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The effect of Elettaria cardamomum extract on anxiety-like behavior in a rat model of post-traumatic stress disorder
... E. cardamomum is cultivated commercially in India and Sri Lanka. Its traditional use is in the treatment of gastrointestinal disorders, but it is also used as an anti-depressant which, over a prolonged period, can enhance cognitive function [33,34]. In vivo studies suggest that alcoholic extracts of E. cardamomum have anxiolytic, anti-depressant, and cognition-enhancing properties, possibly due to its flavonoid content [34,35]. ...
... Its traditional use is in the treatment of gastrointestinal disorders, but it is also used as an anti-depressant which, over a prolonged period, can enhance cognitive function [33,34]. In vivo studies suggest that alcoholic extracts of E. cardamomum have anxiolytic, anti-depressant, and cognition-enhancing properties, possibly due to its flavonoid content [34,35]. The anxiolytic effects of E. cardamomum have been particularly attributed to the high flavonoid content and quercetin levels [34]. ...
... In vivo studies suggest that alcoholic extracts of E. cardamomum have anxiolytic, anti-depressant, and cognition-enhancing properties, possibly due to its flavonoid content [34,35]. The anxiolytic effects of E. cardamomum have been particularly attributed to the high flavonoid content and quercetin levels [34]. In many respects, the protective actions of E. cardamomum against Aβ were like that of J. regia, with a remarkable ability to restoring the chemosensing of G. pallida, and so this plant extract should also be prioritised for further investigations. ...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with unmet medical need. This investigation consisted of testing a range of ethanolic ethnomedicinal plant extracts (n = 18) traditionally used in the treatment of disorders such as anxiety, delirium, and memory loss. They were then screened for in vitro inhibitory activity against acetylcholinesterase (AChE), butylcholinesterase (BuChE), beta-secretase 1/beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), and antioxidant activities. Plants with potent activities were further characterised using a recently developed in vivo model of AD, Globodera pallida. The ability of phytoextracts to protect this organism against amyloid-beta Aβ (1-42) exposure was assessed by measuring chemosensing, survival rate, production of reactive oxygen species (ROS), and antioxidant responses. Extracts (n = 5) from Juglans regia (leaves), Ellettaria cardamomum (seeds), Cinnamomum zeylanicum (bark), Salvia officinalis (leaves/flowers), and Hypericum perforatum (flowers) exerted concentration-dependent inhibitory activities against AChE and BuChE. Three of these plant extracts (i.e., J. regia, E. cardamomum, and S. officinalis) possessed strong concentration-dependent inhibitory activity against BACE1. Furthermore, the five selected medicinal plant extracts not only enhanced significantly (p < 0.05) the nematode’s chemosensing, survival rate, and antioxidant responses (i.e., anti-ROS production, mitochondrial reductase activity, oxidized glutathione (GSSG) to reduced glutathione (GSH) ratio), but also greatly restored (p < 0.05) in a concentration-dependent manner the Aβ (1-42)-induced deleterious changes in these same parameters. In brief, this investigation highlights plant extracts with strong anti-AD activities which could be trialled as novel therapeutic supplements or undergo further biodiscovery research.
... In folk medicine, different parts of E. cardamomum have been used in the treatment of gastrointestinal disorders and also used as stomachic, resolvent, retentive, digestive, antiemetic, carminative and antiputrefactive (during embalmment), and in treating lung congestion, pulmonary tuberculosis, high blood pressure, heart disease and digestive disorders. High flavonoids levels are found filling the seeds and capsules of E. cardamomum and especially, quercetin is in command for anxiolytic effect (Masoumi-Ardakani et al., 2017;Elguindy, 2016). Khatri et al. (2017) has shown the presence of a variety of compounds like Vitamin E, Squalene, Eucalyptol, Stigmast-5-en-3-ol, 4H-1-Benjopyran-4-one, 2,3-dihydro-5, 7-dihydroxy-2-phenyl, Octadecanoic acid, Phytol, Hexadecanoic acid in the methanolic extract of Elettaria cardamomum. ...
... Researchers suggested that cardamom extract would prevent anxious behaviours. This perhaps due to the link between low blood levels of antioxidants to the development of anxiety and other mood disorders (Krolow et al., 2014;Masoumi-Ardakani et al., 2017;Gautam et al., 2012). ...
