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.

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.

Ziziphus jujuba (Rhamnaceae) Alleviates Working Memory Impairment and Restores Neurochemical Alterations in the Prefrontal Cortex of D-Galactose-Treated Rats.

Alzheimer's disease is a progressive cognitive dysfunction. However, pharmacological treatments are symptomatic and have many side effects, opening the opportunity to alternative medicine. This study investigated the antiamnesic effect of the aqueous extract of Ziziphus jujuba on D-galactose-induced working memory impairment in rats. Impairment of working memory was induced by subcutaneous (s.c.) injection of D-galactose (350 mg/kg/day) to rats for 21 days. These animals were then subjected to object recognition and Y-maze tests. Rats with confirmed memory impairment were treated per os (p.o.) with tacrine (10 mg/kg), aspirin (20 mg/kg, p.o.), extract (41.5, 83, and 166 mg/kg, p.o.), and distilled water (10 mL/kg, p.o.) daily for 14 days. At the end of the treatments, alteration in working memory was assessed using the above paradigms. Afterward, these animals were euthanized, and cholinergic, proinflammatory, and neuronal damage markers were analyzed in the prefrontal cortex. Rats administered D-galactose and treated with distilled water had impaired working memory (evidenced by decreased time spent on the novel object and discrimination index) and decreased spontaneous alternation in the Y-maze. D-galactose also decreased the levels of acetylcholinesterase and acetylcholine and increased the level of glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and interferon-gamma (IFN-γ). Treatment with the extract (166 mg/kg) reversed the time spent on the novel object and the discrimination index. It equally increased the percentage of spontaneous alternation. Neurochemical analysis revealed that the extract markedly alleviated acetylcholinesterase activity and neuroinflammation. These observations were corroborated by the reduction in neuronal loss. Taken together, these results suggest that Ziziphus jujuba aqueous extract possesses an antiamnesic effect. This effect seems to involve cholinergic and anti-inflammatory modulations. This, therefore, claims using this plant in the treatment of dementia in Cameroon subject to further studies and trials.