Alzheimer’s disease the most common form of dementia in the elderly is a neurodegenerative disease that affects 44 millions of people worldwide. The first treatments against Alzheimer’s disease are acetylcholinesterase inhibitors; however, these medications are associated with many side effects. Dichrocephala integrifolia is a traditional herb widely used by indigenous population of Cameroon to treat and prevent Alzheimer’s disease and for memory improvement. In this study, we evaluated the effect of the decoction prepared from leaves of D. integrifolia, on scopolamine-induced memory impairment in mice. Seven groups of six animals were used. The first two groups received distilled water for the distilled water and scopolamine groups. The four test groups received one of the four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o.) and the positive control group received tacrine (10 mg/kg), a cholinesterase inhibitor used in the treatment of Alzheimer’s disease, during 10 consecutive days. Scopolamine (1 mg/kg), a cholinergic receptor blocker, administered 30 min after treatments, was used to induce memory impairment to all groups except the distilled water group on day 10 of drug treatment. The behavioral paradigms used to evaluate the effects of the treatment were the elevated plus maze for learning and memory, Y maze for spatial short-term memory, the novel object recognition for recognition memory and Morris water maze for the evaluation of spatial long-term memory. After behavioral tests, animals were sacrificed and brains of a subset were used for the assessment of some biomarkers of oxidative stress (malondialdehyde and reduced glutathione levels) and for the evaluation of the acetylcholinesterase activity. From the remaining subset brains, histopathological analysis was performed. The results of this study showed that, D. integrifolia at the doses of 87.5 and 350 mg/kg significantly (p < 0.01) improved spatial short-term and long-term memory, by increasing the percentage of spontaneous alternation in the Y maze and reducing the escape latency in the Morris water maze. Furthermore, the results of histopathological evaluation showed that D. integrifolia attenuated the neuronal death in the hippocampus induced by scopolamine. The main finding of this work is that D. integrifolia improves learning capacities and counteracts the memory impairment induced by scopolamine. Thus, D. integrifolia can be a promising plant resource for the management of Alzheimer’s disease and memory loss.
Cissus quadrangularis (C. quadrangularis) is a plant of the Vitaceae family known for its anticonvulsant effects in traditional medicine. The objective of this study was to elucidate the anxiolytic and antiepileptic effects of aqueous extract of C. quadrangularis. The mice were divided into different groups and treated for seven consecutive days as follows: a negative control group that received distilled water, po, four test groups that received four doses of the plant (37.22, 93.05, 186.11, and 372.21 mg/kg, po), and a positive control group that received sodium valproate (300 mg/kg, ip). One hour after the first treatment (first day), epilepsy was induced by intraperitoneal administration of a single dose of pilocarpine (360 mg/kg). On the seventh day, the anxiolytic effects of the extract were evaluated in the epileptic mice using the elevated plus maze (EPM) and open field (OP) paradigms. Antioxidant activities and the involvement of gabaergic neurotransmission were determined by measuring the levels of malondialdehyde, reduced glutathione (GSH), GABA, and GABA-transaminase (GABA-T) in the hippocampus of sacrificed epileptic mice. The results show that the extract of C. quadrangularis significantly and dose-dependently increased the latency to clonic and generalized tonic–clonic seizures and decreased the number and duration of seizures. In the EPM, the extract of C. quadrangularis significantly increased the number of entries and the time spent into the open arms and reduced the number of entries and the time spent into the closed arms as well as the number of rearing. The extract of C. quadrangularis also increased the number of crossing, and the time spent in the center of the OP. The level of MDA and the activity of GABA-T were significantly decreased by the extract of C. quadrangularis while reduced GSH and GABA levels were increased. The results suggest that the anticonvulsant activities of C. quadrangularis are accompanied by its anxiolytics effects. These effects may be supported by its antioxidant properties and mediated at least in part by the GABA neurotransmission.
In this study, we investigated antiepileptogenic and neuroprotective effects of the aqueous extract of Pergularia daemia roots (PDR) using in vivo and in vitro experimental models. In in vivo studies, status epilepticus caused by pilocarpine injection triggers epileptogenesis which evolves during about 1–2 weeks. After 2 h of status epilepticus, mice were treated during the epileptogenesis period for 7 days with sodium valproate and vitamin C (standards which demonstrated to alter epileptogenesis), or Pergularia daemia. The animals were then, 1 week after status epilepticus, challenged with acute pentylenetetrazole (PTZ) administration to test behaviorally the susceptibility to a convulsant agent of animals treated or not with the plan extract. Memory was assessed after PTZ administration in the elevated plus maze and T-maze paradigms at 24 and 48 h. Antioxidant and acetylcholinesterase activities were determined in the hippocampus after sacrifice, in vitro studies were conducted using embryonic rat primary cortical cultures exposed to L-glutamate. Cell survival rate was measured and apoptotic and necrotic cell death determined. The results showed that chronic oral administration of PDR significantly and dose-dependently increased the latency to myoclonic jerks, clonic seizures and generalized tonic–clonic seizures, and the seizure score. In addition, PDR at all doses (from 4.9 to 49 mg/kg) significantly decreased the initial and retention transfer latencies in the elevated plus maze. Interestingly PDR at the same doses significantly increased the time spent and the number of entries in T-maze novel arm. PDR significantly increased the activities of acetylcholinesterase and antioxidant enzymes superoxide dismutase, catalase, and total glutathione and proteins, and decreased malondialdehyde level. Furthermore, PDR increased viability rate of primary cortical neurons after L-glutamate-induced excitotoxicity, in a dose dependent manner. Altogether these results suggest that PDR has antiepileptogenic and neuroprotective effects, which could be mediated by antioxidant and antiapoptotic activities.
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