Article

Fragrances in Oolong Tea That Enhance the Response of GABA A Receptors

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

We electrophysiologically investigated the effect of some fragrant compounds in oolong tea on the response of ionotropic gamma-aminobutyric acid (GABA) receptors (GABAA receptors) which were expressed in Xenopus oocytes. Of the tested fragrances in oolong tea, cis-jasmone, jasmine lactone, linalool oxide and methyl jasmonate significantly potentiated the response. Among these, cis-jasmone and methyl jasmonate potently potentiated the response, having a respective dissociation constant of the compound (Kp) and maximum potentiation (Vm) of 0.49 mM and 322% for cis-jasmone, and 0.84 mM and 450% for methyl jasmonate. Inhalation of 0.1% cis-jasmone or methyl jasmonate significantly increased the sleeping time of mice induced by pentobarbital, suggesting that these fragrant compounds were absorbed by the brain and thereby potentiated the GABAA receptor response. Both of these compounds may therefore have a tranquillizing effect on the brain.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Green tea extracts can improve sleep disturbances and stabilize mood in humans [79,80]. Fragrant compounds in oolong tea have tranquilizing effects on the brains of mice [81]. Different active ingredients in tea have various implications for sleep (as shown in Figure 1). ...
... Jasmine lactone, an aromatic substance, constitutes oolong tea's floral and fruity aroma. Studies have shown that inhalation of cisjasmone or methyl jasmonate significantly increases the sleeping time in mice induced by pentobarbital and has a tranquilizing effect on their brains [81]. ...
... Polyphenols can prevent the reuptake of monoamine neurotransmitters and increase cerebral blood flow [122]. Aromatic substances, such as homeopathic jasmine, jasmine lactone, linalool oxide, and methyl jasmonate, significantly enhanced the expression of GABA receptors in Xenopus oocytes and increased the content of 5-HT and GABA in mouse brains [81,92]. ...
Article
Full-text available
Sleep, a conservative evolutionary behavior of organisms to adapt to changes in the external environment, is divided into natural sleep, in a healthy state, and sickness sleep, which occurs in stressful environments or during illness. Sickness sleep plays an important role in maintaining energy homeostasis under an injury and promoting physical recovery. Tea, a popular phytochemical-rich beverage, has multiple health benefits, including lowering stress and regulating energy metabolism and natural sleep. However, the role of tea in regulating sickness sleep has received little attention. The mechanism underlying tea regulation of sickness sleep and its association with the maintenance of energy homeostasis in injured organisms remains to be elucidated. This review examines the current research on the effect of tea on sleep regulation, focusing on the function of tea in modulating energy homeostasis through sickness sleep, energy metabolism, and damage repair in model organisms. The potential mechanisms underlying tea in regulating sickness sleep are further suggested. Based on the biohomology of sleep regulation, this review provides novel insights into the role of tea in sleep regulation and a new perspective on the potential role of tea in restoring homeostasis from diseases.
... In addition, stress-reducing effects have been shown from consumed oolong tea and GABA-fortified oolong tea [149]. Fragrant compounds in oolong tea were investigated for their response on ionotropic GABA A receptors in xenopus oocytes [78]. Cis-jasmone, methyl jasmonate, jasmine lactone, and linalool oxide all significantly potentiated the GABA A receptor response with Cis-jasmone and methyl jasmonate potently potentiated the response. ...
... In addition, sleeping time of mice induced with pentobarbital (known to potentiate the GABA A receptor response) and exposed to inhalation of Cis-jasmone and methyl jasmonate was examined. Results showed that Cis-jasmone and methyl jasmonate significantly increased sleeping time in mice, implying that these fragrant compounds were absorbed by the brain, inducing a tranquillising effect via potentiating a GABA A receptor response [78]. ...
... Despite the lack of direct studies on GABA A receptors, some of the main chemical constituents present in the essential oils and/or aromatic compounds have been evaluated for their GABA A receptor response. Monoterpenes (α-pinene [88,126], linalool [124], borneol [117], linalool oxide [78], thymol [163], carvacrol [124], citronellol, and hinokitiol [88]), alcohol (1-octen-3-ol [124]), lactones (jasmine lactone and lactone derivatives [78]), esters (ethyl phenylpropanoate [107] and methyl jasmonate [78]), cyclic ketone (cis-jasmone [78]), and ethoxy [107] have all shown to potentiate a GABA A receptor response. ...
Article
Full-text available
Aromas have a powerful influence in our everyday life and are known to exhibit an array of pharmacological properties, including anxiolytic, anti-stress, relaxing, and sedative effects. Numerous animal and human studies support the use of aromas and their constituents to reduce anxiety-related symptoms and/or behaviours. Although the exact mechanism of how these aromas exert their anxiolytic effects is not fully understood, the GABAergic system is thought to be primarily involved. The fragrance emitted from a number of plant essential oils has shown promise in recent studies in modulating GABAergic neurotransmission, with GABAA receptors being the primary therapeutic target. This review will explore the anxiolytic and sedative properties of aromas found in common beverages, such as coffee, tea, and whisky as well aromas found in food, spices, volatile organic compounds, and popular botanicals and their constituents. In doing so, this review will focus on these aromas and their influence on the GABAergic system and provide greater insight into viable anxiety treatment options.
... Previous investigations have shown that MJ has anticancer, antinociceptive, antiaggressive, and antidepressant properties [5,7,8]. In addition, Hossain et al. [9] reported that MJ potentiated pentobarbitone sleeping time and enhanced GABA-mediated inhibitory neurotransmission, suggesting the potential benefits in disorders associated with hyperexcitability of the brain such as convulsions and anxiety states. Thus, this present study was carried out to evaluate whether MJ exhibits anticonvulsant and anxiolytic activities in mice. ...
... The effect of MJ on SMA as assessed by the number of line crosses and duration of ambulation in the open field test are presented in Table 4. One-way ANOVA revealed that there were significant differences between the treatment groups: the number of line of crosses [F (9,40) Post-hoc analysis by the Newman-Keuls multiple comparison test revealed that MJ (400 mg/kg) produced marked sedation as shown by the reduced number of line crosses and duration of ambulation in mice (Table 4). However, at lower doses, it did not significantly change the SMA when compared with the control value (Table 4). ...
... Thus, the inability to gain access to the closed chloride ion gate in order to reopen it might explain the failure of MJ to prevent seizures due to picrotoxin. It is our opinion that the enhancement of GABA currents previously reported for MJ [9] might perhaps account for its ability to modify some of the components of convulsions induced by PTZ and picrotoxin in mice. However, further studies using experimental models such as kindling, are necessary to determine if MJ is able to modify the epileptogenesis process. ...
... Previous investigations have shown that MJ has anticancer, antinociceptive, antiaggressive, and antidepressant properties [5,7,8]. In addition, Hossain et al. [9] reported that MJ potentiated pentobarbitone sleeping time and enhanced GABA-mediated inhibitory neurotransmission, suggesting the potential benefits in disorders associated with hyperexcitability of the brain such as convulsions and anxiety states. Thus, this present study was carried out to evaluate whether MJ exhibits anticonvulsant and anxiolytic activities in mice. ...
... The effect of MJ on SMA as assessed by the number of line crosses and duration of ambulation in the open field test are presented in Table 4. One-way ANOVA revealed that there were significant differences between the treatment groups: the number of line of crosses [F (9,40) Post-hoc analysis by the Newman-Keuls multiple comparison test revealed that MJ (400 mg/kg) produced marked sedation as shown by the reduced number of line crosses and duration of ambulation in mice (Table 4). However, at lower doses, it did not significantly change the SMA when compared with the control value (Table 4). ...
... Thus, the inability to gain access to the closed chloride ion gate in order to reopen it might explain the failure of MJ to prevent seizures due to picrotoxin. It is our opinion that the enhancement of GABA currents previously reported for MJ [9] might perhaps account for its ability to modify some of the components of convulsions induced by PTZ and picrotoxin in mice. However, further studies using experimental models such as kindling, are necessary to determine if MJ is able to modify the epileptogenesis process. ...
Article
Full-text available
Methyl jasmonate (MJ) is one of the most well studied plant stress hormones belonging to the jasmonate family. Previous studies had shown that MJ potentiated pentobarbitone sleeping time and enhanced GABA-mediated inhibitory neurotransmission, suggesting potential benefits in disorders associated with hyperactivity of the brain. This study was carried out to evaluate whether MJ has anticonvulsant and anxiolytic properties in mice. Anticonvulsant effect was assessed based on prevention of tonic-clonic seizures induced by chemoconvulsant agents in mice. Anxiolytic property was evaluated utilizing the elevated plus maze (EPM) and light/dark transition paradigms. The effect of MJ on spontaneous locomotor activity (SMA) was also assessed. Mice received intraperitoneal (i.p.) injection of MJ 30 min before the tests were carried out and diazepam (2 mg/kg, i.p.) was used as the reference drug. MJ (50-400 mg/kg) did not protect mice against tonic-clonic convulsions induced by picrotoxin (10 mg/kg, i.p.) or strychnine (3 mg/kg, i.p.). However, MJ (100, 200 and 400 mg/kg) offered 20, 60 and 100 % protection against pentylenetetrazole (100 mg/kg, i.p.)-induced convulsions. In similar manner to diazepam (2 mg/kg), MJ (400 mg/kg) produced a marked sedative effect as shown by decreases in number of line crossed and the duration of ambulation in the open field test. In contrast to daizepam (2 mg/kg), MJ (5-50 mg/kg) did not show anxiolytic effect in the EPM and light-dark transition paradigms. These findings suggest that methyl jasmonate at high doses possessed anticonvulsant property in pentylenetetrazole animal model of epilepsy but did not produce anxiolytic activity in mice.
... In the plants' defense system, MJ plays its strategic functions via stimulation of adjustment strategies, especially the generation of proteinase inhibitor proteins, which are a collection of protective biological constituents [1]. The usefulness of MJ in the amelioration of some neuropsychiatric disorders was first shown by research conducted by Hossain and colleagues [3], where it was found to exhibit tranquilizing property in addition to boosting GABAergic-induced inhibitory neurotransmission. MJ is believed to attain adequate concentration in the brain and exert beneficial psychopharmacological activities as it possesses the ability to diffuse through lipid membranes and permeate numerous biotic membranes like blood-brain-barrier [2,3]. ...
... The usefulness of MJ in the amelioration of some neuropsychiatric disorders was first shown by research conducted by Hossain and colleagues [3], where it was found to exhibit tranquilizing property in addition to boosting GABAergic-induced inhibitory neurotransmission. MJ is believed to attain adequate concentration in the brain and exert beneficial psychopharmacological activities as it possesses the ability to diffuse through lipid membranes and permeate numerous biotic membranes like blood-brain-barrier [2,3]. Also, its effects against limited and prolonged distress in mice have been established [4,5]. ...
Article
Objectives Purinergic signaling pathway has been implicated in maladaptation of animals subjected to chronic stress. Previous studies have shown that methyl jasmonate (MJ) exhibited adaptogenic properties in mice exposed to unpredictable chronic mild stress (UCMS) via antioxidant and neuroprotective-related mechanisms. Methods This study evaluated the role of purinergic system in adaptogenic-like activity of MJ. Male Wistar rats were treated intraperitoneally with vehicle (10 mL/kg) or MJ (25, 50, or 100 mg/kg) 30 min prior exposure to UCMS. Thereafter, rats were assessed for swimming endurance in forced swim test (FST) and post-swimming motor coordination on beam walk test (BWT) apparatus. The rats’ brains were processed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine deaminase, and arginase quantification. Hematological parameters, cholesterol, triglyceride, creatinine, and urea nitrogen were also determined. Results MJ prolonged swimming endurance time and reversed stress-induced post-swimming motor dysfunction. The altered hematological parameters induced by UCMS in rats were significantly (p<0.05) attenuated by MJ. MJ also reversed UCMS-induced alterations of total cholesterol, triglyceride, creatinine, and urea nitrogen levels. MJ averted UCMS-induced alterations in purinergic system by decreasing ATP and ADP hydrolysis, adenosine deaminase, and arginase activities in rats’ brains. Conclusions Overall, these findings further suggest that MJ has adaptogenic-like activity in rats exposed to UCMS, which may be related to modulation of the purinergic signaling pathway.
