Biological Screening of Herbal Drugs

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.