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.
ABSTRACT: 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 ?-terpinene (2.02%), ?-myrcene (1.92%), ?-pinene (1.76%), ?-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.
Project description: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 ?M), 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.
Project description:We investigated the anti-amnesic effects of SJ and fermented SJ (FSJ) on scopolamine (SCO)-induced amnesia mouse model. Mice were orally co-treated with SJ or FSJ (125, 250, and 500?mg/kg) and SCO (1?mg/kg), which was injected intraperitoneally for 14 days. SCO decreased the step-through latency and prolonged latency time to find the hidden platform in the passive avoidance test and Morris water maze test, respectively, and both SCO effects were ameliorated by FSJ treatment. FSJ was discovered to promote hippocampal neurogenesis during SCO treatment by increasing proliferation and survival of BrdU-positive cells, immature/mature neurons. In the hippocampus of SCO, oxidative stress and the activity of acetylcholinesterase were elevated, whereas the levels of acetylcholine and choline acetyltransferase were diminished; however, all of these alterations were attenuated by FSJ-treatment. The alterations in brain-derived neurotrophic factor, phosphorylated cAMP response element-binding protein, and phosphorylated Akt that occurred following SCO treatment were protected by FSJ administration. Therefore, our findings are the first to suggest that FSJ may be a promising therapeutic drug for the treatment of amnesia and aging-related or neurodegenerative disease-related memory impairment. Furthermore, the molecular mechanism by which FSJ exerts its effects may involve modulation of the cholinergic system and BDNF/CREB/Akt pathway.
Project description:Blood-sucking insects use olfactory cues in a variety of behavioral contexts, including host-seeking and aggregation. In triatomines, which are obligated blood-feeders, it has been shown that the response to CO2, a host-associated olfactory cue used almost universally by blood-sucking insects, is modulated by hunger. Host-finding is a particularly dangerous task for these insects, as their hosts are also their potential predators. Here we investigated whether olfactory responses to host-derived volatiles other than CO2 (nonanal, ?-pinene and (-)-limonene), attractive odorant mixtures (yeast volatiles), and aggregation pheromones (present in feces) are also modulated by starvation in the blood-sucking bug Rhodnius prolixus. For this, the responses of both non-starved and starved insects were individually tested at the beginning of the scotophase using a dual-choice "T-shaped" olfactometer, in which one of its arms presented odor-laden air and the other arm presented odorless air. We found that the response of non-starved insects toward host-odorants and odorant mixtures was odor-dependent: insects preferred the odor-laden arm of the maze when tested with ?-pinene, the odorless arm of the maze when tested with (-)-limonene, and distributed at random when tested with yeast volatiles or nonanal. In contrast, starved insects significantly preferred the odor-laden arm of the maze when tested with host-odorants or yeast volatiles. When tested with aggregation be, while starved insects preferred the odorless arm of the maze; insects that were even more starved (8-9 weeks post-ecdysis) significantly preferred the odor-laden arm of the maze. We postulate that this odor- and starvation-dependent modulation of sensory responses has a high adaptive value, as it minimizes the costs and risks associated with the associated behaviors. The possible physiological mechanisms underlying these modulatory effects are discussed.
Project description:The secondary compounds of pines (Pinus) can strongly affect the physiology, ecology and behaviors of the bark beetles (Coleoptera: Curculionidae, Scolytinae) that feed on sub-cortical tissues of hosts. Jack pine (Pinus banksiana) has a wide natural distribution range in North America (Canada and USA) and thus variations in its secondary compounds, particularly monoterpenes, could affect the host expansion of invasive mountain pine beetle (Dendroctonus ponderosae), which has recently expanded its range into the novel jack pine boreal forest. We investigated monoterpene composition of 601 jack pine trees from natural and provenance forest stands representing 63 populations from Alberta to the Atlantic coast. Throughout its range, jack pine exhibited three chemotypes characterized by high proportions of ?-pinene, ?-pinene, or limonene. The frequency with which the ?-pinene and ?-pinene chemotypes occurred at individual sites was correlated to climatic variables, such as continentality and mean annual precipitation, as were the individual ?-pinene and ?-pinene concentrations. However, other monoterpenes were generally not correlated to climatic variables or geographic distribution. Finally, while the enantiomeric ratios of ?-pinene and limonene remained constant across jack pine's distribution, (-):(+)-?-pinene exhibited two separate trends, thereby delineating two ?-pinene phenotypes, both of which occurred across jack pine's range. These significant variations in jack pine monoterpene composition may have cascading effects on the continued eastward spread and success of D. ponderosae in the Canadian boreal forest.
