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The Sedative Effects and Mechanism of Action of Cedrol Inhalation with Behavioral Pharmacological Evaluation
Abstract
It has been reported that cedarwood oil has sedative effects when inhaled. In this study, we evaluated sedative effects of inhaled cedrol, which is a major component of cedarwood oil. Accumulative spontaneous motor activity was significantly decreased in the cedrol-exposed Wistar rats. Similar results were confirmed in caffeine-treated Wistar rats, spontaneously hypertensive rats (SHR), and ddY mice. In addition, exposure to cedrol prolonged pentobarbital-induced sleeping time in Wistar rats. To investigate whether cedrol, which has a very faint aroma, affects the olfactory system, the nasal cavities of Wistar rats were treated with zinc sulfate to reduce olfactory function. Two days later, the pentobarbital-induced sleep time was measured as described above. Compared to intact rats, the sleep prolongation effect was decreased in a lavender-roman chamomile mixed oil exposure positive control group, indicating that olfactory function was impaired. In contrast, prolongation of the sleeping time did not change in the cedrol exposure group. The above findings indicate that cedrol inhalation had marked sedative effects regardless of the animal species or the functional state of the autonomic nerves, suggesting that the mechanism of action is via a pathway other than the olfactory system.
... The question of whether psychopharmacological effects in animals are dependent of olfactory functions is surprisingly not yet entirely clarified. Cedrol (from pine EO) was shown to be sedative in normal rats and rats made anosmic with zinc sulfate (Kagawa et al. 2003). In contrast, a mix of chamomile and lavender oils reduced pentobarbital-induced sleeping time in normal but not anosmic rats and mice (Kagawa et al. 2003). ...
... Cedrol (from pine EO) was shown to be sedative in normal rats and rats made anosmic with zinc sulfate (Kagawa et al. 2003). In contrast, a mix of chamomile and lavender oils reduced pentobarbital-induced sleeping time in normal but not anosmic rats and mice (Kagawa et al. 2003). ...
... Anxiolytic proprieties were observed in rats with the plus maze model after 7 min rose oil inhalation; this is the only report of inhaled effects in animals after a short period of inhalation, although the procedure of leaving four cotton balls embedded with 2 mL of EO lacks standardization (Almeida et al. 2004). As previously mentioned, inhaled cedrol was shown to be sedative in rats (Kagawa et al. 2003), and the inhalation of a volatile mixture from the TCM SuHeXiang Wan composed of 21.4% borneol (29), 33.3% isoborneol (30), 5.9% eugenol (4), and other minor components delayed the appearance of PTZ-induced convulsions suggesting GABAergic modulation (Koo et al. 2004). ...
... It was found that the essential oil of Sabina was mainly composed of monoterpenes, including bornyl acetate and sabinene. The main component of Platycladus orientalis essential oil was cedrol, which had an activation effect and could be used as an antagonist of platelet-activating factor (PAF) receptor, and played an important role in the inflammatory response, human respiratory system and cardiovascular disease [16,23]. ...
To gain insight into the differences in the composition and volatile components content in ancient Platycladus orientalis leaves with different tree ages in Huangdi Mausoleum, the volatile components were identified by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS–SPME–GC–MS) method. The volatile components were statistically analyzed by orthogonal partial least squares discriminant analysis and hierarchical cluster analysis, and the characteristic volatile components were screened. The results exhibited that a total of 72 volatile components were isolated and identified in 19 ancient Platycladus orientalis leaves with different tree ages, and 14 common volatile components were screened. Among them, the contents of α-pinene (6.40–16.76%), sabinene (1.11–7.29%), 3-carene (1.14–15.12%), terpinolene (2.17–4.95%), caryophyllene (8.04–13.53%), α-caryophyllene (7.34–14.41%), germacrene D (5.27–12.13%), (+)-Cedrol (2.34–11.30%) and α-terpinyl acetate (1.29–25.68%) were relatively higher (>1%), accounting for 83.40–87.61% of the total volatile components. Nineteen ancient Platycladus orientalis trees were clustered into three groups through the HCA method based on the 14 common volatile components content. Combined with the results of OPLS–DA analysis, (+)-cedrol, germacrene D, α-caryophyllene, α-terpinyl acetate, caryophyllene, β-myrcene, β-elemene and epiglobulol were the differential volatile components to distinguish ancient Platycladus orientalis with different tree ages. The results revealed that the composition of the volatile components in ancient Platycladus orientalis leaves with different tree ages was different, showing different aroma characteristics, which provided a theoretical reference for the differential development and application of volatile components in ancient Platycladus orientalis leaves.
... In the medical research field, researchers have found multiple functions of plant aroma in therapies (Buchbauer et al., 1993). For example, the volatile aroma of lavender oil help alleviate the distressing symptoms of anxiety (Shaw et al., 2007), the volatile aroma of Selaginella has a tranquilizing effect (Kagawa et al., 2003), and application of plant aroma therapy to patients with dementia has proved to be curative (Thorgrimsen et al., 2003;Fujii et al., 2008). In terms of food consumption, the aroma of fruits and vegetables is an important indicator of their flavour quality. ...
... This study is the first to illustrate an effect of age on olfactory interest in horses. Research on cedar wood is not abundant, but there is some evidence for a relaxing effect of inhaling the odor in rats (Kagawa et al., 2003). This effect could be speculated to affect horses' inhalation behavior, resulting in less sniffing in some horses. ...
In spite of a highly developed olfactory apparatus of horses, implying a high adaptive value, research on equine olfaction is sparse. Our limited knowledge on equine olfaction poses a risk that horse behavior does not match human expectations, as horses might react fearful when exposed to certain odors, which humans do not consider as frightening. The benefit of acquiring more knowledge of equine olfaction is therefore twofold; (1) it can aid the understanding of horse behavior and hence reduce the risk of dangerous situations, and (2) there may be unexplored potential of using odors in several practical situations where humans interact with horses. This study investigated behavior and olfactory sensitivity of 35 Icelandic horses who were presented with four odors: peppermint, orange, lavender and cedar wood in a Habituation/Dishabituation paradigm. The response variables were sniffing duration per presentation and behavioral reaction (licking, biting, snorting, and backing), and data were analyzed for potential effects of age, sex and pregnancy. Results showed that habituation occurred between successive odor presentations (1st vs. 2nd and 2nd vs. 3rd presentations: P < 0.001), and dishabituation occurred when a new odor was presented (1st vs. 3rd presentations: P < 0.001). Horses were thus able to detect and distinguish between all four odors, but expressed significantly longer sniffing duration when exposed to peppermint (peppermint vs. orange, lavender and cedar wood: P < 0.001). More horses expressed licking when presented to peppermint compared to cedar wood and lavender ( P = 0.0068). Pregnant mares sniffed odors less than non-pregnant mares ( P = 0.030), young horses (age 0-5 years) sniffed cedar wood for longer than old horses ( P = 0.030), whereas sex had no effect ( P > 0.050). The results show that horses’ odor exploration behavior and interest in odors varies with age and pregnancy and that horses naïve to the taste of a substrate, may be able to link smell with taste, which has not been described before. These results can aid our understanding of horses’ behavioral reactions to odors, and in the future, it may be possible to relate these to the physiology and health of horses.
... Cedrol has been commonly used worldwide in decorative cosmetics, fine fragrances, shampoos, and soaps, as well as in non-cosmetic products such as detergents [34]. Several studies have demonstrated that inhalation of cedrol induces an increase in parasympathetic activity and a decrease in sympathetic activity, resulting in sedative and relaxant effects [35][36][37][38]. Furthermore, several studies related to the anticancer activity of cedrol have recently reported that cedrol inhibits proliferation of human amelanotic melanoma C32 and renal adenocarcinoma cells [39], induces autophagy and apoptosis in A549 nonsmall cell lung carcinoma cells [40], and suppresses glioblastoma progression by triggering DNA damage and blocking nuclear translocation of the androgen receptor [41]. ...
Proteins related to DNA replication have been proposed as cancer biomarkers and targets for anticancer agents. Among them, minichromosome maintenance (MCM) proteins, often overexpressed in various cancer cells, are recognized both as notable biomarkers for cancer diagnosis and as targets for cancer treatment. Here, we investigated the activity of cedrol, a single compound isolated from Juniperus chinensis, in reducing the expression of MCM proteins in human lung carcinoma A549 cells. Remarkably, cedrol also strongly inhibited the expression of all other MCM protein family members in A549 cells. Moreover, cedrol treatment reduced cell viability in A549 cells, accompanied by cell cycle arrest at the G1 phase, and enhanced apoptosis. Taken together, this study broadens our understanding of how cedrol executes its anticancer activity while demonstrating that cedrol has potential application in the treatment of human lung cancer as an inhibitor of MCM proteins.
... Cedrol has been commonly used worldwide in decorative cosmetics, fine fragrances, shampoos, and soaps, as well as in non-cosmetic products such as detergents [34]. Several studies have demonstrated that inhalation of cedrol induces an increase in parasympathetic activity and a decrease in sympathetic activity, resulting in sedative and relaxant effects [35][36][37][38]. Furthermore, several studies related to the anticancer activity of cedrol have recently reported that cedrol inhibits proliferation of human amelanotic melanoma C32 and renal adenocarcinoma cells [39], induces autophagy and apoptosis in A549 nonsmall cell lung carcinoma cells [40], and suppresses glioblastoma progression by triggering DNA damage and blocking nuclear translocation of the androgen receptor [41]. ...
