Toxic and Behavioural Effects of Harungana Madagascariensis Stem Bark Extract in Mice Infected with Plasmodium Yoelii Nigeriensis
The aim of this study was to determine the LD50 of Harungana madagascariensis ethanolic stem bark extract using subcutaneous route in mice, to assess the sub-acute toxicity of the extract using biochemical parameters and to evaluate the effects of this extract on novelty-induced behaviours in infected mice as well as the assessment of the analgesic activity of the extract with a view of providing data for better understanding of the plant therapeutic index and effects on central nervous system. The acute (LD50) and sub acute toxicity studies of the extract were determined using subcutaneous route in mice. In the sub-acute toxicity of the extract assessed, the following antioxidants indices (Superoxide Dismutase (SOD),Catalase (CAT), Reduced Glutathione (GSH), Nitric Oxide (NO), and Lipid Peroxidation (MDA)) were done using standard spectrophotometric methods to determine the level of toxicity. The novelty-induced behaviours were carried out in malaria infection using suppressive, curative and prophylaxis mode of malaria treatment. The analgesic effect of the extract was also investigated using three modes of nociceptive induced stimuli through acetic acid (chemical) induced-, hot-plate and tail flick (thermal) induced- nociception. Morphine, naloxone and acetylsalicylic acid were used as standard drugs to determine the mechanism of action. The result showed that the acute LD50 was 140 mg/kg which was an indication that the extract may be toxic. The extract reduced MDA and elevated the content of SOD, CAT, GSH and NO. Thus, overproduction of NO may therefore be the probable mechanism through which the extract exerts the indicated toxicity. The result of behavioural studies showed that the extract reduced novelty induced (rearing and grooming) behaviours, exploratory (head-dip) and locomotion (open field) tests in both curative and suppressive tests. These observable novelty-induced behaviours in curative test were not significant (p> 0.05), but were significant (p< 0.05) in suppressive test. However in prophylactic mode of therapy, there effects on the various behavioural patterns increased significantly (p< 0.05). The findings also revealed potent analgesic activity of the extract in the three modes of nociceptive stimuli used. The complimentary analgesic effect of H. madagascariensis couple with the reversed effect of behaviours in prophylactic model could therefore be the mode of treatment employed in traditional medicine which could also explained its therapeutic efficacies in malaria, pain and anemia. This study concluded that H. madagascariensis has a good prophylactic activity against malaria infection, it also possessed good analgesic and antioxidant properties but it should be used with caution due to the observed toxicity.