RESUMEN
African trypanosomiasis, a neglected tropical disease, is caused by diverse species of the protozoan parasite belonging to the genus Trypanosoma. Although anti-trypanosomal medications exist, the increase in drug resistance and persistent antigenic variation has necessitated the development of newer and more efficacious therapeutic agents which are selectively toxic to the parasite. In this study, we assessed the trypanocidal efficacy of Crosspteryx fibrifuga leaf extract (C.f/L-extract) in vitro. Following treatment of T. congolense parasites with C.f/L-extract, we observed a significant decrease in parasite number and an elevation in the expression of the apoptotic markers, Annexin V and 7-Aminoactinomycin D (7AAD). Interestingly, at the same concentration (50 µg/mL), C.f/L-extract was not cytotoxic to murine whole splenocytes. We also observed a significant increase in pro-inflammatory cytokines and nitric oxide secretion by bone marrow derived macrophages following treatment with C.f/L-extract (10 µg/mL and 50 µg/mL) compared to PBS treated controls, suggesting that the extract possesses an immune regulatory effect. Treatment of T. congolense infected mice with C.f/L-extract led to significant decrease in parasite numbers and a modest increase in mouse survival compared to PBS treated controls. In addition, there was a significant increase in CD4+IFN-γ+ T cells and a decrease in CD4+IL-10+ T cells in the spleens of T. congolense infected mice treated with C.f/L-extract. Interestingly, C.f/L-extract treatment decreased the activity of superoxide dismutase (an enzyme that protects unicellular organisms from oxidative stress) in T. congolense parasites but not in splenocytes. Collectively, our study has identified C.f/L-extract as a potential anti-trypanosomal agent that warrant further investigation and possibly explored as a treatment option for T. congolense infection.
RESUMEN
BACKGROUND: Ethnopharmacological practitioners in Nigeria have used aqueous and ethanol extracts of Bridelia micrantha leaves to manage conditions associated with inflammation, and these include diabetes, chest pain, edema, arthritis and joint pains. This study aimed to evaluate the effects of methanol leaf extract of B. micrantha on chronic inflammation and oxidative stress which accompany diabetic conditions, in streptozotocin-induced diabetic Albino Wistar rats. METHODS: The dried leaves were extracted by percolation in 80% methanol:water for 72 h after which the mixture was filtered using Whatman No. 1 (11 µm) filter papers. Acute toxicity studies were done using Wistar rats and given orally up to a dose of 2,000 mg/kg. The animals were monitored for 48 h. The experimental design involved five (5) groups of six (6) albino Wistar diabetic rats each. Groups A, B and C rats received 100, 200 and 400 mg/kg B. micrantha respectively while groups D (negative control) and E (positive control) rats received 10 mL/kg normal saline and 200 mg/kg acetylsalicylic acid (ASA) respectively by gastric gavage for 7 days. Two sterilized cotton pellets (10 mg each) were implanted subcutaneously into both sides of the dorsal area of each diabetic rat in all the groups. Post cotton pellet implantation, rats in three groups (A, B and C) were treated with 100, 200 and 400 mg/kg B. micrantha extract, while those in two groups (D and E) were treated with acetyl salicylic acid (ASA 200 mg/kg) and normal saline (10 mL/kg) respectively by gastric gavage for 7 days. Serum obtained from the animals on Day 8 of the cotton pellet test were used for malondialdehyde (MDA), catalase, superoxide dismutase (SOD) and glutathione (GSH) assays. RESULTS: The administration of the leaf extract up to a dose of 2,000 mg/kg to rats produced absolutely no death or observable signs of toxicity in 48 h. The cotton pellet granuloma weights in 200 mg/kg (44.88±1.2 mg), 400 mg/kg (42.10±1.2 mg) B. micrantha extract treated groups and ASA at 200 mg/kg (43.25±1.8 mg) were significantly lower compared to weight of granuloma (85.50±3.2 mg) obtained in the group treated with normal saline. Serum malondialdehyde (MDA) level in the 200 mg/kg (3.32±0.72 nmol/mL) and 400 mg/kg (1.88±1.27 nmol/mL) B. micrantha extract treated groups were significantly (p<0.05) lower compared to MDA level (6.88±0.79 nmol/mL) in the serum of normal saline treated group. Treatment of diabetic rats with the B. micrantha extract also caused significant (p<0.05) elevation in serum catalase, SOD and GSH levels. CONCLUSIONS: The study showed that B. micrantha methanol leaf extract significantly inhibited some chronic inflammation and oxidative stress parameters in diabetes mellitus.