... In the plants' defense system, MJ plays its strategic functions via stimulation of adjustment strategies, especially the generation of proteinase inhibitor proteins, which are a collection of protective biological constituents [1]. The usefulness of MJ in the amelioration of some neuropsychiatric disorders was first shown by research conducted by Hossain and colleagues [3], where it was found to exhibit tranquilizing property in addition to boosting GABAergic-induced inhibitory neurotransmission. MJ is believed to attain adequate concentration in the brain and exert beneficial psychopharmacological activities as it possesses the ability to diffuse through lipid membranes and permeate numerous biotic membranes like blood-brain-barrier [2,3]. ...
... The usefulness of MJ in the amelioration of some neuropsychiatric disorders was first shown by research conducted by Hossain and colleagues [3], where it was found to exhibit tranquilizing property in addition to boosting GABAergic-induced inhibitory neurotransmission. MJ is believed to attain adequate concentration in the brain and exert beneficial psychopharmacological activities as it possesses the ability to diffuse through lipid membranes and permeate numerous biotic membranes like blood-brain-barrier [2,3]. Also, its effects against limited and prolonged distress in mice have been established [4,5]. ...
Article
Objectives Purinergic signaling pathway has been implicated in maladaptation of animals subjected to chronic stress. Previous studies have shown that methyl jasmonate (MJ) exhibited adaptogenic properties in mice exposed to unpredictable chronic mild stress (UCMS) via antioxidant and neuroprotective-related mechanisms. Methods This study evaluated the role of purinergic system in adaptogenic-like activity of MJ. Male Wistar rats were treated intraperitoneally with vehicle (10 mL/kg) or MJ (25, 50, or 100 mg/kg) 30 min prior exposure to UCMS. Thereafter, rats were assessed for swimming endurance in forced swim test (FST) and post-swimming motor coordination on beam walk test (BWT) apparatus. The rats’ brains were processed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine deaminase, and arginase quantification. Hematological parameters, cholesterol, triglyceride, creatinine, and urea nitrogen were also determined. Results MJ prolonged swimming endurance time and reversed stress-induced post-swimming motor dysfunction. The altered hematological parameters induced by UCMS in rats were significantly (p<0.05) attenuated by MJ. MJ also reversed UCMS-induced alterations of total cholesterol, triglyceride, creatinine, and urea nitrogen levels. MJ averted UCMS-induced alterations in purinergic system by decreasing ATP and ADP hydrolysis, adenosine deaminase, and arginase activities in rats’ brains. Conclusions Overall, these findings further suggest that MJ has adaptogenic-like activity in rats exposed to UCMS, which may be related to modulation of the purinergic signaling pathway.
... Hossain et al. [27] electrophysiologically tested the effect of fragrant compounds in oolong tea on GABA A receptors which were expressed in Xenopus oocytes. Oolong tea is a traditional Chinese tea that is made by withering the plants with strong sun exposure and oxidation. ...
... The inhalation of 0.1% cis-jasmone or methyl jasmonate significantly increased the sleeping time of mice induced by pentobarbital. The results suggest that these fragrant compounds could be absorbed by the brain and thereby potentiated the GABA A receptor response to exerting a tranquilizing effect on the brain [27]. ...
Article
Full-text available
Essential oils and the constituents in them exhibit different pharmacological activities, such as antinociceptive, anxiolytic-like, and anticonvulsant effects. They are widely applied as a complementary therapy for people with anxiety, insomnia, convulsion, pain, and cognitive deficit symptoms through inhalation, oral administration, and aromatherapy. Recent studies show that essential oils are emerging as a promising source for modulation of the GABAergic system and sodium ion channels. This review summarizes the recent findings regarding the pharmacological properties of essential oils and compounds from the oils and the mechanisms underlying their effects. Specifically, the review focuses on the essential oils and their constituents targeting the GABAergic system and sodium channels, and their antinociceptive, anxiolytic, and anticonvulsant properties. Some constituents target transient receptor potential (TRP) channels to exert analgesic effects. Some components could interact with multiple therapeutic target proteins, for example, inhibit the function of sodium channels and, at the same time, activate GABAA receptors. The review concentrates on perspective compounds that could be better candidates for new drug development in the control of pain and anxiety syndromes.
... According to a great deal of data, EOs and their components are mostly positive modulators of the GABA A receptors ( Figure 2). Menthol, thymol and other components increase the Cl − current induced by the GABA neurotransmitter (Table 3) [76][77][78][79][80][81][82]. Such a situation occurs in low (µM) concentrations of EOs. ...
... According to a great deal of data, EOs and their components are mostly positive modulators of the GABAA receptors ( Figure 2). Menthol, thymol and other components increase the Cl − current induced by the GABA neurotransmitter (Table 3) [76][77][78][79][80][81][82]. Such a situation occurs in low (μM) concentrations of EOs. ...
Article
Full-text available
Essential oils (EOs) are lipophilic secondary metabolites obtained from plants; terpenoids represent the main components of them. A lot of studies showed neurotoxic actions of EOs. In insects, they cause paralysis followed by death. This feature let us consider components of EOs as potential bioinsecticides. The inhibition of acetylcholinesterase (AChE) is the one of the most investigated mechanisms of action in EOs. However, EOs are rather weak inhibitors of AChE. Another proposed mechanism of EO action is a positive allosteric modulation of GABA receptors (GABArs). There are several papers that prove the potentiation of GABA effect on mammalian receptors induced by EOs. In contrast, there is lack of any data concerning the binding of EO components in insects GABArs. In insects, EOs act also via the octopaminergic system. Available data show that EOs can increase the level of both cAMP and calcium in nervous cells. Moreover, some EO components compete with octopamine in binding to its receptor. Electrophysiological experiments performed on Periplaneta americana have shown similarity in the action of EO components and octopamine. This suggests that EOs can modify neuron activity by octopamine receptors. A multitude of potential targets in the insect nervous system makes EO components interesting candidates for bio-insecticides.
... MJ was first isolated from the essential oil of Jasminum grandiflorum, a medicinal plant found in most tropical regions of the world, which is now available commercially through chemical synthesis [14]. MJ is a cyclopentanoic compound with high lipid solubility, a property that encourages its bioavailability in the brain [15]. Previous studies have reported that MJ possess anticancer, antinociceptive, anti-aggressive, and antidepressant activities [13][14][15][16][17][18]. ...
... MJ is a cyclopentanoic compound with high lipid solubility, a property that encourages its bioavailability in the brain [15]. Previous studies have reported that MJ possess anticancer, antinociceptive, anti-aggressive, and antidepressant activities [13][14][15][16][17][18]. Considering the fact that MJ provides a defensive mechanism for plants against stress suggests that it might also exhibit an adaptogenic property in providing resistance against stressful conditions in humans. ...
Article
Full-text available
Methyl jasmonate (MJ) is an anti-stress hormone released by plants in response to external stressors and aids adaptation to stress. In this study, we evaluated the anti-stress activity of MJ using the forced swim endurance test (FSET) and anoxic tolerance test in mice. Male Swiss mice were given MJ (25–100 mg/kg, i.p) 30 min before the FSET and anoxic test were carried out. The first occurrence of immobility, duration of immobility, time spent in active swimming, and latency to exhaustion were assessed in the FSET. The onset to anoxic convulsion was measured in the anoxic tolerance test. MJ significantly (p < 0.05) delayed the first occurrence of immobility and shortened the period of immobility, which indicates anti-stress property. MJ also increased the time spent in active swimming and prolonged the latency to exhaustion, which further suggests anti-stress activity. In addition, it also exhibited anti-stress property as evidenced by prolonged latency to first appearance of anoxic convulsions. The results of this study suggest that MJ demonstrated anti-stress activity and may be useful as an energizer in times of body weakness or exhaustion. Although more studies are necessary before concluding on how MJ exerts its anti-stress activity, the present data suggest an action similar to adaptogens in boosting energy and resilience in the face of stress.
... Geraniol, a key constituent of Palmarosa oils and Lemongrass oil exhibited high toxicity to B. tabaci in the present study. Structure toxicity relationship studies have shown that EOs bind to the GABA receptors at anesthetic site and some of the EO constituents like borneol or geraniol are structurally similar to propofol, a known ligand of anesthetic seat of GABA receptors and they potentiate the GABA induced Clcurrent (17,20). The toxicity assays of the present study were done with O/W formulations of EOs, as the stability of the EOs is greatly enhanced by appropriate formulations. ...
Article
Whitefly, Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae) is one of the global polyphagous pests in many agricultural crops. Besides, other control strategies, essential oils are being considered as one of the promising candidates for developing alternative strategies for its management. We evaluated the Oil-in-water (O/W) formulations (47.6 %) of 6-essential oils (pine oil, lemongrass oil, geranium oil, eucalyptus oil palmarosa oil and citral) against B. tabaci to determine their contact toxicity potential and phytotoxicity effects. The GC-MS analyses of test essential oils contained geraniol (69.8 %) in palmarosa oil, δ-3-carene (50.7 %) in pine oil, citronellal (33.4 %) in geranium oil as major constituents. The O/W emulsion formulations were physically stable at room temperature with average droplet size of 136-425 nm. Geranium oil showed high phytotoxicity at 0.125 % concentration in brinjal, Solanum melongena (Variety: MEBH-10) leaves, whereas, the eucalyptus and pine oils were not phytotoxic. Comparatively, palmarosa oil displayed maximum contact toxicity with LC50 and LC90 values of 0.241 and 0.658 % respectively at 24 h and 0.142 and 0.398 % at 48 h after exposure. This study revealed that O/W emulsion formulations of palmarosa and lemongrass oil can be effectively used in whitefly management.
... cis-Jasmone (1) is another naturally occurring jasmonate (Flescher 2005). The few studies reporting the pharmacological effect of cis-jasmone indicate cytotoxic activity in neoplastic cell lines (Tong et al. 2008;Yeruva et al. 2008), depressant of the central nervous system (Hossain et al. 2004) and stimulant of gastrointestinal motility (Hong et al. 2014). The LD 50 was estimated to be 5 g/kg (Scognamiglio et al. 2012). ...
Article
cis-Jasmone is known to activate plan resistance to insects. There are few reports of its pharmacological potential, and this paper presents the topical anti-inflammatory effect of cis-jasmone. cis-Jasmone reduced the oedema induced by arachidonic acid, capsaicin and phenol, but not by croton oil (single and multiple applications). cis-Jasmone presented a mild effect on the histamine model. The most prominent anti-inflammatory effect of cis-jasmone was found in the oedema model induced by capsaicin (TRPV1 agonist). This effect was preventive and therapeutic, and it was similar to the effect shown by the TRPV1 antagonist capsazepine. Molecular docking studies indicated that cis-jasmone may interact with TRPV1. The effect of cis-jasmone remained after incorporation into the formulation. cis-Jasmone has a topical anti-inflammatory effect related to TRPV1 channel antagonism, and the gel-cream containing this terpene may be an alternative for the treatment of skin inflammation.
... It is confirmed that fragrant compounds in oolong tea and 3-O-octanoyl-(+)-catechin (OC) in green tea respectively improve and reduce the response of the γ-aminobutyric acid type A (GABAA) receptor which plays a key role in the central nervous system. 110,111 These indicate that the effects of tea extract on oocytes may be mediated by the hypothalamus-pituitary-ovary axis in vivo (Fig. 1). The abnormal hormone secretion induced by tea extract is also observed in vitro. ...
