Direct Evidence for Using Coriandrum sativum var. microcarpum Essential Oil to Ameliorate Scopolamine-Induced Memory Impairment and Brain Oxidative Stress in the Zebrafish Model.

Essential oil from Coriandrum sativum has been demonstrated to provide various pharmacological properties, such as antioxidant, antimicrobial, antibacterial, antifungal, antidiabetic, anticonvulsive, anxiolytic-antidepressant, and anti-aging properties. This study investigated the mechanism of Coriandrum sativum var. microcarpum essential oil (CSEO, 25, 150, and 300 µL/L) and cognitive impairment and brain oxidative stress in a scopolamine (SCOP, 100 µM) zebrafish model (Danio rerio) of cognitive impairment. Spatial memory, response to novelty, and recognition memory were assessed using the Y-maze test and the novel object recognition test (NOR), while anxiety-like behavior was investigated using the novel tank diving test (NTT). The cholinergic system activity and brain oxidative stress were also evaluated. CSEO was administered to zebrafish once a day for 21 days, while SCOP and galantamine (GAL, 1 mg/L) were delivered 30 min before behavioral testing and euthanasia. Our data revealed that SCOP induced memory dysfunction and anxiety-like behavior, while CSEO improved memory performance, as evidenced by behavioral tasks. Moreover, CSEO attenuated SCOP-induced brain oxidative stress and decreased acetylcholinesterase (AChE) activity. The results demonstrated the potential use of the CSEO in providing beneficial effects by reducing memory deficits and brain oxidative stress involved in the genesis of a dementia state.

Promnesic, Anxiolytic and Antioxidant Effects of Glaucosciadium cordifolium (Boiss.) Burtt & Davis Essential Oil in a Zebrafish Model of Cognitive Impairment.

The purpose of this study was to investigate the effect of Glaucosciadium cordifolium essential oil (GCEO, 25 and 150 µL/L) on anxiety and learning and memory impairment induced by scopolamine (SCOP) in zebrafish. The chemical composition was analyzed by GC-MS, and the results showed that the highest content was limonene followed by α- and ß-pinene, p-cymene and α-phellandrene. The dementia model was induced by SCOP (100 µM), whereas GCEO and galantamine (GAL, 1 mg/L) were delivered to the SCOP-induced model. It was found that GCEO significantly improved memory impairment and anxiety-like response induced by SCOP through the Y-maze, novel object recognition (NOR) test, and novel tank diving tests (NTT). Biochemical analyses showed that GCEO reduced SCOP-induced oxidative damage. Additionally, the cholinergic system activity was improved in the SCOP-induced model by decreasing the acetylcholinesterase (AChE) activity following the exposure to GCEO. It was clear that as a mixture, GCEO displays positive action in improving memory impairment through restoring cholinergic dysfunction and brain antioxidant status.

Aqueous extract of Ceratonia siliqua L. leaves elicits antioxidant, anti-inflammatory, and AChE inhibiting effects in amyloid-ß42-induced cognitive deficit mice: Role of α7-nAChR in modulating Jak2/PI3K/Akt/GSK-3ß/ß-catenin cascade.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder attributed to several etiological factors including cholinergic dysregulation, neuroinflammation, oxidative stress, ß-amyloidogenesis, and tauopathy. This demands the search for multitarget drugs, especially of natural sources owing to their pleiotropic activities and low adverse effects. The present study was conducted to investigate the cognitive-improving potential of Ceratonia siliqua L. (Cs) extract compared with donepezil, an acetylcholinesterase inhibitor, on AD-like pathological alterations induced by single intracerebroventricular amyloid-ß42 (Aß42) injection in mice. Aß42-injected mice were treated with Cs (100 mg/kg/day, po) with or without methyllycaconitine (MLA; 1 mg/kg/day, ip), an α7-nAChR antagonist. Aß42-injected animals demonstrated an elevation of hippocampal Aß42, p-Tau, and acetylcholinesterase. They also showed a decline in phosphorylated levels of Jak2, PI3K, Akt, and GSK-3ß, leading to induction of neuroinflammation and oxidative stress. Noteworthy, Cs improved the histopathological and behavioral variables in addition to mitigating AD hallmarks. It also exerted neuroprotection by reducing NF-κBp65 and TNF-α, while elevating Nrf2 and HO-1, along with stabilizing ß-catenin under the impact of Jak2/PI3K/Akt/GSK-3ß signaling. These beneficial effects of Cs were abrogated by MLA co-administration signifying the α7-nAChR involvement in Cs-mediated effects. Therefore, Cs can ameliorate Aß42-induced neurodegeneration by modulating Jak2/PI3K/Akt/GSK-3ß/ß-catenin axis in an α7-nAChR-dependent manner.

