[IL-03]
PHARMACOLOGY OF MEDICINAL PLANTS

Roberto DELLA LOGGIA
Faculty of Pharmacy, University of Trieste, Italy

From the starting of the history, the human beings have used plants to treat all kind of illness. This lasted for thousand of years and only in the last century pure compounds started to be used as drugs, whereas synthetic molecules were introduced in therapy just fifty years ago. This long use of medicinal plants before the scientific revolution in medicine, together with the important role played by magic and by symbolism in the ancient medicine, have left in our feelings a sense of mystery in the mode of therapeutic action of natural products. It is a very common idea that medicinal plants are something quite different from synthetic drugs: they are natural and natural things have to be "good". The first consequence of this way of thinking is the idea that herbal drugs are totally free from untoward effects. Many people also think that a medicinal plant works as a whole, that it can "fight the illness" by introducing in our organism some kind of "strength of Nature" or by restoring the "natural balance of body", disturbed by modern life and by unnatural chemicals. Ideas like these may be impressive but has no scientific fundament.


Medicinal plants simply contain molecules that are able to interact with receptors to produce a pharmacological response and, by this way, to give a therapeutic effect. It is well known, for instance, that the infusion of Salix alba bark is able to reduce headache and fever: this is due to its content of derivatives like salicine, a glycoside that is well extracted from the bark by hot water. After taking the Salix infusion, the non-absorbable salicine reaches the colon where it is hydrolized by the intestinal flora to salicilic alcohol, that being free from the sugar moiety, is less polar and can be resorbed. After resorbtion, salicilic alcohol reaches the liver where it is metabolized to salicilic acid, a substance that is able to inhibit the enzyme cyclooxigenase. Since ciclooxigenase plays a key role in the inflammatory response, its inhibition results in an anti-inflammatory effect. At last, we can see that the therapeutic effect of the Salix bark is completely explained by some usual pharmacological concepts, like as absorption, metabolism and drug-receptor interaction. It is also interesting to note that salicilic acid is the same metabolic product obtained after taking an Aspirin tablet, and this clearly shows that there are no fundamental differences in the mode of action of synthetic and natural drugs.

This example show clearly that medicinal plants have to be seen as "containers of drugs", that we usually call active principles. Therefore, for the rational use of medicinal plants the same principles of pharmacodynamics and phatmacokinetics used for synthetic drugs have to be applied.

One of the first consequences is that also medicinal plants can cause side effects. We know very well that almost all substances can be toxic: it depends from the dose. Also medicinal plants have to obey to this general law and can be toxic. Of course, in most cases herbal drugs shows a reduced incidence of side effects, but this is simply due to the fact that they has usually a mild action and also the side effects are mild. But some important plants can not be disregarded from this point of view: Ginkgo can give haemorrhages, Hypericum can give phototoxicity, many plants can give allergic responses and so on.
 

Some examples of important side effects of herbal drugs
Gingko
haemorrhages
Hypericum
Phototoxicity, interaction with other drugs
Liquorice
hypokaliemia, hypertension
Polygala
gastritis
Ginseng
Insomnia
Arnica
Allergic reactions
Plants containing pyrrolizidine alkaloids
Liver tumours

The second fundamental principle is that for any plant a threshold dose exists for the therapeutic effect: if the administered amount of active principles does not reach the threshold value, no effect will be obtained. The most important consequence of these facts is that it is of high relevance to know the active substances responsible for the activity of a medicinal plant, and to produce herbal drugs and their preparations with definite content of these substances.

Although no basic differences exist between natural and synthetic drugs, in some cases medicinal plants present a higher pharmacological complexity than synthetic products. Medicinal plants are often characterized by the presence of a mixture of different active principles, each of them with a different pharmacological profile, and therefore they can fight an illness from different points of attack. A good example of this is given by Ginkgo: its leaves contain ginkgolides, that strongly inhibits the Platelet Activating Factor, bilobalide, that reduces the cellular damage from oxygen deprivation, and flavonoids whit anti-oxidant and radical scavenging properties. This three quite different pharmacological actions give to Ginkgo its very particular and interesting therapeutic and preventive properties in pathologies due to circulation deficiencies, such as arteriosclerosis, Alzheimer disease or venous insufficiency. Due to their anti PAF effects, gingkolides reduce the viscosity of blood that can better circulate in the small vessels and supply more oxygen to the tissues. On the other hand, bilobalide helps the cells to survive to short ischemic periods. The anti-oxidant activity of flavonoids plays a beneficial role on the vessel and reduces the age-related alterations.

In other cases the same class of compounds shows different pharmacological properties: Chamomile flavonoids are strong anti-inflammatory agents, more active than indomethacin, but they has also smooth muscle relaxant properties, higher than papaverine, and antimicrobial activity. Therefore, Chamomile preparations are very useful in pathologies in which inflammation is associated with cramps, such as gastritis, but it can help also in situations in which the inflammatory response is bound to an unbalance of the resident microbial flora, such as stomatitis or vaginitis.

Furthermore, whereas synthetic drugs are usually designed to strongly inhibit (or stimulate) one single pathway involved in a pharmacological effect, natural compounds may exert a milder effect on a number different pathways. Drugs as indomethacin or acethylsalicilc acid reduce the inflammatory response by an almost complete block of the cyclooxigenase metabolization of arachidonic acid, but this has as a consequence also the well known side effects of these drugs. On the contrary, flavonoids inhibits moderately the cyclooxigenase but also, to some extent, the lipooxigenase; they block free radicals, they reduce the release of histamine, they stabilize neutrophils and so on. All these mild actions together gives to some flavonoids, such as apigenin, an anti-inflammatory potency higher than that of indomethacin, without the usual side effects of this drug.

Due to the complexity of the composition of medicinal plants, the experimental models used in the pharmacological research on natural drugs have to be a little different from those used for a single pure compound. The sophisticated in vitro methods of the modern pharmacology are usually not suitable in the field of medicinal plants and crude plant extracts or their fraction have to be tested by means of adapted pharmacological models.

[IL-03]