Arches. Photo by Daniel Chia
HOPES: Huntington's Outreach Project for Education, at Stanford
Jun
29
2010

Ginkgo Biloba

Drug Summary: Ginkgo biloba has been shown to have antioxidant and anti-inflammatory properties. Because free radicals and inflammation are believed to be factors involved in the progression of HD, Ginkgo biloba may help in alleviating the symptoms of HD. However, no studies have been done yet on the effects of Ginkgo biloba on people with HD. Instead, preliminary research is being conducted to test the effects of Ginkgo biloba on diseases that also involve inflammation such as Alzheimer’s Disease.

Fig K-1: Gingko Biloba

Ginkgo biloba (G. biloba) is a type of tree that has existed for over 200 million years. Medicinal extracts are made from the dried leaves of the tree and have been used for 5000 years in traditional Chinese medicine for various purposes. The extract has been shown to have protective effects against mitochondrial damage and oxidative stress. Figure K-1 shows an image of Ginkgo leaves.

There are different variants of Ginkgo biloba extracts available on the market today. Among them are EGb 761, LI 1379, and Chinese Ginkgo extract ZGE. These extracts differ in their extraction process as well as composition. The principal constituents of Ginkgo biloba extract include flavonoids, terpenoids (ginkgolides and bilobalide) and different organic acids. The standardized extract usually contains 24% flavonoids and 6% terpenoids. Let us review the different biological activities of these components.

Flavonoids^

The flavonoids contribute to Ginkgo’s antioxidant properties. They have been found to reduce the levels of free radicals, which are highly reactive molecules with unpaired electrons. One way by which flavonoids protect the cell is by reducing cell membrane lipid peroxidation. Lipid peroxidation is defined as the process whereby free radicals “steal” electrons from the lipids in our cell membranes, resulting in cell damage and increased production of free radicals. Lipids include molecules such as fatty acids, cholesterol, and other related compounds. As antioxidants, the flavonoids neutralize the free radicals in our cell, lowering the levels of free radicals available for lipid peroxidation. (For more on free radicals, click here.)

Terpenoids^

The other major components of ginkgo extract are the terpenoids. The terpenoids include bilobalide and the ginkgolides A, B, C, M, and J.

Bilobalides are closely related in structure to the ginkgolides. Bilobalides have been proposed to have protective effects on nerve cells and on the nervous tissue through their role in motor nerve cell regeneration.

The ginkgolides inhibit the activity of the compound known as platelet-activating factor (PAF). PAF reduces inflammation by increasing permeability of blood vessels and contracting various involuntary muscles such as those in airways. (For more on inflammation, click here). PAF activation is also associated with the aggregation of platelets, which aid in blood clotting. Ginkgo supplementation has therefore been associated with anti-inflammatory effects as well as reduced blood clotting.

Fig K-2: Summary of the Effects of Gingko Biloba

Based on these biological properties of its constituent compounds, Ginkgo biloba supplementation may result in antioxidant, anti-inflammatory, and neuroprotective effects. Although the primary cause of HD is still unknown, prominent hypotheses center around injury caused by free radical oxidation damage and chronic inflammation. Given its antioxidant and anti-inflammatory properties, Ginkgo biloba may therefore be beneficial to people with HD. To date, no studies have been done regarding Ginkgo biloba’s effects on people with HD; however, some studies have investigated the effects of Ginkgo biloba on individuals with Alzheimer’s Disease (AD). AD is associated with disease mechanisms that are similar to HD, and so it is possible that some of these findings may be useful for future HD research.

In most of the clinical studies of Ginkgo biloba and Alzheimer’s patients, no serious side effects were noted. However, some case studies reported that people taking Ginkgo experience prolonged bleeding times due to its inhibition of PAF. Two case reports of hemorrhage were reported by people who were taking Ginkgo. Compounds such as aspirin and warfarin that are known to inhibit blood clotting have been found to result in bleeding complications when taken with Ginkgo. However, as of this writing (November 2001), the frequency and magnitude of bleeding complications with Ginkgo supplementation is still unclear.

