Ameliorative effects of Albizia adianthifolia aqueous extract against pentylenetetrazole-induced epilepsy and associated memory loss in mice: Role of GABAergic, antioxidant defense and anti-inflammatory systems.

Albizia adianthifolia (Schumach.) (Fabaceae) is a medicinal herb used for the treatment of epilepsy and memory impairment. This study aims to investigate the anticonvulsant effects of Albizia adianthifolia aqueous extract against pentylenetetrazole (PTZ)-induced spontaneous convulsions in mice; and determine whether the extract could mitigate memory impairment, oxidative/nitrergic stress, GABA depletion and neuroinflammation. Ultra-high performance liquid chromatography/mass spectrometry analysis was done to identify active compounds from the extract. Mice were injected with PTZ once every 48 h until kindling was developed. Animals received distilled water for the normal group and negative control groups, doses of extract (40, 80, or 160 mg/kg) for the test groups and sodium valproate (300 mg/kg) for the positive control group. Memory was measured using Y maze, novel object recognition (NOR) and open field paradigms, while the oxidative/nitrosative stresses (MDA, GSH, CAT, SOD and NO), GABAergic transmission (GABA, GABA-T and GAD) and neuro-inflammation (TNF-α, IFN-γ, IL- 1ß, and IL-6) were determined. Brain photomicrograph was also studied. Apigenin, murrayanine and safranal were identified in the extract. The extract (80-160 mg/kg) significantly protected mice against seizures and mortality induced by PTZ. The extract significantly increased the spontaneous alternation and the discrimination index in the Y maze and NOR tests, respectively. PTZ kindling induced oxidative/nitrosative stress, GABA depletion, neuroinflammation and neuronal cells death was strongly reversed by the extract. The results suggest that the anticonvulsant activity of Albizia adianthifolia extract is accompanied by its anti-amnesic property, and may be supported by the amelioration of oxidative stress, GABAergic transmission and neuroinflammation.

Estrogenic and anti-amnesic potential of Millettia griffoniana Baill. (Fabaceae) ethanolic extract on scopolamine-induced memory impairment in ovariectomized Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dementias including Alzheimer disease (AD) are three times higher in menopausal women than in men. Phytoestrogens, a group of plant-derived compounds are known to alleviate menopausal complaints including dementia. Millettia griffoniana Baill is a phytoestrogen-rich plant used to treat menopausal complaints and dementia. AIM: Evaluating the estrogenic and neuroprotective potential of Millettia griffoniana on ovariectomized (OVX) rats. MATERIALS AND METHODS: The in vitro safety of M. griffoniana ethanolic extract was assayed by MTT in human mammary epithelial (HMEC) and mouse neuronal (HT-22) cells and its lethal dose 50 (LD50) was estimated following OECD 423 guidelines. For estrogenicity, in vitro the well known E-screen assay on MCF-7 cells was performed and in vivo four groups of OVX rats were treated either with 75, 150 and 300 mg/kg M. griffoniana extract doses or estradiol (1 mg/kg BW) for three days; and changes in uterine and vagina were analyzed. Then, for neuroprotective effect, Alzheimer-type dementia induction was achieved by scopolamine (1.5 mg/kg B.W., i.p.) injection four days/week and M. griffoniana extract as well as piracetam (standard) were administered daily for 2 weeks to evaluate the extract's neuroprotective potential. The endpoints were the assessment of learning and working memory, oxidative stress state (SOD, CAT, and MDA) in brain, acetylcholine esterase (AChE) activity and the histopathological changes in hippocampus. RESULTS: No toxic effect was observed when incubating mammary (HMEC) and neuronal (HT-22) cells with M. griffoniana ethanol extract for 24 h and its LD50 was found >2000 mg/kg. The extract also exhibited both in vitro and in vivo estrogenic activities, displayed by a significant (p < 0.01) increment in MCF-7 cells population in vitro and an increase in the epithelium height of the vagina and the wet weight of the uterus mainly with the 150 mg/kg BW extract dose compared to untreated OVX rats. The extract also reversed scopolamine-induced memory impairment in rat by improving learning, working and reference memory. This was associated with an increment in CAT and SOD expression, alongside a decrement in MDA content and AChE activity in hippocampus. Further, the extract reduced neuronal cell loss in hippocampal structures (CA1, CA3 and dentate gyrus). High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) spectra, revealed the presence of numerous phytoestrogens in M. griffoniana extract. CONCLUSION: M. griffoniana ethanolic extract has estrogenic, anticholinesterase and antioxidant activities that could account for its anti-amnesic effects. These findings therefore sheds light on why this plant is commonly used in the therapy of menopausal complaints and dementia.