Fas-associated death domain (FADD) is an adapter molecule that bridges the interaction between receptor-interacting protein 1 (RIP1) and aspartate-specific cysteine protease-8 (caspase-8). As the primary mediator of apoptotic cell death, caspase-8 has two N-terminal death-effector domains (DEDs) and it interacts with other proteins in the DED subfamily through several conserved residues. In the tumor necrosis receptor-1 (TNFR-1)-dependent signaling pathway, apoptosis is triggered by the caspase-8/FADD complex by stimulating receptor internalization. However, the molecular mechanism of complex formation by the DED proteins remains poorly understood. Here, we found that direct DED-DED interaction between FADD and caspase-8 and the structure-based mutations (Y8D/I128A, E12A/I128A, E12R/I128A, K39A/I128A, K39D/I128A, F122A/I128A, and L123A/I128A) of caspase-8 disrupted formation of the stable DED complex with FADD. Moreover, the monomeric crystal structure of the caspase-8 DEDs (F122A/I128A) was solved at 1.7 Å. This study will provide new insight into the interaction mechanism and structural characteristics between FADD and caspase-8 DED subfamily proteins.
... The age effect on sni ng of cedar wood odour could be a result of a deterioration of the older horses' (mean age of older horses: 16) olfactory abilities making cedar wood odour hard to detect, and hence resulting in less sni ng. Research on cedar wood is not abundant, but there is some evidence for a relaxing effect of inhaling the odour in rats 64 . This effect could be speculated to affect horses' inhalation behaviour, resulting in less sni ng in some horses. ...
In spite of the highly developed olfactory apparatus of horses, implying a high adaptive value, research on equine olfaction is sparse. Our limited knowledge on equine olfaction poses a risk that horse behaviour does not match human expectations, as horses e.g. might react fearful when exposed to certain odours which humans do not consider as frightening. The benefit of acquiring more knowledge of equine olfaction is therefore twofold; 1) it can aid the understanding of horse behaviour and hence reduce the risk of dangerous situations occurring, and 2) there may be unexplored potential of using odours in several practical situations where humans interact with horses, i.e. to improve management routines and the situation for the horses. This study investigated the olfactory sensitivity of 35 Icelandic horses who were presented with four odours: peppermint, orange, lavender and cedar wood in a Habituation/Dishabituation paradigm. The response variables were sniffing duration per presentation and behavioural reaction (licking, biting, snorting, and backing), and we moreover analysed the data for any potential effects of age, sex and gestational stage. Results showed horses were able to detect and distinguish between all four odours and showed increased interest for peppermint (Wilcoxon signed rank test: orange vs peppermint: V = 68, P < 0.001, lavender vs peppermint: V = 20, P < 0.001, cedar wood vs peppermint: V = 47, P < 0.001). More horses expressed licking behaviour when presented to peppermint compared to cedar wood and lavender (Fishers Exact test: peppermint vs lavender & peppermint vs cedar wood: OR = 4.40, P = 0.0068). Young horses (age 0-5 years) sniffed cedar wood for longer than old horses (Anova: F = 10.03, p-value = 0.004), and pregnant mares sniffed lavender less than non-pregnant mares (Wilcoxon signed rank test: pregnant vs not pregnant: W = 93, P = 0.02), whereas sex had no effect (Wilcoxon signed rank test: p = 0.4). The results showed that the test paradigm was meaningful for testing olfactory sensitivity in horses, and olfactory interest of horses varied with age and gestational status but not sex.
... Recent studies showed that sesquiterpenes have various therapeutic effects, such as being effective in pain management [9], protection against stroke [10], and RA [11]. Cedrol, a natural sesquiterpene, is known to carry many pharmacological effects, including antioxidant [12], anti-inflammatory [13], antibacterial [14], analgesic [12], sedative [15], hair growth inducer [16], platelet-activating factor (PAF) antagonist [17], and antitumor effects [18]. The present investigation ...
Pharmacological studies revealed that cedrol, a natural sesquiterpene, has antioxidant, anti-inflammatory, and analgesic properties. This study is aimed at evaluating the potential antiarthritic activity of cedrol in a rat experimental model of arthritis induced by using complete Freund’s adjuvant (CFA). Arthritis was induced in Wistar rats by CFA (0.1 ml) injection. Cedrol (10 and 20 mg/kg) and indomethacin (5 mg/kg) were orally administered from day one and continued for 21 days. The antiarthritic activity was assessed through mechanical allodynia and thermal hyperalgesia responses, paw edema assessment, and arthritis scores. Serum TNF-α and IL-1β levels were measured for the evaluation of inflammation. Furthermore, serum oxidative stress markers, including malondialdehyde (MDA) and thiol levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were also assessed. Oral administration of cedrol and indomethacin significantly decreased paw edema and arthritis score. Besides, cedrol and indomethacin significantly decreased pain responses. In the serum of the CFA group, TNF-α, IL-1β, and MDA were higher, while thiol and SOD and GPx were lower than the control group. Treatment by cedrol and indomethacin corrected the biochemical parameters in the serum. In this study, cedrol offers potential antiarthritic properties through its anti-inflammatory and antioxidant effects.
... Moreover, four constituents such as cedrol, geranylgeraniol, sclareol, and ethyl linoleate were shown to have definite pharmacological activities. Cedrol, a kind of sesquiterpene alcohols, expresses various activities such as anticancer, [11,12] anti-inflammatory, [13] sedative, [14] and antifungal. [15][16][17] Zhang [12] investigated that cedrol can inhibit cell proliferation, induce apoptosis in A549 cells via mitochondrial and PI3K/Akt signaling pathways and pro-death autophagy by increasing intracellular production of reactive oxygen species. ...
... In future studies, researchers can evaluate the importance of the olfactory system through pharmacological and physiological alterations induced by inhaled essential oils in olfactory impairment animal models. In another animal study, the authors reported that the sedative effect of inhaling a lavender-Roman chamomile oil mixture was impaired by reduced olfactory function (Kagawa et al., 2003). It can be concluded that the olfactory system has an essential role in inhalation aromatherapy, and olfactory impairment on the effects of inhalation is also related to the different types and active ingredients of the essential oils. ...
Mood disorders, also often referred to as affective disorders, are a group of psychiatric illnesses that severely impact mood and its related functions. The high medical expenditures have placed a significant financial burden on patients and their families. Aromatherapy is an alternative and complementary treatment that utilizes essential oils (EOs) or volatile oils (VOs) to achieve major therapeutic goals. In general, EOs are volatile chemicals that enter the body primarily through skin absorption and/or nasal inhalation. In addition, they can work through oral administration. Inhalation aromatherapy has shown unique advantages for treating mood disorders, especially depression, anxiety and mental disorders such as sleep disorder, which have been validated over the last decade through clinical and animal studies. Accumulating evidence has shown that EOs or VOs can bypass the blood-brain barrier to target brain tissue through the nasal-brain pathway. Subsequently, they act on the cerebral cortex, thalamus, and limbic system in the brain to improve symptoms of anxiety, depression and improve sleep quality. Here, we review the natural aromatic plants’ volatiles or essential oils used commonly as adjuncts to manage mood disorders and illustrate the mechanisms of inhalation aromatherapy, and mainly summarized the application of transnasal inhalation aromatherapy in depression, anxiety, and sleep disorders. We conclude that aromatherapy does not cause side-effects, which is vastly different from commonly used psychotropic drugs. Inhalation aromatherapy via brain-targeted nasal delivery offers potentially efficacious treatment for mental disorders and merits further study.
... In cedarwood (species unknown) oil smoke, cedrol is the major olfactory component. Kagawa et al. (2003) have shown that Wistar rats show significant decrease in motor activity upon inhalation of cedrol, suggesting a sedative effect. Methylsalycilate, a component in the smoke of leaves of Gaultheria fragrantissima Wall., is well known for its analgesic action when used in balms and ointments (Hänsel et al., 1999). ...
- Bachelor (BSc) Biology Honours Programme report -
Certain dried plant species can be bound together for smudging, called “smudge sticks”, are traditionally used in native North-American practices but are also found on the market in the Netherlands, such as in (web)shops that sell spiritual and/or esoteric products. Native American groups, herbalists and conservationists have raised concerns about the possibly increasing demand for traditional smudging plants, such as North American white sage (Salvia apiana Jeps.), in western countries. To gain more insights into the possible unsustainable harvesting of plants used for smudge sticks, it is important to know which plant species are sold and used for this practice. The Dutch application of smudge sticks, the plant species used in these smudges, and the conservation status of said species are topics addressed in this research. We conducted interviews with (online) shop owners, plant breeders and smudge stick users in the Netherlands, collected and identified plant species used in smudge sticks and conducted a literature search to find out what their conservation status was and their phytochemical bioactivity. We were able to identify 12 plant species, of which most (4) belong to the Artemisia genus. All of the bought smudge sticks (except the ones from Indian-Spirit) came from (web)shops that were catered towards spirituality, modern Paganism, or modern witchcraft. Seven plant species found in the obtained smudge sticks are native or endemic to the USA: A. californica, A. ludoviciana, A. tridentata, C. decurrens, E. californicum, H. odorata and S. apiana, of which H. odorata is also native to Eurasia. This suggests that these plants were imported from the USA for their use as smudge sticks in the Netherlands. The growing demand in North American smudge plants in Western countries, their often unclear origin in smudge sticks and, for some species, conservation issues indicate a need for more research on native American plants used in smudge sticks for Western markets.