This reference book is based on the history, cultivation, processing, breeding, protection, phytochemistry, and pharmacological importance of cardamom. Cardamom is scientifically known as Elettaria cardamomum (L.) Maton and is a member of the Zingiberaceae family. It's a shade-loving plant that grows well at an altitude between 600 and 1400 metres above sea level, with annual rainfall ranging from 1300–4000 mm and temperatures ranging from 10 to 35°C. Cardamom is highly cross-pollinated and depends on honeybees for pollination. Cardamom is classified into three types based on the nature of the panicles, namely, Malabar (prostrate panicle), Mysore (erect panicle) and Vazhukka (semi-erect panicle), a natural hybrid between Mysore and Malabar varieties. In India, currently, six research institutions, namely, Cardamom Research Station (CRS), Pampadumpara (Kerala Agricultural University, Kerala), ICAR-Indian Institute of Spices Research (IISR), Kozhikode, Kerala; Cardamom Research Centre, Appangala, Karnataka; Indian Cardamom Research Institute (ICRI), Myladumpara, Kerala and its Regional Research Station, Sakleshpur, Karnataka and Regional Research Station, Mudigere (University of Agricultural and Horticultural Sciences) are engaged in research for the improvement of cardamom farming. These research institutions have begun doing routine surveys to exploit desirable genes using a variety of traditional and modern crop improvement techniques. Also, these research centres/institutes are holding enormous genetic wealth of different accessions. Recently, many researchers have used various biotechnological approaches to conduct studies on micropropagation, assess the diversity in germplasm collections, and elucidate the biotic and abiotic stress tolerance mechanisms in cardamom.
Fungal, bacterial and viral diseases pose severe threats to the successful cultivation of this crop. Major pests of cardamom include thrips, shoot and capsule borer, root grub, and whiteflies. Injudicious pesticide applications to manage pests and diseases rises the residue levels in the cured product, limiting its export value. Bio-pesticides control pest in an eco-friendly manner and are considered as the best alternatives to synthetic pesticides. It includes the effective utilization of microbials (bacteria, fungi, virus, and nematodes), macrobials (predators, parasitoids, and parasites), botanicals, organic amendments, semiochemicals, endophytes, and reduced risk pesticides in managing pest and diseases.
Cardamom is grown in the throughout tropical mountains mainly for its capsules and its essential oil. Cardamom capsules/seeds accumulate essential oil and other bioactive metabolites, which contribute to their distinctive aroma and are used in the functional food, pharmaceutical, and nutraceutical industries. More than 100 secondary metabolites have been identified from cardamom essential oil. The essential oil of cardamom capsules possesses predominantly monoterpene constituents, such as 1,8-cineole, α-pinene, α-terpineol, linalool, linalyl acetate and nerolidol and the ester constituent α-terpinyl acetate all of which have therapeutic benefits including antioxidant, anticancer, antidiabetic, anti-inflammatory, antifungal, antiviral and gastroprotective activities. Cardamom capsules contain substantial concentration of flavonoids like catechin, myricetin, kaempferol and quercetin. Lutein is said to be the most abundant carotenoid in small cardamom. According to recent investigations, cardamom phenolic constituents’ flavonoids, alkaloids, terpenoids, and anthocyanins are being used to treat cardiovascular, pulmonary, kidney, and lung disorders. Cardamom capsules are a nutraceutical and functional food that can protect humans from several chronic diseases when taken daily. Cardamom oil is a new potential natural source for food, aroma, cosmetics, and pharmaceuticals.
Since the 4th century BC, Indian Ayurvedic physicians, as well as Greek and Roman doctors, have used small cardamom capsules to treat bronchitis, asthma, and constipation, as well as colds, coughs, diuretics, carminatives, teeth and gum infections, urinary and kidney disorders, congestion of the lungs, pulmonary tuberculosis, irritation of the eyelids, cataract, nausea, and diarrhoea. Cardamom was used to treat constipation, stomach aches, bladder infections, and dysentery in children in traditional Chinese medicine. Cardamom is also used in Ayurvedic medicine to cure food sickness. Cardamom oils are being employed in the production of plant-based hand lotions and soaps. Digestive problems can be treated with powdered cardamom capsules mixed with pulverised cloves, ginger, and caraway. In addition, using cardamom capsules helps to relieve inflammation and headaches.
This reference book entitled “Cardamom [Elettaria cardamomum (L.) Maton]: Production, Breeding, Management, Phytochemistry and Health Benefits” is comprises of twelve chapters contributed by different authors and provide complete information about this wonderful herb. Its occurrence, history, cultivation, post-harvest processing, botany, crop improvement, biotechnology, protection, ethnopharmacological uses, phytochemistry and pharmacological activities are well described with supporting references.