Aqueous Root Bark Extract of Daniellia oliveri (Hutch. & Dalz.) (Fabaceae) Protects Neurons against Diazepam-Induced Amnesia in Mice.

Daniellia oliveri (DO) is a traditional medicinal plant used for the treatment of diseases such as inflammation, schizophrenia, and epilepsy in Nigeria, Kenya, Congo, and Cameroon. This study was carried out to evaluate the potential neuroprotection effect of the aqueous root bark extract of Daniellia oliveri against diazepam-induced amnesia in mice. Thirty-six adult male mice were distributed into six groups: the three test groups received Daniellia oliveri root bark extract (100, 200, and 300 mg/kg), the normal control group received distilled water (10 ml/kg), a positive control group received piracetam (150 mg/kg), and the negative control received diazepam (2.5 mg/kg). Learning and memory were evaluated using the radial arm maze and the T-maze. Biomarkers of oxidative stress were also quantified in mice brains. Statistical analyses were performed using two-way ANOVA followed by Tukey's post hoc test. Daniellia oliveri root bark aqueous extract decreased the number of working memory errors and number of reference memory errors in amnesic mice evaluated in the radial arm maze. Also, an increase in glutathione activity and a decrease in malondialdehyde levels were noted in the hippocampi homogenate of the extract-treated mice as compared to the diazepam-demented but untreated group. Moreover, pretreatment with Daniellia oliveri aqueous root bark extract reversed the decrease in hippocampal cell density observed in the nontreated diazepam group. Taken together, these results suggest that the aqueous extract of DO leaves possesses antioxidant potential and might provide an opportunity for the management of neurological abnormalities in amnesic conditions.

Anxiolytic and antidepressant effects of Ziziphus mucronata hydromethanolic extract in male rats exposed to unpredictable chronic mild stress: Possible mechanisms of actions.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphus mucronata (ZM) is used traditionally in the treatment of mood and depression. However, no existing scientific data is confirming this traditional claim. AIM OF THE STUDY: The present study was planned to investigate the anxiolytic and antidepressant-like effects of this plant in a stressed-induced depression model in rats. MATERIALS AND METHODS: Depressive-like behaviors were induced by exposing rats to different stress paradigms daily for 30 days. A sucrose preference test was performed to assess anhedonia in rats. Anxiety and depression-related behavior were assessed. The oxidative parameters (lipid peroxidation, SOD and catalase activities) were evaluated. Pindolol and Flumazenil were also used to assess the mechanism of action of ZM extract. RESULTS: The results showed that chronic administration of ZM (150, 300, and 600 mg/kg, p.o., 30 days) and imipramine treatment (20 mg/kg, p.o, 30 days) remarkably (P < 0.05) reversed the UCMS-induced behavioral changes observed in stress vehicle treated rats by reducing sucrose preference, decreased the immobility period in the FST and latency in NSF. Besides, ZM (300 and 600 mg/kg, p.o., 30 days) raised the percentages of time spent and number of open arms entries as well as the number of transitions. Also, ZM (300 mg/kg, (P < 0.05) decreased lipid peroxidation and increased both SOD and catalase activities (300 and 600 mg/kg, (P < 0.05)). These aforementioned behavioral indices were also completely nullified by pindolol a ß-adrenoceptors blocker and 5-HT 1A/1B receptor antagonist but not by flumazenil, a benzodiazepine receptors antagonist. CONCLUSION: ZM improved symptoms of anxiety and depression in behavioral despair paradigm in chronically stressed rats. The observed effects could be due to its capacities to restore the antioxidant status, and probably the modulation of monoamines transmissions.