... Similar to diazepam (positive control), upon administration of caryophyllene oxide, mice locomotor activity was decreased by 61% (p = 0.001), indicating that caryophyllene oxide is a powerful CNS depressant. In previous studies, monoterpenes and sesquiterpenes were also effective in decreasing the excitation provoked by caffeine [3,38]. ...
Chromolaena odorata (L.) R.M.King & H.Rob. essential oil (COEO) was investigated for its sedative activity in mice. The results showed that COEO significantly reduced mice locomotor activity and the most efficient concentrations were 0.04 and 0.00004 mg/cage (volume of the cage 61.2L). Analysis of chemical composition of the oil indicated that caryophyllene oxide (43.75%) was the major compound and bioactivity-guided fractionation of the oil was performed to isolate the compound responsible for activity. The data clearly identified sesquiterpene caryophyllene oxide as the compound inducing COEO sedative activity and it was effective in decreasing mice locomotor activity by 56% and 57% at 0.0004 and 0.04 mg/cage, respectively. In order to understand the action mechanisms, caryophyllene oxide was tested for its effects on the central nervous system (CNS) by using a caffeine pre-excited mice test and a pentobarbital sleeping-induced test in mice. The results showed that caryophyllene oxide is a potent CNS depressant. Nevertheless, it fails to potentiate the effects of pentobarbital on the GABAergic system, nor did flumazenil, a GABAA receptor antagonist, reversed its effects. It was especially interesting to note that β-caryophyllene, the precursor of caryophyllene oxide, demonstrated a similar pattern of sedative activity, and the present work further extends actual knowledge on these naturally occurring sesquiterpenes. The findings in this study reveal the new activity of caryophyllene oxide as an innovative way to manage sleep and CNS-related disorders, and demonstrates a satisfactory effect of two interesting sesquiterpene compounds on the CNS.
... Juniperus virginiana (Cedar wood) oils contain a-cedrene, b-cedrene, thujopsene, cedrol, and widdrol as important volatile compounds (Eller and King 2000;Zhang and Yao 2018). The oil and its active constituent, cedrol, have got sedative effects and also affect autonomic nervous system (Dayawansa et al. 2003;Kagawa et al. 2003). The essential oil from Juniperus virginiana has shown anxiolytic effect in mice by affecting dopamine and 5-hydroxytryptamine levels (Zhang and Yao 2018). ...
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.
... Juniperus virginiana (Cedar wood) oils contain a-cedrene, b-cedrene, thujopsene, cedrol, and widdrol as important volatile compounds (Eller and King 2000;Zhang and Yao 2018). The oil and its active constituent, cedrol, have got sedative effects and also affect autonomic nervous system (Dayawansa et al. 2003;Kagawa et al. 2003). The essential oil from Juniperus virginiana has shown anxiolytic effect in mice by affecting dopamine and 5-hydroxytryptamine levels (Zhang and Yao 2018). ...
... Juniperus virginiana (Cedar wood) oils contain a-cedrene, b-cedrene, thujopsene, cedrol, and widdrol as important volatile compounds (Eller and King 2000;Zhang and Yao 2018). The oil and its active constituent, cedrol, have got sedative effects and also affect autonomic nervous system (Dayawansa et al. 2003;Kagawa et al. 2003). The essential oil from Juniperus virginiana has shown anxiolytic effect in mice by affecting dopamine and 5-hydroxytryptamine levels (Zhang and Yao 2018). ...
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.
... Therefore, Cedrol be a potential candidate for anti-GBM drug development for combination therapy with radiotherapy or TMZ. Several studies demonstrate that Cedrol inhalation can increase parasympathetic activity and decrease sympathetic activity [25,43]. The reports show that Cedrol reveals anxiolytic effect in male mice in doses of 200-1600 mg/kg and significantly increases the percentage of open arm entries (%OAE) and open arm time spent (%OAT) [44]. ...
Glioblastoma (GBM) is the most common and aggressive primary brain tumor with great invasiveness and resistance to chemotherapy, which presents a treatment challenge. In this study, we investigated the antitumor effect of Cedrol, a sesquiterpene alcohol isolated from Cedrus atlantica, against GBM cells in vitro and in vivo. Cedrol was found to potently inhibit cell growth and induce intracellular ROS generation and DNA damage response. In addition, Cedrol induced significant G0/G1 cell cycle arrest and cell apoptosis via the extrinsic (Fas/FasL/Caspase-8) and intrinsic (Bax/Bcl-2/Caspase-9) pathways. In addition, Cedrol had a synergistic effect with temozolomide (TMZ) and reduced drug resistance by blockage of the AKT/mTOR pathway. Cedrol suppressed tumor growth in both orthotopic and xenograft GBM animal models with low or no short-term acute toxicity or long-term accumulative toxicity. In a molecular docking study, Cedrol targeted the androgen receptor (AR), and reduced DHT-mediated AR nuclear translocation, downstream gene KLK3/TMPRSS2 expression and cell proliferation. Our study demonstrates that Cedrol may be a potential candidate for drug development for single or combination treatment with TMZ in GBM therapy.
... Aromatherapy is nonpharmacological methods to reduce anxiety without side effect, depending on the type of aroma, which have effect on neurotransmitters, reflecting on human spirit and physic, and then change his feeling into healthy one (Kyle, 2006). Cedarwood essential oil is known for its sweet and woody fragrance, that has been characterized as warm, comforting, and sedative, thus it is naturally promoting stress relief (Kagawa et al., 2003). ...
... 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). Linalool is the major component of the vapour of lavender essential oils. ...
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.
... Additionally, sesquiterpenes can be a good source for discovering new drug as numerous sesquiterpenes and their derivatives possess interesting biological properties (Bártíková et al. 2014). Cedrol, a natural sesquiterpene, with a very weak aroma has several biological properties including antibacterial (Oh et al. 2011), sedative (Kagawa et al. 2003), anti-tumor property (Loizzo et al. 2008), and the regulation of autonomic nerves (Umeno et al. 2008). Cedrol also exhibits excellent anti-inflammatory activities (Jantan et al. 2005). ...
Injured somatosensory nervous system cause neuropathic pain which is quite difficult to treat using current approaches. It is therefore important to find new therapeutic options. We have analyzed cedrol effect on chronic constriction injury (CCI) induced neuropathic pain in rats. The mechanical and thermal hypersensitivity were evaluated using the von Frey filament, radiant heat and acetone drop methods. The changes in the levels of biomarkers of oxidative stress including malondialdehyde (MDA) and total thiol (SH), as well as inflammatory mediators including Tumour Necrosis Factor alpha (TNF-α) and Interleukin 6 (IL-6) were estimated in the lumbar portion (L4–L6) of neuropathic rats. Administration of cedrol attenuated the CCI-induced mechanical and thermal hypersensitivity. CCI produced an increase in MDA along with a reduction in SH levels in the spinal cord of the CCI rats. Reduced levels of SH were restored by cedrol. Also, the levels of MDA were reduced in the cedrol-treated CCI rats compared to the untreated CCI rats. Besides, level of TNF-α and IL-6 increased in the spinal cord of CCI group and cedrol could reverse it. The current study showed that cedrol attenuates neuropathic pain in CCI rats by inhibition of inflammatory response and attenuation of oxidative stress.
... Cedrol inhalation has a relaxing/sedative effect. The mechanism of action of cedrol was not only in the olfactory pathway but possibly also via the non-olfactory one [13] . The vetiver essential oil has a relaxing/sedative effect. ...
Prolonged stress has a negative impact on health. Stress stimulates hypothalamic-pituitary-adrenal axis leading to increased cortisol hormone level. Excessive cortisol causes immunity suppression, sleep disturbance, and metabolic imbalance. Essential oils have been often used to stimulate relaxation. Lavender, cedarwood, and vetiver have a relaxation effect and they are useful for anxiety and depression. Common applications are aromatherapy inhalation and topical/massage. The aim of this study was to find the effect of lavender, cedarwood, and vetiver balms of reducing plasma cortisol levels. The study design was experimental with post-test-only control group that used 4 control (negative, positive, diazepam 2 mg/kg BW, balm vehicle) and 9 treatment (lavender 10%, 20%, 30%; cedarwood 10%, 20%, 30%; vetiver 10%, 20%, 30%) groups with 9 male Wistar rats in each group. Swim test was applied daily as a stress stimulus and the balms were applied daily on the shaved back for 30 days. Data were shown as mean ± SD and analyzed using Kruskal Wallis and Spearman correlation test with a significant value of p<0.05. We found a significant difference in plasma cortisol levels between control and treatment groups (p = 0.001). The concentration of each essential oil has a significant moderate negative correlation with plasma cortisol level. The three essential oil balms reduced plasma cortisol level of prolonged swim-induced stress rats. The greater essential oils concentration has a greater effect to reduce cortisol level. The 30% concentration of each essential oil has a similar effect to diazepam. The three essential oil balms have a similar effect of reducing cortisol levels. Lavender, cedarwood, and vetiver balms have a beneficial effect as an anti-stress treatment by reducing cortisol hormone level.
Keywords: Cedarwood, cortisol, lavender, stress, vetiver
... The changes of respiratory and cardiovascular which is caused by exposure to cedrol might ameliorate autonomic disturbances in chronic heart failure [30]. The mechanism of cedrol's sedative effects is via a pathway other than the olfactory system regardless of the animal species or the functional state of the autonomic nerves [31,32]. Dimethyl phthalate (0.68%) is a plasticizer that is highly soluble in a wide range of resins. ...
