tips, as well as on the tips of the faster-growing branch tips, where they are alternate and dispersed. With stomata on both sides, leaves are green on top and bottom. The leaves in autumn change to a vivid yellow color before dropping, sometimes in as little as one to fifteen days.¹⁰

Phytochemistry: The main constituents found in the leaf extracts of GBL are found to be terpene lactones (Ginkgolide B, Ginkgolide A, Bilobalide,Ginkgolide C, Ginkgolide J) and flavonoids (Quercetin, Quercetin-3-β-D glucoside, Rutin, Kaempferol, Quercetin, Isorhamnetin).¹¹

Pharmacological actions: GBL exhibits different pharmacological properties that are summarized in Table 2.

Pharmacotherapeutics: GBL is used to improve quality of life in mild dementia and (age-associated) cognitive impairment. Once more serious problems have been ruled out by a physician, traditional herbal medicinal products are used to relieve the sensation of cold hands and feet and heaviness in the legs that are linked with minor circulation disorders. There have been reports of specific organ bleeding (ocular, nasal, brain, and gastrointestinal hemorrhages). Headache, lightheadedness, diarrhea, abdominal pain, nausea, and vomiting are typical adverse effects.²⁷

Posology: The adult dose is 120-240mg once a day which should last for at least 8 weeks. However, the physician will rule out the other causes if he finds out no improvement after 3 months.²⁷

GBL is a tree indigenous to People Republic of China and has been cultivated due to its beneficial effects since long. It is also known as ‘Living Fossil’ due to its ancient order. Its various plants parts are used in traditional Chinese medicines, however, recent research mainly focuses on ginkgo extract. These extracts are used in supplements that are associated with various health claims related to memory functions and blood problems. Raw ginkgo seed causes intoxication so it must be cooked before use. People with a history of angina should use the seed with cautions. The herb is safe at the normal suggested dosage. However, there are reports of few patients who became allergic to the herb and suffered various side effects. Traditional practitioners must take all necessary measures while prescribing the GBL.

None.

Authors declare no conflict of interest.

1. Casane D, Laurenti P. Why coelacanths are not 'living fossils. BioEssays. 2013;35(4):332–338.
2. Mathers TC, Hammond RL, Jenner RA, et al. Multiple global radiations in tadpole shrimps challenge the concept of living fossils. PeerJ. 2013;1:e62.
3. Grandcolas P, Nattier R, Trewick S. Relict species: a relict concept?. Trends Ecol Evol. 2014;29(12):655–663.
4. Lynch M. The rate of evolution in mammals from the standpoint of the neutral expectation. The American Naturalist. 1990;136(6):727–741.
5. Sun W. Ginkgo biloba L. IUCN Red List of Threatened Species; 1998.
6. Integrated Taxonomic Information System. Ginkgo biloba L.
7. Usher C, White J, Ridsdale C. Eyewitness Companions: Trees: Identification, Forests, Historic Species, Wood Types. DK publishing; 2005.
8. Ansari AA, Gill SS, Abbas ZK, et al. Plant Biodiversity: Monitoring, Assessment and Conservation. CABI; 2016.
9. More on Morphology of the Ginkgoales; 2000.
10. http://ginkgo.dm.pagesperso-orange.fr/GINKGO/GbMorphology.htm
11. Sati P, Pandey A, Rawat S, et al. Phytochemicals and antioxidants in leaf extracts of Ginkgo biloba with reference to location, seasonal variation and solvent system. J Pharm Res. 2013;7(9):804–809.
12. Butler M, Nelson VA, Davila H, et al. Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2018;168(1):52–62.
13. Dai CX, Hu CC, Shang YS, et al. Role of Ginkgo biloba extract as an adjunctive treatment of elderly patients with depression and on the expression of serum S100B. Medicine (Baltimore).  2018;97(39):e12421.
14. Zhang WF, Tan YL, Zhang XY, et al. Extract of Ginkgo biloba treatment for tardive dyskinesia in schizophrenia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011;72(5):615–621.
15. Savaskan E, Mueller H, Hoerr R, et al. Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials. Int Psychogeriatr. 2018;30(3):285–293.
16. Gillian K, Lauren DA, Louise HW. Acute effects of Ginkgo biloba extract on vascular function and blood pressure. Plant Foods Hum Nutr. 2011;66(3):209–211.
17. Ameneh M, Dzung PL, David YM. Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative MR perfusion imaging: a pilot study. Neuroradiology. 2011;53(3):185–191.
18. Sherif IO, Al-Shaalan NH. Hepatoprotective effect of Ginkgo biloba extract against methotrexate-induced hepatotoxicity via targeting STAT3/miRNA-21 axis. Drug Chem Toxicol. 2022;45(4):1723–1731.
19. Wang Z, Zhang P, Wang Q, et al. Protective effects of Ginkgo Biloba Dropping Pills against liver ischemia/reperfusion injury in mice. Chin Med. 2020;15(1):122.
20. Woon PJ, Jung KH, Seok CW. Short-term effects of Ginkgo biloba extract on peripapillary retinal blood flow in normal tension glaucoma. Korean J Ophthalmol. 2011;25(5):323–328.
21. Gamal EM, Aly EM, Mahmoud SS, et al. FTIR assessment of the effect of Ginkgo biloba leaf extract (EGb 761) on mammalian retina. Cell Biochem Biophys. 2011;61(1):169–177.
22. Chu X, Ci X, He J. A novel anti-inflammatory role for ginkgolide B in asthma via inhibition of ERK/MAPK signaling pathway. Molecules. 2011;16(9):7634–7648.
23. Tao Z, Jin W, Ao M, et al. Evaluation of the anti-inflammatory properties of the active constituents in Ginkgo biloba for the treatment of pulmonary diseases. Food & Function. 2019;10(4):2209–2220.
24. Dal BE, Rigo GL, Campos PM, et al. Photoprotective effects of tropical formulations containing a combination of Ginkgo biloba and green tea extracts. Phytother Res. 2011;25(12):1854–1860.
25. Mashhadi ZN, Irani M, Mask MK, et al. A systematic review of clinical trials on Ginkgo (Ginkgo biloba) effectiveness on sexual function and its safety. Avicenna J Phytomed. 2021;11(4):324–331.
26. Meston CM, Rellini AH, Telch MJ. Short-and long-term effects of Ginkgo biloba extract on sexual dysfunction in women. Arch Sex Behav. 2008;37(4):530–547.
27. European Union herbal monograph on Ginkgo biloba L., folium; 2015. 8 p.