Insights into Pharmacological Activities of Nicotine and 6-Hydroxy-L-nicotine, a Bacterial Nicotine Derivative: A Systematic Review.

The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically active metabolite of a nicotine derivative produced by bacteria named 6-hydroxy-L-nicotine (6HLN) on memory, oxidative stress, and the activity of the cholinergic system in the brain was examined. A search in the PubMed, Science Direct, Web of Science, and Google Scholar databases, limiting entries to those published between 1992 and 2023, was conducted. The search focused specifically on articles about nicotine metabolites, memory, oxidative stress, and cholinergic system activity, as well as enzymes or pathways related to nicotine degradation in bacteria. The preliminary search resulted in 696 articles, and following the application of exclusion criteria, 212 articles were deemed eligible for inclusion. This review focuses on experimental studies supporting nicotine catabolism in bacteria, and the chemical and pharmacological activities of nicotine and its metabolite 6HLN.

Pinus halepensis Essential Oil Ameliorates Aß1-42-Induced Brain Injury by Diminishing Anxiety, Oxidative Stress, and Neuroinflammation in Rats.

The Pinus L. genus comprises around 250 species, being popular worldwide for their medicinal and aromatic properties. The present study aimed to evaluate the P. halepensis Mill. essential oil (PNO) in an Alzheimer's disease (AD) environment as an anxiolytic and antidepressant agent. The AD-like symptoms were induced in Wistar male rats by intracerebroventricular administration of amyloid beta1-42 (Aß1-42), and PNO (1% and 3%) was delivered to Aß1-42 pre-treated rats via inhalation route for 21 consecutive days, 30 min before behavioral assessments. The obtained results indicate PNO's potential to relieve anxious-depressive features and to restore redox imbalance in the rats exhibiting AD-like neuropsychiatric impairments. Moreover, PNO presented beneficial effects against neuroinflammation and neuroapoptosis in the Aß1-42 rat AD model.

Sweroside Ameliorated Memory Deficits in Scopolamine-Induced Zebrafish (Danio rerio) Model: Involvement of Cholinergic System and Brain Oxidative Stress.

Sweroside is a secoiridoid glycoside and belongs to a large group of naturally occurring monoterpenes with glucose sugar attached to C-1 in the pyran ring. Sweroside can promote different biological activities such as antifungal, antibacterial, hepatoprotective, gastroprotective, sedative and antitumor, antioxidant, and neuroprotective activities. Zebrafish were given sweroside (12.79, 8.35, and 13.95 nM) by immersion once daily for 8 days, along with scopolamine (Sco, 100 µM) 30 min before the initiation of the behavioral testing to cause anxiety and memory loss. Employing the novel tank diving test (NTT), the Y-maze, and the novel object recognition test (NOR), anxiety-like reactions and memory-related behaviors were assessed. The following seven groups (n = 10 animals per group) were used: control, Sco (100 µM), sweroside treatment (2.79, 8.35, and 13.95 nM), galantamine (GAL, 2.71 µM as the positive control in Y-maze and NOR tests), and imipramine (IMP, 63.11 µM as the positive control in NTT test). Acetylcholinesterase activity (AChE) and the antioxidant condition of the brains were also evaluated. The structure of sweroside isolated from Schenkia spicata was identified. Treatment with sweroside significantly improved the Sco-induced decrease of the cholinergic system activity and brain oxidative stress. These results suggest that sweroside exerts a significant effect on anxiety and cognitive impairment, driven in part by the modulation of the cholinergic system activity and brain antioxidant action.

