GINKGO BILOBA AND GLAUCOMA

GUEST AUTHOR

FAKHRA KHAN

AJMAL KHAN TIBBIYA COLLEGE

ALIGARH, INDIA

INTRODUCTION

Glaucoma is a multifactorial neurodegenerative disorder.

One school of thought emphasizes the role of vascular dysregulation, mitochondrial dysfunction, oxidative stress, ischemia and release of certain factors in the pathogenesis of glaucomatous optic atrophy (GOA).

Conventional medications used in the treatment of glaucoma do not focus on improving ocular blood flow (OBF), primarily being concerned with lowering of intra-ocular pressure (IOP).

However, complementary and alternative medicines (CAM) may have a role in the management of glaucoma because of their varied modes of action.

According to one study conducted in India, as many as 5-10% patients reportedly use CAM for their glaucoma therapy.

Bhartiya S, Ichhpujani P. Complementary and alternate management of glaucoma: the verdict so far. J Curr Glaucoma Pract. 2014;8:54-57.

Ginkgo biloba (GB) has multiple facets in the management of glaucoma, including neuroprotection, anti-oxidation, vasodilatation and reduced blood viscosity.

This blog post takes a look at this CAM product which is widely being used in glaucoma.

PHARMACOLOGY OF GINKGO BILOBA EXTRACT

EGb-761 is a standardized GBE (Ginkgo biloba extract) that has much of the toxic Gingkolic Acid removed, leaving behind the active component of flavonoid glycosides (22-27%) and terpene lactones (5-7%).

The terpene lactones in GBE are: ginkgolides A,B and C and bilobalide.

These active components have a role in glutamate-induced excitotoxicity.

The anti-oxidative properties of GBE, may be due to its ability to both scavenge reactive oxygen species (ROS) directly and inhibit the generation of them.

GBE, especially bilobalide, stabilizes the mitocohnodria which in turn could lead to the reduction of ROS production.

The antagonistic action of Ginkgolid-B on platelet activator factor (PAF) may also play a role in neuroprotection. PAF concentration increases during trauma and hypoxia, and regulation of PAF may slow apoptosis and enhance post-ischemic recovery.

It can also reduce lipid peroxidation and GBE supplementation reduces erythrocyte malendialdehyde (MDA) levels.

GBE increases erythrocyte deformability, which improved blood viscosity and visco-elasticity, potentially facilitating blood perfusion.

GBE may also promote blood perfusion via endothelium dependent vasodilatation.

GINKGO AND OCULAR BLOOD FLOW

GBE significantly increased end-diastolic velocity in the ophthalmic artery in all retrobulbar blood vessels.

Ginkgo Biloba significantly reduces retinal vessel diameter (p <0.05 vs. baseline).

Optic nerve head blood flow significantly increased in response to GB, but the effect is not significant when compared to placebo.

GBE significantly increased end diastolic velocity in the ophthalmic artery and in all retrobulbar blood vessels, reduced vascular resistance in the central retinal and nasal short posterior ciliary artery, increased superior and inferior temporal retinal capillary mean blood flow and increased ratio of active to inactive retinal capillaries.

GINKGO NEUROPROTECTION AND ANTIOXIDANT EFFECTS

GBE has been therapeutically used for several decades to increase peripheral and cerebral blood flow as well as the treatment of dementia.

The extract contains multiple compounds such as flavoids and terperoids that are thought to contribute to its neuroprotective and vasotropic affects.

GBE treatment for 5-months did not change IOP, but did show significantly reduced retinal ganglion cell loss.

In optic nerve crush injury models, higher retinal ganglion cell (RGC) survival rates were observed on treatment with GBE.

GBE can stabilize and protect against mitochondrial dysfunction in different type of cells.

GINKGO AND VISUAL FIELD OUTCOMES

Quranta et al evaluated visual field outcomes after GBE supplementation in 27 patients with normal tension glaucoma (NTG) and pre-existing progressive VF defects.

Individuals who received 40 mg GBE TID for 4 weeks had statistically significant improvement in VF indices when compared to placebo.

The effects were assumed to be due to improved OBF, the GBE’s positive effect on cognitive function, leading to increased retinal sensitivity, alertness and concentration.