Article
Full-text available
Tea is the second most popular beverage in the world and beneficial to health. It has been demonstrated that tea polyphenols can reduce the risk of diseases, such as cancers, diabetes, obesity, Alzheimer's disease, etc. But the knowledge of tea extract on the female germline is limited. Folliculogenesis is a complicated process and prone to be affected by ROS. Tea polyphenols can reduce the accumulation of ROS in folliculogenesis and affect oocyte maturation. Tea extract also influences granulosa cell proliferation and expansion during oocyte growth and maturation. However, the studies about the benefits of tea extract on female germline are few, and the underlying mechanisms are obscure. In the present study, we will mainly discuss the effects of tea extract on ovarian function, oocyte maturation, and the underlying possible mechanisms, and according to the discussion, we suggest that tea extract may have benefits for oocytes at an appropriate dose.
... These findings have been described as inspiring evidence that may encourage its development for the treatment of cancer and other debilitating diseases that require prolonged therapy [1,5,7,[10][11][12][13][14][15]. Meanwhile, the possibility of its potential usefulness in neuropsychiatric disorders stemmed from the reports of Hossain et al. [16], which have shown that MJ exhibited sedative effect and enhanced GABAergic neurotransmission. These findings have led to extensive studies on the effects of MJ on neurological disorders and the mechanisms underlying its neuroprotective activity in rodents [17][18][19][20][21][22][23]. ...
Article
Full-text available
Methyl jasmonate (MJ) is a derivative of the jasmonate family which is found in most tropical regions of the world and present in many fruits and vegetables such as grapevines, tomato, rice, and sugarcane. MJ is a cyclopentanone phytohormone that plays a vital role in defense against stress and pathogens in plants. This has led to its isolation from plants for studies in animals. Many of these studies have been carried out to evaluate its therapeutic effects on behavioral and neurochemical functions. It has however been proposed to have beneficial potential over a wide range of neurological disorders. Hence, this review aims to provide an overview of the neuroprotective properties of MJ and its probable mechanisms of ameliorating neurological disorders. The information used for this review was sourced from research articles and scientific databases using 'methyl jasmonate', 'behavior', 'neuroprotection', 'neurodegenerative dis-eases', and 'mechanisms' as search words. The review highlights its influences on behavioral patterns of anxiety, aggression , depression, memory, psychotic, and stress. The molecular mechanisms such as modulation of the antioxidant defense, inflammatory biomarkers, neurotransmitter regulation, and neuronal regeneration, underlying its actions in managing neurodegenerative diseases like Alzheimer's and Parkinson's diseases are also discussed. This review, therefore, provides a detailed evaluation of methyl jasmonate as a potential neuroprotective compound with the ability to modify behavioral and molecular biomarkers underlying neurological disorders. Hence, MJ could be modeled as a guided treatment for the management of brain diseases.
... One electrophysiological study concluded that jasmonates extracted from oolong tea significantly potentiate GABAA receptors in vitro. The same study reported that the inhalation of methyl jasmonate and cis-jasmone significantly increased the tranquilizing effects of pentobarbital on the mouse brain, mirroring the sedative, anxiolytic effects of GABAA receptor potentiation in vivo (Hossain et al., 2004). The JAs are also popularly used in methods of aromatherapy to manage symptoms of neurological disorders (Eduviere et al., 2016), where they might also contribute to analgesic effects through modulation of the GABAergic system (Wang, Heinbockel, 2018). ...
Preprint
Full-text available
My MSc by Research dissertation, which consists of two pre-print pieces: a literature review and an original research manuscript. I explored the mechanisms by which jasmonate compounds (a class of phytohormones) can reduce neuroinflammation. My research serves as evidence that jasmonates interact with prostaglandin E2 signaling, suggesting that prostaglandin pathways may be key to the development of chronic neuroinflammation that contributes to ALS, Alzheimer's, Parkinson's, and other neurodegenerative diseases.
... They are known to decrease neuroinflammation as well(Adebesin et al. 2017). The plant oil reported to have tranquilizing effects on brain upon inhalation by numerous neurochemical mechanisms(Hossain et al. 2004; Umukoro et al. 2018). ...
Chapter
Sickle cell anemia (SCA) is an inherited disorder in the β-globin chain of hemoglobin that affects millions of people around the world, especially children. This disease prevalently occurs in some Mediterranean and Saharan Africa. For the treatment of SCA patients, a wide range of drugs have been explored by targeting antisickling activity, γ-globulin induction, antiplatelet effect, etc., but hardly a few drugs have shown potential to combat with this complex disease phenomenon. In spite of unprecedented advances in modern system of medicine, people in the disease-prone area have been taking traditional medicinal plants or plant-derived products to increase the life span of patients. Moreover, numerous clinical trials have been going on for the use of natural products under the purview of symptomatic management of SCA. This chapter is focused on the effect of natural products in pure form or characterized phytoconstituents on particularly inhibition of hemoglobin polymerization. This summarized information will be beneficial for further exploration of new therapeutics in the treatment arena of SCA.
... They are known to decrease neuroinflammation as well(Adebesin et al. 2017). The plant oil reported to have tranquilizing effects on brain upon inhalation by numerous neurochemical mechanisms(Hossain et al. 2004; Umukoro et al. 2018). ...
... They are known to decrease neuroinflammation as well(Adebesin et al. 2017). The plant oil reported to have tranquilizing effects on brain upon inhalation by numerous neurochemical mechanisms(Hossain et al. 2004;Umukoro et al. 2018). ...
Chapter
Presently, neurological disorders form a major proportion of non-communicable diseases. Their incidence has increased due to several factors such as lifestyle changes, changes in dietary patterns, and increased psychological stress. Due to increase in awareness regarding these disorders by health-care professionals and general public, increasing number of cases are diagnosed with every passing year. This presents a challenge, especially in under-developed and developing countries, where the public health-care systems are not well established and penetration of health insurance cover is relatively much lower. Alternative medicine has traditionally been used in several cultures around the world to treat neurological problems. Essential oils and other plant volatiles have a long history of traditional use for ameliorating symptoms of neurological and psychological disorders. Essential oils of lavender, rose, lemon balm, etc. have shown good promise. Further, modern research has validated some of the claims with regard to relieving of neural and psychological issues by plant VOCs. Some of these have been shown to modulate key enzymes that are targets for depression therapy. In the present chapter we have presented an overview of above, and toward the end we have attempted to identify lacunas in this area which may help to formulate future research strategies.
... Previous studies have shown that persistent stress down-regulate GABAergic neurons [27][28] and this may contribute to convulsive seizures associated with oxygen deprivation in a hermetic vessel in mice. MJ has been previously reported to increase the brain levels of GABA and enhanced GABA currents in experimental models [29], however, the relevance of these findings in its ability to promote resilience in the face of anoxic stress needs further investigations. Exposure of animals to uncontrollable stress activates the HPA axis, which leads to increase in concentrations of cortisol in plasma and brain tissues. ...
Article
Objectives Repeated exposure to anoxic stress damages the brain through cortisol-mediated increases in oxidative stress and cellular-antioxidants depletion. Thus, compounds with antioxidant property might confer protection against anoxic stress-induced brain injuries. In this study, we further examined the protective effect of methyl jasmonate (MJ), a potent anti-stress agent against anoxic stress-induced convulsions in mice. Methods Thirty-six male Swiss mice randomized into six groups (n=6) were given MJ (25, 50 and 100 mg/kg, i.p.) or vehicle (10 mL/kg, i.p.) 30 min before 15 min daily exposure to anoxic stress for 7 days. The latency(s) to anoxic convulsion was recorded on day 7. The blood glucose and serum corticosterone levels were measured afterwards. The brains were also processed for the determination of malondialdehyde, nitrite, and glutathione levels. Results Methyl jasmonate (MJ) delayed the latency to anoxic convulsion and reduced the blood glucose and serum corticosterone levels. The increased malondialdehyde and nitrite contents accompanied by decreased glutathione concentrations in mice with anoxic stress were significantly attenuated by MJ. Conclusions These findings further showed that MJ possesses anti-stress property via mechanisms relating to the reduction of serum contents of corticosterone and normalization of brain biomarker levels of oxidative stress in mice with anoxic stress.
... Jasminum grandiflorium have sedative effect on the brain upon inhalation. It indicates that these fragrant compounds have various effects on various diseases (Hossain et al. 2004). When these fragrant compounds are absorbed by the brain the GABA receptor response is initiated (Kagawa et al. 2003). ...
Article
Essential oils (EOs) are natural products obtained from different parts of a plant, such as flower, leaves, stems, fruits, seeds, roots, barks, or resin. It represents an important part of traditional pharmacopeia practices in healing of human ailments. It is used as raw materials in cosmetics, spices, foods, perfumes, and in treatment of several health disorders. There are several methods for extracting EOs from plants. They are the methods like hydro-distillation, steam distillation, hydro diffusion and cold pressing to name a few. The use of EOs as antimicrobial and pharmaceutical agents for curing various diseases has gained a considerable attraction of researchers in recent times. The complex mixture of EOs and their constituents have been reported to inhibit human pathogens, insects, and another harmful organism. The current review focusses on the chemical bioactive components of EOs, methods of extraction, chemical constituent, different plants as source of extraction and its application towards the treatment of various diseases in our day to day life, in vivo validation of essential oil, nanoformulation of essential oils.
... This oil showed an inhibitory effect on the central nervous system via the gamma-aminobutyric acid (GABA)-ergic system (64). The inhalation of fragrances in oolong tea (cis-jasmone and methyl jasmonate) increased the sleeping time of mice induced by pentobarbital, suggesting that these compounds have a tranquillizing effect on the brain and thereby potentiated the GABA receptor response (65). In a study conducted by Barocelli et al. (66) rodents inhaled lavender EOs (100 mg/kg) during 60 min and analgesic effects on rats were observed. ...
Article
Essential oils are products obtained from plants, by steam distillation, mechanical processes of citrus fruit epicarp, or dry distillation after separation of the aqueous phase by physical processes. They are usually composed of secondary metabolites of aromatic plants with oxygenated structures such as alcohols, ketones, aldehydes, and esters, presenting therapeutic properties such as antibacterial, antifungal and antioxidant activities. Essential oils are used in the pharmaceutical, food, and fragrance industries. The increasing use of plants by the pharmaceutical industry makes the study of essential oils crucial to design new bioactive delivery systems. This paper presents aliterature review that summarizes the best advanced data regarding the use of essential oils and their volatile constituents for biomedical applications with focuses on innovative pharmaceutical formulations. Nonetheless, it seems clear that more clinical evaluations are required until essential oils can be considered as possible applications in pharmacy or as adjuvants to current medications.
... Moreover, in vivo studies have also confirmed that MJ did not produce local or systemic adverse effects, irrespective of the route of exposure in both humans and laboratory animals (Belsito et al., 2012;Cesari et al., 2014). Meanwhile, previous preclinical investigations have revealed that MJ has sedative effect and potentiated GABAmediated inhibitory neurotransmission suggesting its benefits in neuropsychiatric diseases (Hossain et al., 2004). However, over the years, there is increasing interest in the development of MJ as a therapeutic drug for the treatment of diseases with inflammation as a major underlying factor. ...
... The scheme in Figure 7 offers an overview of the actions of MeJA in the brain cells in opposition to the modifications induced by arthritis, which should be a helpful guide in the discussion that follows. The scheme in Figure 7 assumes that MeJA easily crosses biological membranes including the blood brain barrier, as demonstrated experimentally and indeed expected from a lipid soluble substance [3,52]. The black arrows refer mainly to the modifications caused by arthritis whereas the red dotted arrows indicate the main sites of action of MeJA. ...
Article
Full-text available
Methyl jasmonate (MeJA), common in the plant kingdom, is capable of reducing articular and hepatic inflammation and oxidative stress in adjuvant-induced arthritic rats. This study investigated the actions of orally administered MeJA (75–300 mg/kg) on inflammation, oxidative stress and selected enzyme activities in the brain of Holtzman rats with adjuvant-induced arthritis. MeJA prevented the arthritis-induced increased levels of nitrites, nitrates, lipid peroxides, protein carbonyls and reactive oxygen species (ROS). It also prevented the enhanced activities of myeloperoxidase and xanthine oxidase. Conversely, the diminished catalase and superoxide dismutase activities and glutathione (GSH) levels caused by arthritis were totally or partially prevented. Furthermore, MeJA increased the activity of the mitochondrial isocitrate dehydrogenase, which helps to supply NADPH for the mitochondrial glutathione cycle, possibly contributing to the partial recovery of the GSH/oxidized glutathione (GSSG) ratio. These positive actions on the antioxidant defenses may counterbalance the effects of MeJA as enhancer of ROS production in the mitochondrial respiratory chain. A negative effect of MeJA is the detachment of hexokinase from the mitochondria, which can potentially impair glucose phosphorylation and metabolism. In overall terms, however, it can be concluded that MeJA attenuates to a considerable extent the negative effects caused by arthritis in terms of inflammation and oxidative stress.