Neuroprotective Effect of Yucca schidigera Roezl ex Ortgies Bark Phenolic Fractions, Yuccaol B and Gloriosaol A on Scopolamine-Induced Memory Deficits in Zebrafish.

Y. schidigera contains a number of unusual polyphenols, derivatives of resveratrol and naringenin, called spiro-flavostilbenoids, which have potent in vitro anti-inflammatory, antioxidant, and moderate cholinesterase inhibitory activities. To date, these compounds have not been tested in vivo for the treatment of neurodegenerative diseases. The aim of the present study was to evaluate the effects of both single spiro-flavostilbenoids (yuccaol B and gloriosaol A) and phenolic fractions derived from Y. schidigera bark on scopolamine-induced anxiety and memory process deterioration using a Danio rerio model. Detailed phytochemical analysis of the studied fractions was carried out using different chromatographic techniques and Nuclear Magnetic Resonance (NMR). The novel tank diving test was used as a method to measure zebrafish anxiety, whereas spatial working memory function was assessed in Y-maze. In addition, acetylcholinesterase/butyrylcholinesterase (AChE/BChE) and 15-lipooxygenase (15-LOX) inhibition tests were performed in vitro. All pure compounds and fractions under study exerted anxiolytic and procognitive action. Moreover, strong anti-oxidant capacity was observed, whereas weak inhibition towards cholinesterases was found. Thus, we may conclude that the observed behavioral effects are complex and result rather from inhibition of oxidative stress processes and influence on cholinergic muscarinic receptors (both 15-LOX and scopolamine assays) than effects on cholinesterases. Y. schidigera is a source of substances with desirable properties in the prevention and treatment of neurodegenerative diseases.

Angelica purpurascens (Avé-Lall.) Gilli. Essential Oil Improved Brain Function via Cholinergic Modulation and Antioxidant Effects in the Scopolamine-Induced Zebrafish (Danio rerio) Model.

Angelica purpurascens (Avé-Lall.) Gilli. is a medicinal plant that displays antioxidant, anticholinesterase, and neuroprotective properties. The effect of A. purpurascens essential oil (APO) on memory impairments and brain oxidative stress in zebrafish (Danio rerio) treated with scopolamine (Sco), as well as the underlying mechanism involved, were investigated in this study. Exposure to Sco (100 µM) resulted in anxiety in zebrafish, as assessed by the novel tank diving test (NTT), whereas spatial memory and novelty response dysfunctions, as evidenced by the Y-maze test and novel object recognition test (NOR), were noticed. When zebrafish were given Sco and simultaneously given APO (25 and 150 µL/L, once daily for 13 days), the deficits were averted. An increase in brain antioxidant enzymes, a reduction of lipid peroxidation, and protein oxidation were linked to this impact. Furthermore, acetylcholinesterase (AChE) activity was significantly reduced in the brains of APO-treated zebrafish. The main detected components in the APO composition were ß-phellandrene (33.80%), sabinene (6.80%), α-pinene (5.30%), germacrene-D (4.50%), α-phellandrene (4.20%), and p-cymene (3.80%) based on gas chromatography-mass spectrometry (GC-MS) investigations. Our findings show that APO's beneficial effect in a zebrafish model of Sco-induced memory impairment is mediated through multiple mechanisms, including the restoration of cholinergic system function and the improvement of the brain antioxidant state. As a result, APO could be employed as a potential source of bioactive molecules with useful biological properties and medicinal uses.