Chinese fir is an important economic tree species in China. In addition to the application of alive trees and wood, the abundant chemical compositions of Chinese fir as a non-wood resource also have very important position. This study used Chinese fir wood powder as material, analyzing the chemical composition of Chinese fir volatiles by Fourier transform infrared spectroscopy (FT-IR), thermogravimetry (TG), pyrolisis-gas chromatography-mass spectrometry (Py-GC-MS), thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). Through the analysis of the detected we can know that volatiles main were phenolic (cedrol, alpha-bisabolol and beta-eudesmol), ester (dimethyl phthalate, diisobutyl phthalate and dibutyl phthalate), ketone (hydroxyacetone and benzofuran) and aldehyde (hexanal and nonanal) and so on. This compounds and their derivatives can use at wide medical, biology, cosmetics and textile industry.
... Cinnamaldehyde, (E)-has strong acaricidal activity, in addition to the ticks pecies of larvae also achieve high killing [34]; Phenol, 2-methoxy-3-(2-propenyl)-in antibacterial, showing high antibacterial activity; Propanoic acid, 2-methyl-, 3-hydroxy-2, 2,4-trimethylpentylester has detoxification, cough, and expect orantand reinforcing the effect of blood. Blood can be used to treat acute and chronic bronchitis, pharyngitis, and tonsillitis [35,36]; Benzene, 1,2,3-trimethoxy-5-(2-propenyl)-itself has antioxidant effects, and can play an anti-inflammatory and antithrombotic effect in the human body, in addition to hyperlipidemia crowd it also has the effect to flowering blood pressure [37]; Cedrol has a clear sedative effect on the emotional stability has a certain role in promoting [38]; 7-Methyl-Z-tetradecen-1-ol acetate has the effect of removing heat and relieving cough in the human body and effectively treating dry cough and sore throat caused by fire [39]; 1,2-Benzenedicarboxy licacid,bis(2-methylpropyl) ester have a certain anti-canceractivity, and pharmaceutical applications can be used for the synthesis of cancer drugs [40]. ...
Dalbergia granadillo’s human health components were studied using PY-GC-MS, TDS-GC-MS, and GC-MS. The composition of known human health functions was studied by reviewing available literature. The 7-Methyl-Z-tetradecen-1-olacetate has the effect of removing heat and relieving cough in the human body and effectively treat both dry cough and sore throat caused by fire; 1,2-Benzene dicar boxy licacid, bis (2-methyl propyl) ester hasacertainanti-cancer activity, pharmaceutical applications can be used for the synthesis of cancer drugs.
... Because there was no difference between the volume that produced the best antihyperalgesic effect (LaEO 100 μl) and the naive and control groups, the possibility of a sedative effect of LaEO inhalation that could cause a misinterpretation in the evaluation of hyperalgesia was discarded. Woronuk et al. (2011) described that the absorption of essential oils through the respiratory system can occur in two ways: (i) absorption by the lungs and nasal mucosa into the bloodstream, bringing the active compounds to the central nervous system (CNS) and acting directly on neurotransmission and ii) olfactory, where intranasal administration crosses the blood-brain barrier, and the substances reach the CNS through olfactory neuronal pathways (Kagawa et al., 2003;Hanson and Frey, 2008;Faturi et al., 2010). However, an interesting study by Chioca and collaborators (Chioca et al., 2013) showed that stimulation of the olfactory system is not necessary for the anxiolytic effect produced by the inhalation of LaEO, since this effect was still preserved in mice with anosmia. ...
Lavandula angustifolia (LaEO) essential oil has been widely used by aromatherapy in the treatment of various clinical conditions, with evidence of its analgesic and anti-inflammatory potential. Our results demonstrate that sixty-five substances were identified in LaEO. Among the compounds found, the major ones were linalool (30.61%) and linalyl acetate (20.36%). We found that LaEO inhalation reduces mechanical hyperalgesia in conditions of chronic inflammatory and neuropathic pain. Furthermore, this effect seems to be mediated by peripheral and central opioid and cannabinoid 2 receptors. The findings of the present study suggests that the LaEO inhalation is effective on the chronic pain treatment.
... 21 In addition, exposure to cedrol modulated spontaneous activity of rats. 22 These results strengthened the suggestion that cedrol may cause a potential anxiolytic-like effect. ...
Cedrol, mainly derived from Juniperus virginiana L. essential oil, has been demonstrated the anxiolytic effect, although its mechanism of action is still not fully established. In the present study, male ICR mice were submitted to the elevated plus maze (EPM) and light-dark box (LDB) tests to investigate the putative mechanism of anxiolytic effect. WAY100635 (5-HT1A receptor antagonist), flumazenil (benzodiazepine receptor antagonist), SCH23390 (dopamine D1 receptor antagonist) or sulpiride (dopamine D2/D3 receptor antagonist) were used in the behavioral experiment to determine the mechanism of action of cedrol. Subsequently, the monoamine neurotransmitter levels were evaluated after behavioral tests. The data suggest that no significant effect in behavioral parameters were observed after sole intraperitoneal (i.p.) injection of antagonists compared to saline group. The anxiolytic effect of cedrol in behavioral procedures was blocked by either WAY100635 or flumazenil. The anxiolytic effect of cedrol (1200 mg/kg) was effectively antagonized by SCH23390 (0.125 mg/kg). Furthermore, cedrol decreased the DA and NE levels in hippocampus, striatum and hypothalamus. The present findings suggest that the dopaminergic system (D1 receptor) rather than serotoninergic or GABAergic system may potentially be involved in the modulation of cedrol-induced anxiolytic-like behaviors in mice.
... It has been reported that the main mechanism of aromatherapy may be related to the limbic system of the brain. Aroma components stimulate olfactory cells, which transmit signals to the brain and affect the autonomic nervous system and hormone secretion [13]. Odor particles reach the limbic system through the olfactory nerve, producing sedative and relaxing effects that affect blood pressure, heart rate, memory and stress response [14]. ...
Backgrounds:
The chemical composition of many essential oils indicates that they have sedative and hypnotic effects, but there is still a lack of systematic studies on the sedative and hypnotic effects of essential oils. In addition, aromatherapy does not seem to have the side effects of many traditional psychotropic substances, which is clearly worthwhile for further clinical and scientific research. The clinical application of essential oils in aromatherapy has received increasing attention, and detailed studies on the pharmacological activities of inhaled essential oils are increasingly needed.
Hypothesis/purpose:
As insomniacs are usually accompanied by symptoms of depression and anxiety of varying degrees, based on the theory of aromatherapy of Traditional Chinese Medicine, this experiment is to study a Compound Anshen essential oil that is compatible with Lavender essential oil, Sweet Orange essential oil, Sandalwood essential oil and other aromatic medicine essential oils with sedative and hypnotic effects, anti-anxiety and anti-depression effects. To study the sedative and hypnotic effects of Compound Anshen essential oil inhaled and the main chemical components of Compound Anshen essential oil, and to compare and analyze the pharmacodynamics of diazepam, a commonly used drug for insomnia.
Methods:
The Open field test and Pentobarbital-induced sleep latency and sleep time experiments were used to analyze and compare the sedative and hypnotic effects of inhaling Compound Anshen essential oil and the administration of diazepam on mice. The changes of 5-HT and GABA in mouse brain were analyzed by Elisa. The main volatile constituents of Compound Anshen essential oil were analyzed by gas chromatography-mass spectrometry (GC-MS).
Results:
Inhalation of Compound Anshen essential oil can significantly reduce the spontaneous activity of mice, reduce latency of sleeping time and prolong duration of sleeping time. The results of enzyme-linked immunosorbent assay showed that Compound Anshen essential oil can increase the content of 5-HT and GABA in mouse brain. The main volatile chemical constituents of the Compound Anshen essential oil are D-limonene (24.07%), Linalool (21.98%), Linalyl acetate (15.37%), α-Pinene (5.39%), and α-Santalol (4.8%).
Conclusion:
The study found that the inhalation of Compound Anshen essential oil has sedative and hypnotic effect. This study provides a theoretical basis for further research and development of the sedative and hypnotic effects of Compound Anshen essential oil based on the theory of aromatherapy.
... 14) In animal experiments, exposure to cedrol appeared to induce a sedative effect regardless of the animal species. 17,18) Therefore, we surmised that cedrol might have relaxant and anxiolytic properties. This hypothesis was supported by our previous study, in which we demonstrated, in animal models of anxiety, that intraperitoneal (i.p.) administration of ERO and cedrol exhibited an anxiolytic effect on male ICR mice, via the 5-HTnergic and dopaminergic (DAnergic) pathways. ...
Cedrol has been reported to be effective in reducing anxiety of male mice. The limited application of females in animal models of anxiety makes it difficult to systematically investigate new drug substitutes with potential anxiolytic activity. In the present study, we investigated the behavioral response of female ICR mice to cedrol after intraperitoneal (i.p.) administration using the elevated plus maze (EPM) and the light–dark box (LDB) test, followed by determination of neurochemical changes in brain. The data suggested that cedrol at dose of 1200–1600 mg·kg⁻¹ exhibited anxiolytic activity on the female mice, as reflected by greater percentage of entries into the open arms and time spent in the open arms in the EPM, and greater transitions between chambers and percentage of time spent in the light chamber in the LDB. Cedrol increased the level of 5-hydroxytryptamine (5-HT), decreased the level of dopamine (DA), reduced the ratio of 5-hydroxyindoleacetic acid (5-HIAA)/5-HT and increased the ratio of 3,4-dihydroxyphenyl acetic acid (DOPAC)/DA, compared with the control group, indicative of an anxiolytic-like effect on female mice via the 5-HTnergic or DAnergic pathways.