... Moreover, in vivo studies have also confirmed that MJ did not produce local or systemic adverse effects, irrespective of the route of exposure in both humans and laboratory animals (Belsito et al., 2012;Cesari et al., 2014). Meanwhile, previous preclinical investigations have revealed that MJ has sedative effect and potentiated GABAmediated inhibitory neurotransmission suggesting its benefits in neuropsychiatric diseases (Hossain et al., 2004). However, over the years, there is increasing interest in the development of MJ as a therapeutic drug for the treatment of diseases with inflammation as a major underlying factor. ...
Article
Oxidative stress and neuroinflammation play key roles in the initiation and progression of Parkinson's disease (PD), a neurodegenerative disorder, associated with the loss of nigrostriatal dopaminergic pathway. Thus, compounds that can mitigate oxidative stress and neuroinflammation are being investigated as promising agents for the treatment of PD. This study was designed to evaluate the effects of methyl jasmonate (MJ), a potent antioxidant and anti-inflammatory compound on parkinsonian-like symptoms and the underlying biochemical changes induced by rotenone (Rot) in mice. To this end, the effects of graded doses of MJ (25, 50 and100 mg/kg, i.p.) on motor dysfunctions, cognitive and depressive-like disorders induced by Rot (2.5 mg/kg, i.p.) were evaluated. The specific brain regions (striatum, prefrontal cortex and hippocampus) of the animals were processed for various biochemical studies. Rot-treated mice showed reduced motor activity, postural instability, cognitive and depressive-like disorders. Rot also increased brain levels of malondialdehyde (MDA), nitrite, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and acetyl-cholinesterase (AChE) activity. Moreover, Rot reduced the concentration of glutathione (GSH) and increased immnopositive cells of NF-κB and α-synuclein expressions in these brain regions. However, pretreatment with MJ, attenuated the parkinsonian-like symptoms and reduced the brain levels of MDA/nitrite, TNF-α and IL-6 induced by Rot. MJ also reduced AChE activity and down-regulate the expressions of NF-κB and α-synuclein in the brain of Rot-treated mice. These findings suggest that MJ has anti-parkinsonian-like activity, which may be related to the inhibition of oxidative stress, release of pro-inflammatory cytokines, and down regulation of NF-κB and α-synuclein expressions.
... Different monoterpenoids were reported to bind to ionotropic GABA receptors in human, rodents and insects. Linalool, menthol, camphor, carvone, borneol and other monoterpenoids were suggested to be positive allosteric modulators of mammalian GABA receptors (Hall et al., 2004;Hossain et al., 2004;Granger et al., 2005). ...
Article
Six natural monoterpenes (1,8-cineole, (-)-citronellal, limonene, α-pinene, pulegone and 4-terpineol) showed high acaricidal activity by fumigant and contact actions against adult females of the two-spotted spider mite, Tetranychus urticae Koch. The monoterpenes exhibited varying degrees of acaricidal potency using contact toxicity test after 24 and 48 h of treatment, where the LC 50 values were <160 and 45 mg/L, respectively. In fumigation test, of these six monoterpenes, pulegone exhibited the highest toxicity (LC 50 = 3.81 mg/L air), while (-)-citronellal had the lowest fumigant toxicity (LC 50 = 15.20 mg/L air). All compounds had high inhibitory effect on acetylcholinesterase (AChE) and gama amino butyric acid transaminase (GABA-T) activities. Pulegone was the most AChE inhibitor (IC 50 = 8.79 mg/L), while 4-terpineol revealed the lowest inhibitory effect (IC 50 = 32.82 mg/L). However, limonene caused the highest inhibition of GABA-T (IC 50 = 11.37 mg/L). The molecular docking studies revealed that the compounds displayed different binding interactions with the amino acid residues at the catalytic sites of AChE and GABA-T enzymes. Noncovalent interactions especially van der Waals, hydrogen bonding as well as hydrophobic was found between the compounds and the enzymes. A significant relationship was found between the docking score and the biological activity of monoterpenes compared to the standard acaricide pyridaben. In silico ADMET properties were also performed and displayed potential for the development of good acaricidal candidates.
... Moreover, there exist a large variety of plants which emit several kinds of odors potentially able to act on animals' including humans' health [44]. For instance, several ones emit toxic compounds [45,46] while other ones, as jasmine [47] as well as valerian and passiflora [33] are known to have a calming effect. An important point must be underlined on the basis of the works made by Moss and co-authors [4] on one hand, and those made by Bradley and co-authors [37] as well as us on the other hand. ...
... These odorants have been previously associated with anti-stresslike effects in rodents. WHI and JAS are thought to produce anxiolytic and analgesic effects through actions on the gamma-aminobutyric acid (GABA) system (Hossain et al., 2002(Hossain et al., , 2004. T2H attenuates stress induced by electrical foot shock, TMT odor (Nikaido et al., 2011), and the forced swim test (Kim et al., 2005;Watanabe et al., 2011). ...
Article
Perinatal exposure to bisphenol A (BPA) causes several alterations in brain function and behavior. In previous studies, we showed that prenatal treatment with low-level BPA impaired gender-specific behavior, enhanced depression-like behavior, and augmented behavioral responses to predator odor in rats. On this premise, we hypothesized that BPA-treated rats were more susceptible to predator odor stress. To test the potential neural mechanism underlying this effect, we conducted an electrophysiological study of neurons in the medial amygdala—a regional component of the olfactory pathway with high estrogen and androgen receptor expression, and thus a potential target of BPA—in rats exposed to BPA. Extracellular recordings were obtained during the presentation of 3 plant odors and 3 predator odorants. Odor-responsive neurons in BPA-exposed rats showed greater activity in response to fox odor than did those in control rats. This finding complements the results of our previous behavioral study in which BPA-exposed rats exhibited enhanced avoidance behavior in response to fox odor. Given the close relationship between olfactory signaling and the stress response system, we suspect that BPA modifies the olfactory pathway at the level of the medial amygdala and thus modulates the corresponding stress response.
... Furthermore, MJ selectively kills cancer cells without causing toxicity to normal cells [Fingrut and Flescher, 2002;Cesari et al., 2014]. Although MJ is widely used to treat depression, nervousness, and improve memory in aromatherapy, the finding that MJ demonstrated sedative effect and enhanced GABA currents [Hossain et al., 2004] provided the first experimental evidences supporting a mechanistic basis for its therapeutic benefits in neuropsychiatric disorders. Moreover, MJ demonstrated adaptogenic, antiamnesic, and antipsychotic activities in rodents Umukoro et al., 2016;Annafi et al., 2017] and exhibited antidepressant-like activity in mice subjected to acute stress models of forced swimming (FST) and tail suspension (TST) tests. ...
Article
The effects of methyl jasmonate (MJ; 5, 10, 20 mg/kg, i.p), a natural product widely used for the relief of stress, depression, and exhaustion on unpredictable chronic mild stress (UCMS)-induced depression-like behaviors in mice was assessed and compared to those of imipramine (IMP; 10 mg/kg, i.p). MJ and IMP were given 30 min before exposure to UCMS with the procedure repeated daily for 2 weeks; 24 h after the stress session, the tail suspension test (TST) and sucrose preference test were assessed. MJ decreased immobility time in the TST and reversed impaired intake of sucrose relative to the stressed control suggesting antidepressant-like activity. MJ also reduced UCMS-induced increases in corticosterone and MDA (malondialdehyde) levels and attenuated UCMS-induced decreases in GSH and TNF-α levels and SOD activity. These findings suggest that MJ attenuated UCMS-induced depressive-like behaviors through decreased levels of corticosterone and decreasing oxidative stress and neuroinflammation in mouse brain.Drug Dev Res, 2017.
... However, the role of MJ in neuropsychiatric disorders was envisaged based on the studies of Hossain et al. [10], which revealed that MJ enhanced GABA currents and demonstrated sedative effect when given through inhalation in rodents. Also, we have reported in our previous studies that MJ has anti-nociceptive [11], anti-aggressive [12], anti-amnesic [13] and adaptogenic or anti-stress [14] activities in validated animal models. ...
Article
Purpose: The efficacy of current antidepressant drugs has been compromised by adverse effects, low remission and delay onset of action necessitating the search for alternative agents. Methyl jasmonate (MJ), a bioactive compound isolated from Jasminum grandiflorum has been shown to demonstrate antidepressant activity but its mechanism of action remains unknown. Thus, the role of monoaminergic systems in the antidepression-like activity of MJ was investigated in this study. Materials and methods: Mice were given i.p. injection of MJ (5, 10 and 20mg/kg), imipramine (10mg/kg) and vehicle (10mL/kg) 30min before the forced swim test (FST) and tail suspension test (TST) were carried out. The involvement of monoaminergic systems in the anti-depressant-like effect of MJ (20mg/kg) was evaluated using p-chlorophenylalanine (pCPA), metergoline, yohimbine, prazosin, sulpiride and haloperidol in the TST. Results: MJ significantly decrease the duration of immobility in the FST and TST relative to control suggesting antidepressant-like property. However, pretreatment with yohimbine (1mg/kg, i.p., an α2-adrenergic receptor antagonist) or prazosin (62.5μg/kg, i.p., an α1-adrenoceptor antagonist) attenuated the antidepressant-like activity of MJ. Also, pCPA; an inhibitor of serotonin biosynthesis (100mg/kg, i.p) or metergoline (4mg/kg, i.p., 5-HT2 receptor antagonist) reversed the anti-immobility effect of MJ. Sulpiride (50mg/kg, i.p., a D2 receptor antagonist) or haloperidol (0.2mg/kg, i.p., a dopamine receptor antagonist) reversed the anti-immobility effect of MJ. Conclusion: The results of this study suggest that serotonergic, noradrenergic and dopaminergic systems may play a role in the antidepressant-like activity of MJ.
... MJ is well known as a hormone that help plants to adapt to external stressors through the formation of defensive chemical substances that protect plants against aversive conditions (Bowles 1990;Cesari et al. 2014). Previous preclinical studies have revealed that MJ has sedative effect and potentiated GABA-mediated inhibitory neurotransmission, which suggest its potential usefulness in neuropsychiatric disorders (Hossain et al. 2004). In addition, we have earlier shown that intraperitoneal injection of MJ produced antiaggressive and memoryenhancing effects in experimental animals (Umukoro et al. 2012;Eduviere et al. 2015) suggesting potential benefits in the alleviation of some of the symptoms of psychosis. ...
Article
Full-text available
Psychosis is a chronic neuropsychiatric disorder that affects millions of individuals worldwide and impairs the quality of life and productivity of the patients. The clinical efficacy of antipsychotic drugs has been compromised by adverse effects, relapse, and therapeutic failures, thus necessitating search for alternative agents. Methyl jasmonate (MJ) is a bioactive compound reported to have beneficial effects in various neurological disorders. This study was undertaken to investigate the antipsychotic-like effects of MJ in mice. Male Swiss mice were pretreated intraperitoneally with MJ (25-100 mg/kg) or vehicle (10 mL/kg) 60 min prior to bromocriptine (5 mg/kg) or acute injection of ketamine (10 mg/kg). Thereafter, each mouse was observed for stereotype behaviors for 2 min at 10, 15, 20, 30, and 45 min post-bromocriptine injection. Another set of mice received MJ (25-100 mg/kg) or vehicle (10 mL/kg) 60 min after chronic ketamine injection (20 mg/kg, i.p) once daily for 14 consecutive days. Afterwards, locomotor activity and memory function in this sequence were evaluated using open field and Y-maze tests. The levels of malondialdehyde (MDA) and glutathione (GSH) and activity of catalase and superoxide dismutase (SOD) in the brain were determined. MJ significantly inhibited stereotypy behavior induced by bromocriptine or acute ketamine injection, which suggest antipsychotic-like activity. It also attenuated hyper-locomotion and memory deficits induced by chronic injection of ketamine in mice. The increased oxidative stress as shown by the altered brain levels of MDA, GSH, and activity of antioxidant enzymes induced by chronic injection of ketamine was reduced by MJ. Taken together, these findings suggest that MJ demonstrated antipsychotic-like property via mechanism related to its antioxidant property and interference with dopaminergic neurotransmission.
