ABSTRACT
The toxicity profile of medicinal plants is an important preclinical requirement in the development of phytomedicines. The cytotoxic and genotoxic effects of the leaf of Uvaria chamae P. Beauv (Annonaceae) and stem bark of Morinda lucida Benth (Rubiaceae) were investigated in order to provide information on their safety as antimalarial plants. The methanol extract of U. chamae and ethanol (70%) extract of M. lucida were separately orally administered (125, 250, and 750 mg/kg/day) to mice for 10 consecutive days. Cyclophosphamide (50 mg/kg, single dose) and distilled water were used as positive and negative controls, respectively. The mice were injected with colchicine (0.04%) intra-peritoneally 24 h after the last administration of the extracts and the bone marrows harvested. Giemsa-stained slides of bone marrow cells were microscopically assessed for dividing cells to determine the mitotic index (MI) and scored for chromosomal aberrations (CA) according to standard methods. chamae exhibited dose-dependent cytotoxicity. At 750 mg/kg, the MI was significantly (p < 0.05) lower (1.81 ± 0.04) than that of cyclophosphamide (5.83 ± 0.04). The lower the MI, the higher the cytotoxicity. The activity of M. lucida was not significantly different (p > 0.05) from that of the negative control. The total CA observed from treatment with both plants at all doses were significantly (p < 0.05) greater than that of control. This study concluded that U. chamae showed both cytotoxicity and genotoxicity while M. lucida exerted only genotoxic effect. Nevertheless, the two plants should be used with caution in antimalarial therapy.
Subject(s)
Antimalarials/toxicity , Bone Marrow Cells/drug effects , Chromosome Aberrations/chemically induced , Morinda/toxicity , Plant Extracts/toxicity , Uvaria/toxicity , Animals , Antimalarials/isolation & purification , Bone Marrow Cells/pathology , Dose-Response Relationship, Drug , Ethanol/chemistry , Female , Male , Methanol/chemistry , Mice , Mitosis/drug effects , Mitotic Index , Morinda/chemistry , Phytotherapy , Plant Bark , Plant Extracts/isolation & purification , Plant Leaves , Plant Stems , Plants, Medicinal , Risk Assessment , Solvents/chemistry , Uvaria/chemistryABSTRACT
The extracts of nine selected Nigerian medicinal plants were investigated on Trypanosoma brucei brucei infected mice. The anti-inflammatory properties of hexane fraction of the most promising U. chamae extract was assessed by acute oedema of the mice paw model while the modulatory effect of the extract on Delayed-Type Hypersensitivity (DTH) response on in vivo leucocytes mobilization was evaluated. 'Dose-probing acute toxicity tests' established an oral and intraperitoneal LD50 for T. ivorensis stem bark as >1600 < 5000 mg/kg and 100 mg/kg respectively, while the oral LD50 of Uvaria. chamae was >5000 mg/kg. Extracts of Khaya senegalensis, Harungana madagascariensis, Terminalia ivorensis, Curcuma longa, Ocimum gratissimum and Alcornea cordifolia showed weak anti-trypanosomal effect and did not exhibit significant clearance in parasitemia at the test dose administered compared with the positive control (Diminal®). However, the leaf extract of U. chamae and its hexane fraction demonstrated a significant response (P < 0.01). The fraction at 1000 mg/kg inhibited oedema by 107%. Uvaria. chamae demonstrated both antitrypanosomal and anti-inflammatory properties by increasing the survival time of infected mice due to reduction in parasitemia caused by T. brucei brucei.
