Antimalarial Efficacy and Safety of Senna occidentalis (L.) Link Roots Extract

Abstract

Senna occidentalis (L.) Link has been used worldwide in traditional treatment of many diseases and conditions. In Kenya, a decoction from the plant roots taken orally is used as a cure for malaria. Several studies have demonstrated that extracts from the plant possess antiplasmodial activity, in vitro. However, the safety and curative potency of the plant root against established malaria infection is yet to be scientifically validated, in vivo. On the other hand, there are reports on variation in bioactivity of extracts obtained from this plant species, depending on the plant part used and place of origin among other factors. In this study, the antimalarial activity and safety of Senna occidentalis roots extract was demonstrated in vitro, and in mice. Methanol, ethyl acetate, chloroform, hexane and water extracts of S. occidentalis root were tested for in vitro antiplasmodial activity against Plsmodium falciparum. The most active extracts were evaluated for cytotoxicity using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The extracts were then evaluated for curative potency and safety in Plasmodium berghei infected mice by monitoring parasite suppression and survival rates of the animals. In addition, whole blood and serum were collected from the animals and examined for changes in hematological and biochemical parameters respectively, using automated analyzers. Kidney, liver, lung, spleen and brain tissues were harvested from mice and examined for changes in organ architecture. Lastly, the bioactive extract was partitioned by column chromatography and the resultant fractions evaluated for antiplasmodial potency, in vitro. All of the solvent extracts tested in this study inhibited the propagation of P. falciparum, strain 3D7, in vitro, with polar extracts being more active than non-polar ones. Methanolic extracts had the highest activity (IC50 =1.76) while hexane extract displayed the lowest activity (IC50 =18.47). At the tested concentrations, methanolic and aqueous extracts exhibited high selectivity index against P. falciparum strain 3D7 (SI > 10) in the cytotoxicity assay. Further, the extracts significantly suppressed the propagation of P. berghei parasites (P < 0.05) in mice and increased the survival time of the infected animals (P < 0.0001). Infected mice that were treated with the extract depicted a significantly low level of total leucocytes (p < 0.01), red blood cell distribution width (p < 0.01) and a significantly high hemoglobin concentration (p < 0.001) compared to the infected animals that were administered with the vehicle only. The infected animals that were treated with the extract exhibited a significantly low level of urea, creatinine, bilirubin, and alkaline phosphatase (p < 0.05), compared to infected animals that were given the vehicle only. The level of sodium, potassium and chloride ions, lymphocytes, granulocytes, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration, total protein, albumin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total platelets, mean platelet volume (MPV) and platelet distribution width of the infected animals treated with the extract was not significantly affected, compared with those of the infected animals that were given the vehicle only (p > 0.05). The extract alleviated organ pathological changes in the infected mice. The extract did not induce any remarkable adverse effect on the growth, hematological and biochemical parameters of uninfected animals (p > 0.05). In addition, administration of the extract did not alter the gross appearance and histological architecture of the organs, implying that the extract was well tolerated in mice. All the fractions exhibited antiplasmodial activity against P. falciparum, in vitro, with one of the them depicting better activity when compared to the parent extract. In conclusion, Senna occidentalis (L.) Link root extract exhibits good antimalarial activity against P. falciparum and P. berghei, and may be safe in mice. The plant root could, therefore, be developed further into an antimalarial therapy to help in the fight against malaria.