The Aqueous Extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum Mixture Protects Striatal Neurons and Movement-Associated Functionalities in a Rat Model of Diabetes-Induced Locomotion Dysfunction.

Among the many complications of type 2 diabetes (T2D), locomotor disorders have been poorly studied and understood. Therefore, no disease-modifying treatment is usually considered. The study aimed to investigate the effect of the aqueous extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) mixture on locomotor activity in fructose/streptozotocin-induced diabetic rats. T2D was induced by 10% fructose orally (6 weeks) and streptozotocin (STZ, 35 mg/kg, i.v.) in 25 male rats. Diabetic animals received distilled water, metformin (200 mg/kg), or the aqueous extract of the SNP mixture (75, 150, or 300 mg/kg). A 10-minute open field test was performed in diabetic rats (glycemia: 126 and 350 mg/dL) to assess locomotor activity before and after treatment. A group of 5 normal rats (NC) served as controls throughout the study. Rats were sacrificed, and the striatum was removed for biochemical and histological studies. In untreated diabetic rats, fructose/STZ administration resulted in hyperglycemia that altered locomotor function as characterized by increased freezing time, decreased mobility time, number of lines crossed, and total travel time compared to NC. MDA, TNF-α, INF-γ, and nitrite levels were elevated in the striatum of diabetic rats, while catalase activity and GSH levels were decreased, indicating oxidative stress and neuroinflammatory changes. In untreated diabetic rats, the microstructure of the HE-stained striatum revealed lipid vacuolation (hydropic degeneration) of the parenchyma, indicating a loss of neuronal integrity. The locomotor dysfunction was significantly improved by the aqueous extract of the SNP mixture, both biochemically and histologically. As a result, our findings support the mixture's ability to correct diabetes-related locomotion disorders as a glucose-lowering product and antioxidant, anti-inflammatory, and neuroprotective agent. These results justify the use of the aqueous extract of a combination of these three plants to manage diabetes and neuroinflammatory complications in Northern Cameroon.

Acute and sub-acute toxicity of a lyophilised aqueous extract of the aerial part of Spilanthes africana Delile in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Spilanthes africana is a plant used in several countries for the treatment of toothache, malaria, fracture, pneumonia, and dysentery. In order to establish the safety of aerial part of the plant extract, the acute and sub-acute toxicity of the aqueous extract of this plant has been evaluated in male and female young rats. MATERIAL AND METHODS: In acute toxicity, the effects of a single oral dose (2,000 mg/kg and 5,000 mg/kg) of the lyophilised aqueous extract have been determined. General behaviour, adverse effects and mortality were determined for up to 14 days. In sub-acute treatment, the effects of the extract in daily single oral administration at the doses of 250, 500 and 1,000 mg/kg during 28 days were evaluated. One group treated at the dose of 1,000 mg/kg for 28 days was let without treatment during 14 days to assess the possible reversibility of the harmful effects of the extract. Body weight, food and water intakes, biochemical and haematological parameters were recorded. Histopathological examination of liver, kidney and lungs were assessed. RESULTS: In acute study, a single administration of the aqueous extract at the doses of 2,000 mg/kg or 5,000 mg/kg did not induce mortality. Thus, the LD50 of the aqueous extract of S. africana has been estimated higher than 5,000 mg/kg. Four hours after administration of the extract, a reduction of the mobility, sensitivity to the noise and to touch has been observed. In sub-acute study, the administration of the extract during 28 days at all doses did not significantly modify the body weight. On the haematological analysis, a decrease of the rate of monocytes and a rise of lymphocytes counts were observed among the male group. In both sexes, it appeared a decrease of the rate of granulocytes two weeks after stopping the treatment. It has also been observed in different groups among the females, an increase of the mean corpuscular content and the mean concentration in haemoglobin as well as an increase of platelets. A significant decrease of transaminases, alkaline phosphatase, triglycerides, and a significant increase of total bilirubin compared to the normal group has been observed. There was a significant decrease in renal catalase in both sexes compared with different control groups. Besides, a significant increase of the kidney rates of glutathione and malondialdehyde have also been observed in the female treated at the doses of 1,000 mg/kg. Histopathological analysis has shown vascular congestion and leucocyte infiltrations in the liver of animals treated at the dose of 1,000 mg/kg. This congestion has been marked in satellite group. In the kidney female satellite group, tubular clarifications have been observed and disappear when stopping the treatment. CONCLUSION: These results show that the aqueous extract of S. africana given by the oral route is slightly toxic. However in sub-acute treatment, higher doses could provoke functional and structural changes in the organism which could in part reversible. Thus the extract should be used with caution.

Sclerocarya birrea (Anacardiaceae) stem-bark extract corrects glycaemia in diabetic rats and acts on beta-cells by enhancing glucose-stimulated insulin secretion.

Sclerocarya birrea is a plant widely used as traditional medication for the treatment of diabetes in sub-Saharan regions. However, the mechanism of action is unknown and only hypoglycaemic effects of S. birrea extract (SBE) in diabetic rats have been reported to date. Here, we tested aqueous extracts of S. birrea on insulin-secreting INS-1E cells and isolated rat islets. Following 24 h of treatment at 5 microg/ml, the extract markedly potentiated glucose-stimulated insulin secretion. Neither basal insulin release nor non-nutrient stimulation was affected. The potentiation of the secretory response at stimulatory glucose appeared after 12 h of treatment. No acute effects were observed and, at the effective concentration, SBE was safe regarding cell integrity and differentiation. The mechanism of action of the SBE was related to glucose metabolism as both ATP generation and glucose oxidation were enhanced following the 24-h treatment. In streptozotocin-induced diabetic rats, SBE administration corrected glycaemia and restored plasma insulin levels after 2 weeks of treatment. These data show direct action of S. birrea on insulin-secreting cells and favour further delineation for use of the plant in the management of diabetes.