The Anti-Sickling Properties oF Senna Alata and Senna Podocarpa (Fabaceae) Extracts.
A Thesis Submitted to the School of Postgraduate Studies, University of Lagos.
Nigeria is home to the largest population of sickle cell anemia (SCA) patients, with more than 150 000 children born annually with the disease. Due to the side effects of some drugs eg. hydroxyurea used in the management of SCA, developing novel drugs from traditional medicinal plants can serve as a means to improve the management of this disease. Therefore the possible role(s) of some medicinal plants in the management of sickle cell anemia were investigated. Aqueous ethanol extract of five medicinal plants, namely, Cajanus cajan (beans and leaves), Smilax kraussiana (leaves), Alchornea cordifolia (leaves), Senna alata (leaves), Senna podocarpa (leaves) and “Jana”, a herbal formulation were screened for their membrane stabilising effects on human erythrocytes containing haemoglobin S (HbS) using the osmotic fragility test. Two plants, S.alata and S.podocarpa, were selected, base on their fragilogram for further studies and their aqueous methanol leaf extracts were evaluated for membrane stabilising and antisickling activities. The antioxidant activities of these selected plants extract were also investigated in aqueous system using 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity (DRSA) and DNA protection assay, while that of the lipid system was done using thiobarbituric acid reactive substances (TBARS) assay. The toxicity profile of hydromethanolic leaf extract of S.alata and S.podocarpa administered at low (200 mg kg bwt-1), medium (600 mg kg bwt-1) and high (1000 mg kg bwt-1) daily oral doses for 15, 35 and 63 days, to young (6 -8 weeks old) albino rats was investigated. Relative organ weights, haematological indices, serum biochemistry, tissue pathology, erythrocyte membrane protein profile as well as sperm-head morphology were used to assess safety. The extracts were also evaluated for their in vitro cytotoxicity activity against K562 mammalian cell line. Aqueous methanol leaf extract of Senna alata and Senna podocarpa at an optimal concentration of 200 and 800 µg ml-1 respectively significantly (P < 0.05) lowered the mean corpuscular fragility values of HbSS RBC, thus conferring 66.01 % and 17.71 % membrane stabilization respectively, while the antisickling efficiency of S.podocarpa was significantly (P < 0.05) lower than that of S.alata. The DRSA of the hydromethanolic leaf extract of S.podocarpa and S.alata showed a dose-dependent response. Senna podocarpa showed DNA protection activity at all doses tested, while Senna alata showed pro-oxidant activity at 10 µg ml-1 and 1000 µg ml-1. The liver weight expressed as a fraction of brain weight was significantly (P < 0.05) elevated over the control by 200- and 600 mg kg.bwt-1 dose of S.alata and S.podocarpa, while a significant (P < 0.05) increase in testis weight was also noticed in the Senna podocarpa 1000 mg kg-1bwt group. A significant (P < 0.05) elevation of plasma ALT activity was induced by S.podocarpa at 600 mg kg-1bwt after nine weeks exposure. The hematocrit was significantly (P < 0.05) elevated by all tested doses of the two extracts. The growth rate and cell viability of K562 cells were reduced by the extracts. The findings of this study revealed that the leaf extract of S.alata and S.podocarpa increased the PCV values as well as the antioxidant capacity of blood, and also had an inhibitory effect on the basal level of liver lipid peroxidation. The extracts also had cytotoxic effect on K562 cells compared to the herbal preparation Nicosan.