... Moreover, MJ has also gained international recognition as a plant hormone, which has been shown in various studies to aid adaptation of plants to external stressors through the formation of proteinase inhibitor proteins; array of defensive chemical substances that protect plants against aversive conditions [2,3]. However, the findings from previous studies showing that MJ exhibited sedative effect and enhanced inhibitory neurotransmission mediated by GABAergic system, raised the possibility of its potential usefulness in neuropsychiatric disorders [4]. Moreover, our previous studies revealed that intraperitoneal injection of MJ demonstrated antidepressant, anti-aggressive and anti-nociceptive activities in mice [5][6][7]. ...
Article
Full-text available
This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p < 0.05). Increased brain oxidative stress and nitric oxide levels in LPS-treated mice were significantly decreased by MJ. It offers protection against LPS-induced neuronal degeneration of the prefrontal cortex and CA1 of the hippocampus, suggesting neuroprotective effect. Taken together, these findings showed that MJ offers protection against LPS-induced memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.
... Some of the sage (Salvia) species evoke anticonvulsant, antiepileptic, and antidepressant effects, whereas Sideritis species are consumed in Mediterranean countries because of their analgesic and anticonvulsant health benefits [10,11]. Animal studies demonstrated that some natural tea components prolong the sleeping time through the potentiation of GABA A R response [12]. Further, L-theanine, which is present in green tea leaves, displays anxiolytic activity in humans [13]. ...
Article
Full-text available
Potentiation of γ-amino butyric acid (GABA)-induced GABAA receptor (GABAAR) activation is a common pathway to achieve sedative, sleep-enhancing, anxiolytic, and antidepressant effects. Presently, a three-component test system was established for the identification of novel GABAAR modulating food plants. In the first step, potentiation of GABA-induced response of the GABAAR was analysed by two-electrode voltage clamp (TEVC) for activity on human α1β2-GABAAR expressed in Xenopus laevis oocytes. Positively tested food plants were then subjected to quantification of GABA content by high-performance liquid chromatography with fluorescence detection (HPLC–FLD) to exclude test foods, which evoke a TEVC-response by endogenous GABA. In the third step, specificity of GABAA-modulating activity was assessed by TEVC analysis of Xenopus laevis oocytes expressing the homologous glycine receptor (GlyR). The three-component test was then applied to screen 10 aqueous extracts of food plants for their GABAAR activity. Thus, hop cones (Humulus lupulus) and Sideritis sipylea were identified as the most potent specific GABAAR modulators eliciting significant potentiation of the current by 182 ± 27 and 172 ± 19 %, respectively, at the lowest concentration of 0.5 μg/mL. The extracts can now be further evaluated by in vivo studies and by structural evaluation of the active components.
... Thus, reactions carried out by microalgae are similar to other ones typical for micro-organisms. All results of biotransformations by microalgae are collected in Table 2. (Hossain et al. 2004). ...
Article
Monoterpenes are widely used in food technology, cosmetic and pharmaceutical industries and as compounds of agricultural importance. It is known that compounds comprising this class can be transformed by a variety of organisms, namely by: bacteria, fungi, yeasts, plants or isolated enzymes. Biotransformations as one of the most important tools of green chemistry, allow obtaining new products by using whole cells of microorganisms or isolated enzymes in mild reaction conditions. Therefore biotransformations of monoterpenes, by different type of reaction such as: epoxidation, oxidation and stereoselective hydroxylation, resulted in the production of so desired, enantiomerically defined compounds that can be advised as natural seem to be interesting. Bearing in mind that such processes are carried out also by easy to maintain, photoautotrophic microorganisms cultivated at large scale, this paper is focused on biotransformations of acyclic, monocyclic and bicyclic monoterpenes by freshwater or haliphylic cyanobacteria and microalgae on the way of mainly stereoselective hydroxylation. Moreover, aspects of potential industrial application of obtained products in medicine, perfume, cosmetics and food industry are discussed.This article is protected by copyright. All rights reserved.
Article
This study evaluates the pharmacological potential of cis-jasmone (CJ) in adult zebrafish (Danio rerio; aZF). Initially, aZF (n = 6/group) were pretreated (20 µL; p. o.) with CJ (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.5% Tween 80). The animals were submitted to acute toxicity and locomotion tests, pentylenetetrazole-induced seizure, carrageenan-induced abdominal edema, and cinnamaldehyde-, capsaicin-, menthol-, glutamate-, and acid saline-induced orofacial nociception. The possible mechanisms of anticonvulsant, anxiolytic, and antinociceptive action were evaluated. The involvement of central afferent fibers sensitive to cinnamaldehyde and capsaicin and the effect of CJ on the relative gene expression of TRPA1 and TRPV1 in the brain of aZF were also analyzed, in addition to the study of molecular docking between CJ and TRPA1, TRPV1 channels, and GABAA receptors. CJ did not alter the locomotor behavior and showed pharmacological potential in all tested models with no toxicity. The anticonvulsant effect of CJ was prevented by flumazenil (GABAergic antagonist). The anxiolytic-like effect of CJ was prevented by flumazenil and serotonergic antagonists. The antinociceptive effect was prevented by TRPA1 and TRPV1 antagonists. Chemical ablation with capsaicin and cinnamaldehyde prevented the orofacial antinociceptive effect of CJ. Molecular docking studies indicate that CJ interacted with TRPA1, TRPV1, and GABAA receptors. CJ inhibited the relative gene expression of TRPA1 and TRPV1. CJ has pharmacological potential for the treatment of seizures, anxiety, inflammation, and acute orofacial nociception. These effects are obtained by modulating the GABAergic and serotonergic systems, as well as the TRPs and ASIC channels.
Article
Full-text available
For immobile plants, the main means of protection against adverse environmental factors is the biosynthesis of various secondary (specialized) metabolites. The extreme diversity and high biological activity of these metabolites determine the researchers’ interest in plants as a source of therapeutic agents. Oxylipins, oxygenated derivatives of fatty acids, are particularly promising in this regard. Plant oxylipins, which are characterized by a diversity of chemical structures, can exert protective and therapeutic properties in animal cells. While the therapeutic potential of some classes of plant oxylipins, such as jasmonates and acetylenic oxylipins, has been analyzed thoroughly, other oxylipins are barely studied in this regard. Here, we present a comprehensive overview of the therapeutic potential of all major classes of plant oxylipins, including derivatives of acetylenic fatty acids, jasmonates, six- and nine-carbon aldehydes, oxy-, epoxy-, and hydroxy-derivatives of fatty acids, as well as spontaneously formed phytoprostanes and phytofurans. The presented analysis will provide an impetus for further research investigating the beneficial properties of these secondary metabolites and bringing them closer to practical applications.
Chapter
Herbal oils, also known as oil extracts, are obtained from herbs and plant sources; they possess therapeutic benefits. It is well-known that synergistically a combination of nutrients, bioactive components, antioxidants and biostimulants proved to be more effective. These therapeutic compounds can be obtained from herbs using gentle nondestructive oil extraction techniques. There are different extraction techniques like solvent extraction, hydro-distillation, and steam are used for extracting oils. The composition of herbal oils varies depending upon these extraction techniques. Their chemistry is different from each other and the amount of herbal oil also varies from plant to plant and species to species within the same plant. In this chapter, different herbal oils extracted from various plants (citrus, rosemary, oregano, etc.) and their significant therapeutic benefits are reviewed. According to studies, 30% of herbal oils are being used to treat rheumatoid arthritis and joint diseases where as 10% is being used for arthralgia as antiinflammatory. Moreover, 20% herbal oil is used for the treatment for various skin diseases where as 10% used orally to treat and improve the neuro-functioning as neuro-tonics. Gastrointestinal disorders also treated with the use of herbal oils.
Research
Full-text available
The study was planned with a rationale to investigate the anxiolytic potential of Cardamom oil (50mg/kg) against experimentally induced anxiety model such as Light and Dark Box transition test in albino rats. The control, test (Cardamom oil, 50mg/kg) and standard (buspirone 1 mg/kg) treated rats are placed in the center of light and dark box apparatus one by one with head facing towards dark box and the preference of animals towards dark and light box are noted for a period of 5 minutes. The behavioral parameters that were recorded are time spent in light box, time spent in dark box and number of entries in light and dark box. The cardamom oil (50mg/kg) showed significant anxiolytic activity in albino rats by increasing in time spent by the animals in light box (197.33±52.78 sec) when compared to the control rats (19± 9.262 sec) in the light and dark box apparatus. Hence it can be concluded that cardamom oil (50mg/kg) exhibits anxiolytic activity. Phytochemical screening of cardamom oil reveals the presence of steroid, oil, fats and carbohydrates. Hence the above mentioned active constituents of cardamom oil may be involved in its anxiolytic potential.
Article
Background: Psychosocial distress, depression, or anxiety can occur in up to 50% of women after a breast cancer diagnosis and mastectomy. The purpose of this study was to assess the potential benefit of lavender oil as a perioperative adjunct to improve anxiety, depression, pain, and sleep in women undergoing microvascular breast reconstruction. Methods: This was a prospective, single-blinded, randomized, controlled trial of 49 patients undergoing microvascular breast reconstruction. Patients were randomized to receive lavender oil or placebo (coconut oil) throughout their hospitalization. The effect of lavender oil on perioperative stress, anxiety, depression, sleep, and pain was measured using the hospital anxiety and depression scale, Richards-Campbell Sleep Questionnaire, and the visual analogue scale. Results: Twenty-seven patients were assigned to the lavender group and 22 patients were assigned to the control group. No significant differences were seen in the perioperative setting between the groups with regard to anxiety (p = 0.82), depression (p = 0.21), sleep (p = 0.86), or pain (p = 0.30) scores. No adverse events (i.e., allergic reaction) were captured, and no significant differences in surgery-related complications were observed. When evaluating the entire cohort, postoperative anxiety scores were significantly lower than preoperative scores (p < 0.001), while depression scores were significantly higher postoperatively as compared with preoperatively (p = 0.005). Conclusion: In the setting of microvascular breast reconstruction, lavender oil and aromatherapy had no significant adverse events or complications; however, there were no measurable advantages pertaining to metrics of depression, anxiety, sleep, or pain as compared with the control group.
Article
Full-text available
Diseases transmitted by vectors have been plaguing man since time immemorial causing millions of deaths annually. The highest occurrence reportedly occurs in tropical and subtropical areas where malaria, the commonest vector-borne disease, is highest. The management of vector-borne diseases has been basically by controlling their vectors using synthetic insecticides: the pyrethroids, organophosphates, organochlorines: carbamates. Reports have shown that these insecticides pollute the environment, result in bio-magnification and affect non-target organisms mostly man thereby raising health concern. Also, there is development of insecticide resistance in the disease vectors, which may hamper the effective use of the insecticides. These negative effects associated with the use of synthetic insecticides emphasize the need for alternative method of control. The control of disease vectors with the use of herbal-based products that have insecticidal properties is promising as it is safe to non-target organisms, eco-friendly, bio-degradable, less expensive and the development of resistance in the vectors is more or less absent. The insecticidal activity of plant herbs is attributed to the presence of complex mixture of bio-active compounds, which act as anti-feedants, oviposition deterrents, repellents, attractants, etc. Using relevant literatures, this paper discussed disease vectors, method of transmission of vector-borne diseases, the need for alternative method of disease vector control and the most common plants employed in the control of disease vectors including their families, products, bio-active compounds, their activity and mode of action. Use of plant herbs and their products can therefore, serve as alternative method for vector control programme.
