INVESTIGATION OF THE TOXICOLOGICAL AND PHARMACOLOGICAL ACTIVITY OF A HYDROETHANOLIC EXTRACT OF BOOPHONE DISTICHA BULB
GADAGA, LOUIS L.
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Boophone disticha is a highly poisonous bulb. It has been used systemically in traditional medical practice in Zimbabwe and neighbouring countries for the management of various central nervous system conditions including hysteria. Abuse of the plant by teenagers in Zimbabwe for its claimed hallucinogenic effects has also been reported, with the advent of serious toxicity in some cases. The aim of the present work was to describe the symptomatology, neurotoxicological effects and lethality of acute and subacute ingestion and of a hydro-ethanolic plant extract of the bulb of Boophone disticha in rats. Initially, we set out to estimate the LD50 of this extract using a modified Up-and-down procedure for acute toxicity determination. We then used a Functional Observational Battery (FOB) to identify the neurotoxicological effects of the extract after both acute and repeated oral intake. Additionally we studied the genotoxic potential of the Boophone extract using the Ames test. Finally we sought to investigate the putative neuropharmacological effects i.e. anxiolytic-like and antidepressant-like activity in a murine model. Findings in the acute toxicity and neurotoxicological assessment, showedan estimated oral LD50 of between 120 and 240 mg/kg. For doses of 240 mg/kg and less, signs of toxicity began approximately 10 minutes after gavage, and the most prominent initial signs were head tremors (at 50 mg/kg) and body tremors, severe body tremors(>360 mg/kg) followed by convulsions. Generally, symptoms of toxicity lasted approximately 2 hours for doses of 240 mg/kg and less; and 3 hours for doses over 240 mg/kg for animals that survived. These results point to a rapid gastrointestinal absorption of the active principles in the plant extract. The most prominent neurotoxicological effects were increased flaccid limb paralysis and spastic hind-limb paralysis. Tachypnoea was noted at low doses and higher doses produced laboured breathing. The retropulsion observed with higher doses could indicate the reported hallucinogenic effects of the plant extract. Subacute assessment showed the similar profile symptoms as with acute toxicity.The main subacute toxic effects of Boophone disticha like the acute effects seem to be mediated via interference with the neuronal pathways especially the central dopaminergic and motor neurons. Target organs, as observed by changes in organ weight appear to be liver, small and large intestines, stomach, central nervous system and peripheral nervous system. Boophone disticha extract was genotoxic from concentrations 1000μg/plate and above with both TA98 and TA100 Salmonella typhimurium species irrespective of the metabolic status of the system. The 500μg/plate concentrations of the Boophone extract were not associated with any genotoxicity and 2500μg/plate concentration is potential cytotoxic which could have masked the genotoxic effects at this concentration. P a g e | vi Boophone disticha extract showed Anxiolytic-like activity in the elevated plus maze test by significantly changing the percentage time spent in open arms, number of open arm entries, rearing, unprotected head dips and stretch attend postures. The 10m/kg dose had the most prominent effects compared to the higher dose which were comparable to the positive control. Repeated dosing enhanced the antidepressant-like activity of the Boophone extract. Therefore from the pharmacological findings of our studies, despite being very toxic Boophone disticha proved to be an important source of lead compounds for future drug development. Therefore further investigations are necessary to determine the target site and efficacy of Boophone alkaloids with in vivo models.