SOME NEUROPHARMACOLOGICAL STUDIES OF EXTRACT AND FRACTIONS OF CRINUM ZEYLANICUM(L.) (AMARYLLIDACEAE)BULB IN LABORATORY ANIMALS
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ABSTRACT
Crinum zeylanicum is a medicinal plant used in folk medicine for management of general debility, infantile seizures and pain. Some neuropharmacological effects of methanolic bulb extract of Crinum zeylanicum were studied in laboratory animals.The Phytochemical screening of the methanolic bulb extract and its solid residue fraction (SRF) were carried out using standard procedures. Quantitave determination of the elemental content of Crinum zeylanicum bulb and its methanolic bulb extract was carried out using atomic absorption spectrophotometer. The oral and intraperitoneal acute toxicities of themethanolic bulb extract and its solid residue fraction were carried out in mice and rats using modified Lorke‟s method. The effect of the methanolic bulb extract was studied on gross behaviour in mice using Irwin method, on pentobarbitoneinduced sleep time, spontaneous motor activity, exploratory behaviour also in mice usinghole board, motor coordination (rota-rod) andapomorphine –induced stereotypy. The anticonvulsant activity of the methanolic bulb extract and SRF was evaluated using chemical convulsants in mice (Pentylenetetrazole, picrotoxin, strychnine, pilocarpine, and 4-aminopyridine) and electrically using maximal electric shock in a day old chicks. The analgesic activity of the extract was evaluated using acetic acid induced writhing test in mice, formalin induced pain in rats and hot plate test in mice.Chronic oral toxicity study of the methanolicbulb extract was carried out in male and female Wistar rats for 90 days. The assessment of toxic effect of the extract was evaluated on feed and water intake, change in body weight, haematological and biochemical parameters. Histopathological evaluation of the internal organs was also carried out.The Phytochemical test revealedpresence of balsam, sterols, terpenes, resins carbohydrate, tannins, phylobatannins, saponins, flavonoids, alkaloids and volatile oils while vii anthraquinones, phenols and glycoside were absent. Sterols, alkaloids and terpenes were present in SRF. The elemental analysis showed presence of sodium, potassium, calcium, magnesium, manganese, lead, iron and nickel in the bulb material and the methanolic bulb extract while chromium was present only in the bulb. The oral median lethal dose of the methanolic bulb extract was greater than 5000 mg/kg body weight while the intraperitoneal median lethal dose was 3807.88 mg/kg body weight in mice and rats respectively.The oral and intraperitonealmedian lethal doses (LD50) of the solid residue fraction were 470 and 77.49 mg/kg body weight respectively. The Irwin test revealed that the extract possesses central depressant effect.The methanolic bulb extract and SRF significantly (p<0.01) shortened the onset of sleep and prolonged the duration of sleep. The methanolic bulb extract significantly (p<0.001) decreased spontaneous motor activity but had no effect on motor co-ordination.The extract significantly (p<0.001) decreased the number of head dips in the hole board. The methanolic bulb extractsignificantly (p<0.0001) decreasedapomorphine-induced stereotypy in mice.The methanolic bulb extract and SRF protected mice against pentylenetetrazole- and pilocarpine-induced seizures in mice.Themethanolic bulb extract did not protect while SRF protected mice against picrotoxin-induced seizures in mice dose-dependently.The extract did not protect mice against strychnine and 4-aminopyridine- seizures butsignificantly (p<0.05) delayed onset of tonic hind limb extension in mice. The extract did not protect while SRF at 100 mg/kg and 20 mg/kg phenytoin protected 90 and 100% of the chicks respectively against maximal electric shock-induced seizures. The methanolic bulb extract showed significant analgesic effect against acetic acidinduced pain in mice, formalin-induced pain in rats and thermal-induced pain in mice on hot plate. The methanolic bulb extract did not produce adverse clinical signs and death at doses of 250, 500 and 1000 mg/kg administered for 90 days in rats. The viii methanolicbulb extract at 500 and 1000 mg/kg suppressed feed intake and increased water intake significantly (p<0.001) in the 12th and 13th weeks of the study in female rats. The methanolic bulb extract had no effect on feed intake, water intake and body weight of male rats.The changes in the haematological parameters in male and female rats were within normal range values. Significant (p<0.05-0.001) increase in liver function enzymes and lipid profiles were observed in female and male rats at 42 and 90- days while other biochemical parameters remained normal.The relative organ weight of all organs studied in female and male rats remained normal at 42 and 90-days. Histopathology revealedlivercongestion and cellular infiltrationat 1000 mg/kg body weight after 90 days of administration in female and male rats.The results obtained provided evidence based scientific support for its potential therapeutic benefits and safety of themethanolic bulb extract in the management of epilepsy, psychosis and painful disorders.
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