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

Abstract

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.

Anxiolytic, Promnesic, Anti-Acetylcholinesterase and Antioxidant Effects of Cotinine and 6-Hydroxy-L-Nicotine in Scopolamine-Induced Zebrafish (Danio rerio) Model of Alzheimer’s Disease

“…In a previous study, Zanandrea et al [ 46 ] showed that SCOP administration (100 µM for 1 h) to zebrafish did not alter the specific activity of AChE compared to control fish. In contrast, several other reports have demonstrated that SCOP (100 µM for 30 min) increased the activity of this enzyme in the zebrafish brains [ 36 , 37 , 38 , 92 , 93 ]. Ziani et al [ 41 ] showed that NIC (1 mg/L for 3 min) increases the AChE activity when it is co-administered with a compound that provokes a fear response in zebrafish but not when NIC is administered alone.…”

“…The biochemical results obtained in this study indicated that COT and 6HLN exhibit an antioxidant profile in the SCOP-induced zebrafish model of AD. Several reports showed that SCOP treatment induces oxidative stress in the brain of zebrafish [ 36 , 37 , 38 , 92 , 93 ] or rodents [ 64 , 96 , 97 , 98 , 99 ]. In a cell line derived from Danio rerio gill tissue, NIC treatment (3–7 mg/L for 12 h) has been shown to induce intracellular ROS generation in a dose-dependent manner [ 100 ].…”

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

“…Oxidative stress is one of the pathways responsible for Sco-induced amnesia. The pro-oxidative effects of Sco have been documented as it decreases the activity of antioxidant enzymes such as SOD, CAT, and GPX [63,64] and increased the concentration of malondialdehyde (MDA), which is the main marker of lipids peroxidation [64,65]. Also, numerous studies have shown the pro-cognitive impact of antioxidant compounds on Sco-induced memory damage, possibly by attenuating oxidative stress markers [27,58].…”

Teratogenic, Oxidative Stress and Behavioural Outcomes of Three Fungicides of Natural Origin (Equisetum arvense, Mimosa tenuiflora, Thymol) on Zebrafish (Danio rerio)

“…These emotional responses involve profound changes and specified activity patterns in the zebrafish brain [ 75 ]. Although a recent study has shown Thymol to improve the cholinergic nervous system and antioxidative stress in a cognitive dysfunction model [ 21 ], no supporting behavioural information could be found for zebrafish embryo. Yet, Thymol has been shown to affect the behaviour (depression- and antidepressant-like) of mice [ 76 , 77 ].…”

“…For instance, horsetail ( Equisetum arvense ) was the first approved basic substance according to the European Regulation (EC) 1107/2009 [ 13 ], but, although not considered as a substance of concern, it has been associated with potential neurodevelopmental toxicity [ 14 ]. Likewise, “jurema preta” ( Mimosa tenuiflora ) has been described as teratogenic to higher vertebrates [ 15 , 16 ], and Thymol, the main monoterpene phenol isolated from plants from the Lamiaceae family such as Thymus vulgaris L. [ 17 ], has been shown to cause developmental abnormalities in chicken and zebrafish embryos [ 18 , 19 , 20 ] and to regulate cholinergic and antioxidant systems in cognitive dysfunctional zebrafish [ 21 ]. However, although current research shows its antifungal properties [ 17 , 22 , 23 ] and some commercial pesticide products based on natural compounds are available on the market, there is a lack of sufficient neurodevelopmental information, and further studies are needed to clarify their environmental risk to non-target organisms to define efficient and appropriate use patterns.…”