Chapter
In the current era, the consumption and utilization of fruits and vegetables is gaining significant importance as an effective tool to maintain human health. In this context, phytochemicals and bioactive molecules from fruits and vegetables are also becoming chemo-preventive agent against various maladies. Among these, persimmon (Diospyros kaki L.) fruit belongs to the family Ebenaceae and is used as a medicinal plant since many years to cure different human disorders, such as cancer, diabetes, cardiovascular, obesity, and so on. Persimmon fruit has significant protective effects against various types of human syndromes. Their effectual role is mainly owing to the presence of significant amounts of antioxidants such as phenolic acids, flavonoids, anthocyanins, vitamins, and other phenolic 268compounds. These bioactive compounds have the potential to scavenge and neutralize the free radical chain reaction before causing any deleterious effects to the body. Research-based evidences strongly assert that application of persimmon ingredients provides protection against hyper-lipidemia and hyperglycemia. Conclusively, persimmon and its components have potential as one of the effective modules in diet-based therapy.
Article
Monoterpene alcohols (MTAs) are characteristic flavour-imparting compounds in sweet potato shochu (Japanese distilled spirit) that are liberated following hydrolysis by specific enzymes during fermentation. In the present study, we evaluated the effect of an exogenously added diglycoside-specific β-glycosidase (β-primeverosidase) on aroma formation during shochu brewing using various sweet potato species to address whether MTAs are predominantly present as diglycosidic precursors in raw materials. The results showed that the amount of MTAs produced from enzyme-treated mash was dramatically increased by 2- to 9-fold compared with untreated controls, and the increase varied with sweet potato species. In addition, levels of methyl salicylate, 1-octene-3-ol and ethyl benzoate were also elevated by enzyme treatment. These results indicate that a large amount of MTAs and other volatile aroma compounds are stored in the form of disaccharide β-glycosides such as β-primeverosides in sweet potato. This enzyme may therefore be useful for controlling aroma formation during shochu manufacturing, and may ultimately contribute to diversifying shochu quality.
Article
Background: Systolic blood pressure of rats decreases significantly following exposure to the odor generated from the Maillard reaction of protein digests with xylose. In the current study, we identified active odorants that affect blood pressure and demonstrated the mechanism of action. Results: Among the four potent odorants that contribute most to the odor of the Maillard reaction sample, 2,5-dimethyl-4-hydroxy-3(2H)-furanone and 5-methylpyrazine-2-methanol decreased systolic blood pressure significantly. The earliest decrease in blood pressure was observed 5 min after exposure to 2,5-dimethyl-4-hydroxy-3(2H)-furanone. Application of zinc sulfate to the nasal cavity eliminated the effect. Furthermore, gastric vagal (parasympathetic) nerve activity was elevated and renal sympathetic nerve activity was lowered after exposure to 2,5-dimethyl-4-hydroxy-3(2H)-furanone. Conclusion: It is indicated that 2,5-dimethyl-4-hydroxy-3(2H)-furanone affects blood pressure through the olfactory system, and the mechanism for the effect of 2,5-dimethyl-4-hydroxy-3(2H)-furanone on blood pressure involves the autonomic nervous system.
Article
Sideritis plants and their extracts have been used in traditional medicine as sedatives, anxiolytics and anticonvulsant agents. Pinenes are the most prevalent of the volatile aroma components in Siderites extracts and the pinene metabolites myrtenol and verbenol have been identified as the most potent positive allosteric modulators of synaptic GABAA receptors composed of α1β2 and α1β2γ2 subunits. In view of their therapeutic spectrum, we wondered whether these two terpenoids would also augment tonic GABA currents mediated by extrasynaptic GABAA receptors containing the δ subunit. When we expressed α4β2δ receptors in HEK293 cells, we found that co-application of myrtenol or verbenol enhanced whole-cell current responses to GABA by up to 100%. Consistent with their effects on heterologous α1β2γ2 receptors, we found that myrtenol and verbenol, when co-applied with GABA via local perfusion, increased the amplitude and area of miniature inhibitory postsynaptic potentials (mIPSCs) recorded in whole-cell voltage-clamp recordings from granule cells in the dentate gyrus of mouse hippocampal brain slices. In addition, co-application of terpenoids with GABA was also able to enhance tonic GABA current, measured from the change in baseline current and current noise, compared to GABA perfusion alone. Our results suggest that myrtenol and verbenol act as positive allosteric modulators at synaptic and extrasynaptic GABAA receptors, thereby augmenting phasic and tonic GABAergic inhibition. Thus, our study reveals an important pharmacological and therapeutic target of bicyclic monoterpenoids.
Article
Full-text available
Methyl jasmonate (MJ) is an anti-stress hormone released by plants in response to external stressors and aids adaptation to stress. In this study, we evaluated the anti-stress activity of MJ using the forced swim endurance test (FSET) and anoxic tolerance test in mice. Male Swiss mice were given MJ (25–100 mg/kg, i.p) 30 min before the FSET and anoxic test were carried out. The first occurrence of immobility, duration of immobility, time spent in active swimming, and latency to exhaustion were assessed in the FSET. The onset to anoxic convulsion was measured in the anoxic tolerance test. MJ significantly (p < 0.05) delayed the first occurrence of immobility and shortened the period of immobility, which indicates anti-stress property. MJ also increased the time spent in active swimming and prolonged the latency to exhaustion, which further suggests anti-stress activity. In addition, it also exhibited anti-stress property as evidenced by prolonged latency to first appearance of anoxic convulsions. The results of this study suggest that MJ demonstrated anti-stress activity and may be useful as an energizer in times of body weakness or exhaustion. Although more studies are necessary before concluding on how MJ exerts its anti-stress activity, the present data suggest an action similar to adaptogens in boosting energy and resilience in the face of stress.
Article
Current research effort focuses on the development of safer natural compounds with multipronged mechanisms of action that could be used to ameliorate memory deficits in patients with Alzheimer's disease, as cure for the disease still remains elusive. In this study, we evaluated the effect of methyl jasmonate (MJ), a naturally occurring bioactive compound on memory, acetylcholinesterase activity and biomarkers of oxidative stress in mice. Male Swiss mice were treated with intraperitoneal injection of MJ (10-40 mg/kg) alone or in combination with scopolamine (3 mg/kg) once daily for 7 days. Thirty minutes after the last treatment, memory functions were assessed using Y-maze and object recognition tests. Thereafter, acetylcholinesterase activity and levels of biomarkers of oxidative stress were assessed in mice brains using standard biochemical procedures. MJ significantly enhanced memory performance and reversed scopolamine-induced cognitive impairment in mice. MJ demonstrated significant inhibition of acetylcholinesterase activity suggesting increased cholinergic neurotransmission. It further decreased malondialdehyde concentrations in mouse brain indicating antioxidant activity. Moreover, MJ significantly increased glutathione levels and activity of antioxidant enzymes (catalase and superoxide dismutase) in mice brains. The increased oxidative stress; evidenced by elevated levels of malondialdehyde and decreased antioxidant defense systems in scopolamine-treated mice was attenuated by MJ. The results of this study suggest that MJ may be useful in conditions associated with memory dysfunctions or age-related cognitive decline. The positive effect of MJ on memory may be related to inhibition of oxidative stress and enhancement of cholinergic neurotransmission through inhibition of acetylcholinesterase activity. Copyright © 2015. Published by Elsevier Inc.
Book
The second edition of this book is virtually a new book. It is the only comprehensive text on the safety of essential oils, the first review of essential oil/drug interactions, and it provides detailed essential oil constituent data not found in any other text. Much of the existing text has been re-written, and 80% of the text is completely new. There are 400 comprehensive essential oil profiles and almost 4000 references. There are new chapters on the respiratory system, the cardiovascular system, the urinary system, the digestive system and the nervous system. For each essential oil there is a full breakdown of constituents, and a clear categorization of hazards and risks, with recommended maximum doses and concentrations. There are also 206 Constituent Profiles. There is considerable discussion of carcinogens, the human relevance of some of the animal data, the validity of treating an essential oil as if it was a single chemical, and the arbitrary nature of uncertainty factors. There is a critique of current regulations.
Article
Full-text available
The present study was conducted to further explore plant-derived essential oils that possess an anticonflict effect using the Geller type conflict test in ICR mice. The benzodiazepine anxiolytic diazepam increased the response (lever pressing) rate during the alarm period (i.e., an anticonflict effect), but the 5-HT1A partial agonist buspirone did not. Oils of juniper, cypress, geranium and jasmine did not produce any effect in this test. Frankincense oil decreased the response rate during the safe period at 1600 mg/kg, but did not exhibit any effect on the response rate during the alarm period. In contrast, lavender oil increased the response rate during the alarm period in a dose-dependent manner in the same manner as diazepam. These results indicate that not only rose oil but also lavender oil possess an anticonflict effect in mice.
Article
Full-text available
Caffeine has been imbibed since ancient times in tea and coffee, and more recently in colas. Caffeine owes its psychostimulant action to a blockade of adenosine A(2A) receptors, but little is known about its intracellular mechanism of action. Here we show that the stimulatory effect of caffeine on motor activity in mice was greatly reduced following genetic deletion of DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000). Results virtually identical to those seen with caffeine were obtained with the selective A(2A) antagonist SCH 58261. The depressant effect of the A(2A) receptor agonist, CGS 21680, on motor activity was also greatly attenuated in DARPP-32 knockout mice. In support of a role for DARPP-32 in the action of caffeine, we found that, in striata of intact mice, caffeine increased the state of phosphorylation of DARPP-32 at Thr 75. Caffeine increased Thr 75 phosphorylation through inhibition of PP-2A-catalysed dephosphorylation, rather than through stimulation of cyclin-dependent kinase 5 (Cdk5)-catalysed phosphorylation, of this residue. Together, these studies demonstrate the involvement of DARPP-32 and its phosphorylation/dephosphorylation in the stimulant action of caffeine.
Article
We synthesized nine kinds of diglycosides and a monoglycoside of 2-phenylethanol to investigate the substrate specificity of the purified beta -primeverosidase from fresh leaves of a tea cultivar (Camellia sinensis var. sinensis cv. Yabukita) in comparison with the apparent substrate specificity of the crude enzyme extract from tea leaves. The crude enzyme extract mainly showed beta -primeverosidase activity, although monoglycosidases activity was present to some extent. The purified beta -primeverosidase showed very narrow substrate specificity with respect to the glycon moiety, and especially prominent specificity for the beta -primeverosyl (6-O-beta -D-xylopyranosyl-beta -D-glueopyranosyl) moiety. The enzymes hydrolyzed naturally occurring diglycosides such as beta -primeveroside, beta -vicianoside, beta -acuminoside, beta -gentiobioside and 6-O-alpha -L-arabinofuranosyl-beta -D-glucopyranoside, but were unable to hydrolyze synthetic unnatural diglycosides. The purified enzyme was inactive toward 2-phenylethyl beta -D-glucopyranoside. The enzyme hydrolyzed each of the diglycosides into the corresponding disaccharide and 2-phenylethanol. These results indicate the beta -primeverosidase, a diglycosidase, to be a key enzyme involved in aroma formation during the tea manufacturing process.
Article
The equivalent mixture of cis-3-hexenol and trans-2-hexenal (hexenol/hexenal), 'green odor', is known to have a healing effect on the psychological damage caused by stress. Behavioral studies in humans and monkeys have revealed that hexenol/hexenal prevents the prolongation of reaction time caused by fatigue. In the present study, we investigated which brain regions are activated by the odor of hexenol/hexenal using positron emission tomography with alert monkeys. Regional cerebral blood flow (rCBF) in the prepyriform area (the primary olfactory cortex) was commonly increased by the passive application of odor: acetic acid, isoamylacetate or hexenol/hexenal. We observed rCBF increases in the orbitofrontal cortex (the secondary olfactory cortex) by these olfactory stimuli in two of three monkeys, and found no predominance of laterality of the activated hemisphere. Furthermore, rCBF increase in the cerebellum was observed in two of three monkeys, and the odor of acetic acid increased rCBF in the substantia innominata in all monkeys. In addition to these olfactory related regions, the anterior cingulate gyrus was activated by the odor of hexenol/hexenal. These findings suggest that the increase of rCBF in the anterior cingulate gyrus by the odor of hexenol/hexenal may contribute the healing effects of this mixture observed in the monkey.
