Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice

Liu, Wei; Zhu, Yudan; Wang, Yongli; Qi, Shenglan; Wang, Yuwen; Ma, Chao; Li, Shuping; Jiang, Bo; Cheng, Xuemei; Wang, Zhengtao; Zhenyu, Xuan; Wang, Changhong

doi:10.1016/j.jep.2017.04.019

Cited by 29 publications

(13 citation statements)

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“…A transgenic animal model of AD demonstrated a falling Glu level ( Nilsen et al, 2012 ), and the serum and plasma metabolomics also indicated a decrease of Trp, 5-HT, Glu, Phe, Tyr in AD model mice or patients ( Vermeiren et al, 2014 ; González-Domínguez et al, 2015 ; Weng et al, 2015 ; Corso et al, 2017 ; Li et al, 2018 ). Correspondingly, our results proved that the scopolamine-induced dementia was accompanied by the decrease of ACh, L -Trp, 5-HT, L -Glu, L -Phe, L -Tyr and the elevation of Ch and γ-GABA, which is in agreement with the previous studies ( Scali et al, 1999 ; Nilsen et al, 2012 ; Lee et al, 2014 ; Vermeiren et al, 2014 ; González-Domínguez et al, 2015 ; Kumar and Singh, 2015 ; Weng et al, 2015 ; Zhou et al, 2016 ; Corso et al, 2017 ; Liu et al, 2017 ). Neurotransmitters play an important role in the brain circuit involved in many aspects of learning and memory, especially the cholinergic, serotonergic, glutametargic, and GABAergic neurotransmitters ( Vermeiren et al, 2014 ; Kumar and Singh, 2015 ; Zhou et al, 2016 ).…”

Section: Discussionsupporting

confidence: 93%

“…In the present study, the memory ameliorating effects of HAL (2, 5, and 10 mg/kg) and HAR (10, 20, and 30 mg/kg) on scopolamine-induced mice were compared using MWM behavioral evaluation. Scopolamine (1 mg/kg) was verified to damage the spatial learning and memory ability of mice in MWM task, which was consistent with our previous studies ( He et al, 2015a ; Liu et al, 2017 ). After treatments with HAL (L, M, and H dosages) and HAR (M and H dosages), the escape latency and path length were decreased and the passing frequency were increased effectively ( Figures 2 , 3 ), demonstrating that HAL and HAR administrations noticeably improved the learning and spatial memory of the scopolamine-induced mice, and the improvements of HAL were more significant than those of HAR.…”

Section: Discussionsupporting

confidence: 91%

“…In spatial probe trial (day 15 of drug treatments), the platform was removed from the tank. Each mouse was placed into the water tank from the quadrant (for instant, the Northwest) opposite from the previous platform location (target quadrant) to receive 60 s memory retention test ( Lee et al, 2016 ; Liu et al, 2017 ; Malik et al, 2017 ). The time in target quadrant and crossing number were recorded.…”

Section: Methodsmentioning

confidence: 99%

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Analogous β-Carboline Alkaloids Harmaline and Harmine Ameliorate Scopolamine-Induced Cognition Dysfunction by Attenuating Acetylcholinesterase Activity, Oxidative Stress, and Inflammation in Mice

Wang

et al. 2018

Front. Pharmacol.

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The analogous β-carboline alkaloids, harmaline (HAL) and harmine (HAR), possess a variety of biological properties, including acetylcholinesterase (AChE) inhibitory activity, antioxidant, anti-inflammatory, and many others, and have great potential for treating Alzheimer’s disease (AD). However, studies have showed that the two compounds have similar structures and in vitro AChE inhibitory activities but with significant difference in bioavailability. The objective of this study was to comparatively investigate the effects of HAL and HAR in memory deficits of scopolamine-induced mice. In the present study, mice were pretreated with HAL (2, 5, and 10 mg/kg), HAR (10, 20, and 30 mg/kg) and donepezil (5 mg/kg) by intragastrically for 7 days, and were daily intraperitoneal injected with scopolamine (1 mg/kg) to induce memory deficits and then subjected to behavioral evaluation by Morris water maze. To further elucidate the underlying mechanisms of HAL and HAR in improving learning and memory, the levels of various biochemical factors and protein expressions related to cholinergic function, oxidative stress, and inflammation were examined. The results showed that HAL and HAR could effectively ameliorate memory deficits in scopolamine-induced mice. Both of them exhibited an enhancement in cholinergic function by inhibiting AChE and inducing choline acetyltransferase (ChAT) activities, and antioxidant defense via increasing the antioxidant enzymes activities of superoxide dismutase and glutathione peroxidase, and reducing maleic diadehyde production, and anti-inflammatory effects through suppressing myeloperoxidase, tumor necrosis factor α, and nitric oxide as well as modulation of critical neurotransmitters such as acetylcholine (ACh), choline (Ch), L-tryptophan (L-Trp), 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (γ-GABA), and L-glutamic acid (L-Glu). Furthermore, the regulations of HAL on cholinergic function, inflammation, and neurotransmitters were more striking than those of HAR, and HAL manifested a comparable antioxidant capacity to HAR. Remarkably, the effective dosage of HAL (2 mg/kg) was far lower than that of HAR (20 mg/kg), which probably due to the evidently differences in the bioavailability and metabolic stability of the two analogs. Taken together, all these results revealed that HAL may be a promising candidate compound with better anti-amnesic effects and pharmacokinetic characteristics for the treatments of AD and related diseases.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

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Analogous β-Carboline Alkaloids Harmaline and Harmine Ameliorate Scopolamine-Induced Cognition Dysfunction by Attenuating Acetylcholinesterase Activity, Oxidative Stress, and Inflammation in Mice

Wang

et al. 2018

Front. Pharmacol.