Graphical Abstract Fullsize Image
... α-Cedrol is a sesquiterpene alcohol with a very weak aroma. It has antibacterial, sedative activities (KAGAWA et al., 2003). α-Cedrol is dehydrated to α-cedrene in the presence of acid. ...
Fragaria viridis Weston essential oils from leaves and fruits were obtained by hydrodistillation. The composition of the essential oil from leaves and fruits was analyzed by GC-MS. 39 components were identified in leaves oil representing 67.3-80.7% of the oil composition. The main components of the essential oil from leaves of
F. viridis were β-linalool (0.8-8.9%), n-nonanal (0.5-8.6%), tetra-
decanal (2.1-5.9%), nerolidol (2.1-4.8%), an unidentified component (1.9-6.6%), α-bisabolol (0.8-6.7%), phytol (18.4-47.4%), an unidentified component (0.9-8.2%) depending on the growth conditions. The fruit oil was composed of 34 compounds representing 42.0-70.7% of the total composition of the oil. The main components of the essential oil from fruits of F. viridis were m/p-xylene (2.4-14.0%), isoledene (4.7-8.5%), methyleugenol (3.3-8.4%), α-cedrene (2.5-3.9%), an unidentified component (3.4-9.1%), α-muurolene (6.8-11.3%), nerolidol (1.1-4.8%), α-cedrol (1.7-8.0%), α-bisabolol (2.3-5.0%), an unidentified component (0-25.6%) depending on the growth conditions. This is the first report of the chemical composition of the essential oils obtained from the leaves and fruits of green strawberry (Fragaria viridis Weston).
... [10][11][12] It is a sesquiterpene compound with a high boiling point (molecular weight, 222.37), which has been reported to have antispasmodic, sedative, anti-cancer, antifungal, analgesic and anti-inammatory effects. [13][14][15][16][17][18] Its safety for topical administration has been conrmed. 19,20 Our previous studies demonstrated that topically applied cedrol (dissolved in 85% ethanol) could effectively promote hair growth and prevent chemotherapy-induced alopecia by stimulating hair regeneration and prolonging the anagen phase of hair follicles. ...
Topical use of cedrol ethanol has been reported to have a beneficial effect on hair loss. However, the use of cedrol has been limited by application-related issues, such as poor water solubility and volatile features. Therefore, the present study developed a cream formulation of cedrol and evaluated various physicochemical parameters of the prepared cream. The optimized cedrol cream was selected after orthogonal tests and determined further. The dermatopharmacokinetics were studied to investigate the absorption difference between cedrol cream and cedrol ethanol after dermal application, and the concentrations of cedrol in skin were analysed by the gas chromatography-mass spectrometry (GC-MS) method. By comparison, the area under the curve (AUC0-24 h) of cedrol cream was almost three times higher than that of cedrol ethanol. Moreover, this study was undertaken to evaluate the hair growth promoting efficacy of cedrol cream in C57BL/6 mice and Wistar rats. Macroscopic assessment and alopecia score showed that C57BL/6 mice treated with cedrol cream showed a faster production of pigmentation and a higher score at different growth stages than other groups. The hair length of the cedrol cream-treated group was much longer than those of the cedrol ethanol and minoxidil groups. Histological analyses indicated that in the cedrol ethanol group, most follicles of the C57BL/6 mice were in the catagen phase, whereas nearly 83% of hair follicles in the cedrol cream group remained in the anagen phase. Taken together, our data strongly suggest that the cream formulation of cedrol has a stronger hair growth promotion effect, gave no irritation and was safe for topical administration.
... The mechanism of the hypnotic effect of the aromatic treatment of ELE is unknown. In a study investigating the hypnotic effect of aromatherapy, it was suggested that aromatic treatment may show the hypnotic effect via not only olfactory function but also sensory nerve endings located in the lungs and the lower airway [40]. The mechanism of the hypnotic effect using the aromatic treatment with ELE has to be addressed in future studies. ...
... Les informations « olfactives » sont directement analysées par différentes parties du cerveau grâce à un mécanisme complexe sans que nous en ayons conscience, ce qui explique que le cerveau peut déclencher spontanément une réponse comportementale appropriée (fuite, sourire, séduction, ravissement, …) ainsi qu'une action spécifique sur l'organisme (énergisante, relaxante, calmante). Les odeurs jouent donc un rôle très important dans notre équilibre psycho-émotionnel en permettant d'établir des relations avec notre environnement (Field et al., 2005;Heuberger et al., 2004Kagawa et al., 2003;Kline et al., 2000;Ryan et al., 2008;Satoh and Sugawara, 2003;Soudry et al., 2011;Sugawara et al., 2000). ...
Ce travail contribue à la conception d’un système de détection-diffusion contrôlant en temps réel la concentration en huile essentielle dans un espace confiné. L’objectif est d’assurer la reproductibilité des conditions d’exposition aux stimuli olfactifs de sujets vivants, afin de tester les impacts neurosensoriels provoqués. La principale contrainte est de pouvoir mesurer, avec de bonnes qualités de rapidité et précision, la concentration odorante d’une atmosphère. Pour la détection gazeuse, le choix s’est porté sur un dispositif basé sur des capteurs de gaz commerciaux à base d’oxyde métalliques (nez électronique), couplé à un étalonnage préalable sous concentrations fixes d’huile essentielle de pin. Un équipement expérimental a été mis au point afin d’étudier, de caractériser et surtout d’optimiser les performances de ce dispositif. De premières études ont permis de classer les capteurs selon la rapidité, la sensibilité et le niveau de dérives, et d’optimiser la procédure de mesures : cycle d’exposition gazeuse de 75sec suivie de 350sec de régénération des capteurs sous air pur. Une caractérisation a été menée à partir de mesures systématiques réalisées sous diverses variations (croissantes, décroissantes, aléatoires) de concentration, prenant ainsi en compte toutes les formes possibles de dérive. Afin de réduire les erreurs dues à ces dérives, un prétraitement original a été initié en normalisant les signaux de réponse, grâce à la réponse de chaque capteur prise en fin de régénération. Deux descripteurs normalisés (conductance moyenne et maximale) ainsi que la valeur maximale de la courbe dérivée de chaque réponse temporelle ont été définis pour chaque capteur. L’exploitation de la base de données constituée à l’aide de ces trois paramètres par des méthodes de classification ACP et AFD montrent la difficulté de différencier les hautes concentrations, même en éliminant les deux capteurs les moins performants. Une toute nouvelle approche est alors proposée en combinant la technique de correction orthogonale des signaux (OSC), conduisant à la suppression des informations non pertinentes de la base de données, suivie d’une régression des moindres carrés partiels (PLS) adaptée aux problèmes de multi-colinéarité et au nombre élevé de variables. L’association de ces méthodes permet une meilleure discrimination des fortes concentrations, tout en garantissant le maximum de stabilité au modèle de régression et la précision d’estimation requise des concentrations gazeuses. Enfin, cette discrimination a été optimisée en remplaçant les trois paramètres représentatifs précédents par l’intégralité des signaux de réponse, le temps de calcul nécessaire restant modique. Une très bonne évaluation de la concentration gazeuse dans toute la gamme utilisée a alors été obtenue. Nous avons ainsi élaboré un modèle robuste et précis pour l’étalonnage de notre système, grâce à des méthodes d’analyse et de prétraitement judicieux, qui permet d’entreprendre la réalisation du prototype.
... The efficacy of cedrol, which is a phytoncide, a component of sesquiterpene alcohols contained in cedar and hinoki cypress scents, and an aromatic component used in aromatherapy, has been emphasized. Cedrol exhibits relaxation effects as discussed elsewhere [1][2][3], and its scent may reduce stress, thereby contributing to various stressful life situation. However, cedrol may induce sleep as reported by Sano et al. [4], which is dangerous by case. ...
Background: Cedrol exhibits relaxation effects, and its scent may reduce stress, thereby contributing to various stressful life situation. However, cedrol has also been reported to induce sleep, which is dangerous by case. Therefore, studies are needed in order to determine whether the relaxation or sleep-inducing effects of cedrol are induced under stressful situation and also how to only attain the former. Method: A cross-over open study was conducted. Subjects were randomly divided into two groups (n = 3 per group). After one course of the Kraepelin test and additional dumbbell lifting before and after the test was performed, subjects entered the placebo or cedrol exposure room, and rested in a sitting position for 20 minutes. Electrocardiographic, electroencephalographic, and blood pressure measurements as well as VAS assessments were conducted. Result: In the present study, no stress response was clearly detected. However, the results of analyses with respect to individuals suggested that cedrol exhibited relaxation effects, and that it did not induce sleep under the conditions adopted in this study.
... Decreased spontaneous motor activity in normal, caffeine-treated and hypertensive rats and mice, and prolonged pentobarbitalinduced sleeping time in normal and anosmic rats (408 μg/mL in air 1.0 L/min) [58] 6. ...
