SOME NEUROPHARMACOLOGICAL STUDIES ON ETHANOL EXTRACT AND FRACTIONS OF TAPINANTHUS GLOBIFERUS A. RICH MISTLETOE ON VITELLARIA PARADOXA HOST IN LABORATORY ANIMALS
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Abstract:
Tapinanthus globiferus is a semi-parasite mistletoe which grows on branches of large number of trees including Vitellaria paradoxa. It used locally in the management of insomnia, epilepsy, anxiety, headaches and hypertension. This study evaluated the toxicity and neuropharmacological properties of ethanol extract and fractions of T. globiferus. These were carried out using standard methods. Phytochemical screening of T. globiferus ethanol extract (TgE) revealed presence of alkaloids, anthraquinones, flavonoids, cardiac glycosides, saponins, steroids terpenoids and tannins variously distributed among the fractions. The intraperitoneal LD50 of TgE was 1,300 and 3,800 mg/kg in mice and rats respectively and ˃5,000 mg/kg orally. However, fractions of ethylacetate and ethylacetate water insoluble intraperitoneal LD50 were 1,400 and 1,100 mg/kg respectively, and 3,800 mg/kg each for butanol and residual aqueous in mice. Oral administration of TgE for 28 days in rats produced no effects on body weight and serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total protein at 87.5, 175 and 350 mg/kg, but at 350 mg/kg, serum levels of total bilirubin and conjugate bilirubin were significantly (p ≤ 0.05) elevated while packed cell volume, haemoglobin and red blood cell were decreased. TgE produced significant (p ≤ 0.05) decreases in serum urea, creatinine and sodium concentrations, and increases in potassium and chloride concentrations at 175 and 350 mg/kg, whereas bicarbonate concentrations were unaffected at all doses compared to 1.0 ml/kg normal saline control. Liver sections at 175 and 350 mg/kg showed distortion and degeneration of hepatocytes but no toxic effects at 87.5 mg/kg. Kidney and spleen architecture were normal at 87.5 and 175 mg/kg, but 350 mg/kg resulted in degeneration of Bowman’s capsule, tubular degeneration and blood vessel distractions in kidney, as well as degeneration in red pulp and necrosis of epithelial cells in spleen sections (×100 H and E). TgE and fractions significantly (p ≤ 0.05) decreased onset and increased duration of diazepam-induced sleep but ethylacetate insoluble fraction had no effect at tested doses compared to control. Ethylacetate fraction (EF) was the most active among the fractions but produced no effect in ketamine-induced sleep at all tested doses. TgE and EF were significantly (p ≤ 0.05) reduced number of head dips in hole-board at tested doses. However, bicuculline at 5 mg/kg increased number of head dips which were antagonisted by EF and diazepam at 300 and 2 mg/kg respectively. TgE produced significant (p ≤ 0.05) increased in number of foot slips in beam-walk at 350 mg/kg and EF at 300 mg/kg, while BF showed no activity at 250, 500 and 1,000 mg/kg compared to control. TgE produced no effect in elevated plus-maze and number of entries and time spent in open arms at 175 and 350 mg/kg. TgE did not exhibit effect in number of rearing at tested doses but at 350 mg/kg reduced number of steps climbed in staircase. However, TgE significantly (p ≤ 0.05) reduced number of lines crossed and rearing at 175 and 350 mg/kg respectively in open field and offered significant effect in duration of haloperidol-induced catalepsy at 350 mg/kg, apomorphine-induced climbing behaviour at 87.5 and 175 mg/kg and no effect in duration of immobility in tail suspension at all doses compared to control. Antiseizure activities tested showed that TgE had no effect on onset of seizure compared to control in PTZ, STN, and PRT-induced seizures but offered 16.67, 33.33 and 50 % protection against PTZ and PRT at 87.5, 175 and 350 mg/kg. However, TgE did not protect mice and chicks against STN- and MES-induced seizures respectively. The study showed that extract and ethylacetate fraction of T. globiferus are less toxic and contained active constituents which have sedative effects and minimum anticonvulsant properties.