Origanum vulgare ssp. hirtum (Lamiaceae) Essential Oil Prevents Behavioral and Oxidative Stress Changes in the Scopolamine Zebrafish Model.

Origanum vulgare ssp. hirtum has been used as medicinal herbs promoting antioxidant, anti-inflammatory, antimicrobial, and neuroprotective activities. We investigated the protective effects and the mechanism of O. vulgare ssp. hirtum essential oil (OEO) on cognitive impairment and brain oxidative stress in a scopolamine (Sco)-induced zebrafish (Danio rerio) model of cognitive impairment. Our results show that exposure to Sco (100 µM) leads to anxiety, spatial memory, and response to novelty dysfunctions, whereas the administration of OEO (25, 150, and 300 µL/L, once daily for 13 days) reduced anxiety-like behavior and improved cognitive ability, which was confirmed by behavioral tests, such as the novel tank-diving test (NTT), Y-maze test, and novel object recognition test (NOR) in zebrafish. Additionally, Sco-induced brain oxidative stress and increasing of acetylcholinesterase (AChE) activity were attenuated by the administration of OEO. The gas chromatography-mass spectrometry (GC-MS) analyses were used to elucidate the OEO composition, comprising thymol (38.82%), p-cymene (20.28%), and γ-terpinene (19.58%) as the main identified components. These findings suggest the ability of OEO to revert the Sco-induced cognitive deficits by restoring the cholinergic system activity and brain antioxidant status. Thus, OEO could be used as perspective sources of bioactive compounds, displaying valuable biological activities, with potential pharmaceutical applications.

Insights on the Inhibitory Power of Flavonoids on Tyrosinase Activity: A Survey from 2016 to 2021.

Tyrosinase is a multifunctional copper-containing oxidase enzyme that initiates melanin synthesis in humans. Excessive accumulation of melanin pigments or the overexpression of tyrosinase may result in skin-related disorders such as aging spots, wrinkles, melasma, freckles, lentigo, ephelides, nevus, browning and melanoma. Nature expresses itself through the plants as a source of phytochemicals with diverse biological properties. Among these bioactive compounds, flavonoids represent a huge natural class with different categories such as flavones, flavonols, isoflavones, flavan-3-ols, flavanones and chalcones that display antioxidant and tyrosinase inhibitor activities with a diversity of mechanistic approaches. In this review, we explore the role of novel or known flavonoids isolated from different plant species and their participation as tyrosinase inhibitors reported in the last five years from 2016 to 2021. We also discuss the mechanistic approaches through the different studies carried out on these compounds, including in vitro, in vivo and in silico computational research. Information was obtained from Google Scholar, PubMed, and Science Direct. We hope that the updated comprehensive data presented in this review will help researchers to develop new safe, efficacious, and effective drug or skin care products for the prevention of and/or protection against skin-aging disorders.

Baicalein 5,6-Dimethyl Ether Prevents Memory Deficits in the Scopolamine Zebrafish Model by Regulating Cholinergic and Antioxidant Systems.

Baicalein 5,6-dimethyl ether, a bioactive flavonoid isolated for the first time from Alnus rugosa, was explored for its capability to relieve memory deficits and decrease oxidative stress. We examined the neuropharmacological effects of baicalein 5,6-dimethyl ether on scopolamine (Sco)-induced zebrafish (Danio rerio) anxiety, amnesia, and brain oxidative stress and attempted to elucidate the underlying mechanisms. Anxiety-like behavior, exploratory behavior, and memory performance were measured using novel tank-diving test (NTT), Y-maze, and novel object recognition (NOR) tests. For 10 days, baicalein 5,6-dimethyl ether (1, 3, and 5 µg/L) was administered through immersion, whereas Sco (100 µM) was delivered 30 min before behavioral tests. Treatment with baicalein 5,6-dimethyl ether reduced anxiety and memory impairment, and increased exploratory behavior in specific tests, along with significant protection from neuronal oxidative stress in the brain tissue of Sco-treated zebrafish. Antioxidant and anti-acetylcholinesterase (AChE) activities of baicalein 5,6-dimethyl ether in the Sco-induced zebrafish were further confirmed using in vivo assays. In Sco-treated zebrafish, baicalein 5,6-dimethyl ether regulated cholinergic function by inhibiting AChE activity. Baicalein 5,6-dimethyl ether may be a promising candidate compound for treating anxiety and amnesia by restoring cholinergic activity and reducing brain oxidative stress, according to our findings.