Anticholinesterase and Antioxidant Potential of Hydromethanolic Extract of Ziziphus mucronata (Rhamnaceae) Leaves on Scopolamine-Induced Memory and Cognitive Dysfunctions in Mice.

Ziziphus mucronata Willd, also known as "buffalo thorn," belongs to the family Rhamnaceae. Its bark and leaves are used in folk medicine for the treatment of various deficiencies related to nociception, inflammation, mood, and depression. Still, there is a lack of scientific data regarding its potential effect on learning and memory process. The present study was designed to investigate the neuroprotective potential of Ziziphus mucronata (ZM) on learning and memory impairment in a scopolamine-induced model of dementia in mice. The phytochemical analysis revealed five cyclopeptide alkaloids (sanjoinines) in the extract from Ziziphus Mucronata leaves using LC-HRMS, and the structural characterization of these compounds was determined via MS/MS. Alzheimer-type amnesia was induced by an intraperitoneal injection of scopolamine (1 mg/kg) to mice for 7 consecutive days. ZM (150 mg/kg, 300 mg/kg, and 600 mg/kg) and piracetam (150 mg/kg) were orally administrated to mice daily for a period of 14 days. Memory-related behavioural parameters were evaluated using the radial arm maze task for 7 days, Y-maze, and novel object recognition task. At the end of protocol schedule, animals were sacrificed, and the levels of acetylcholinesterase, malondialdehyde, catalase, and superoxide dismutase were determined in brain homogenates. Histological studies of the hippocampus were subsequently performed. The long-term scopolamine-injected group decreased the spontaneous alternation (Y-maze), the discrimination index, and the time taken to explore the new object (novel object recognition task). These effects were significantly reversed by ZM at all the doses tested. In the radial arm maze task, ZM (300 and 600 mg/kg) significantly decreased the working and reference memory errors when compared with the demented group. Scopolamine-mediated changes in AChE activity were also attenuated by ZM in mice. In addition, extract-treated groups showed a significant increase in the level of CAT and SOD activity and decreased levels of MDA in the mice brains, as compared with the control group. The present study suggests that ZM could have an important role in neuroprotection on this scopolamine-induced model of Alzheimer-type dementia.

Emilia coccinae (SIMS) G Extract improves memory impairment, cholinergic dysfunction, and oxidative stress damage in scopolamine-treated rats.

BACKGROUND: E. coccinae (SIMS) G. (Asteraceae) is an annual plant commonly found throughout the plain of the Central Africa and widely used in Cameroonian folk medicine for the treatment of fever and convulsions in children. We previously reported that the methanolic extract of this plant improved spatial memory. However no underlying mechanism was explored. The present study was undertaken to investigate the effects of the hydroalcoholic extract of Emilia coccinae on memory in scopolamine treated rats and to propose possible mechanisms of action. METHODS: Novel object recognition and Y-maze paradigm were used to test memory while oxidative profile, AChE and ACh level of the whole brain were assessed to outline the mechanism of nootropic activity of the extract. 200 and 400 mg/kg of the extract were chronically administrated during 14 consecutive days in separate groups of scopolamine intraperitoneal treated rats (1.5 mg/kg). RESULTS: The hydroalcoholic extract of Emilia coccinae (HEEC) at the dose of 200 mg/kg significantly improved the memory of rats and reversed the amnesia induced by scopolamine. In addition, we showed that this extract is decreasing the acetyl cholinesterase activity while also increasing the acetylcholine levels in the brain. HEEC (200 and 400 mg/kg) significantly increased antioxidant enzyme activities (SOD, GSH and CAT) and reduced lipid peroxidation (MDA level) in the rat whole brain homogenates. CONCLUSIONS: Taken together, our results suggested that the hydroalcoholic extract of Emilia coccinae ameliorated the cognitive dysfunction in scopolamine treated rats through the blockage of the oxidative effect of scopolamine and inhibition of AChE activity.