RESUMO
Avicennia africana is an important ethnomedicinal plant that has long been used to treat malaria and several other diseases. Despite the plant's antimalarial and other therapeutic properties, there is limited evidence-based data on its potential toxicity. Hence, the purpose of the current study was to assess the safety of A. africana leaf ethanolic extract (AAE). The study was designed to ascertain the cytotoxic effects of the crude extract on red blood cells (RBCs) as well as the acute and subacute toxicity in Wistar albino rats in accordance with Organization for Economic Co-operation and Development (OECD) guidelines "Test No. 423" and CPMW/SWP/1042/99. The pulverized, shade-dried plant leaves were sequentially macerated with 70% ethanol to obtain the crude extract (AAE). The extract's cytotoxic activity (CC50) against the uninfected human red blood cells (RBCs) was determined using the 3-(4,5-Dimethylythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. For the acute toxicity studies, the rats (male and female) were divided randomly into six groups of five rats (n = 5) and dosed orally once with the following dose levels: 100, 300, 1000, 3000, and 5000 mgkg-1, p.o. of the extracted AAE, with the control group receiving only the vehicle. In the repeated dose toxicity studies, the rats (both sexes) were orally administered daily with AAE at 100, 300, and 1000 mgkg-1 for 14 days. Rat body weights were measured, and blood samples were tested for haematological and biochemical markers. Internal organs like the heart, kidney, liver, and spleen were collected, inspected, and weighed, and histological examinations were performed. The median lethal dose (LD50) value is greater than 5000 mgkg-1 body weight, with no significant change in bodyweight or relative organ weight (ROWs) of the extract-treated groups or control group. The extract showed greater cytotoxicity activity (CC50), which was >100 µg/mL, compared to the reference drug (artesunate).The dosage groups of 100 and 300 mgkg-1bwt had neutrophilia and lymphocytopenia (p < 0.05). However, changes in these haematological parameters may not be dose dependent and could be stress related. All the serum biochemical markers studied in rats given AAE did not show any significant change (p > 0.05). Histopathological examination of internal organs of AAE-treated rats did not show any significant abnormalities resulting from the extract treatment compared to the control group. Based on the findings in the present study, the LD50 value of AAE was found to exceed 5000 mgkg-1 in the acute toxicity test, while the no observed adverse effect level (NOAEL) in rats was 1000 mgkg-1 p.o. In the sub-acute toxicity tests. Histopathological analysis revealed no morphological abnormalities in the vital organs.
RESUMO
Background: The emergence of widespread drug-resistant strains of the malaria parasites militates against strives for more potent antimalarial drugs. Aim: The present study evaluated the antimalarial activity of A. africana ethanolic crude extract in vitro and in vivo against Plasmodium berghei -infected mice in anticipation of acquiring scientific evidence for it used by mangrove dwellers to treat malaria in Ghana. Methodology: The pulverized dried leaves were extracted with 70% ethanol (v/v) and screened for phytochemicals using standard protocols. The in vitro antimalarial activity was investigated against chloroquine-sensitive Plasmodium falciparum (Pf3D7 clones), MRA-102, Lot:70032033, via SYBR® Green I fluorescent assay method using positive control Artesunate (50-1.56 × 10-3 µg/mL). In the in vivo studies, doses (200-1500 mg/kg) of AAE were used in the 4-day suppressive and curative tests, using P. berghei-infected mice. Artemether/lumefantrine (1.14 mg/kg) and normal saline were used as positive and negative control respectively. Results: The phytochemical analysis revealed the presence of alkaloids, saponins, flavonoids, glycosides, tannins, terpenoids and phytosterols. The extract showed an IC50 of 49.30 ± 4.40 µg/mL in vitro and demonstrated complete parasite clearance at dose 1500 mg/kg in vivo with a suppressive activity of 100% (p < 0.0001) in the 4-day suppressive test. The extract demonstrated high curative activity (p < 0.0001) at 1500 mg/kg with 100% parasite inhibition and the oral LD50 > 5000 mg/kg in mice. Conclusion: The results demonstrated that A. africana crude extract has antimalarial activity both in vitro and in vivo supporting the traditional use of the plant to treat malaria.