Article
1. The effects of the volatile anaesthetics enflurane, halothane and isoflurane on gamma-aminobutyric acid (GABA)A receptor-mediated chloride currents were studied in cultured rat hippocampal neurones. Transient current responses were obtained by brief pressure application of GABA to the cell body of neurones under voltage clamp. 2. All three anaesthetics increased the peak amplitude and duration of current 2. All three anaesthetics increased the peak amplitude and duration of current responses to brief applications of GABA. These effects were fully reversible, and did not involve alterations in the reversal potential for GABA responses. 3. The experimental concentrations of anaesthetics were measured directly using gas chromatography. The enhancement of GABA currents increased with increasing anaesthetic concentration. Clinically effective concentrations of anaesthetics (between 1 and 1.5 times MAC (minimum alveolar concentration) produced significant enhancement of GABA currents. 4. These results demonstrate that the changes in the time course of synaptic inhibition reported in the presence of the volatile anaesthetics are likely to result from modification of the function of postsynaptic GABAA receptor-channel complexes. These findings also support the hypothesis that GABAA receptor complexes serve as common molecular target sites for a variety of structurally diverse anaesthetic molecules.
Article
Since binding of an agonist to an ionotropic neurotransmitter receptor causes not only channel opening, but also desensitization of the receptor, inhibition of the receptor by the antagonist sometimes becomes very complicated. The transient state kinetics of ligand association and dissociation, and desensitization of the receptor were considered on the basis of the minimal model proposed by Hess' group, and the following possibilities were proposed. 1) When an agonist is simultaneously applied to the receptor with an antagonist whose affinity to the receptor is extremely strong and different from that of the agonist, it is usually impossible to estimate the real inhibition constant exactly from the responses because desensitization of the receptor proceeds before the equilibrium of the ligand binding. Simultaneous addition of the antagonist with strong affinity to the receptor may apparently accelerate inactivation (desensitization) of the receptor. The association rate constant of the antagonist can be estimated by analyses of the rate of the inactivation in the presence and the absence of the antagonist. 2) A preincubated antagonist with a slow dissociation rate constant, i.e., a very effective inhibitor, may cause apparent noncompetitive inhibition of the receptor, since the receptor is desensitized by an agonist as soon as the antagonist dissociates from the receptor and the dissociation of the antagonist from the receptor becomes the rate-determining step. A nicotinic acetylcholine receptor (nAChR) was expressed in Xenopus oocytes by injecting mRNA prepared from Electrophorus electricus electroplax and used for the experiments on inhibition by an antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Animal lines selected for differences in drug sensitivity can be used to help determine the molecular basis of drug action. Long-sleep (LS) and short-sleep (SS) mice differ markedly in their genetic sensitivity to ethanol. To investigate the molecular basis for this difference, mRNA from brains of LS and SS mice was expressed in Xenopus oocytes and the ethanol sensitivity of gamma-aminobutyric acid A (GABAA)- and N-methyl D-aspartate (NMDA)-activated ion channels was tested. Ethanol facilitated GABA responses in oocytes injected with mRNA from LS mice but antagonized responses in oocytes injected with mRNA from SS animals. Ethanol inhibited NMDA responses equally in the two lines. Thus, genes coding for the GABAA receptor or associated proteins may be critical determinants of individual differences in ethanol sensitivity.
Article
The objective of the present study was to clarify the relation between drug transport to the cerebrospinal fluid (CSF) from the nasal cavity and the lipophilicity of the drug using hydrophilic sulfonamides as model drugs. The nasal cavity of the rat was perfused in a single pass system and the concentrations of sulfonamides in plasma and CSF were measured. The drug concentrations in CSF and plasma after nasal perfusion were compared with those after intravenous (i.v.) administration. The drug concentrations in the CSF were remarkably high after nasal perfusion in comparison with those after i.v. administration, though the time course of the plasma concentration was not much different from that after i.v. administration. These results suggested the existence of a direct transport pathway of the sulfonamides from the nose to the CSF. In addition, the drug concentrations in the CSF increased with increasing the lipophilicity of the drugs (the partition coefficient (Pc) of the drugs between isoamyl alcohol and pH 7.4 phosphate buffer). A significant correlation was observed between the drug concentrations in CSF and Pc. In conclusion, the direct transport pathway of the sulfonamides from the nose to the CSF was confirmed and, with regard to drugs with comparatively low lipophilicity, the degree of the transport depended on its Pc.
1. Effects of a new stressful manipulation, forced shaking stress at low temperature (4 degrees C) (FSLT stress), on sleeping induced by pentobarbital were investigated 70 min following its application. 2. Repeated application (7 times) decreased the duration of sleep induced by pentobarbital-Na (45 mg/kg, i.p.) in mice without affecting that induced by ketamine-HCl and chloral hydrate. This effect of FSLT stress disappeared 3 days after termination of application. 3. The latency of nociceptive response in hot-plate test increased in a naloxone-sensitive manner by single and repeated FSLT stress when tested immediately (2 min) after but not 70 min after the last stress application. 4. Diazepam (0.3 mg/kg, i.p.) significantly prolonged the duration of sleep induced by pentobarbital (45 mg/kg, i.p.) in stressed animals without changing that in unstressed animals. The effect of diazepam was blocked by Ro 15-1788 (10 mg/kg, i.p.), a specific benzodiazepine receptor antagonist. 5. Repeated FSLT stress thus appears to decrease pentobarbital sleep by inducing functional changes in the central nervous system and the GABAergic system may partially participate in FSLT stress-induced decrease in pentobarbital sleep.
Article
General anaesthetics are much more selective than is usually appreciated and may act by binding to only a small number of targets in the central nervous system. At surgical concentrations their principal effects are on ligand-gated (rather than voltage-gated) ion channels, with potentiation of postsynaptic inhibitory channel activity best fitting the pharmacological profile observed in general anaesthesia. Although the role of second messengers remains uncertain, it is now clear that anaesthetics act directly on proteins rather than on lipids.
Article
To study the effects of lipid hydroperoxide on ionotropic neurotransmitter receptors, gamma-aminobutyric acid (GABA), N-methyl-D-aspartate (NMDA), and non-NMDA receptors (GABARs, NMDARs, and non-NMDARs, respectively) were expressed in Xenopus oocytes that received an injection of mRNA prepared from rat whole brain. Linoleic acid (LA) and its hydroperoxide 13-L-hydroperoxylinoleic acid (LOOH) prepared with soybean lipoxygenase inhibited the response of GABARs in the presence of GABA at high concentrations. The inhibition was stronger when the inhibitors were perfused 1 min before a mixture of GABA and the inhibitors than when they were perfused simultaneously with GABA. On the other hand, only LOOH potentiated the response of GABARs in the presence of GABA at low concentrations, possibly increasing the affinity of GABA to the receptors. Both LA and LOOH accelerated the rate of desensitization of GABARs, but LOOH did not affect their equilibrium between the active and desensitized form of the receptors. They also inhibited the response of NMDARs in a noncompetitive manner but barely inhibited the response of non-NMDARs in the presence of kainate at various concentrations. These results suggest the possibility that production of lipid hydroperoxide modulates the neural transmission in the brain, especially through GABARs.
Article
We found that inhaling chamomile oil vapour decreased restriction stress-induced increases of plasma ACTH level in ovariectomized rat. The plasma ACTH level decreased further when diazepam was administered along with inhaling chamomile oil vapour. Flumazenile blocked the decrease in plasma ACTH level induced by inhaled chamomile oil vapour.
Article
(1) Considerable evidence has accumulated that the molecular target of general anesthetics in the central nervous system is the GABA(A) receptor, the major mediator of inhibitory synaptic transmission. This receptor is actually a family of ligand-gated chloride channel proteins, each a heteropentameric membrane-spanning structure. (2) Regional variation in anesthetic actions on the central nervous system may parallel a corresponding regional variation in pharmacological subtypes of GABA(A) receptors. These result from differential regional expression of approximately 18 subunit genes. (3) Receptors of varying subunit composition show differential sensitivity to GABA, modulatory drugs, and biological regulatory mechanisms. Regional variation in allosteric modulation of GABA(A) receptor binding and function can be reconstituted in certain recombinant receptor subunit combinations expressed in heterologous cells. (5) Differential sensitivity to anesthetics for various GABA(A) receptor subunits also allows the use of the chimeric and site-directed mutagenesis approach in attempting to define domains of the protein which participate in the binding and actions of anesthetics.
Article
To study the effects of perfume and phytoncid on GABAA receptors, ionotropic GABAA receptors were expressed in Xenopus oocytes by injecting mRNAs that had been prepared from rat whole brain. Essential oil, perfume and such phytoncid as leaf alcohol, hinokitiol, pinene, eugenol, citronellol and citronellal potentiated the response in the presence of GABA at low concentrations (10 and 30 microM), possibly because they bound to the potentiation-site in GABAA receptors and increased the affinity of GABA to the receptors. Since it is known that the potentiation of GABAA receptors by benzodiazepine, barbiturate, steroids and anesthetics induces the anxiolytic, anticonvulsant and sedative activity or anesthetic effect, these results suggest the possibility that the intake of perfume or phytoncid through the lungs, the skin or the intestines modulates the neural transmission in the brain through ionotropic GABAA receptors and changes the frame of the human mind, as alcohol or tobacco does.
Article
Steroids influence neuronal function by binding to intracellular receptors that can act as transcription factors and regulate gene expression. In addition, some so-called 'neuroactive steroids' are potent modulators of an array of ligand-gated ion channels and of distinct G-protein coupled receptors via nongenomic mechanisms, and they can influence sleep and memory. This article describes how these neuroactive steroids modulate neurotransmitter receptors and addresses the neuropsychopharmacological potential that arises from the intracellular crosstalk between genomic and nongenomic steroid effects. Neuroactive steroids could also have a role in the response to stress and the treatment of psychiatric disorders, such as depression, and, as they affect a broad spectrum of behavioral functions through their unique molecular properties, they could constitute a yet unexploited class of drugs.
Article
The present study examined the pharmacological actions of four different plant-derived essential oils (rose, ylang-ylang, camomile, orange) in two types of conflict tests using ICR mice. In the Vogel conflict test, in which any drinking behavior of the mice was punished by an electric shock, the benzodiazepine agonist, diazepam (DZ), increased the number of electric shocks the mice received. This number increased after administration of rose oil. In contrast, ylang-ylang, camomile, and orange oil did not produce such an effect in this test. In the Geller conflict test where lever-pressing of mice was reinforced by food pellets and then punished by electric shock, response (lever-pressing) rate during the alarm period was increased as well by the positive control drug, DZ. Similarly, the response rate during the alarm period increased after administration of rose oil. Here as well, ylang-ylang, camomile, and orange oils did not produce an anticonflict effect. In the Vogel conflict test, the anticonflict effect of DZ was reversed by the benzodiazepine antagonist, flumazenil (Ro15-1788) (FL). However, the effect of rose oil in this test was not antagonized by FL. The present study showed that rose oil possesses anticonflict effects, and that the effects are not mediated by the benzodiazepine binding site of the GABA(A) receptor complex. Such pharmacological actions may at least partially account for human behavioral effects attributed to essential oils.
Article
6-O-beta-D-Xylopyranosyl-beta-D-glucopyranosides (beta-primeverosides) of (Z)-3-hexenol and trans-linalool 3,7-oxide were newly isolated from fresh leaves of a tea cultivar (Camellia sinensis var. sinensis cv. Yabukita). In addition, the already identified beta-primeverosides of benzyl alcohol, methyl salicylate, and trans-linalool 3,6-oxide from an oolong tea cultivar were isolated from the Yabukita cultivar. It was confirmed that all aglycones of the linalool oxide glycosides isolated here were of the optically active S-form by chiral GC after enzymatic hydrolysis with glycosidase.
