VIEWS & REVIEWS

A green approach to grey matter

-Kate Palmer-

In countries such as India. Japan and China, medicinal plants and herbs have been used to treat CNS disorders for thousands of years. From presentations at the Collegium Internationale Neuro-Psychopharmacologicum (CINP) congress [Washington DC, US; June 19941. it is obvious that there is now increasing interest in plants as a source of CNS-active agents in Western countries.

Modern drug development is extremely costly, in both financial and environmental terms. Furthermore, many agents induce substantial adverse effects. These factors have provided the impetus for turning towards plants as a potential source of inexpensive and less toxic drugs. Dr BN Dhawan from the Central Drug Research Institute in Lucknow, India, believes that the search for plant-derived drugs for treating CNS disorders should concentrate on those disorders for which 'modern' medicines have proved inadequate, such as memory disorders.

'Real phannacology' In the US, the Kational Institute of Mental Health

(KIMH) has an extensive screening programme for assessing medicinal plants. Potentially useful plants are identified from 'ethnopharmacological' inform­ation, i.e. the knowledge of local cultures and people and their use of medicinal plants.

State-of-the-art in vitro investigations show that many of the plant extracts possess' real pharma­cology', says Dr Jerry Cott from the NIMH. For example, Hypericum perforatum (St John's wort) has been traditionally used as an antidepressant and anxiolytic. It inhibits monoamine oxidase and binds with high affinity to adenosine receptors and GABA-\ receptors. Passiflora incarnata (passion flower) has been used for the treatment of insomnia and has affinity for GABA-\ and GAB All receptors, the chloride channel, and AMPA, glycine and NMDA excitatory amino acid receptors.

Animal studies have shown that several plant extracts have CNS effects, including sedative, anticonvulsant, antipsychotic, analgesic, nootropic and antidepressant activity.

Treatment of memory dysfunction ... One of the areas for which plant-derived treatments

appear to hold particular promise is the field of learning and memory disorders.

Bacosides A and B are derived from the Indian plant Bacopa monneri. These agents improve learning time in several animal tests of memory and learning. They are not toxic after single or repeated administration. Interestingly, the mechanism of action does not seem to be related to effects on the cholin­ergic system. However, bacosides do prevent the increase in brain lipid peroxides induced by stress. This is suggestive of a protective effect on neuronal degradation.

Himbacine is an alkaloid isolated from the bark of the trees of the Galbulimima species found in Australia. It is a reasonably selective muscarinic ~h­and M4-antagonist. Presynaptic Me-receptors act as autoreceptors and control cholinergic tone. Himbacine is a competitive antagonist of these autoreceptors,

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i.e. it attenuates agonist-mediated inhibition of acetylcholine release.

Huperzine A is an active component of a moss used in traditional Chinese medicine, HlIperzia serrata. Preclinical studies show that huperzine A inhibits cholinesterase activity in \'itro and in vivo. And in animal behavioural studies, it was shown to reverse scopolamine-induced amnesia.

Promising clinical data on huperzine A were also presented at the conference. A double-blind, multi­centre trial of huperzine A (mean dose 300 !lg/day; n = 67) was compared with piracetam (mean dose 2.4 g/day; n = 34) in patients with age-associated memory impairment and organic dementia. Therapy was administered over 4 weeks.

Memory and cognitive function were assessed using memory quotient and the Mini-Mental state examination, respectively. Improvements in memory were observed in both treatment groups. In certain subgroups of patients, the improvement in memory was greater in huperzine A-treated patients than those receiving piracetam. No difference in the incidence of adverse effects was seen between the 2 groups. Gastrointestinal disturbances and dizziness were the most common adverse effects in patients receiving huperzine A.

Longer term studies with a placebo-controlled design are obviously needed to substantiate these initial findings.

... and possible prevention The leaves of the Ginkgo biloba tree contain

several acti ve extracts, including ginkgolides and flavonoids. Ginkgolides are specific antagonists of platelet-activating factor (PAF), with ginkgolide B (BN 52021) being the most potent. Flavonoids act as free radical scavengers.

Ginkgo preparations increase blood supply to the brain by inducing vasorelaxation and decreasing blood viscosity. They also appear to increase cerebral tolerance to hypoxia.

This combination of cerebroprotective actions suggests a potential use of Gingko preparations in the treatment of cerebral insufficiency. There is some evidence that cerebral insufficiency in elderly individuals leads to symptoms that may be early indicators of dementia.

Plant combinations Kampo (Japanese herbal) medicine involves

combining plants that have specific qualities to give an individualised healthcare programme. Some of these plants, such as Ginseng radix, are well known in Western countries.

Cncontrolled clinical trials of kampo medicinal products have suggested efficacy in several CNS

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A green approach - continued

disorders. Kami-Kihi-to is a combination of 14 plants and is effective in major depression and 'neurosis' (chronic depressive state with or without anxiety). Yokukan-sann-ka-chinnpi-hannge is composed of 9 plants and has been shown to be effective in neurosis.

Brahmyadiyoga is a traditional Indian medicine composed of 6 plants. A placebo-controlled study in patients with schizophrenia conducted in India demonstrated that this combination of plants was almost as effective as chlorpromazine and had no neurological adverse effects.

Bulleyaconitine A is isolated from Aconitum bulleyanum, a Chinese medicinal herb. This compound has potent analgesic activity. Pharmacological studies have shown it to be 15-to 66-times as potent as morphine. Furthermore, it does not appear to induce any morphine-like tolerance.

Word of warning Despite the promise shown by many plant extracts,

Dr Dhawan sounded a word of warning. Large quantities of some plants are needed to obtain an active extract. Therefore, steps must be taken to ensure that this valuable source of medicinal products is not decimated by overzealous development.

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