An aqueous macerate of Ziziphus jujuba reduces long-term spatial memory impairment in D-galactose treated rats: role of anti-inflammatory pathways.

Pharmacological treatments against Alzheimer disease provide only symptomatic relief and are associated with numerous side effects. Previous studies showed that a concoction of Ziziphus jujuba leaves possesses anti-amnesic effects in scopolamine-treated rats. More recently, an aqueous macerate of Z. jujuba leaves has been shown to reduce short-term memory impairment in D-galactose-treated rats. However, no study on the effect of an aqueous macerate of Z. jujuba on long-term memory impairment was performed. Therefore, this study evaluates the effect of an aqueous macerate of Z. jujuba on long-term spatial memory impairment in D-galactose-treated rats. Long-term spatial memory impairment was induced in rats by administering D-galactose (350 mg/kg/day, s.c.), once dailyfor 21 days. On the 22nd day, the integrity of this memory was assessed using the Morris water maze task. Rats that developed memory impairment were treated with tacrine (10 mg/kg, p.o.), or aspirin (20 mg/kg, p.o.), or extract (41.5, 83, and 166 mg/kg, p.o.), once daily, for 14 days. At the end of the treatment, memory impairment was once more assessed using the same paradigm. Animals were then euthanized, and some pro-inflammatory cytokine markers were analyzed in the hippocampus or blood. The extract at all doses significantly reduced the latency to attain the platforming of the water maze test. The extract (83 mg/kg) also increased the time spent in the target quadrant during the retention phase. The extract markedly reduced the concentration of pro-inflammatory cytokine markers in the hippocampus and blood. Together, these results suggest that this aqueous extract Z. jujuba reduces long-term spatial memory impairment. This effect may be mediated in part by its anti-inflammatory activity.

An aqueous extract of Khaya senegalensis (Desv.) A. Juss. (Meliaceae) prevents seizures and reduces anxiety in kainate-treated rats: modulation of GABA neurotransmission, oxidative stress, and neuronal loss in the hippocampus.

Ethnopharmacological relevance: Temporal lobe epilepsy is the most common form of drug-resistant epilepsy. Therefore, medicinal plants provide an alternative source for the discovery of new antiepileptic drugs. Aim of the study: This study was aimed at investigating the antiepileptic- and anxiolytic-like effects of an aqueous extract of Khaya senegalensis (K. senegalensis) in kainate-treated rats. Methods: Seventy-two rats received a single dose of kainate (12 mg/kg) intraperitoneally. Those that exhibited two hours of status epilepticus were selected and monitored for the first spontaneous seizure. Then, animals that developed seizures were divided into 6 groups of 8 rats each and treated twice daily for 14 days as follows: negative control group received per os (p.o.) distilled water (10 ml/kg); two positive control groups received either sodium valproate (300 mg/kg, p.o.) or phenobarbital (20 mg/kg, p.o.); and three test groups received different doses of the extract (50, 100, and 200 mg/kg, p.o.). In addition, a group of 8 normal rats (normal control group) received distilled water (10 ml/kg, p.o.). During the treatment period, the animals were video-monitored 12 h/day for behavioral seizures. At the end of the treatment period, animals were subjected to elevated plus-maze and open field tests. Thereafter, rats were euthanized for the analysis of γ-aminobutyric acid (GABA) concentration, oxidative stress status, and neuronal loss in the hippocampus. Results: The aqueous extract of K. senegalensis significantly reduced spontaneous recurrent seizures (generalized tonic-clonic seizures) and anxiety-like behavior compared to the negative control group. These effects were more marked than those of sodium valproate or phenobarbital. Furthermore, the extract significantly increased GABA concentration, alleviated oxidative stress, and mitigated neuronal loss in the dentate gyrus of the hippocampus. Conclusion: These findings suggest that the aqueous extract of K. senegalensis possesses antiepileptic- and anxiolytic-like effects. These effects were greater than those of sodium valproate or phenobarbital, standard antiepileptic drugs. Furthermore, these effects are accompanied by neuromodulatory and antioxidant activities that may be related to their behavioral effects. These data justify further studies to identify the bioactive molecules present in the extract for possible future therapeutic development and to unravel their mechanisms of action.

Antiamnesic and Neuroprotective Effects of an Aqueous Extract of Ziziphus jujuba Mill. (Rhamnaceae) on Scopolamine-Induced Cognitive Impairments in Rats.

BACKGROUND: Alzheimer's disease is a neurological condition that affects about 44 million people worldwide. The available treatments target symptoms rather than the underlying causes. Ziziphus jujuba (Rhamnaceae) is widely used in traditional Cameroonian medicine to treat diabetes, pain, infections, and dementia. Previous studies reported that Z. jujuba aqueous macerate improves working memory impairment, but no study on the antiamnesic effect of a concoction of Z. jujuba in rats has been performed. Therefore, this study aimed to assess the antiamnesic and neuroprotective effects of an aqueous extract of Z. jujuba on scopolamine-induced cognitive impairments in rats. METHODS: Learning and memory impairments were induced in rats by administering scopolamine (1 mg/kg, i.p.) to 58 rats for 15 days. Rats that developed learning and memory impairments in Morris water maze and Y-maze paradigms were divided into 7 groups (8 rats each) and treated daily for 15 days as follows: the normal control group received distilled water (10 ml/kg, p.o.), the negative control group received distilled water (10 ml/kg, p.o.), positive control groups either received donepezil (1.2 mg/kg, p.o.) or tacrine (10 mg/kg, p.o.), and the three test groups were given the extract (29, 57, and 114 mg/kg, p.o.). At the end of treatments, learning and memory impairments were determined using the same paradigms. Animals were then euthanized, and biochemical parameters of oxidative stress, inflammation, and apoptosis were analyzed in the hippocampus and prefrontal cortex. RESULTS: On the 4th day of the acquisition phase in the Morris water maze, Z. jujuba (29 and 114 mg/kg) reduced (p < 0.001) the latency to reach the platform, while in the retention phase, Z. jujuba (57 and 114 mg/kg) decreased (p < 0.001) the time to reach the platform and increased the time in the target quadrant (p < 0.05) compared to control. Surprisingly, the extract failed to affect spontaneous alternations in the Y-maze. Furthermore, the extract (29, 57, and 114 mg/kg) reversed (p < 0.001) scopolamine-induced oxidative stress, inflammation, and apoptosis. This was supported by the reduction of neuronal alterations in the hippocampus and prefrontal cortex. CONCLUSIONS: Compared to donepezil, a standard drug against Alzheimer's disease, these findings suggest that Z. jujuba extract possesses antiamnesic and neuroprotective effects, and these effects are mediated in part through antioxidant, anti-inflammatory, and antiapoptotic activities. These findings help to explain its use in treating psychiatric disorders in Cameroon's folk medicine.