However, the effects of GBE on VF performance were temporary and did not persist after the 4-week washout period.

Another study by Guo et al. used a similar model to study the effects of GBE on 28 Chinese patients with newly diagnosed NTG. The outcomes of this study were visual field indices as well changes in contrast sensitivity. No statistically significant difference in either of these outcomes was seen after GBE treatment.

Racial differences also played an important role as one of the study population is from Italy and the other one is from China. Such differences contribute to altered OBF and NTG causation.

A Korean study found GBE did not improve VF indices, but did have slower progression of VF changes after GBE treatment compared with progression of VFs seen prior to starting GBE.

SAFETY PROFILE

Ginkgo is usually considered safe.

Studies used total daily dose of 80-600 mg GBE using supplementation of atleast 22 weeks. There was no statistical difference in side-effects when GBE was compared with placebo.

Other studies show that the concurrent use of GBE and acetylsalicylic acid did not find any difference in bleeding time, coagulation parameter or platelet function when compared with acetylsalicylic acid alone.

CONCLUSION

Ginkgo biloba has multiple facets in the management of glaucoma including neuroprotection, anti-oxidation, vasodilatation and reduced blood viscosity.

Animal models suggest that GBE may have a neuroprotective effect on RGCs. However, the clinical effect on glaucoma outcomes such as VF performance is inconclusive.

BOTANICAL CHARACTERISTICS OF GINKGO BILOBA

PROF. SYED MOHAMMAD AHMAD

Ex- Head of the Department of Botany,

Saifia College, Bhopal, India

Although little about the ecology of the plant in the wild is known, even under conditions of cultivation, Ginkgo is long-lived and eventually forms massive trees, around 30 meters in height and upto 9 meters in truck circumference. Particularly large trees occur in Japan, where one giant in the Chosenji Temple has a diameter of 4.86 meters. The home of Ginkgo, however, is China and not Japan.  The Chinese used to revere the older and larger tress as the “homes of the spirits”. Some of the trees are reportedly over 1000 years old.

The longevity of the tree is attributed to its ability to withstand insects, disease and pollution due to the pharmaceutically active compounds in its leaves. 

The fruit consists of a foul-smelling pulp, surrounding a cream-colored, thin-shelled, sweet kernelled stone. The starchy part of the seed, primarily the endosperm is eaten in China and Japan, either roasted or cooked; they are reported to be toxic when eaten raw. The expressed juice causes erythema (abnormal redness of skin due to local congestion), edema (effusion of fluid into the interstices of cells in tissue spaces or into body cavities), papules (small, some-what pointed elevations of the skin, usually inflammatory), pustules (small elevations of the skin containing pus), accompanied by intense itching.

The medicinal value of ginkgo can be traced back to the oldest Chinese Materia Medica dating back to around 3000 BC. The traditional Chinese medicine describes the ability of ginkgo leaves to benefit the brain, to relieve cough and symptoms of asthma. It is also known to act as an anti-oxidant, inhibit platelet aggregation, stabilize cell membranes, improve oxygen and glucose utilization by the tissues and reduce arteriolar spasms. It is highly effective in cerebral vascular insufficiency, poor blood circulation, memory loss, phlebitis and tinnitus.

There are a number of compounds isolated from Ginkgo biloba. Standardized extract provides flavonglycosides, gingkolides A,B & C and bilobalides. The last two mentioned substances increase blood supply, especially to the brain, enhancing tissue utilization of oxygen and glucose. Gingkolides inhibit a substance called PAF (Platelet Activating Factor), which is responsible for platelet aggregation and clot formation. PAF is also involved in many inflammatory and allergic reactions which cause arteriolar spasm and reduce blood supply. This substance has also been implicated in acute asthmatic attacks and it has been suggested that ginkgo may be of benefit to asthmatics.

Other applications of Ginkgo:

• Ginkgo extract is also effective in improvement of arterial circulation.
• Cold hands and feet.
• Chillblains (a sore or inflamed swelling, as on the feet or hands, caused by exposure to cold).
• Prevention and recovery from strokes.
• Poor short-term memory.
• Senile dementia, dizziness and mastalgia.