Research on Ginkgo Biloba^

Fig K-3: Effect of Gingko Biloba on Nerve Cells Exposed to H2O2

Oyama, et al. (1996) hypothesized that Ginkgo biloba treatment would have beneficial effects on cells exposed to the free radical hydrogen peroxide. The researchers first exposed nerve cells to hydrogen peroxide to see what happens to the cells after administration of hydrogen peroxide. They discovered that prolonged exposure to hydrogen peroxide resulted in the death of many nerve cells. To test the protective effects of Ginkgo biloba, nerve cells were treated with Ginkgo biloba extract for 1 hour before adding hydrogen peroxide. Ginkgo biloba treatment was found to increase the number of surviving nerve cells after hydrogen peroxide exposure. The researchers then compared the effects of Ginkgo biloba treatment 1 hour before, immediately after, and 1 hour after cells were exposed to hydrogen peroxide. They discovered that although Ginkgo biloba had protective effects when applied either immediately after or 1 hour after hydrogen peroxide exposure, the beneficial effects were weaker than that of treatment before hydrogen peroxide exposure. Figure K-3 shows a graph depicting the effects of Ginkgo biloba treatment.

Studies by other researchers showed that Ginkgo biloba extract exerted neuroprotective effects on nerve cells exposed to the hydroxyl radical, another type of free radical. The extract also had a scavenging effect on superoxide anions, which are also free radicals. Together with the results of the current study, it is believed that Ginkgo biloba may have neuroprotective effects on nerve cells suffering from cell damage induced by free radicals. Because free radical damage is hypothesized to play a role in the progression of HD, Ginkgo biloba treatment on HD cells may have beneficial effects.

Le Bars, et al. (1997) examined the effects of a particular extract of Ginkgo biloba on people with Alzheimer’s Disease (AD). Damage by free radicals and inflammation has been implicated as one of the mechanisms by which AD cells die. The researchers hypothesized that treatment with an antioxidant and anti-inflammatory molecule such as Ginkgo biloba may have beneficial effects on people with AD.

The extract the researchers used in this study was EGb 761, which is a particular extract of Ginkgo biloba used in Europe to alleviate symptoms associated with several cognitive disorders. Participants included 309 demented patients with mild to moderately severe cognitive impairment caused by Alzheimer’s Disease.

The participants were randomly assigned to treatment with Egb (120 mg/day) or a placebo. The trial was conducted for 52 weeks (13 months) in 6 research centers in the United States. The researchers assessed changes in 3 areas: cognitive impairment, daily living and social behavior, and overall psychopathology.

The results of the study indicated that Ginkgo biloba treatment was able to produce beneficial effects in 2 of the 3 outcomes: cognitive impairment and daily living and social behavior. No differences in overall psychopathology between the treated and placebo group were observed.

The results of this study indicated that Ginkgo biloba treatment may slow the deterioration of some people with AD. However, the researchers stated that more trials should be conducted to examine the effects of various dosages on slowing deterioration caused by AD to ensure that the proper dosage is administered. Furthermore, the exact mechanism of action by which Ginkgo biloba exerts its effects remains unknown. More research is also needed to reveal these mechanisms, in order to better explore the full therapeutic potential of Ginkgo biloba.

Mahdy et al. (2011) found that ginkgo biloba might repair some of the neurological problems caused by a toxin, 3-Nitropropionic acid (3-NP). When injected into the brains of mice, 3-NP mimics the effects of HD: it causes many of the biological and behavioral changes that are seen in people with HD. But mice that were treated with both 3-NP and ginkgo biloba showed milder neurodegenerative problems than those treated with 3-NP alone. Several biochemical changes that occur upon exposure to 3-NP were mitigated in animals that were treated with ginkgo biloba. Authors suggest that ginkgo biloba’s antioxidant properties, antiapoptotic effects, and improvement of energy metabolism were responsible for the neuroprotective effects.

For further reading^

  1. Oyama, et al. “Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide.” Brain Research. 1996; 712:349-352.
    This study reported that G. biloba was able to protect nerve cells exposed to various free radicals.
  2. LeBars, et al. “A Placebo-Controlled, Double-Blind, Randomized Trial of an Extract of Ginkgo Biloba for Dementia.” JAMA. 1997; 278(16): 1327-1332.
    This study reported that G. biloba treatment resulted in cognitive and behavioral improvements in people with Alzheimer’s Disease.
  3. Mahdy HM, Tadros MG, Mohamed MR, Karim AM, Khalifa AE. The effect of Ginkgo biloba extract on 3-nitropropionic acid-induced neurotoxicity in rats. Neurochem Int. 2011 Jul 31. This technical study reported that Ginkgo biloba treatment in mice relieved some of the problems caused upon injection of 3-NP, a chemical that mimics HD

-E. Tan, 11-22-01; Updated by P. Chang, 5/6/03; updated by M. Hedlin, 8/11/11