Mental disease and the dinosaur tree

Towards the end of the Palaeozoic era, a class of trees known as the Ginkopsidas began to take root amid the cycads and conifers. Throughout the Mesozoic the class did fairly well ¹, becoming moderately abundant wherever the teeth of leaf-grazing dinosaurs would let it. Some two hundred million years later, however, Ginko biloba, better known as the ginkgo or maidenhair tree, is the sole survivor of that ancient lineage. Though fairly common as an ornamental plant in the gardens of Asia, Europe and North America, in the wild it hangs on only in the Chekiang province of China. ² What no dinosaur suspected was that this plant had properties that might help in the future fight against dementia, Alzheimer's disease and other disorders.

A long medicinal pedigree

The tree found its way into the pharmacopoeia of the Far East more than two thousand years ago. ³ Parts of it, when made into a tea, are still used in China for treating asthma and bronchitis. ⁴ More recently, the West has shown medical interest in the specie for other reasons. Martindale's Extra Pharmacopoeia ⁵ records seven types of preparations of the plant - either on its own or in combination with other ingredients - for treating cerebral and peripheral vascular disorders and the impairment of mental function.

Ginkgo extract and mental illness

For some years, a standardised ginkgo leaf extract known as EGb 761 has been associated with moderate improvement in people suffering memory loss, cognitive impairment and Alzheimer's-type dementia. ⁶ ⁷ ⁸ ⁹ Controversy still exists, however, with respect to its true effectiveness. ¹⁰ Some authors claim there is no good evidence to show that ginkgo extract prevents mental deterioration or helps restore cognitive function. Others are more optimistic. In a recent study comparing the efficacy of EGb 761 with tacrine, donepezil, rivastigmine and metrofonate - cholinesterase inhibitors commonly prescribed for Alzheimer's disease - the extract was reported to be equally effective at treating mild to moderate forms of the disorder.¹²

Possible mechanisms of action

How ginkgo extract might actually work is open to debate. EGb 761 contains several biologically active compounds including flavonoid glycosides such as kaempferol, quercetin and isorhamnetin, and terpenoids such as the ginkolides and bilbobalide.¹³ Any of these, either individually or in combination, might have beneficial effects. The following are some mechanisms of action currently under discussion.

INHIBITION OF PLATELET AGGREGATION

The ginkgolides are known to be highly specific inhibitors of platelet activating factor (PAF).¹⁴ PAF causes platelet aggregation which could lead to blood clotting in small vessels and consequent neural hypoxia. Inhibiting PAF may prevent this hypoxia, resulting in better neuronal function, perhaps manifested in some Alzheimer's sufferers as improved cognition. This mechanism might also help in restoring blood flow after small strokes.

VASOREGULATORY EFFECTS

Ginkgo extract has a vasoregulatory action on arteries, veins and capillaries, resulting in increased blood flow.¹⁵ Improving the tone of vessels in the brain and increasing the supply of oxygen and nutrients would be beneficial to neurons suffering hypoxia.

ANTIOXIDANT ACTIVITY

Ginkgo flavonoids have been identified as antioxidants - compounds that mop up free radicals. The latter are thought to be at the root of many neurological diseases. ¹⁶ Flavonoids may work by reducing free radical injury to endothelial cells, thus slowing down arteriosclerosis. ¹⁷ In early brain ischemia they may protect cells from free radicals produced by the release of fatty acids and the accumulation of PAF.¹⁸

Recently, ginkgo flavonoids have been reported to provide protection against nitrous oxide-stimulated protein kinase C toxicity in rat hippocampal cells.¹⁹ They may provide protection in other parts of the brain, too.

Kaempferol has recently been identified as an inhibitor of monoamine oxidase (MAO) A and B, and to protect against NMDA receptor-induced toxicity.²⁰ The inhibition of MAO has long been used in the treatment of depression and Parkinson's disease. The aliphatic N-methylproparglyamines, recognised MAO-B inhibitors, can protect and even rescue neurons from free radicals produced during the autoxidation of dopamine.²¹ The kaempferol in ginkgo extract might therefore protect neurons via the same or a similar mechanism.

CHOLINERGIC EFFECTS

Recent work has also shown ginkgo extract to reduce scopolamine-induced amnesia, to modulate pre-synaptic choline uptake and acetylcholine release, to up-regulate post-synaptic muscarinic receptors and to have indirect effects on cholinergic function via modulation of the serotinergic system.²² Since malfunction of the cholinergic system in the brain is implicated in the appearance and progression of Alzheimer's disease, ginkgo extract may prove beneficial to some sufferers.

Giving ginkgo

Ginkgo extract is available as drops, tablets and infusions, usually from health or herbal medicine stores. Injectable sources can also be obtained. It is one of the most commonly prescribed drugs in France and Germany ²³ and annual sales have reached $300 million in the USA.

However, like any drug, self-medication should be avoided. There are reports that ginkgo extract can increase bleeding in patients taking aspirin or other anticoagulants and little is known about its possible interaction with other drugs. Further, a physician must decide upon the appropriate dosage. Would-be takers could easily be confused by the different concentrations of the extract in different formulations.

A palaeological panacea?