In vivo antimalarial activity, toxicity and phytochemical Composition of securidaca longepedunculata fresen. (polygalaceae)
The search for new, safe and efficacious agents against malaria is of precedence. This is attributed to resistance of current chemotherapeutic agents to the malaria parasites and increased toxicity of currently available antimalarial drugs. To address this challenge, increased efforts are required aimed at discovering new agents against malaria. Natural products from plant biodiversity have continued to play a pivotal role towards drug discovery against malaria and other diseases. Despite the wide use of medicinal plants to control and treat conditions with malaria-like symptoms, little has been done to evaluate their safety, efficacy and phytochemical composition, to validate the claimed anecdotal efficacy. The current study was designed to investigate in vivo antimalarial activity and efficacy, in vitro cytotoxicity, in vivo acute toxicity and phytochemical composition of aqueous and organic crude extracts from Securidaca longepedunculata Fresen. (Polygalacea). A four day suppressive standard test was used to investigate in vivo anti-malarial activity of the crude extracts. The in vitro cytotoxicity was evaluated using a tetrazolium salt MTT (3-[4.5-dimethylthiazol-2-yl]-2.5- diphenyltetrazolium bromide) colorimetric method, based on reagent cleavage by mitochondrial dehydrogenase in viable cells. The in vivo acute oral toxicity was carried out on healthy 6-8 weeks old female Swiss albino mice using the Organization for Economic Cooperation and Development (OECD 423) guidelines. Standard methods were used for phytochemical screening. The standard anti-malarial drug employed for positive control; chloroquine showed percentage parasitaemia suppressions of 96.99% after 4 days of treatment. Chloroquine did not show any significant difference (p>0.05) in comparison with that from the percentage parasitaemia xv suppression exhibited by the aqueous and organic root extract of S. longepedunculata after the 4 days treatment of mice infected with P. berghei. The highest level of clearance was observed in chloroquine treated group, with percentage parasitaemia on day 4 as 0.68 ± 0.17 as compared to 22.58 ± 0.84 of the negative control group. S. longepedunculata root organic and aqueous crude extracts equally demonstrated a good suppression of parasitaemia on day 4 with a with percentage parasitaemia of 1.93 ± 0.37 and 2.78 ± 0.46 respectively. Both organic and aqueous extracts were non-toxic at 2000 mg/kg of bdw i.e. LD50>2000 mg/kg. None of the extract tested was potentially toxic to HEp-2 cell lines, CC50 > 100μg/ml. The following phytochemicals were demonstrated to be present in the crude extracts: steroids, alkaloids, anthraquinones, flavonoids, tannins, saponins and cardiac glycosides. This study has demonstrated that the crude extracts are a potential source of a new class of antimalarial drugs. The extracts have got very good antimalarial activity and are not toxic in vivo mice model. This study recommends further work aimed at hit identification for antimalarial activity through bioactivity guided fractionation, isolation and purification of compounds responsible for the observed antimalarial activity. The purified and identified hits could be used for lead development for antimalarial activity as well as biomarkers for standardization of S. longepedunculata herbal preparations for use against malaria. This study recommends in vitro testing of these extracts for their activity against P. falciparum in order to consider them as potential sources for antimalarial drug development for human malaria. The study also recommends elucidation of mechanisms of action and investigations of active compounds in terms of structure-activity relationship with modifications of the structure to enhance efficacy.