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STUDIES ON THE EFFECT OF THE EXTRACT AND CONSTITUENTS OF NERIUM OLEANDER LEAVES ON THE CENTRAL NERVOUS SYSTEM OF MICE

Haque, Atiya Ziaul (1997) STUDIES ON THE EFFECT OF THE EXTRACT AND CONSTITUENTS OF NERIUM OLEANDER LEAVES ON THE CENTRAL NERVOUS SYSTEM OF MICE. PhD thesis, University of Karachi, Karachi.

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Abstract

The history of drugs is intimately woven with plants from earliest times, and even today plant products find extensive use in both traditional and modern systems of medicine. Indeed, many drugs including morphine, cocaine, reserpine, quinine, digitalis, atropine, vincristine, and vinbalstine are a few examples of pure chemicals; some used clinically, others used as tools for understand ling the mechanism of action of action of other drugs. Beside pure chemicals herbal mixtures are also used in developing countries. In Nigeria, the extract of roots of Rauwolfia serpentine (Apocynaceae family) has been used as sedative hypnotic, in epilepsy and anxiety state (Srivasta, 1987). More recently other species of Rauwolfia have demonstrated sedative (Madawala, et al. 1994) and antipsychotic effect Obembe, et. Al 1994). The extract of Rauwolfia vomitaria is successfully used for treatment of psychiatric illnesses. In the present studies, we selected Nerium oleander, a plant of the same family that has been extensively studied for cardiovascular (Nazar, et.al., 1970), hepatoprotective (Fengbi, et.al 1989), diuretic (Takahashi, 1948), hypoglycemic (jalil et al. 1986), and many other activities. However, its effects on behavior on central nervous system (CNS) has not been studied. The study was carried out to observe the effects of various crude, partially purified fractions and pure constituents on behavior pattern in mice. The results showed that fractions of the leaves extract induced sedation at low dose and hypnosis at high doses which was an evidence of their effect on the CNS. Many of the known sedative hypnotics exert their action by modifying GABA-ergic system in the CNS (Lundberg, et. Al, 1975). The fractions were further studied using various parameters indicative of CNS activity. These included locomotor studies, motor coordination /muscle relaxation and interaction with hexobarbital antagonism to known convulsants; studies of the effect of extract on amino acid neurotransmitters were also performed. The results of these studies showed a significant decreased in locomotion counts, decrease in motor performance and enhancement of heoxbarbital sleeping time. Our findings indicated that these fractions act by facilitation of GABA-Ergic transmission. Furthermore, behavioral effects of GABA agonists exhibited sedation hypo motility and impairment of motor execution (Loschoer, et. Al, 1989). Muscimol and THIP, both GABA agonists, have been reported to potentiate Phenobarbital hypnosis (Evans, Hill, 1978, Sivam, et. al.,1982). Targeting further into the mechanism/s of action we studied the effect of these fractions on drug induced convulsions. For this purpose we used three GABA antagonists PTZ, bicuculline and picrotoxin and one glycine antagonist strychnine. One of the fractions N-1 of Nerium oleander leaves completely blocked the convulsions induced by GABA receptor antagonists, bicuculline and picrotoxin but not those induced by strychnine, a glycine antagonist or PTZ. Some other fractions showed 40-60 % protection against convulsions induced by bicuculline and picrotoxin. Benzodiazepines and barbiturates are known to antagonize convulsions (Guidotti, et. al, 19983), whereas diazepam blocks the convulsions induced by picrotoxin and bicuculline and to a lesser extent those induced by strychnine(Curtis, et. al., 1976.) These findings suggest that the fractions act by altering the GABA ergic system in the CNS. To find out the possible mechanism/s neurotransmitter amino acid levels were determined in discrete brain regions of both treated and control mice. The results of these studies showed a significant decrease in glutamate and an increased in cortical GABA levels. Similar results have been reported by vernadakis, Woodbury, (1990) with DPH in rats. Benzodiazepine and barbiturate have been reported to decrease aspartate and glutamate levels (Chapman, et. al,. 1978, Carlson, chapman, 1981) This study demonstrated for the first time the sedative/ hypnotic effects in the leaves extract/ fractions of Nerium oleander (Zia, et. al., 1993, 1995) and sedative activity in pure constituents (Siddiqui et. al., accepted 1997). It also suggests that the fractions exert their effects possible by modifying GABA-ergic

Item Type:Thesis (PhD)
Uncontrolled Keywords:nerium oleander leaves, nervous system, mice, gaba, antagonist, ptz, bicuculline, picrotoxin, glycine antagonist, strychnine, sedative effects, hypnotic effects, neurotransmitters, glycine, glutamate, aspartate
Subjects:Biological & Medical Sciences (c) > Medical Sciences (c2) > Pharmacology & therapeutics(c2.6)
ID Code:951
Deposited By:Mr. Muhammad Asif
Deposited On:24 Nov 2006
Last Modified:04 Oct 2007 21:03

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