Project description:To quantify the emission rate of monoterpenes (MTs) from diverse natural sources, the sorbent tube (ST)-thermal desorption (TD) method was employed to conduct the collection and subsequent detection of MTs by gas chromatography. The calibration of MTs, when made by both mass spectrometric (MS) and flame ionization detector (FID), consistently exhibited high coefficient of determination values (R2 > 0.99). This approach was employed to measure their emission rate from different fruit/plant/vegetable (F/P/V) samples with the aid of an impinger-based dynamic headspace sampling system. The results obtained from 10 samples (consisting of carrot, pine needle (P. sylvestris), tangerine, tangerine peel, strawberry, sepals of strawberry, plum, apple, apple peel, and orange juice) marked ?-pinene, ?-pinene, myrcene, ?-terpinene, R-limonene, ?-terpinene, and p-cymene as the most common MTs. R-limonene was the major species emitted from citrus fruits and beverages with its abundance exceeding 90%. In contrast, ?-pinene was the most abundant MT (37%) for carrot, while it was myrcene (31%) for pine needle. The overall results for F/P/V samples confirmed ?-pinene, ?-pinene, myrcene, ?-terpinene, and ?-terpinene as common MTs. Nonetheless, the types and magnitude of MTs released from fruits were distinguished from those of vegetables and plants.
Project description:The chemical composition of the essential oil from Juniperus formosana leaves and its contact and repellent activities against Tribolium castaneum and Liposcelis bostrychophila adults were investigated. The essential oil of J. formosana leaves was obtained by hydrodistillation and analyzed by GC-MS. A total of 28 components were identified and the main compounds in the essential oil were ?-pinene (21.66%), 4-terpineol (11.25%), limonene (11.00%) and ?-phellandrene (6.63%). The constituents ?-pinene, 4-terpineol and d-limonene were isolated from the essential oil. It was found that the essential oil exhibited contact activity against T. castaneum and L. bostrychophila adults (LD50 = 29.14 ?g/adult and 81.50 µg/cm², respectively). The compound 4-terpineol exhibited the strongest contact activity (LD50 = 7.65 ?g/adult). In addition, data showed that at 78.63 nL/cm², the essential oil and the three isolated compounds strongly repelled T. castaneum adults. The compounds ?-pinene and d-limonene reached the same level (Class V) of repellency as DEET (p = 0.396 and 0.664) against L. bostrychophila at 63.17 nL/cm² after 2 h treatment. The results indicate that the essential oil and the isolated compounds have potential to be developed into natural insecticides and repellents to control insects in stored products.
Project description:Butyrylcholinesterase (BChE) is a non-specific enzyme with clinical pharmacological and toxicological significance, which was a renewed interest as therapeutic target in Alzheimer's disease (AD) nowadays. Here, all-atom molecular dynamics simulations of butyrylcholinesterase with tacrine complex were designed to characterize inhibitor binding modes, strengths, and the hydrogen-bond dependent non-covalent release mechanism. Four possible release channels were identified, and the most favorable channel was determined by random acceleration molecular dynamics molecular dynamics (RAMD MD) simulations. The thermodynamic and dynamic properties as well as the corresponding Detour-forward delivery mechanism were determined according to the classical molecular dynamics (MD) simulations accompanied with umbrella sampling. The free energy barrier of the tacrine release process for the most beneficial pathway is about 10.95 kcal/mol, which is related to the non-covalent interactions from the surrounding residues, revealing the specific binding characteristics in the active site. The residues including Asp70, Ser79, Trp82, Gly116, Thr120, Tyr332, and His438 were identified to play major roles in the stabilization of tacrine in the pocket of BChE, where hydrogen bonding and ?-? interactions are significant factors. Tyr332 and Asp70, which act as gate keepers, play crucial roles in the substrate delivery. The present results provide a basic understanding for the ligand transport mechanism depending on the BChE enzymatic environment, which is useful for the design of BChE inhibitors in the future.