Effects of the Hydroethanolic Extract of Lycopodium selago L. on Scopolamine-Induced Memory Deficits in Zebrafish.

This scientific research focused on the production of hydroethanolic extract of the plant species Lycopodium selago L. (L. selago) by the ultrasound-assisted extraction (USAE) and the identification of biocompounds with high antioxidant activity is of interest for possible phytotherapeutic treatment against Alzheimer's disease (AD). The extract was phytochemically analyzed to investigate polyphenols, flavonoids, and identify the sesquiterpenoid alkaloid huperzine A (HupA), which is known in the literature for its great relevance in AD. Evaluation and comparison of the antioxidant activity of the extract were performed by four complementary spectrophotometric methods (DPPH, FRAP, ABTS, ORAC). In vitro tests of the extract showed an excellent reciprocal link between the concentration of polyphenols and the measurement of the antioxidant activity of the extract with the sesquiterpenoid HupA. To confirm the antioxidant activity, L. selago hydroethanolic extract was administered in vivo to zebrafish (Danio rerio) with a pattern of scopolamine-induced cognitive impairment. Moreover, this study explored a possible correlation between the expression of oxidative stress markers in the brain tissue with the behavior of the scopolamine zebrafish model. In vivo tests showed that this fern could be used as a nutritional supply and as a phytotherapeutic method to prevent or treat various neurodegenerative diseases that call for high-nutritive-value medications.

Anxiolytic and Antidepressant-Like Effects of Conyza canadensis Aqueous Extract in the Scopolamine Rat Model.

Conyza canadensis is a plant widely used in traditional medicine in Morocco for the treatment of varied health challenges. However, to the best of our knowledge, there is no scientific study justifying the traditional use of Conyza extract as an anxiolytic and antidepressant agent. Moreover, data regarding the polyphenolic fraction is limited. Therefore, the present study was conducted to investigate the chemical composition of an aqueous extract obtained from the aerial parts of Conyza, its antioxidant potential, and the anxiolytic and antidepressant-like effects of the sample (100 and 200 mg/kg body weight (bw)) in the scopolamine (Sco) (0.7 mg/kg bw) rat model. To achieve this purpose, a variety of antioxidant tests (including free radical-scavenging activity and lipoxygenase-inhibitory potential assays) and behavioral procedures, such as the elevated plus-maze and forced swimming tests, were performed. The results demonstrated that the aqueous extract of Conyza canadensis is rich in catechins and flavonoids which possess good antioxidant activity. Additionally, concentrations of 100 and 200 mg/kg of the extract exhibited significant anxiolytic and antidepressant-like profiles following scopolamine treatment. Therefore, we propose that the use of Conyza canadensis could be a new pharmacological target for the amelioration of major depression.

Neuroprotective and Antioxidant Enhancing Properties of Selective Equisetum Extracts.

