Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways.

Parkia biglobosa (Jacq.) R. Br. (Fabaceae) is a widely distributed tree, used in traditional medicine to treat amebiasis, hookworm infection, ascariasis, asthma, sterility, dental pain, headaches, cardiac disorders, and epilepsy. To date, no study on the effect of an aqueous extract of P. biglobosa on epileptogenesis and associated neuropsychiatric disorders has been undertaken. Therefore, this study aimed to investigate antiepileptogenic-, antiamnesic-, and anxiolytic-like effects of an aqueous extract of P. biglobosa using pentylenetetrazole (PTZ)-induced kindling in mice. Animals were divided into six groups of eight mice each. Thus, a PTZ group received distilled water (10 ml/kg, per os), a positive control group received sodium valproate (300 mg/kg, p.o.), and three test groups received the aqueous extract of P. biglobosa (80, 160, and 320 mg/kg, p.o.).In addition, a control group of eight mice receiving distilled water (10 ml/kg, p.o.) was formed. The treatments were administered to mice, 60 min before administration of PTZ (20 mg/kg, i.p.). These co-administrations were performed once daily, for 22 days. The number and duration of seizures (stages 1, 2, 3, and 4 of seizures) exhibited by each mouse were assessed for 30 min during the treatment period. Twenty-four hours following the last administration of the treatments and PTZ, novel object recognition and T-maze tests were performed to assess working memory impairment in mice, while the open field test was performed to assess anxiety-like behavior. After these tests, the animals were sacrificed, and the hippocampi were collected for biochemical and histological analysis. During the period of PTZ-kindling, the extract at all doses completely (p < 0.001) protected all mice against stages 3 and 4 of seizures when compared to sodium valproate, a standard antiepileptic drug. The extract also significantly (p < 0.001) attenuated working memory impairment and anxiety-like behavior. In post-mortem brain analyses, the extract significantly (p < 0.001) increased γ-aminobutyric acid (GABA) level and reduced oxidative stress and inflammation. Histological analysis showed that the aqueous extract attenuated neuronal degeneration/necrosis in the hippocampus. These results suggest that the extract is endowed with antiepileptogenic-, anti-amnesic-, and anxiolytic-like effects. These effects seem to be mediated in part by GABAergic, antioxidant, and anti-inflammatory mechanisms. These results suggest the merit of further studies to isolate the bioactive molecules responsible for these potentially therapeutically relevant effects of the extract.

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.

Anti-inflammatory and acetylcholinesterase activity of extract, fractions and five compounds isolated from the leaves and twigs of Artemisia annua growing in Cameroon.

BACKGROUND: Natural products, including those derived from higher plants have, over the years, contributed greatly to the development of modern therapeutic drugs. Due to the medicinal importance in traditional practice and the diversified biology and chemistry of the constituents from Artemisia spp., the genus has been receiving growing attention. The aim of this study was to investigate the ability of the ethanol extract, four fractions (F1-F4) and five compounds namely artemisinin (1), scopoletin (2), chrysosplenetin (3), eupatin (4) and 3-O-ß-d-glucopyranoside of sitosterol (5) isolated from A. annua to modulate the activity of anticholinesterase (AchE) and the production of nitric oxide (NO) in LPS-activated RAW 264.7 macrophages. RESULTS: At the lowest concentration tested (6.25 µg/mL), the crude extract and fraction F2 had the highest NO inhibitory activity (72.39 and 71.00 % inhibition respectively) without significant toxicity on the viability of macrophage cells (93.86 and 79.87 % of cell viability respectively). The crude extract inhibited AchE activity by 71.83 % (at 1 mg/mL) with an IC50 value of 87.43 µg/mL while F2 and F4 were the most active fractions (IC50 values of 36.75 and 28.82 µg/mL). Artemisinin (1) and chrysosplenetin (3) had the highest AChE activity with 71.67 and 80.00 % inhibition (at 0.1 mg/mL) and IC50 values of 29.34 and 27.14 µg/mL, respectively. CONCLUSION: Our results validate the traditional use of A. annua and could help to support the usefulness of this plant in the treatment of inflammatory and neurological disorders especially where nitric oxide and a cholinesterase are involved.