Major depressive disorder (MDD), which is called as recurrent depressive disorder, clinical is a mental condition that leads to a feeling of sadness and low self-esteem in an individual. Approximately 10% of the population suffering from depressive disorder at present. Treatment of depression by western psychiatry has several shortcomings viewed from the eastern point of view. Most medications for major depression have strong side effects. No effective treatment exists for people who are just feeling temporarily low. Patients need easy usable, less time consuming, compatible formulation so Aromatherapy is better option. In this, aromatic/essential oil is used that can easily administrate through inhalation and skin, and easily can be used by patient. The aim of this review is to explore the aromatherapy effect on major depressive disorders through various researches carried out on aromatherapy including its description and pharmacological activities.
... Essential oil components might be absorbed into the circulatory system, reach the CNS, and act on receptors of neurotransmitters to induce the effects (Kagawa et al., 2003). However, in inhalation aromatherapy, aroma component molecules are dissolved in the mucus on the olfactory mucosa and stimulate olfactory cells, and then the aroma information is converted to electric signals and transmitted to the olfactory nerve and olfactory bulb (OB) (Amir et al., 1999). ...
Ethnopharmacological relevance:
Cedrus atlantica essential oil (CaEO) presents analgesic and anti-inflammatory sedative properties. However, it remains unknown whether CaEO alleviates acute postoperative pain.
Materials and methods:
Here, we investigated the effect of CaEO on postoperative pain and its mechanisms related to the descending pain control in Swiss males mice induced by a plantar incision surgery (PIS) in the hindpaw.
Results:
Inhalation of CaEO (5', 30' or 60') markedly reduced mechanical hypersensitivity. This effect was prevented by pre-treatment with naloxone or p-chlorophenylalanine methyl ester (PCPA, 100mg/kg, i.p.)-induced depletion of serotonin. In addition, p-alpha-methyl-para-tyrosin (AMPT, 100mg/kg, i.p.)-induced depletion of norepinephrine, intraperitoneal injection of the α2-adrenergic receptor antagonist yohimbine (0.15mg/kg, i.p.) or haloperidol (1mg/kg, i.p.) an antagonist of dopaminergic (D1 and D2) receptors prevented the effect of CaEO on hypersensitivity.
Conclusions:
These findings suggest that CaEO alleviates postoperative pain by activating the descending pain modulation pathways on the opioidergic, serotonergic, noradrenergic (α2-adrenergic) and dopaminergic (dopamine D1 and D2 receptors) systems.
Excellent health-promoting effects of cedrol (CED), including anti-inflammatory, anti-arthritic, and antinociceptive effects, have been reported. The present study aimed to investigate the preventive effects of CED on high-fat diet (HFD)-induced obesity and the related metabolic syndrome, and to delineate the underlying mechanism. Ten-week-old C57BL/6J mice were fed chow, HFD, or HFD supplemented with CED (0.2% w/w) for 19 weeks. Results demonstrated that CED effectively reduced HFD-induced body weight gain, decreased visceral fat pad weight, and significantly prevented adipocyte hypertrophy in mice. HFD-induced hepatic steatosis, glucose intolerance, insulin resistance, and gluconeogenesis were ameliorated by CED supplementation. 16S rRNA analysis revealed that CED did not change gut microbiota composition at the phylum and genus levels, indicating that CED may have limited effects on gut microbiota in HFD-fed mice. Further transcriptome analysis of epididymal white adipose tissue revealed reprogrammed RNA profiles by CED. These results demonstrate that incorporating CED in the diet can prevent HFD-induced obesity and related metabolic syndrome, and highlight that CED could be a promising dietary component for obesity therapeutic intervention. This article is protected by copyright. All rights reserved.
Purpose: The objective of this study was to evaluate the quality of five different types of agarwood from Vietnam and 4 other areas and analyze the volatile chemical components by gas chromatography mass spectrometry (GC-MS). We attempted to identify the ingredients that have previously been reported to have skin health benefits, and reviewed their potential future use as raw materials for natural cosmetics.Methods: The five sources of Aquilaria crassna (A. crassna ) were from Vietnamese, Indonesian, Malaysian, Myanmar, and Cambodian agarwoods. The volatile chemical components of each agarwood were analyzed by GC-MS. The Vietnamese agarwood was selected as a standard by identifying A. crassna through DNA analysis.Results: GC-MS analysis revealed that ‘sesquiterpene’ was contained in all the agarwood samples. The four sesquiterpene components, italicene ether, epi-γ-eudesmol, δ-guaiene, and α-agarofuran were commonly detected in all agarwood samples. Eight simple volatile aromatic compound components (1-octanol, 4-(4-methoxyphenyl)-2-butanone, 4-phenyl-2-butanone, benzaldehyde, ethylbenzene, nonanal, octanal, and 2-ethyl-1-hexanol) were commonly detected. The sesquiterpene components, α-agarofuran, β-selinene, α-curcumene, and α-santalol have been reported to have anti-inflammatory, antioxidant, antibacterial, and anti-skin cancer properties, respectively.Conclusion: This study demonstrated a substantial difference in the quality of the volatile component composition in each of the four source areas other than A. crassna from Vietnam. Agarwood contains sesquiterpene, which has a unique fragrance and is beneficial for skin health, and it is expected to be utilized as a raw material for natural cosmetics and developed in the future as a functional cosmetic with high added value.
Chapter 7: Role of Aroma Therapy in relieving pain
Chapter 8: Aromatherapy for relieving mental stress
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.
In spite of the highly developed olfactory apparatus of horses, implying a high adaptive value, research on equine olfaction is sparse. Our limited knowledge poses a risk that horse behaviour does not match human expectations. The benefit of acquiring more knowledge of equine olfaction is therefore twofold; 1) it can aid the understanding of horse behaviour and hence reduce the risk of dangerous situations, and 2) there may be unexploited potential of using odours in several practical situations where humans interact with horses. This study investigated olfactory abilities of, 35 Icelandic, horses who were presented to four odours: peppermint, orange, lavender and cedarwood. The response variables were sniffing duration per presentation and behavioural reaction (licking, biting, snorting, and backing). Results showed horses were able to detect and distinguish between all four odours and showed increased interest (significantly longer sniffing duration) for peppermint. More horses expressed licking behaviour when presented to peppermint compared to cedarwood and lavender. Young horses sniffed cedarwood for longer than old horses, and pregnant mares sniffed lavender less than non-pregnant mares. In conclusion, the test paradigm seemed meaningful for horses, and olfactory interest of horses varied with age and gestational status but not sex.
Sesquiterpenoids have been identified as natural compounds showing remarkable biological activities found in medicinal plants. There is great interest in developing methods to obtain sesquiterpenoids derivatives and biotransformation is one of the alternative methods for structural modification of complex sesquiterpenes structures. Biotransformation is a great drug design tool offering high selectivity and green method. The present review describes a comprehensive summary of biotransformation products of sesquiterpenoids and its structural modification utilizing a variety of biocatalysts including microorganisms, plant tissue culture and enzymes. This review covers recent literatures from 2007 until 2020 and highlights the experimental conditions for each biotransformation process.
Various essential oils from plants and fragrance components such as monoterpenes have been discovered to reduce spontaneous movements in mice; thus, it has been made clear that the odor itself has the sedative activity. In the present study, we examined the sedative activity of the odors of fragrance components added to eye drops; l-menthol, d-camphor, phenylethyl alcohol, and geraniol, which are often used as refreshers or preservatives. Each fragrance component was administered by the inhalation route to mice, and the sedative effects were evaluated using an open field test. The results showed that four components administered via inhalation to mice significantly decreased the amount of spontaneous motor activity in a dose-dependent manner, indicating that all four components have a sedative effect. The optimal concentrations at which l-menthol, d-camphor, phenylethyl alcohol, and geraniol showed the highest sedative activity were 4 × 10–2 mg per cage, 4 × 10–4 mg per cage, 4 × 10–2 mg per cage, and both 4 × 10–4 and 4 × 10–2 mg per cage, respectively. The AUC graph of geraniol was represented as a W-shaped curve, suggesting that the sedative action of geraniol was biphasic. The present finding demonstrates a new perspective on a possible pharmacological property of eye drop additives used with no expected pharmacological functions.
In this paper we report the analysis of essential oils from the woods of C. libani and P. pinea and from the berries of J. excelsa. Several differences were observed with respect to previous studies. In particular, the wood of C. libani was mainly characterized by sesquiterpenes with himachalenes isomers, (E)- and (Z)-α-atlantones and α-acorenol (7.0%) as most representative compounds; in P. pinea wood oil and J. excelsa berries oil were observed differences mainly among the minor components with different isomers of some specific compounds not previously recognized. The oils were assessed in selected bioactivity tests. C. libani wood oil resulted the most active in both the antioxidant and cytotoxic (against human A375 malignant melanoma, human MDA-MB 231 breast adenocarcinoma and human HCT116 colon carcinoma cell lines) tests; on the other hand in the antimicrobial assay it was observed a different susceptibility of different bacteria to the different oils. All the oils exerted a remarkable activity against the yeast Candida albicans. Taken together, these results support some of the traditional uses of these three plants in the Mediterranean area and give evidence of their potential on an industrial level.