The sterile stems belonging to the Equisetum species are often used in traditional medicine of various nations, including Romanians. They are highly efficient in treating urinary tract infections, cardiovascular diseases, respiratory tract infections, and medical skin conditions due to their content of polyphenolic derivatives that have been isolated. In this regard, this study aimed to provide the chemical composition of the extracts obtained from the Equisetum species (E. pratense, E. sylvaticum, E. telmateia) and to investigate the biological action in vitro and in vivo. For the chemical characterization of the analyzed Equisetum species extracts, studies were performed by using ultra-high-performance liquid chromatography (UHPLC-DAD). In vitro evaluation of the antioxidant activity of the plant extracts obtained from these species of Equisetum genus was determined. The neuroprotective activity of these three ethanolic extracts from the Equisetum species using zebrafish tests was determined in vivo. All obtained results were statistically significant. The results indicate that E. sylvaticum extract has a significant antioxidant activity; whereas, E. pratense extract had anxiolytic and antidepressant effects significantly higher than the other two extracts used. All these determinations indicate promising results for the antioxidant in vitro tests and neuroprotective activity of in vivo tests, particularly mediated by their active principles.

Bay Leaf (Laurus Nobilis L.) Incense Improved Scopolamine-Induced Amnesic Rats by Restoring Cholinergic Dysfunction and Brain Antioxidant Status.

Bay leaf (Laurus nobilis L.) has been shown to possesses various biological activities such as wound healing activity, antioxidant activity, antibacterial activity, antiviral activity, immunostimulant activity, anticholinergic activity, antifungal activity, insect repellant activity, anticonvulsant activity, antimutagenic activity, and analgesic and anti-inflammatory activity. The present study aimed to investigate whether the bay leaf incense (BL) elicits the memory formation via the action on the cholinergic system using a scopolamine (Sco)-induced rat model. Rats were exposed to BL over 5 min in a smoking chamber apparatus once daily for 22 days, whereas memory impairment was induced by Sco (0.7 mg/kg), a muscarinic receptor antagonist, delivered 30 min before each behavioral test. The phytochemical composition of BL was achieved by gas chromatograph-mass spectrometry (GCMS). Behavioral effects in rats were assessed by Y-maze, radial arm maze (RAM), and novel object recognition (NOR) paradigms. Additionally, the acetylcholinesterase (AChE) activity and the oxidative stress markers in the rat hippocampus were also evaluated. Exposure to BL significantly ameliorated Sco-induced cognitive impairment and oxidative stress in the rat hippocampus. The obtained results suggested that BL-induced ameliorative cognitive effects are mediated by enhancement of the cholinergic system and antioxidant activities.

Optimization of Ultrasonic Extraction to Obtain Erinacine A and Polyphenols with Antioxidant Activity from the Fungal Biomass of Hericium erinaceus.

Hericium erinaceus is a medicinal fungal species that produces the active biological metabolite erinacine A with strong antioxidant activity. The classical extraction techniques used to date to obtain metabolites from this fungal species require high consumption of resources and energy and, in the end, prove to be expensive and inefficient, especially on a biomedical scale. The aim of this research is based on the development of an ultrasonic extraction (UE) method for the identification and extraction of biological compounds with high antioxidant activity from the mycelia of H. erinaceus biomass developed through a solid cultivation process. The extraction process was optimized by varying parameters to determine the best extraction yield of metabolites involved in such antioxidant activity, using the response surface methodology (RSM). The physicochemical analyses were oriented towards the investigation of polyphenols, flavonoids, and the diterpenoid erinacine A. It is highlighted that there is a very good mutual connection between the concentration of polyphenols and flavonoids in the extracts studied and the diterpenoid erinacine A. Also, this study describes an efficient and qualitative extraction method for extracting natural antioxidants from the H. erinaceus mushroom, since toxic solvents were not used in the developed extraction procedure. This biomass can be used both as a food source and as a possible phytotherapeutic tool in the prevention or treatment of various neurodegenerative disorders that require drugs with strong antioxidant activity.

Thymus vulgaris Essential Oil Protects Zebrafish against Cognitive Dysfunction by Regulating Cholinergic and Antioxidants Systems.