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“…The effect of modafinil on the learning and memory of sleep-deprived mice was evaluated by the Morris water maze (MWM) test as described previously (Liu et al, 2017). The time-course of the experiment is illustrated in Figure 1.…”

Section: Morris Water Maze Test and Sleep Deprivation Proceduresmentioning

confidence: 99%

Modafinil protects hippocampal neurons by suppressing excessive autophagy and apoptosis in mice with sleep deprivation

Cao

Liu

et al. 2019

British J Pharmacology

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Background and Purpose: Sleep deprivation compromises learning and memory in both humans and animals, and can be reversed by administration of modafinil, a drug promoting wakefulness. Dysfunctional autophagy increases activation of apoptotic cascades, ultimately leading to increased neuronal death, which can be alleviated by autophagy inhibitors. This study aimed to investigate the alleviative effect and mechanism of modafinil on the excessive autophagy occurring in the hippocampus of mice with deficiency of learning and memory induced by sleep deprivation. Experimental Approach: The Morris water maze was used to assess the effects of modafinil on male C57BL/6Slac mice after 48-hr sleep deprivation. The HT-22 hippocampal neuronal cell line was also used. Nissl staining, transmission electron microscope, immunofluorescence, Western blot, transient transfection, and autophagy inducer were used to study the effect and mechanism of modafinil on hippocampal neurons with excessive autophagy and apoptosis. Key Results: Modafinil improved learning and memory in sleep-deprived mice, associated with the inhibition of excessive autophage and apoptosis and an enhanced activation of the PI3K/Akt/mTOR/P70S6K signalling pathway in hippocampal neurons. These effects of modafinil were abolished by rapamycin. In addition, modafinil suppressed the aberrant autophagy and apoptosis induced by rapamycin and reactivated PI3K/Akt/mTOR/P70S6K signals in HT-22 cells. Conclusions and Implications: These results suggested that modafinil alleviated impaired learning and memory of sleep-deprived mice potentially by suppressing excessive autophagy and apoptosis of hippocampal neurons. This novel mechanism may add to our knowledge of modafinil in the clinical treatment of impaired memory caused by sleep loss.Abbreviations: DG, dentate gyrus; 3-MA, 3-methyladenine; mTOR, mammalian target of rapamycin; MWM, Morris water maze; p62, ubiquitin-binding protein p62 or sequestosome-1; P70S6K, ribosomal protein S6 kinase; p-Akt, phosphorylated PKB; p-P70S6K, phosphorylated ribosomal protein S6 kinase; p-PI3K, phosphorylated PI3K

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“…A decrease of the ACh often follows cholinergic cell depletion in the basal forebrain. One approach is to inactivate AChE activity, a critical enzyme that cleaves synaptic ACh and stops neuronal signals [ 3 ]. Cholinesterase inhibitors decrease the ACh extrasynaptic metabolism, increase the neurotransmitter’s synaptic residence time, and improve postsynaptic stimulation.…”

Section: Introductionmentioning

confidence: 99%

Ameliorative Effects of Rhoifolin in Scopolamine-Induced Amnesic Zebrafish (Danio rerio) Model

et al. 2020

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Rhoifolin (Rho) exerts many biological activities such as anticancer, antidiabetic, hepatoprotective, antirheumatic, antibacterial, and antiviral properties. The neuroprotective action of this compound has not been studied. The goal of this study was to investigate the improvement impact of Rho on scopolamine (Sco)-induced zebrafish anxiety, amnesia, and brain oxidative stress and to elucidate the underlying mechanisms involved. Zebrafish were treated with Rho (1, 3, and 5 μg/L) for nine consecutive days and were subsequently subjected to Sco (100 μM) 30 min before behavioral tests (novel tank diving test, Y-maze, and novel object recognition tests). Rho was isolated from Chorisia crispiflora (Malvaceae) leaves and identified by different spectroscopic techniques. To further assess the possible mechanisms of Rho in enhancing the memory capacities in zebrafish, the in vivo antioxidant status and acetylcholinesterase (AChE) activity was also evaluated. Rho from Chorisia crispiflora leaves was identified. Rho could alleviate anxiety, memory deficits, and brain oxidative stress in Sco-treated zebrafish and could regulate the cholinergic function by inhibiting the AChE activity. Our results demonstrated that Rho could be a promising candidate compound against anxiety and amnesia by restoring the cholinergic activity and the amelioration of brain oxidative stress.

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Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice

Cited by 29 publications

References 25 publications

Analogous β-Carboline Alkaloids Harmaline and Harmine Ameliorate Scopolamine-Induced Cognition Dysfunction by Attenuating Acetylcholinesterase Activity, Oxidative Stress, and Inflammation in Mice

Analogous β-Carboline Alkaloids Harmaline and Harmine Ameliorate Scopolamine-Induced Cognition Dysfunction by Attenuating Acetylcholinesterase Activity, Oxidative Stress, and Inflammation in Mice

Modafinil protects hippocampal neurons by suppressing excessive autophagy and apoptosis in mice with sleep deprivation

Ameliorative Effects of Rhoifolin in Scopolamine-Induced Amnesic Zebrafish (Danio rerio) Model

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