The book contains latest information pertaining to cardamom and its cultivation. The information provided in this book will be very useful for students, academicians, researchers, and scientists, as well as others interested/involved nutraceutical and pharmaceutical industries.
... As sustained elevations in serum corticosterone induce animals and humans' anxious behavior, its low circulating concentration might be a direct effect of cardamom intake in the hypothalamus. It has been shown that the EC compound quercetin inhibits CRH mRNA expression in the PVN through the activation of GABA A receptors and has anxiolytic effects [36][37][38]. Moreover, the increased food intake of EC-fed mice could not be due to the hyperphagic effects of corticosterone. ...
Cardamom seed (Elettaria cardamomum (L.) Maton; EC) is consumed in several countries worldwide and is considered a nutraceutical spice since it exerts antioxidant, anti-inflammatory, and metabolic activities. In obese individuals, EC intake also favors weight loss. However, the mechanism for these effects has not been studied. Here, we identified that EC modulates the neuroendocrine axis that regulates food intake, body weight, mitochondrial activity, and energy expenditure in mice. We fed C57BL/6 mice with diets containing 3%, 6%, or 12% EC or a control diet for 14 weeks. Mice fed the EC-containing diets gained less weight than control, despite slightly higher food intake. The lower final weight of EC-fed mice was due to lesser fat content but increased lean mass than control. EC intake increased lipolysis in subcutaneous adipose tissue, and reduced adipocyte size in subcutaneous, visceral, and brown adipose tissues. EC intake also prevented lipid droplet accumulation and increased mitochondrial content in skeletal muscle and liver. Accordingly, fasting and postprandial oxygen consumption, as well as fasting fat oxidation and postprandial glucose utilization were higher in mice fed with EC than in control. EC intake reduced proopiomelanocortin (POMC) mRNA content in the hypothalamic arcuate nucleus, without an impact on neuropeptide Y (NPY) mRNA. These neuropeptides control food intake but also influence the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes. Thyrotropin-releasing hormone (TRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) and circulating triiodothyronine (T3) were lower in EC-fed mice than in control. This effect was linked with decreased circulating corticosterone and weight of adrenal glands. Our results indicate that EC modulates appetite, increases lipolysis in adipose tissue and mitochondrial oxidative metabolism in liver and skeletal muscle, leading to increased energy expenditure and lower body fat mass. These metabolic effects were ascribable to the modulation of the HPT and HPA axes. LC-MS profiling of EC found 11 phenolic compounds among which protocatechuic acid (23.8%), caffeic acid (21.06%) and syringic acid (29.25%) were the most abundant, while GC-MS profiling showed 16 terpenoids among which costunolide (68.11%), ambrial (5.3%) and cis-α-terpineol (7.99%) were identified. Extrapolation of mice-to-human EC intake was performed using the body surface area normalization equation which gave a conversion equivalent daily human intake dose of 76.9–308.4 mg bioactives for an adult of 60 kg that can be obtained from 14.5–58.3 g of cardamom seeds (18.5–74.2 g cardamom pods). These results support further exploration of EC as a coadjuvant in clinical practice.
... Mesua nagassarium (Siru naga poo) is a blood purifier and cardiotonic[21]. Elettaria cardamomum (Ellam) is known for its anti inflammatory, anti oxidant activity[22]. Piper nigrum (Pepper) is known for its anti oxidant, anti hypotensive, anti inflammatory activity[23]. The Patient have no signs symptoms of AWS such as tremulousness of hands, increased anxiety and agitation and decreased sleep with headache after 48 days of treatment with Inji rasayanam, Amukkara chooranam and Bhrami nei. ...
Addictive use of Alcohol has been a considerable health problem, not only having impact on individual and families, but creates a lasting social burden on the society. One third of the Indian population is using alcohol in an unhealthy manner, the complications are wide and varied among which, the Alcohol withdrawal syndrome (AWS) is the dominant factor. AWS is a set of symptoms that can occur when a heavy drinker suddenly stops or significantly reduces their alcohol intake. The presentation varies from mild sleep loss or anxiety to the life threatening situation like delirium (confusion). The excessive intake of unwholesome alcohol leads to Mathathiyam (Kudiveri Noi in the Siddha – Indian Tamil language) and it degrades knowledge and health according to Siddha medicine and practise. Manifestation occur as per the aggravated/ vitiated three biological forces (Vali, Azhal, Iyyam – Indian Tamil language) leads to cause impair the quality or efficiency of life, and which may even leads to death. Hence, there is a need for AWS management at an early stage. The aim is to minimize the withdrawal symptoms which prevents complications and reduces the intense use for alcohol using the siddha system of medicines. The efficacy of Inji rasayanam (Rejuvenator), Brahmi nei (Medicated ghee), and Ammukkara chooranam (Medicated powder) for AWS is well known. Therefore, it is of interest to describe the case of a 35 years old male patient presented with AWS and treated with Siddha drugs for 48 days. The condition was assessed before and after treatment using the clinical institute withdrawal assessment for alcohol scale revised (CIWA-Ar). Data shows effective management of AWS using the Siddha medicines.
