CogniPlex - Ginkgo biloba leaf [24% flavones + 6% lactones; Ginkgolic acid ≤ 5ppm] powder extract

CogniPlex Key Facts

• A gold standard ginkgo extract complying to EU, US and JP specifications and standards
• Proprietary hydro-alcoholic extraction process, free from contaminants and adulteration

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Background

Ginko biloba (commonly known as Ginkgo) or maidenhair tree belongs to the Ginkgoaceae family, originating in China before spreading to Korea and Japan and eventually introduced to Europe and North America. The leaves of Ginkgo have a long history of use in Chinese medicine, usually consumed as a tea to provide a relaxing effect for asthma and bronchitis. More recently, the use of Ginkgo is focused on the treatment of cognitive decline, memory, peripheral claudication and tinnitus (Sierpina et al., 2003).

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Chemistry

Ginkgo Biloba contains flavonoid glycosides, terpenes lactones and Ginkgolic acids. CogniPlex is a premium quality Ginkgo biloba leaf extract produced by a proprietary Hydroalcoholic extraction process and standardised to 24% of flavone glycosides and 6% terpene lactones. Ginkgolic acid content of Cogniplex is less than 5 ppm (typically nil) to ensure consumer health and safety. Many Ginkgo imitators on the market also add Rutin or other flavonoids to increase the content of flavones in their product, however the ratio of Quercetin to Kaempferol and of Isorhamnetin to Quercetin are indicators of the authenticity of the extract. CogniPlex has been tested and contains less than 3% Rutin as well as having a Quercetin / Kaempferol ratio of 0.8 to 1.2 and a Isorhamnetin/ Quercetin ratio of no less than 0.15. As well as this, the levels of free Quercetin, free Kaempferol and Free Isorhamnetin are also indicators of the nature of the extract. CogniPlex contains NMT 1.0%, 1.0% and 0.4% of these respectively.

Brief Identification of Ginkgo Flavone Glycosides in CogniPlex.

Quercetin

CAS – 117-39-5
Molecular Formula – C15H10O7
Molecular Weight – 302.23 g/mol
IUPAC – 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one

Kaempferol

CAS – 520-18-3
Molecular Formula – C15H10O6
Molecular Weight – 286.24 g/mol
IUPAC – 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one

Isorhamnetin

CAS – 480-19-3
Molecular Formula – C16H12O7
Molecular Weight – 316.26 g/mol
IUPAC – 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one

Brief Identification of Terpene Lactones in CogniPlex.

Ginkgolide A

CAS – 15291-75-5
Molecular Formula – C20H24O9
Molecular Weight – 408.4 g/mol
IUPAC – (1R,3R,6R,7S,8S,10R,11S,13S,16S,17R)-8-tert-butyl-6,17-dihydroxy-16-methyl-2,4,14,19-tetraoxahexacyclo[8.7.2.01,11.03,7.07,11.013,17]nonadecane-5,15,18-trione

Ginkgolide B

CAS – 15291-77-7
Molecular Formula – C20H24O10
Molecular Weight – 424.4 g/mol
IUPAC – 8-tert-butyl-6,12,17-trihydroxy-16-methyl-2,4,14,19-tetraoxahexacyclo[8.7.2.01,11.03,7.07,11.013,17]nonadecane-5,15,18-trione

Ginkgolide C

CAS – 15291-76-6
Molecular Formula – C20H24O11
Molecular Weight – 440.4 g/mol
IUPAC – (1R,3R,6R,7S,8S,9R,10S,11R,12S,13S,16S,17R)-8-tert-butyl-6,9,12,17-tetrahydroxy-16-methyl-2,4,14,19-tetraoxahexacyclo[8.7.2.01,11.03,7.07,11.013,17]nonadecane-5,15,18-trione

Ginkgolide J

CAS – 107438-79-9
Molecular Formula – C20H24O10
Molecular Weight – 424.4 g/mol
IUPAC – (1R,3R,6R,7S,8S,9R,10S,13S,16S,17R)-8-tert-butyl-6,9,17-trihydroxy-16-methyl-2,4,14,19-tetraoxahexacyclo[8.7.2.01,11.03,7.07,11.013,17]nonadecane-5,15,18-trione

Bilobalide

CAS – 33570-04-6
Molecular Formula – C15H18O8
Molecular Weight – 326.30 g/mol
IUPAC – (1S,4R,7R,8S,9R,11S)-9-tert-butyl-7,9-dihydroxy-3,5,12-trioxatetracyclo[6.6.0.01,11.04,8]tetradecane-2,6,13-trione

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Ginkgo Biloba and Health

While the use of Ginkgo is commonly focused on cognition and the treatment of cognitive decline, research has indicated that Ginkgo has multiple mechanisms of action and therefore has uses in numerous conditions. The two main mechanisms of action are related to the antagonism of Platelet Activating Factor (PAF) by the ginkgolides and second is the antioxidant action of flavonoids (Liu et al., 2018; Priyanka et al., 2014). The flavonoid component of Ginkgo has also been shown to lessen the lipid accumulation associated with up-regulation of carnitine palmitoyl transferase 1A in the beta-oxidation of long-chain fatty acids, therefore being beneficial in the prevention and treatment of non-alcoholic fatty liver disease (Wang et al., 2012). Other benefits observed are from Ginkgo’s functions as a neuroprotective agent, a free-radical scavenger and a membrane stabiliser, however the mechanisms of action of Ginkgo are not limited to these (Sierpina et al., 2003).