Thymus vulgaris L. is an aromatic herb used for medicinal purposes such as antimicrobial, spasmolytic, antioxidant, anti-inflammatory, antinociceptive, antitumor, and may have beneficial effects in the treatment of Alzheimer's disease. The present study aimed to investigate whether Thymus vulgaris L. essential oil enhances cognitive function via the action on cholinergic neurons using scopolamine (Sco)-induced zebrafish (Danio rerio) model of memory impairments. Thymus vulgaris L. essential oil (TEO, 25, 150, and 300 µL/L) was administered by immersion to zebrafish once daily for 13 days, whereas memory impairment was induced by Sco (100 µM), a muscarinic receptor antagonist, delivered 30 min before behavioral tests. Spatial memory was assessed using the Y-maze test and novel object recognition test (NOR). Anxiety and depression were measured in the novel tank diving test (NTT). Gas Chromatograph-Mass Spectrometry (GC-MS) analysis was used to study the phytochemical composition of TEO. Acetylcholinesterase (AChE) activity and oxidative stress response in the brain of zebrafish were determined. TEO ameliorated Sco-induced increasing of AChE activity, amnesia, anxiety, and reduced the brain antioxidant capacity. These results suggest that TEO may have preventive and/or therapeutic potentials in the management of memory deficits and brain oxidative stress in zebrafish with amnesia.

Memory-Enhancing Effects of Origanum majorana Essential Oil in an Alzheimer's Amyloid beta1-42 Rat Model: A Molecular and Behavioral Study.

Origanum L. (Lamiaceae) is an important genus of medicinal and aromatic plants used in traditional medicine since ancient times as culinary herbs and remedies. The aim of the present study was to evaluate the chemical composition, as well as the biochemical and cellular activities of freshly prepared Origanum majorana L. essential oil (OmEO) in an Alzheimer's disease (AD) amyloid beta1-42 (Aß1-42) rat model. OmEO (1% and 3%) was inhaled for 21 consecutive days, while Aß1-42 was administered intracerebroventricularly to induce AD-like symptoms. Our data demonstrate that OmEO increased antioxidant activity and enhanced brain-derived neurotrophic factor (BDNF) expression, which in concert contributed to the improvement of cognitive function of animals. Moreover, OmEO presented beneficial effects on memory performance in Y-maze and radial arm-maze tests in the Aß1-42 rat AD model.

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

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.

Cognitive Facilitation and Antioxidant Effects of an Essential Oil Mix on Scopolamine-Induced Amnesia in Rats: Molecular Modeling of In Vitro and In Vivo Approaches.

The present study investigated the capability of an essential oil mix (MO: 1% and 3%) in ameliorating amnesia and brain oxidative stress in a rat model of scopolamine (Sco) and tried to explore the underlying mechanism. The MO was administered by inhalation to rats once daily for 21 days, while Sco (0.7 mg/kg) treatment was delivered 30 min before behavioral tests. Donepezil (DP: 5 mg/kg) was used as a positive reference drug. The cognitive-enhancing effects of the MO in the Sco rat model were assessed in the Y-maze, radial arm maze (RAM), and novel object recognition (NOR) tests. As identified by gas chromatography-mass spectrometry (GC-MS), the chemical composition of the MO is comprised by limonene (91.11%), followed by γ-terpinene (2.02%), ß-myrcene (1.92%), ß-pinene (1.76%), α-pinene (1.01%), sabinene (0.67%), linalool (0.55%), cymene (0.53%), and valencene (0.43%). Molecular interactions of limonene as the major compound in MO with the active site of butyrylcholinesterase (BChE) was explored via molecular docking experiments, and Van der Waals (vdW) contacts were observed between limonene and the active site residues SER198, HIS438, LEU286, VAL288, and PHE329. The brain oxidative status and acetylcholinesterase (AChE) and BChE inhibitory activities were also determined. MO reversed Sco-induced memory deficits and brain oxidative stress, along with cholinesterase inhibitory effects, which is an important mechanism in the anti-amnesia effect. Our present findings suggest that MO ameliorated memory impairment induced by Sco via restoration of the cholinergic system activity and brain antioxidant status.