Project description:The mountain pine beetle (Dendroctonus ponderosae; MPB) is an eruptive bark beetle species affecting pine forests of western North America. MPB are exposed to volatile monoterpenes, which are important host defense chemicals. We assessed the toxicity of the ten most abundant monoterpenes of lodgepole pine (Pinus contorta), a major host in the current MPB epidemic, against adult MPB from two locations in British Columbia, Canada. Monoterpenes were tested as individual volatiles and included (-)-?-phellandrene, (+)-3-carene, myrcene, terpinolene, and both enantiomers of ?-pinene, ?-pinene and limonene. Dose-mortality experiments identified (-)-limonene as the most toxic (LC50: 32??L/L), and (-)-?-pinene (LC50: 290??L/L) and terpinolene (LC50: >500??L/L) as the least toxic. MPB body weight had a significant positive effect on the ability to survive most monoterpene volatiles, while sex did not have a significant effect with most monoterpenes. This study helps to quantitatively define the effects of individual monoterpenes towards MPB mortality, which is critical when assessing the variable monoterpene chemical defense profiles of its host species.
Project description:Pinus eldarica (Pinaceae), an evergreen plant, is distributed across the warm and dry climates of western Asia, including Asia Minor, the Middle East, and land surrounding the Caspian Sea. Essential oils (EOs) from different aerial parts of this tree have been used in traditional medicine. We aimed to investigate the chemical profile and antimicrobial activity of the EO from P. eldarica grown in northwestern Iran. EO from the needles, bark, and pollen were extracted with boiling water using a Clevenger apparatus at yield of 0.7-1.2 cm3/100 g of dry plant material. The main chemical components of the EO from the needles were D-germacrene (18.17%), caryophyllene (15.42%), γ-terpinene (12.96%), and β-pinene (10.62%); those from the bark were limonene (16.99%), caryophyllene oxide (13.22%), and drimenol (13.2%); and those from the pollen were α-pinene (25.64%) and limonene (19.94%). In total, 83 constituents were characterized in the EOs, using gas chromatography mass spectrometry analysis; mainly, sesquiterpene hydrocarbons in needle EO and monoterpene hydrocarbons in pollen and bark EOs. β-Pinene, β-myrcene, limonene, and caryophyllene were identified in the EOs from all three plant parts. The antibacterial and antifungal properties of the EOs were examined: pollen EO exhibited antibacterial activity against Escherichia coli; bark EO inhibited the growth of Candida albicans and Staphylococcus aureus; and the needle EO inhibited the growth of S. aureus. Thus, the EOs from aerial parts of P. eldarica can benefit the EO industry and antibiotic development.
Project description:The current study aimed at investigating the existence of the cross state-dependent learning between morphine and scopolamine (SCO) in mice by passive avoidance method, pointing to the role of CA1 area.The effects of pre-training SCO (0.75, 1.5, and 3 μg, Intra-CA1), or morphine (1, 3, and 6 mg/kg, intraperitoneal (i.p.) was evaluated on the retrieval of passive avoidance learning using step-down task in mice (n=10). Then, the effect of pretest administration of morphine (1.5, 3, and 6 mg/kg, i.p.) was examined on passive avoidance retrieval impairment induced by pre-training SCO (3 μg/mice, Intra-CA1). Next, the effect of pretest Intra-CA1 injection of scopolamine (0.75, 1.5, and 3 μg/mice) was evaluated on morphine (6 mg/kg, i.p.) pre-training deficits in this task in mice.The pre-training Intra-CA1 injection of scopolamine (1.5 and 3 μg/mouse), or morphine (3 and 6 mg/kg, i.p.) impaired the avoidance memory retrieval when it was tested 24 hours later. Pretest injection of both drugs improved its pre-training impairing effects on mice memory. Moreover, the amnesia induced by the pre-training injections of scopolamine (3 μg/mice) was restored significantly (P<0.01) by pretest injections of morphine (3 and 6 mg/kg, i.p.). Similarly, pretest injection of scopolamine (3 μg/mice) restored amnesia induced by the pre-training injections of morphine (6 mg/kg, i.p.), significantly (P<0.01).The current study findings indicated a cross state-dependent learning between SCO and morphine at CA1 level. Therefore, it seems that muscarinic and opioid receptors may act reciprocally on modulation of passive avoidance memory retrieval, at the level of dorsal hippocampus, in mice.