Article
To investigate the kinetics of both the potentiation and desensitization of the response of ionotropic GABAA receptors (GABAA receptors) in the presence of various compounds, we expressed receptors composed of α, and β subunits by injecting cells with the cRNAs synthesized from cloned bovine GABAAA receptor cDNAs and measured the electrical responses of the cells electrophysiologically with or without the compounds. The potentiation of the GABAA receptor-mediated response was quantitatively analyzed using a simple model with the assumption that the receptors have two identical binding sites for GABA molecules with a dissociation constant of K1 and one potentiation site for the compound with a dissociation constant of Kp and that the binding of the compound to the potentiation site only increases the affinity of the GABA binding sites, changing K1 to Klp. The estimated Kp and Klp were dependent on the functional groups and the chain length of the compounds. These results could be satisfactorily analyzed using this simple modeL The potentiation of the GABAA receptor-mediated response by the components of essential oils used for aromatherapy was also examined. These compounds accelerated the decay of the response, possibly due to desensitization of the receptors, which was also analyzed on the basis of the model.
Article
To study the effects of tea components on ionotropic gamma-aminobutyric acid (GABA) receptor response, ionotropic GABA receptors (GABA(A) receptors) were expressed in Xenopus oocytes by injecting cRNAs synthesized from cloned cDNAs of the alpha(1) and beta(1) subunits of the bovine receptors, and their electrical responses were measured by a voltage clamping method. Extracts of green tea, black tea, and oolong tea in an aqueous solution induced the GABA-elicited response, which showed that these teas contain GABA, whereas coffee does not. Caffeine weakly inhibited the response in a competitive manner (K(i) = 15 mM), and (+)-catechin inhibited it in a noncompetitive one (K(i) = 1.7 mM). Especially, two catechin derivatives, (-)-epicatechin gallate and (-)-epigallocatechin gallate, inhibited the response strongly. Alcohols such as leaf alcohol or linalool potentiated the response, possibly because their binding to the potentiation site enhances the GABA-binding affinity to GABA(A) receptors when they bind. Extracts of green tea made with ethyl ether, which must contain lipophilic components of green tea, inhibited the response elicited by GABA, possibly because the amounts of caffeine and catechin derivatives were much larger than fragrant alcohols in such extracts of tea.
Article
Steroids influence neuronal function through binding to cognate intracellular receptors which may act as transcription factors in the regulation of gene expression. In addition, certain so-called neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially distinct 3alpha-reduced metabolites of progesterone and deoxycorticosterone are potent positive allosteric modulators of gamma-aminobutyric acid type A (GABA(A)) receptors. However, also classical steroid hormones such as 17beta-estradiol, testosterone and progesterone are neuroactive steroids because they may act as functional antagonists at the 5-hydroxytryptamine type 3 (5-HT(3)) receptor, a ligand-gated ion channel or distinct glutamate receptors. A structure-activity relationship for the actions of a variety of steroids at the 5-HT(3) receptor was elaborated that differed considerably from that known for GABA(A) receptors. Although a bindings site for steroids at GABA(A) receptors is still a matter of debate, meanwhile there is also evidence that steroids interact allosterically with ligand-gated ion channels at the receptor membrane interface. On the other hand, also 3alpha-reduced neuroactive steroids may regulate gene expression via the progesterone receptor after intracellular oxidation into 5alpha-pregnane steroids. Animal studies showed that progesterone is converted rapidly into GABAergic neuroactive steroids in vivo. Progesterone reduces locomotor activity in a dose-dependent fashion in male Wistar rats. Moreover, progesterone and 3alpha-reduced neuroactive steroids produce a benzodiazepine-like sleep EEG profile in rats and humans. During major depression, there is a disequilibrium of such 3alpha-reduced neuroactive steroids which is corrected by successful treatment with antidepressant drugs. Neuroactive steroids may further be involved in the treatment of depression and anxiety with antidepressants in patients during ethanol withdrawal. Studies in patients with panic disorder suggest that neuroactive steroids may also play a role in modulating human anxiety. Both the genomic and non-genomic effects of steroids in the brain may contribute to the pathophysiology of psychiatric disorders and the mechanisms of action of antidepressants. Neuroactive steroids affect a broad spectrum of behavioral functions through their unique molecular properties and may represent a new treatment strategy for neuropsychiatric disorders.
Article
The effect of jasmine tea odor on the autonomic nervous system was investigated by a power spectral analysis of the heart rate variability. We assigned eight volunteers to two groups with either a predilection for or antipathy toward the jasmine tea odor. We tested both high- and low-intensity jasmine tea odors. The low-intensity odor was produced by diluting 20-fold the jasmine tea used for the high-intensity odor test. The low-intensity odor produced an increase in parasympathetic nervous activity in both the predilection and antipathy groups. The high-intensity odor produced an increase in parasympathetic nervous activity in the predilection group, but an increase in sympathetic nervous activity in the antipathy group. The odor of Chinese green tea, a basic ingredient of jasmine tea, produced no effects similar to those of the jasmine tea odor. These results suggest that the jasmine tea odor activated the parasympathetic nerve, whereas the higher-intensity odor activated the sympathetic nerve in those subjects who disliked the odor.
Article
It is known that the target of most mood-defining compounds such as ethanol is an ionotropic gamma-aminobutyric acid receptor (GABA(A) receptor). The potentiation of the response of these inhibitory neurotransmitter receptors induces anxiolytic, sedative, and anesthetic activities in the human brain. Because both extracts of whiskey by pentane and fragrant components in whiskey potentiate the GABA(A) receptor-mediated response, GABA(A) receptors were expressed in Xenopus oocyte by injecting cRNAs prepared from the cloned cDNA for the alpha(1) and beta(1) subunits of the bovine receptors in order to study the effects of whiskey itself on the GABA(A) receptor-mediated response. Whiskey itself also potentiated the electrical responses of GABA(A) receptors generally more than ethanol at the same concentration as that of the whiskey. The potentiation of the GABA(A) receptor-mediated response increased with the aging period of the whiskey. Inhalation of whiskey to mice increased the sleeping time induced by pentobarbital more than that of the same concentration of ethanol as the whiskey. These results suggest that not only ethanol but also minor components in whiskey play an important role in the potentiation of GABA(A) receptor-mediated response and possibly the sedative effect of whiskey. Although the minor components are present in extremely small quantities compared with ethanol in alcoholic beverages, they may modulate the mood or consciousness of humans through the potentiation of the GABA(A) receptor response after absorption into the brain, because these hydrophobic compounds are easily absorbed into the brain across the blood-brain barrier and are several thousands times as potent as ethanol in the potentiation of the GABA(A) receptor-mediated response.
Article
The effects of both coffee components and coffee extract on the electrical responses of GABA(A) receptors expressed in Xenopus oocytes were studied by injecting cRNAs of the alpha(1) and beta(1) subunits of the bovine receptors. The aqueous extract of coffee dose-dependently inhibited the GABA-elicited responses, whereas the lipophilic extract of coffee by diethyl ether slightly potentiated it at low doses (0.1-0.4 microL/mL) but showed inhibition at high doses (0.5-0.8 microL/mL). Theophylline inhibited the response in a noncompetitive mechanism (K(i) = 0.55 mM), whereas theobromine and trigonelline hydrochloride inhibited it in a competitive manner, K(i) = 3.8 and 13 mM, respectively. Benzothiazole, catechol, 2,4-dimethylstyrene, guaiacol, 1-octen-3-ol, sotolone, and 2,3,5-trimethylphenol potentiated the responses significantly. Potentiation elicited by guaiacol and sotolone was independent of GABA concentrations, whereas that by 1-octen-3-ol was dependent. When 1-octen-3-ol (100 mg/kg) was orally administered to mice prior to intraperitoneal administration of pentobarbital, the sleeping time of mice induced by pentobarbital increased significantly.
Article
To investigate the effect of green odor on the elevation of the plasma adrenocorticotropic hormone (ACTH) levels and body temperature (T(b)) induced by stress, adult male rats were subjected to a 2-h immobilization stress and exposed to green odor or its vehicle only. In comparison with the vehicle group, animals in the green odor group showed a significant reduction in plasma ACTH levels at the end of the stress when green odor was applied during the stress. The elevated plasma ACTH levels 2 days after the stress were reduced by green odor applied 0, 1, 2, 4 or 6 h after the beginning of the stress. Neither the immediate nor the long-lasting plasma ACTH response was affected by a prestress treatment of green odor. T(b) elevation was evident following the end of the stress and during the light phase the day after the stress. Both the immediate and the long-lasting elevations in T(b) were attenuated by green odor. These data suggest that green odor extracted from green leaves has a relieving effect on plasma ACTH and T(b) levels induced by an immobilization stress for not only immediate but also long-lasting periods.
Article
It is well-known that the target of most mood-defining compounds is an ionotropic gamma-aminobutyric acid receptor (GABA(A) receptor). The potentiation of the response of these inhibitory neurotransmitter receptors induces anxiolytic, sedative, and anesthetic activity in the human brain. To study the effects of whiskey fragrance on the GABA(A) receptor-mediated response, GABA(A) receptors were expressed in Xenopus oocyte by injecting rat whole brain mRNA or cRNA prepared from the cloned cDNA for the alpha(1) and beta(1) subunits of the bovine receptors. Most whiskey components such as phenol, ethoxy, and lactone derivatives potentiated the electrical responses of GABA(A) receptors, especially ethyl phenylpropanoate (EPP), which strongly potentiated the response. When this compound was applied to mice through respiration, the convulsions induced by pentetrazole were delayed, suggesting that EPP was absorbed by the brain, where it could potentiate the GABA(A) receptor responses. The extract of other alcoholic drinks such as wine, sake, brandy, and shochu also potentiated the responses to varying degrees. Although these fragrant components are present in alcoholic drinks at low concentrations (extremely small quantities compared with ethanol), they may also modulate the mood or consciousness of the human through the potentiation of the GABA(A) receptor response after absorption into the brain, because these hydrophobic fragrant compounds are easily absorbed into the brain through the blood-brain barrier and are several thousands times as potent as ethanol in the potentiation of the GABA(A) receptor-mediated response.
Systemic absorption and metabolism of essential oils in rats by holistic vapor exposure
  • S Inoue
  • H Yamaguchi
Inoue, S., and Yamaguchi, H., Systemic absorption and metabolism of essential oils in rats by holistic vapor exposure. Aroma Res. (in Japanese), 1(4), 77–81 (2000).
Relaxation effects of wine aroma
  • H Nagai
  • Y Koga
  • Y Hirayasu
  • Y Nakamura
  • H Takahashi
Nagai, H., Koga, Y., Hirayasu, Y., Nakamura, Y., and Takahashi, H., Relaxation effects of wine aroma. Aroma Res. (in Japanese), 1(4), 48–52 (2000).
Tea Components and Their Function
  • K Ina
  • K Sakata
  • I Tomita
Ina, K., Sakata, K., Tomita, I., and Isemura, M., ''Tea Components and Their Function'' (in Japanese), Kougakusyuppan, Kawasaki, pp. 1–185 (2002).
The effect of odor of whiskey on the human brain function: the study by using ERP and Pet
  • Y Shutara
  • Y Koga
  • K Nagata
  • I Kanno
  • H Hujita
  • T Nakagawa
  • H Nagai
  • K Takemasa
Shutara, Y., Koga, Y., Nagata, K., Kanno, I., Hujita, H., Nakagawa, T., Nagai, H., and Takemasa, K., The effect of odor of whiskey on the human brain function: the study by using ERP and Pet. Rinsyonoha (in Japanese), 36, 161–167 (1994).
Encyclopedia of Aromatherapy
  • S Hayashi
Hayashi, S., ''Encyclopedia of Aromatherapy'' (in Japanese), Tokyudo Shuppan, Tokyo, pp. 1–260 (1998).