Cognitive Decline / Dementia / Alzheimer’s Disease

Research has indicated that the effects and benefits seen from the use of Ginkgo biloba in patients with Alzheimer’s disease and dementia is comparable to the benefits seen with pharmaceutical interventions (Kleijnen & Knipschild, 1992; Sierpina et al., 2003). Numerous studies have demonstrated that Ginkgo biloba can stabilise or slow the decline in cognition function and behaviour in individuals with cognitive impairment and dementia (Tan et al., 2014). In some individuals, dementia and mild cognitive impairment can be accompanied by neuropsychiatric symptoms such as anxiety, depression and irritability. It has been seen that individuals with these symptoms can benefit greater from the use of ginkgo (Brondino et al., 2013; Garvrilova et al., 2014). In individuals with impaired cognition, there appears to be an improvement with both an acute single dose of Ginkgo (Kennedy et al., 2000) and long-term use (Rai et al., 1991), with the latter potentially resulting in more positive outcomes (Liu et al., 2020).

Intermittent Claudication

Ginkgo has demonstrated that it has potential use in individuals who suffer with intermittent claudication, also known as vascular claudication. Intermittent claudication is an early symptom of peripheral arterial disease, a debilitating atherosclerotic disease that is associated with an increased risk of cardiovascular morbidity and mortality (Pittler & Ernst, 2000; Meru et al., 2005). Intermittent claudication results in leg muscle pain and cramping due to inadequate blood supply. Numerous studies have shown that ginkgo use in individuals suffering from intermittent claudication decreases pain during walking (Sierpina et al., 2003).

Tinnitus

Tinnitus is a very common condition in which individuals experience internal sounds in one or both of their ears, in the absence of any external sounds (Baguley et al., 2013). These sounds can be ringing, hissing or sizzling, amongst many other possible sounds, and they can be constant or intermittent. The exact causes of tinnitus can differ greatly and are often unknown and therefore treatment can be difficult. However, the use of ginkgo in individuals with tinnitus has shown to result in a much quicker disappearance time of symptoms and it has been identified as a potentially effective treatment for the condition (Sierpina et al., 2003).

Metabolic Syndrome

Metabolic syndrome is a term given to a group of interconnected conditions including obesity, hypertension and insulin resistance that can then lead to diabetes and cardiovascular disease (Eisvand et al., 2020). There is evidence to suggest that ginkgo can be beneficial in the treatment of Metabolic syndrome. Dyslipidemia is an integral part of Metabolic syndrome and is characterised by decreased levels of high-density lipoprotein cholesterol, enhancement of low-density lipoprotein and irregular triglyceride levels. Ginkgo has been found to possess a protective effect on human lipid profiles through the lowering of these low-density lipoproteins and triglycerides, and raising high-density lipoprotein levels, resulting in a more favourable blood lipid profile (Eisvand et al., 2020). As well as this, the use of ginkgo has also been shown to cause an increase in energy expenditure and reduction in food intake which can ultimately lead to a decrease in body weight, having a positive effect on individuals with Metabolic syndrome. Another mechanism of action by which ginkgo can have a positive effect on Metabolic syndrome is via its protective effect on high blood pressure through the enhanced expression of endothelial nitric oxide and mRNA. In individuals with Metabolic syndrome, a factor that contributes to the development of conditions such as type 2 diabetes and cardiovascular disease is an increase in levels of both glucose and insulin within their bloodstream. Ginkgo has demonstrated an ability to increase the uptake of glucose in muscles and liver, resulting in less circulating insulin as well as increasing insulin sensitivity ultimately meaning less circulating glucose and insulin (Eisvand et al., 2020).

Glaucoma

Glaucoma is one of the world’s leading causes of blindness and is characterised by progressive optic nerve damage and selective loss of retinal ganglion cells (Hirooka et al., 2004). There is evidence to show that ocular vasculature dysfunction and oxidative stress are associated with glaucomatous damage. Ginkgo extracts have been found to improve ocular blood flow and possess antioxidative properties, subsequently reducing the damage caused by the condition (Kang & Lin, 2020). Studies have also found that Ginkgo may potentially reduce retinal ganglion cell loss (Hirooka et al., 2004). Oxidative stress may potentially contribute to glaucomatous damage and a Ginkgo has shown to possess antioxidative properties, this is another reason that it may be beneficial for individuals with glaucoma (Kang & Lin, 2020).

