Tranquilizing medicinal plants: their CNS effects and active constituents - Our experience

Abstract

Mental disorder is a psychological or behavioral pattern that occurs in an individual and is thought to cause distress or disability that is not expected as part of normal development or culture. Mental and neurological disorders are highly prevalent worldwide with 450 million people estimated to be suffering from them. They are responsible for about one per cent of deaths and they account for almost eleven per cent of disease burden the world over. Magnitude of neurological disorders is huge and they are priority health problems globally. The extension of life expectancy and the ageing of the general populations in both developed and developing countries are likely to increase the prevalence of many chronic and progressive physical and mental conditions including neurological disorders. The proportionate share of the total global burden of disease due to neuropsychiatric disorders is projected to rise to 14.7% by 2020 (World Health Organization, WHO). There are many different categories of mental disorders, and many different facets of human behavior and personality that can become disordered. Mental illnesses are classified according to the symptoms that a patient experiences, as well as the clinical features of the illness. Some of the major categories of mental illness include anxiety disorders, cognitive disorders, developmental disorders, dissociative disorders, mood disorders, personality disorders, schizophrenia and substance abuse disorders. Anxiety is defined as a subjective emotional state of uneasiness, not pleasant and even fearful. When the anxiety reaches pathological levels the subject experiments conductual changes, apprehension, motor troubles, sweating, hypertension, etc. The term sedation implies a general slowing down of cognitive functioning, whereas a hypnotic specifically means the induction of sleep itself. Tranquilization, on the other hand, signifies emotional calming, that may or may not lead to sleep, but does not induce the feeling of drowsiness. So calmness of mind may the better facilitate normal physiological sleep mechanisms to function; whilst stress of any kind will mediate against them. Traditional medicine has many cures for these ailments, most of them based on herbal preparations, but also modern medicinal chemistry has provided several drugs which are more or less effective, for the same purpose. The most spectacular success was achieved in 1957 with the synthesis of the benzodiazepines (Sternbach 1978), which still are, after 50 years of intense clinical research and use, the near-best medication to treat mental disorders. Benzodiazepines, however, also produce several side-effects like sedation, muscle relaxation, alcohol incompatibility, amnesia and addiction (Woods et al. 1992). These drawbacks have to be carefully considered in clinical therapeutical applications. Although benzodiazepines are laboratory products they were found also in nature and, appropriately, their first detection was in the mammalian brain (Sangameswaran et al. 1986). They were then identified in many other sources like foods; rumen, plasma and cow´s and human´s milk (Medina and Paladini 1993). When we attempted detection of benzodiazepines in several plants, including some used to prepare tranquilizing infusions, unexpectedly discovered that some flavonoids present in them, were ligands for the benzodiazepine binding site of the gamma amino butyric acid receptor type A (GABAA) (Medina et al. 1989 and the reviews: Medina et al., 1997 and 1998; Paladini et al., 1999; Marder and Paladini 2002). A search for novel pharmacotherapy from medicinal plants for psychiatric illnesses has progressed significantly in the last twenty years. This is reflected in the large number of herbal preparations for which psychotherapeutic potential has been evaluated in a variety of animal models. A considerable number of herbal constituents whose behavioral effects and pharmacological actions have been well characterized may be good candidates for further investigations that may ultimately result in clinical use. Herbal remedies that have demonstrable psychotherapeutic activities have provided a potential to psychiatric pharmaceuticals and deserve increased attention in future studies. This chapter deals with plants possessing central nervous system (CNS) effects. However, because of the huge amount of plants belonging to this category, we decided to select a few plants and to focus our attention on them, mostly concerning the constituents that have significant therapeutic effects in animal models of CNS disorders.