It is well-known that drugs when administered to the body never produce ‘new’ effects but get by modifying existing physiological systems. Observation of visible effects of plant extracts on intact animals can give information of their pharmacological activity and possible use as therapeutic agents.
Biological
Screening of Herbal Drugs
INTRODUCTION
It is well-known that drugs when administered to the body
never produce ‘new’ effects but get by modifying existing physiological
systems. Observation of visible effects of plant extracts on intact animals can
give information of their pharmacological activity and possible use as
therapeutic agents. The species commonly used for this purpose are mouse and
rat. Availability of suitable worksheets is essential to enable systematic
observation of valuable symptoms. Elaborate procedures, using mice and cats,
have been described by Irwin (1964). Reinhard (1982) has published a simplified
scheme for mice. His article also contains descriptions of a number of tests
for specific activities, which can be performed in mice. Malone (1977) has
devised screening protocols for rats, which are suitable for working with
natural products, partly purified fractions or pure compounds. Rats are
injected intraperitoneally with the samples and observed at defined time
intervals for one day. Observations are then performed once a day for one week,
after which the animals are killed and examined. The test protocol contains
observation of 58 parameters and has been named by Hippocrates, the ‘father of
medicine’. Sandberg (1967) made minor modifications to the original protocol
(55 parameters). Malone (1977) has published a modi-fied worksheet with 63
parameters and has also discussed computerization of the procedure, allowing
comparison of the pharmacological profile of an unknown sample with similar
profiles of known drugs.
Modern chemical methods have led to a dramatic increase in
the number of natural or synthetic molecules available for pharmacological
research. At the same time, recent developments in cellular and molecular
pharmacol-ogy provide an increasing number of selective tests able to identify
the activity and the mechanisms of action of biologically active molecules.
Paradoxically, however, the availability of numerous sophisticated techniques
do not necessarily make pharmacological research much easier.
Molecular graphics have not yet proven very serviceable in
the investigation of novel molecules. On the other hand, the probability of
assessing the biological activity of new drugs by stochastic screening with
modern reliable methods remains limited, unless viable working hypotheses can
first be made as to their overall effect.
This difficulty could be partly overcome by intermediate
screening methods, on the basis of global or functional tests. Such methods
have been developed in various domains of biology, such as cardiovascular
research or in the identification of antimitotic or immunosuppressive drugs.
However, only very few methods are available as yet for application to the
cases of neurotropic substances. Most global tests for screening neurotropic
drugs are outdated; adequate behavioural tests are only capable of detecting a
few transmitters like activities, and such a situation represents three
limiting factor in an area characterized by particularly rapid developments.
The number of identified transmitter substances has increased from less than 10
to over 50 in a few years. In addition, several are neuropeptides, an
important, but still relatively unexplored class of biologically active
molecules. Peptides of marine origin represent an important source of natural
substances still awaiting systematic screening.
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