... In small animals, quercetin was shown to alleviate fear and depression. [40,41]. ...
The use of live cells to synthesize green nanoparticles (NPs) is a promising and novel bio nanotechnology method. Chemical and physical methods are utilized to synthesize NPs; however, biological approaches are preferred because they are ecologically friendly, safe, healthful, cost-effective, accessible, and effective sources of high productivity and purity. Toxic and hazardous substances, as well as the use of external reducing, stabilizing, or capping agents, are not necessary for the green synthesis of NPs. Cardamom seeds, which are little Capsules (fruits) of Elettaria cardamomum (Family (Zingiberaceae)], have been used in herbal medicine to treat a wide range of ailments, including asthma, tooth and gum infections, cataracts, nausea, diarrhea, and cardiac, digestive, and kidney problems. Cardamom capsules have a number of additional health benefits that are important from both a traditional and current pharmacological perspective. MO-NPs (metal oxide nanoparticles) have caused quite a stir in recent years due to their diverse set of properties. Elettaria cardamomum is high in polyphenolic compounds and flavonoids, making it a viable green source for large-scale, low-cost, and environmentally friendly MgO-NP production. UV-Visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) with EDS are used to investigate the phytoassisted synthesis of MgO. (Energy dispersive X-ray spectroscopy). Researchers have successfully disseminated suitable MO-NPs for obtaining significant results by leveraging their numerous desirable qualities, such as those found in the pharmaceutical, ceramics, textile, electronic, and fertilizer industries.
... Dried materials (250 g) were extracted by using the percolation technique with methanol for 72 h at 21 曟 . Then, the extract was filtered by a filter paper and evaporated at 50 曟 in a vacuum and reserved at −20 曟 for further examinations [11]. ...
... An animal study demonstrated that high flavonoids contents of Elettaria cardamomum (L.) Maton especially quercetin possesses anti-depressant and anxiolytic effect. 30 The Extracts of Coriandrum sativum L. might produce an antidepressant-like effect by interacting with a1 adrenoreceptor dopamine D2 receptor and GABAergic receptor, through increasing level norepinephrine and dopamine and decreasing level of Dopamine. 42 Phyllanthus emblica L. contains flavonoids, saponins, and tannins that possess activity against many CNS disorders like depression and anxiety. ...
Background and aim
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders characterized by chronic recurrent abdominal pain related to a change in bowel habit or defecation frequency and commonly accompanied by anxiety and depression affecting about 10% population globally. Jawarish Shahi (JS) is a special dosage form prepared for gastrointestinal disorders in Unani medicine containing Phyllanthus emblica L., Terminalia chebula Retz., Coriandrum sativum L., Elettaria cardamomum (L.) Maton and Salix caprea L. Considering the antioxidant, immunomodulatory, antispasmodic analgesic, antidiarrheal, antisecretory, laxative, anti-inflammatory, anxiolytic, and antidepressant properties, the present study was aimed to evaluate the efficacy of JS in IBS.
Experimental procedure
This single-arm open-labeled clinical trial was conducted on 26 male and female patients of IBS according to Rome IV criteria, aged 18–50 years with moderate symptoms. JS was given 7 g orally twice a day after meal with water for 45 days. IBS Severity Scoring Scale (IBS-SSS) was used for efficacy outcomes and the difference was analyzed from baseline to the subsequent follow-ups.
Results
Data analysis of subsequent followup showed a significant decrease in IBS-SSS scores except for 2nd followup, scores decreased from 229.50 ± 75.91 to 203.12 ± 71.71 (p < 0.1018), 150.61 ± 55.32 (p < 0.0001), and 123.76 ± 54.81 (p < 0.0001) at 0, 15th, 30th, 45th day of follow up respectively.
Conclusion
The present study revealed that JS is safe and effective in reducing the overall symptoms of IBS in respect to its severity and impact on quality of life and can be used as an alternate as well as a complementary treatment in IBS.