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Trademark

CogniPlex is a trademark of Vita Actives, EU trademark number 013882204.

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References

1. Baguley, D., McFerran, D. and Hall, D., 2013. Tinnitus. The Lancet, 382(9904), pp.1600-1607.
2. Brondino, N., De Silvestri, A., Re, S., Lanati, N., Thiemann, P., Verna, A., Emanuele, E. and Politi, P., 2013. A Systematic Review and Meta-Analysis ofGinkgo bilobain Neuropsychiatric Disorders: From Ancient Tradition to Modern-Day Medicine. Evidence-Based Complementary and Alternative Medicine, 2013, pp.1-11.
3. Eisvand, F., Razavi, B. and Hosseinzadeh, H., 2020. The effects of Ginkgo biloba on metabolic syndrome: A review. Phytotherapy Research, 34(8), pp.1798-1811.
4. Gavrilova, S., Preuss, U., Wong, J., Hoerr, R., Kaschel, R. and Bachinskaya, N., 2014. Efficacy and safety of Ginkgo biloba extract EGb 761 ® in mild cognitive impairment with neuropsychiatric symptoms: a randomized, placebo‐controlled, double‐blind, multi‐center trial. International Journal of Geriatric Psychiatry, 29(10), pp.1087-1095.
5. Hirooka, K., Tokuda, M., Miyamoto, O., Itano, T., Baba, T. and Shiraga, F., 2004. The Ginkgo biloba extract (EGb 761) provides a neuroprotective effect on retinal ganglion cells in a rat model of chronic glaucoma. Current Eye Research, 28(3), pp.153-157.
6. Kang, J. and Lin, S., 2018. Ginkgo biloba and its potential role in glaucoma. Current Opinion in Ophthalmology, 29(2), pp.116-120.
7. Kennedy, D., Scholey, A. and Wesnes, K., 2000. The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. Psychopharmacology, 151(4), pp.416-423.
8. Kleijnen, J. and Knipschild, P., 1992. Ginkgo biloba. The Lancet, 340(8828), pp.1136-1139.
9. Liu, H., Ye, M. and Guo, H., 2020. An Updated Review of Randomized Clinical Trials Testing the Improvement of Cognitive Function of Ginkgo biloba Extract in Healthy People and Alzheimer’s Patients. Frontiers in Pharmacology, 10.
10. Liu, X., Yang, J., Niu, W., Jia, W., Olaleye, O., Wen, Q., Duan, X., Huang, Y., Wang, F., Du, F., Zhong, C., Li, Y., Xu, F., Gao, Q., Li, L. and Li, C., 2018. Human pharmacokinetics of ginkgo terpene lactones and impact of carboxylation in blood on their platelet-activating factor antagonistic activity. Acta Pharmacologica Sinica, 39(12), pp.1935-1946.
11. Meru, A., Mittra, S., Thyagarajan, B. and Chugh, A., 2006. Intermittent claudication: An overview. Atherosclerosis, 187(2), pp.221-237.
12. Pittler, M. and Ernst, E., 2000. Ginkgo Biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. The American Journal of Medicine, 108(4), pp.276-281.
13. Priyanka, A., Nisha, V., Anusree, S. and Raghu, K., 2014. Bilobalide attenuates hypoxia induced oxidative stress, inflammation, and mitochondrial dysfunctions in 3T3-L1 adipocytes via its antioxidant potential. Free Radical Research, 48(10), pp.1206-1217.
14. Rai, G., Shovlin, C. and Wesnes, K., 1991. A double-blind, placebo-controlled study of Ginkgo biloba extract (‘Tanakan’) in elderly outpatients with mild to moderate memory impairment. Current Medical Research and Opinion, 12(6), pp.350-355.
15. Sierpina, V., Wollschlaeger, B. and Blumenthal, M., 2003. Ginkgo Biloba. American Family Physician, 1;68(5), pp.923-926.
16. Tan, M., Yu, J., Tan, C., Wang, H., Meng, X., Wang, C., Jiang, T., Zhu, X. and Tan, L., 2014. Efficacy and Adverse Effects of Ginkgo Biloba for Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis. Journal of Alzheimer's Disease, 43(2), pp.589-603.
17. Wang, S., Xie, Z., Chen, J., Wang, K., Wei, T., Zhao, A. and Zhang, Q., 2012. Inhibitory effect ofGinkgo bilobaextract on fatty liver: Regulation of carnitine palmitoyltransferase 1a and fatty acid metabolism. Journal of Digestive Diseases, 13(10), pp.525-535.