The essential oil obtained from Dysphania ambrosioides leaves (DAEO) has antifungal, antioxidant, and antimicrobial properties. This study investigated DAEO’s chemical composition and its sleep-promoting effects via administration by inhalation in ddY mice. Ascaridole (35.5%) and p-cymene (47.2%) were the major components. To obtain insight into DAEO’s effects on the central nervous system (CNS), ascaridole and p-cymene were evaluated for sedative activity by using the caffeine-treated excitatory mouse model. DAEO administration significantly decreased locomotor activity at all doses except 0.000 04 mg per 400 μL of triethyl citrate. Both ascaridole and p-cymene were highly effective in decreasing locomotor activity of excited mice by more than 50%. In addition, ascaridole and p-cymene prolonged the pentobarbital-induced sleeping duration by 42% and 77%, respectively. These effects were antagonized by coadministration of gamma-aminobutyric acid (GABAA)-benzodiazepine receptor antagonist, flumazenil (3 mg/kg), indicating that the GABAergic system mediates the sedative effect. Finally, inhaled ascaridole and p-cymene had no negative effect on motor coordination, as observed during the Rota-rod test. Therefore, via activation of the GABAergic system, ascaridole and p-cymene mediate the sleep-promoting effect of DAEO. The results further extend the knowledge on their use as potential promising natural products for the management of sleep disorders and CNS-related ailments.
The first total synthesis of juniperanol, the tricyclic sesquiterpenoid enantiomer of α-cedrol is described. The synthesis relies on stereoselective gold-catalyzed Ohloff-type propargylic ester rearrangement performed on a 10 g scale, and a carbocationic cascade in the presence of acetyl methanesulfonate. The ability of juniperanol to interfere in glucose processes in different cell types is described.
Cedrol is an extremely versatile sesquiterpene alcohol that was approved by the Food and Drug Administration of the United States as a flavoring agent or adjuvant and has been commonly used as a flavoring ingredient in cosmetics, foods and medicine. Furthermore, cedrol possesses a wide range of pharmacological properties including sedative, anti-inflammatory and cytotoxic activities. Commercial production of cedrol relies on fractional distillation of cedar wood oils, followed by recrystallization, and little has been reported about its biosynthesis and aspects of synthetic biology. Here, we report the cloning and functional characterization of a cedrol synthase gene (Lc-CedS) from the transcriptome of the glandular trichomes of a woody Lamiaceae plant Leucosceptrum canum. The recombinant Lc-CedS protein catalyzed the in vitro conversion of farnesyl diphosphate into the single product cedrol, suggesting that Lc-CedS is a high-fidelity terpene synthase. Co-expression of Lc-CedS, a farnesyl diphosphate synthase gene and seven genes of the mevalonate (MVA) pathway responsible for converting acetyl-CoA into farnesyl diphosphate in Escherichia coli afforded 363 μg/L cedrol as the sole product under shaking flask conditions. Transient expression of Lc-CedS in Nicotiana benthamiana also resulted in a single product cedrol with a production level of 3.6 μg/g fresh weight. The sole production of cedrol by introducing of Lc-CedS in engineered E. coli and N. benthamiana suggests now alternative production systems using synthetic biology approaches that would better address sufficient supply of cedrol.
Alternate forms of drug crystals display different physicochemical properties. These include stability, dissolution rate, bioavailability and solubility, which can affect pharmacokinetics and pharmacodynamics. It is therefore important to compare the crystal forms of cedrol to obtain optimal anti-inflammatory and analgesic effects. This study, for the first time, obtained and reports three novel forms (I-III) of cedrol polymorphs. The three forms of cedrol were recrystallized from seven organic solvents by slow cooling or volatilization and identified by thermal analysis, fourier transform infrared spectroscopy, scanning electron microscopy and powder X-ray diffraction analysis. Form I originated from acetone and cyclohexane. Form II was obtained from ethanol, ethyl acetate, acetonitrile and n-hexane. Form III was recrystallized from methanol. The anti-inflammatory and analgesic activities of the three crystalline forms were evaluated by acetic acid induced writhing in mice, the hot plate method, carrageenan induced mouse paw edema models, Xylene-induced mouse ear edema models and cotton pellet-induced mouse granuloma models. Experimental results revealed that the highest performance was achieved from Form I. These findings are of great significance during the early research study of cedrol polymorphs.
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.
Analyses of high- and low-cedrol volatile leaf oils of Juniperus semiglobosa from India showed the taxon to be rich in sabinene (12.3–29.2%), p-cymene (0.4–8.5%), terpinen-4-ol (trace-11.0%) with cedrol ranging from 34.1 to 1.5%. Contrary to some reports, comparisons of the volatile leaf oils of Juniperus semiglobosa from India with those from J. excelsa from Greece indicates that J. semiglobosa is not conspecific with J. excelsa.
The hypothesis that the essential oil fromTagetes minuta L. can interact with biological membranes was investigated by assessing its ability of perturbing the binding of a benzodiazepine
[flunitrazepam (FNTZ)] to crude membranes from chick brains. The essential oil fromT. minuta L. inhibited [3H]FNTZ specific binding to chick brain membranes. These values were obtained from the analysis of the saturation curve for
the kinetic parameters: dissociation equilibrium constant (Kd)=2.47±0.32 nM, maximal binding (Bmax)=556±5 fmoles/mg protein, and Hill coefficient (n)=1.00±0.07 in the absence, and Kd=6.73±1.4 nM, Bmax=583±69 fmoles/mg protein, and n=1.02±0.08 in the presence of 29 μg/mL of essential oil. The essential oil could self-aggregate
with a critical micellar concentration (CMC) of 60 μg/mL. The marked increase in [3H]FNTZ nonspecific binding starting at 60 μg of essence per mL was due to that phenomenon and revealed the ability of self-aggregated
structures to interact with membranes. [3H]FNTZ specific binding decrement as a function of essence concentration cannot be ascribed merely to oil's micelles ability
of trapping the lipophilic radioligand molecules, because the discontinuous behavior that characterizes a monomer-aggregate
phase transition was not shown. Oil's components might behave as competitive inhibitors or allosteric modulators of FNTZ specific
binding. However, their ability to increase FNTZ nonspecific binding at concentrations below oil's CMC suggests that this
effect may be due to oil's partitioning into the lipid bilayer. This latter phenomenon would induce an increment in membrane
fluidity and a change on FNTZ binding site toward a lower affinity conformation. Therefore, the essential oil components can
interact with brain membranes either as monomers, by partitioning into the lipid bilayer, or as self-aggregated structures,
through an adsorption to the membrane surface.
Linalool is a monoterpene compound reported to be a major component of essential oils in various aromatic species. Several Linalool-producing species are used in traditional medical systems, including Aeolanthus suaveolens G. Dom (Labiatae) used as anticonvulsant in the Brazilian Amazon. Psychopharmacological in vivo evaluation of Linalool showed that this compound have dose-dependent marked sedative effects at the Central Nervous System, including hypnotic, anticonvulsant and hypothermic properties. The present study reports an inhibitory effect of Linalool on Glutamate binding in rat cortex. It is suggested that this neurochemical effect might be underlining Linalool psychopharmacological effects. These findings provide a rational basis for many of the traditional medical use of Linalool producing plant species.
The dried leaves of Vitex negundo was extracted with petroleum ether. The active fraction of the extract was separated by column chromatographic technique, and the Acute toxicity studies were done using swiss albino mice of either sex. Three dose levels (125, 167, 250 mg/kg b.w.) were chosen to study analgesic, anti-convulsant and sedative-hypnotic-activities using swiss albino mice of either sex, The leaf extract potentiated the sedative-hypnotic effect of pentobarbitone and diazepam significantly (P ≤ 0.01) in a dose dependent manner, while it did not produce sleep in mice itself. The extract showed significant analgesic activity and prolonged the analgesia produced by morphine and pethidine, whereas, the anticonvulsant activity against strychnine and leptazole was found only at high dose levels (250 mg/kg b.w).
In order to clarify the effect of odors of seven coniferous woods on human, contingent negative variation (CNV) and electroencephalogram (EEG) were measured. Four of the species used, hinoki (Chamaecyparis obtusa), sugi (Cryptomeria japonica), akamatsu (Pinus densiflora), and hiba (Thujopsis dolabrata var. hondai), were grown in Japan, and three of them, Alaska cedar (Chamaecyparis nootkatensis), Douglas fir (Pseudotsuga menziesii), and western red cedar (Thuja plicata), were grown in the United States. The concentrations of their wood odors were analysed by gas-liquid chromatography. The total concentration of monoterpene hydrocarbon in the wood odors was held to less than 3ppb. The amplitudes of early components of CNV and the α/β wave ratio of EEG at the frontal (Fz) and central (Cz) regions between in the presence and absence of wood odors were compared 5 male and 5 female volunteers ranging in age from 20 to 26 were examinated. The result obtained are summerized as follows : (1) In the presence of wood odors, the early CNV amplitudes at Fz decreased at a statistical level of significance of 5% or better. (2) The α/β wave ratio of EEG increased significantly at Cz with hiba wood odor (p<0.01). (3) The decrease of the early CNV amplitude at Fz is related to the concentration of α-pinene in the wood odors.
Daidai (Citrus aurantium L. var. cyathifera Y. Tanaka) peel oil was extracted by cold-pressing. The flavour components of daidai were quantitatively determined using two internal standards with GC and GC-MS. The characteristic flavour components of daidai were examined by GC-olfactometry. The percentages by weight of hydrocarbons (16 compounds), esters (12 compounds), alcohols (11 compounds) and aldehydes (10 compounds) were approximately 96.4%, 2.1%, 0.3% and 1.1%, respectively. Geranial, octyl acetate, geraniol, octanal, cedrol, cis-limonene oxide, trans-2-decenal, linalyl acetate and β-elemol were identified as characteristic flavour components of daidai. Terpenes were the major components of daidai peel oil, but they contributed little to the characteristic flavour of daidai. Linalyl acetate and β-elemol had the highest flavour dilution factors. The results of the omission test showed geraniol, octanal, linalyl acetate and cis-limonene oxide to be the active components of the daidai flavour.
