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.

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%), β-myrcene (1.92%), β-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.

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.

Tribulus terrestris L. (Tt) has been recently gaining attention for its pharmacological value, including its neuroprotective activities. In this study, we explore the neuroprotective effects of a Tribulus terrestris extract in a zebrafish (Danio rerio) model of scopolamine (SCOP)-induced memory impairment and brain oxidative stress. SCOP, an anticholinergic drug, was employed to replicate fundamental aspects of Alzheimer’s disease (AD) in animal models. The fish were treated with ethanolic leaf extract (ELE) from Tt (1, 3, and 6 mg/L) for 15 days. SCOP (100 µM) was administered 30 min before behavioral tests were conducted. Molecular interactions of the major compounds identified via UPLC-PDA/MS in Tt fractions with the active site of acetylcholinesterase (AChE) were explored via molecular docking analyses. Terrestrosin C, protodioscin, rutin, and saponin C exhibited the most stable binding. The spatial memory performance was assessed using the Y-maze test, and memory recognition was examined using a novel object recognition (NOR) test. Tt extract treatment reversed the altered locomotion patterns that were caused by SCOP administration. Biochemical analyses also verified Tt’s role in inhibiting AChE, improving antioxidant enzyme activities, and reducing oxidative stress markers. The present findings pave the way for future application of Tt as a natural alternative to treat cognitive disorders.

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.

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.