Prenatal exposure to valproic acid (VPA) has been shown to increase the risk of autism in children. This study examined the effect of metformin on VPA‐induced autism spectrum disorders in rats. Pregnant albino rats administered VPA (500 mg/kg, i.p.) or normal saline (10 mL/kg, i.p.; vehicle‐control) on gestational day 12.5. The pups were given metformin (5, 50 or 500 mg/kg, p.o.) or vehicle (10 mL/kg, p.o.) daily from postnatal day (PND) 21–50. Social behaviour, spatial learning/reference memory, repetitive behaviour and anxiety were assessed using the three‐chamber social assay, Morris water maze (MWM), Y maze and elevated plus maze tests (EPM), respectively. On PND 51, the animals were euthanized and brains removed for biochemical assay. In utero VPA exposure caused significant reduction in sociability index, social novelty preference index in three‐chambered apparatus and spatial learning and reference memory deficits in the MWM task as well as increase in repetitive/anxiety‐like behaviour in Y maze and EPM tests, respectively, which were ameliorated by post‐treatment with metformin in a dose‐dependent manner. Moreover, prenatal VPA increased malondialdehyde (MDA) and nitrite levels as well as deficits in antioxidant enzymes activities in the hippocampus and prefrontal cortex (PFC) which were attenuated by metformin administration. Similarly, VPA‐induced increase in acetylcholinesterase activity in the hippocampus and PFC were attenuated by postnatal treatment with metformin. Findings from this study showed that postnatal administration of metformin prevented valproic acid‐induced autistic‐like behaviour. Hence, metformin could be a potential adjunct in the management of autism spectrum disorders.
Results showed that MS had antidepressant activity possibly mediated through α-adrenergic and D dopaminergic receptors, without significant anxiolytic effect.
Madam F. Kayes Bitters® is an herbal formulation commonly used in Nigeria and some African countries in the management of diabetes mellitus and other diseases conditions. This study evaluated the in-vivo hypoglycaemic activity, as well as acute toxicity of the polyherbal formulation to provide its efficacy and safety. Healthy albino mice (20-30 g) and Sprague Dawley female rats (90-130 g) were used for this study. Acute toxicity study (LD50) of the herbal formulation was determined by methods originally described by Miller and Tainter in 1994. Following oral dosing with glucose (2 g/kg) in normal fasted animals, herbal formulation (HF) at various doses was administered and blood glucose levels at 30 minutes, 60 minutes, 90 minutes, and 120 minutes were taken and recorded. Diabetes was induced using alloxan 150 mg/kg and diabetic rats were given the HF at doses of 50, 100, and 200 mg/kg with glibenclamide 2.5 mg/kg used as standard drug treatment. Blood glucose level was determined on 1st day, 7th day, 14th and 21st day. The LD50 was greater than 5g/kg with oral administration. The oral glucose tolerance test showed that the group that received 100 mg/kg HF showed a significant reduction (p<0.05) in glucose level after 120 minutes when compared to the basal level of glucose recorded. All treated diabetic groups showed a significant decrease in glucose level on the 21st day. The herbal formulation of Hydrastis canadesis Aloe capensis, Echinacea angustifolia and honey exhibited a significant glucose-lowering activity in alloxan-induced diabetic rats.
Autism is a lifelong neurodevelopmental disorder characterized by impairments in social interaction and repetitive patterns of behaviour. Prenatal exposure to valproic acid (VPA) has been shown to increase the risk of autism in children. In this study, we examined the effect of metformin on VPA-induced autism spectrum disorders in rats. Pregnant albino rats administered VPA (500 mg/kg, i.p.) or normal saline (10 ml/kg, i.p.; vehicle-control) on gestational day 12.5. The pups were given metformin (5, 50 or 500 mg/kg, p.o.) or vehicle (10 ml/kg, p.o.) daily from postnatal day 21 to 50. Social behaviour, spatial learning/ reference memory, repetitive behaviour and anxiety were assessed using the three-chamber social assay, Morris water maze, Y-maze and elevated plus maze (EPM), respectively. Postnatal day 50, the animals were sacrificed and brains removed for biochemical assay. Pretreatment of rats pups with VPA caused a reduction in sociability index (P< 0.001, 0.21± 0.03) when compared to the control animals (3.56± 0.36) which was dose dependently and significantly ameliorated by metformin. Moreover, VPA reduced social preference evidenced in significant increase in time spent in the familiar chamber and reduction in time spent in the novel chamber compared to the control animals in the three-chamber social behaviour apparatus. Metformin administration caused dose dependent increase in time spent in novel chamber suggestive of improvement in social behaviour. In the Morris water maze task, VPA caused deficit in spatial learning ability which was dose dependently ameliorated by metformin evidenced in significant reduction of escape latency time and increase in time spent at quadrant location indicative of improvement in spatial learning and reference memory, respectively. Prenatal VPA increased repetitive (Y-maze) and anxiety (EPM) behaviours which were significantly attenuated by metformin treatment. VPA-induced increase in malondialdehyde level and deficit in antioxidant enzymes activities as well as increase in acetylcholinesterase activity in the hippocampus and prefrontal cortex were attenuated by metformin treatment. Findings from this study showed that post natal administration of metformin prevented valproic acid-induced autistic behaviour. Hence, metformin could be a potential drug in the management of autism spectrum disorders
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