Fragrance compounds and essential oils with sedative effects influence the motility of mice in inhalation studies under standardized conditions. A significant drop in the motility of mice was registered following exposure to these fragrances. The same results were achieved when the mice were artificially induced into overagitation by intraperitoneal application of caffeine and subsequently subjected to inhalation of fragrance compounds and essential oils. These results proved the sedative effects of these fragrants via inhalative exposure in low concentrations. Blood samples were taken from the mice after a 1-h inhalation period. Chromatographic and spectroscopic methods were used to detect and characterize the actual effective compounds after solid-phase extraction. Serum concentrations of 42 different substances, including fragrance compounds, were found in low ranges (ng/mL serum). The results contribute to the correct interpretation of the term aromatherapy (i.e., a stimulating or sedative effect on the behaviour of individuals only upon inhalation of fragrance compounds).
(1) Shavings from the Eastern Red Cedar (Juniperus virginiana) were examined for three diverse biological properties, i.e. enzyme induction, procarcinogenicity and insecticidal activity. (2) The ability of a cedar environment to stimulate liver drug-metabolizing enzymes in mice was confirmed by lowered values for barbiturate sleeping time. (3) In susceptible strains of mice (C3H-Avy, C3H-AvyfB and CBA/J) the use of cedar shavings as bedding increased significantly the incidence of spontaneous tumors of the liver and mammary gland, and also reduced the average time at which tumors appeared. (4) Cedar and some of its derivatives (Oil of Cedarwood, cedrene, cedrol) disrupted the reproductive and developmental cycle of a number of insects, including the Peanut Trash Bug (Elasmolomus sordidus), the Indian Meal Moth (Plodia interpunctella) and the Forage Mite (Tyrophagus putrescentiae).
Deafferentation of the vomeronasal system by cutting the vomeronasal nerves severely impaired mating behavior in 44% of male hamsters over a 1--2 month period of postoperative testing, but the remaining males mated normally after the surgery. Damage to the main olfactory bulbs, concomitant to vomeronasal nerve cuts, did not account for this behavioral difference. Subsequent deafferentation of olfactory system by intranasal infusion of zinc sulfate solution (5 g ZnSO4--7H2O in 95 ml 0.5% NaCl) had no effect on intromission or ejaculation latencies of sham vomeronasal cut males but eliminated mating behavior 2 days after treatment in males with bilateral vomeronasal nerve cuts. Some of these males recovered the behavior in 1--3 weeks of post zinc sulfate testing. Histological analyses of the olfactory mucosa in 7 males on day 2 after zinc sulfate showed that 89--97% of the mucosa had been destroyed in 6 out of 7 of the males and 78% in the seventh. We conclude that destruction of the vomeronasal system irreparably reduces arousal necessary for mating in some hamsters but in other males sufficient arousal for this behavior to occur is mediated through the olfactory system, presumably in conjunction with other sensory inputs. Subsequent removal of the olfactory input in these animals eliminates the behavior.
The essential oil obtained from the plant Blumea membranacea produced a marked and long lasting fall in blood pressure in anaesthetized dogs. The oil exerted a direct depressant action on frog heart and spasmolytic effect on rabbit ileum. It also depressed the conditioned avoidance response, adversely affected rotarod performance and potentiated the pentobarbitone induced hypnosis in rats.
The effect of empenthrin, a synthetic pyrethroid, on pentobarbital (PTB)-induced sleeping time was examined in mice and rats. In mice, pretreatment with empenthrin prolonged PTB-induced sleeping time in a dose-dependent manner. The maximum effect on PTB-sleeping time was noted when mice were pretreated orally with empenthrin 2-4 h before PTB injection. However, empenthrin did not change the sleeping time induced by diethyl ether which is hardly metabolized in liver. Empenthrin inhibited the clearance of serum PTB in mic, but did not change the PTB concentration in serum at which animals recovered from sleeping. To examine the effect of PTB on metabolic enzymes in mouse liver, PTB was incubated aerobically with a hepatic microsomal fraction in the presence of NADPH at 37 degrees C. Empenthrin inhibited the vitro metabolism of PTB dose-dependently. In rats, empenthrin neither changed the PTB sleeping time, nor inhibited the clearance of serum PTB. No inhibitory effect of empenthrin was observed on the in vitro metabolism of PTB using rat hepatic microsomal fraction. These findings indicate that empenthrin prolongs PTB-sleeping time in mice through an inhibition of the PTB-metabolizing enzyme(s) in the liver , an effect that does not occur in rats. Also, there is a clear species-specificity in the inhibitory effect of empenthrin on the PTB-metabolizing enzyme(s).
Agarwood (Jinkoh in Japanese), one of the Oriental medicines, is used as a sedative. The benzene extract of this medicine showed a prolonged effect on the hexobarbital-induced sleeping time, and hypothermic effects in terms of rectal temperature, a suppressive effect on acetic acid-writhing, and a reduction of the spontaneous motility in mice. By repeated fractionation, oral administration in mice, and pharmacological screening, the active principles, jinkoh-eremol and agarospirol, were obtained from the benzene extract. They also gave positive effects on the central nervous system by peritoneal and intracerebroventricular administration. They decreased both methamphetamine- and apomorphine-induced spontaneous motility. The level of homovanillic acid in the brain was increased by them, while the levels of monoamines and other metabolites were unchanged. Similar results were seen in chlorpromazine-administered mice. Therefore, jinkoh-eremol and agarospirol can be considered to be neuroleptic.
Our knowledge of the conservation techniques used in the Old Kingdom of ancient Egypt is limited. Examinations of a clavicle fragment of the mummy of Idu II, secretary general of the pine wood trade office (2150 +/- 50 BC), revealed saturation with a wealth of sodium and wood tar compounds, many of which were highly antiseptic as no microbial contamination was noticed. This pretreatment had ensured the preservation of bone alkaline phosphatase in an enzymically and immunologically active form. This extends the use of embalming to one thousand years earlier than previously thought.
We investigated whether exposure to the odor of extracted cedar essence (CE) has (i) an influence on spontaneous activity and sleep-wake states of rats and (ii) a sleep-promoting effect on human daytime nap after taking an ordinary night's sleep. In rats exposed to CE, spontaneous activities and amount of wake were significantly decreased, while the amount of non-rapid eye movement (NREM) sleep was significantly increased. In human daytime nap, NREM sleep stage 2 latency was significantly shortened after exposure to CE.
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.
The paradigm of conditioned place preference has been widely used to demonstrate the rewarding properties of psychomotor stimulants. Such drugs also stimulate locomotor activity. Repeated administration of low doses of psychomotor stimulants causes progressive increases in the locomotor stimulating effect, a phenomenon termed behavioral sensitization. Using a new activity monitor (SCANET MV-10LD) that simultaneously measures the amount of time spent and the distance traveled in each side of a two-compartment chamber, the present study assessed place preference conditioning and locomotor sensitization following repeated administration of cocaine or methamphetamine (MAP) in mice. We examined the effect of environmental factors on these activities using two different types of chamber: one having a single cue, and the other having dual cues for the discrimination of compartments. In both types of chamber, cocaine (5-20 mg/kg) and MAP (1-2 mg/kg) similarly produced conditioned place preference. However, repeated cocaine administration caused the development of locomotor sensitization only in the single-cue chamber. On the other hand, repeated administration of MAP resulted in the development of sensitization in both types of chamber. The findings indicate that environmental factors differentially affect the development of locomotor sensitization, but not place preference conditioning, following repeated administration of cocaine or methamphetamine. The advantages of this new system will be discussed.
Various plant-derived essential oils (EOs) have traditionally been used in the treatment of mental disorders, despite a lack of scientific evidence. In a previous study, we demonstrated that certain EOs possess behavioral effects, a finding that supports our original hypotheses that EOs possess psychoactive actions. The present study was conducted in order to obtain further evidence to support our hypothesis. Peppermint oil, a type of EO, is believed to be effective for treating mental fatigue. When the oil was administered intraperitoneally to ICR mice, the ambulatory activity of mice increased dramatically. We identified alpha-pinene, beta-pinene, (R)-(+)-limonene, 1,8-cineol, isomenthone, menthone, menthol, (R)-(+)-pulegone, menthyl acetate and caryophyllene as constituent elements of peppermint oil by GC-MS analysis. We then examined the effect of each constituent element of peppermint oil on ambulatory activity in mice. Intraperitoneal administration of 1,8-cineol, menthone, isomenthone, menthol, (R)-(+)-pulegone, menthyl acetate and caryophyllene significantly increased ambulatory activity in mice, suggesting that these chemicals are the behaviorally active elements of peppermint oil. Intravenous administration of these substances to mice induced a significant increase in ambulatory activity at much lower doses. The present study provides further evidence demonstrating that EOs possess pharmacological actions on behavior. In addition, our finding revealed that the action of peppermint oil comes from its constituent elements.
Induction of three drug-metabolizing enzymes occurred in liver microsomes of mice and rats kept on softwood bedding of either red cedar, white pine, or ponderosa pine. This induction was reversed when animals were placed on hardwood bedding composed of a mixture of beech, birch, and maple. Differences in the capacity of various beddings to induce may partially explain divergent results of studies on drug-metabolizing enzymes. The presence of such inducing substances in the environment may influence the pharmacologic responsiveness of animals to a wide variety of drugs.