... A video camera at top of the field recorded F I G U R E 1 Timeline diagram these elements and animals' performance was recorded by Noldus Ethovision system, version 7.1. Number of rearings was recorded by the experimenter (Masoumi et al., 2017). ...
Early-life experiences, including parental care, affect cognitive performance later in life. Being exposed to early-life maternal separation (MS) increases susceptibility to stress-related psychopathology. Previous studies suggest that MS could induce learning and memory impairments. Since enriched environment (EE) provides more opportunities for exploration and social interaction, in the present study we evaluated the effects of a short EE paradigm with a duration of 13 days on cognitive abilities of maternally separated rats (MS; 180 min/day, postnatal day (PND) 1–21) during adolescence in four experimental groups: Control, Control+EE, MS, and MS+EE. Plasma corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels were also measured in experimental animals. We also studied the induction of long-term potentiation (LTP) in the slices of hippocampal CA1 area. The behavioral and electrophysiological assessments were started at PND 35. MS caused higher basal CORT levels in plasma and impaired spatial learning, memory, and social interaction. LTP induction was also impaired in MS rats and plasma BDNF levels were reduced in these animals. MS also induced more anxiety-like behavior. Short EE reduced plasma CORT levels had the potential to improve locomotor activity and anxiety-like behavior in MS+EE rats and reversed MS-induced impairments of spatial learning, memory, and social behavior. LTP induction and plasma BDNF levels were also enhanced in MS+EE rats. We concluded that short EE might be considered as a therapeutic strategy for promoting cognition.
... The chemopreventive effect of cardamom has also been demonstrated earlier to control colorectal cancer [12] and to prevent papillomagenesis on the skin [9]. Furthermore, cardamom extract was found to lessen PTSD-like anxiety symptoms in test animals [13]. One study found that when cardamom was consumed during pregnancy, offspring showed enhanced learning, memory, and behavior [14]. ...
Background
Cardamom ( Elettaria cardamomum ) is a spice and exhibits potent antioxidant and biological activities through distinct molecular mechanisms. However, the anticancer effect of cardamom was not explored yet in Ehrlich solid tumor (EST)-bearing mice.
Objectives
This investigation was aimed to evaluate the anti-cancer effects of green cardamom (GCar) alone or combined with the anti-cancer drug cyclophosphamide in an in vivo model to explore its mechanistic role in tumor cell death in EST-bearing mice.
Methods
Ehrlich ascites tumor cells were injected in the mice and 5 days later the animals treated with GCar and/or cyclophosphamide for 10 days. Twenty-four hours from the last treatment, animals were sacrificed for the different measurements.
Results
Data recorded for tumor size, percentage of tumor growth inhibition, tumor growth delay and mean survival time of EST-bearing mice demonstrated the effective role of GCar alone or combined with CPO as a promising anti-cancer agent because it reduced tumor size. GCar elevated the mean survival time of EST-bearing mice compared to that of untreated EST and EST + CPO groups. Analysis of qPCR mRNA gene and protein expression revealed that GCar alone or combined with CPO were promising anticancer agents. After the treatment of EST with GCar, the apoptotic-related genes and proteins were significantly modulated. GCar induced markedly significant decreases in oxidative stress biomarkers and a significant increment in glutathione levels and that of antioxidant enzymes. With a marked diminish in liver and kidney function biomarkers.
Conclusion
The results revealed that GCar could serve as an apoptotic stimulator agent, presenting a novel and potentially curative approach for cancer treatment, inducing fewer side effects than those of the commercially used anti-cancer drugs, such as CPO.
... A video camera on the top of the field recorded these elements and the animals' performance was recorded by the Noldus Ethovision system, version 7.1. The number of rearing behavior was recorded by the experimenter (Masoumi et al., 2017). ...
Early life adversity (ELA) is a predisposing factor for the development of behavioral and emotional disorders later in life. In humans, primates and rodents, interruption in the mother-infant relationships, and disorganized maternal care negatively influence appropriate behavioral responses and may cause cognitive deficits. Epidemiological studies suggest that ELA-induced behavioral alterations can be transmitted across generations. In this study, we investigated the cognitive abilities of male and female rats in the second filial (F2 ) generations whose mother, father, or both of their parents were undergoing a 180 min/day maternal separation (MS) paradigm during infancy (post-natal day (PND) 1-21). Cognitive abilities (in the open field, Morris water maze, and social interaction task) of F2 pups were tested during adolescence. Our results showed that although the mother-MS group of both sexes showed normal cognitive behavior, father-MS female pups showed more anxiety in the open field, and social interaction and spatial memory impaired in this group. These impairments were not pronounced in every detail in father-MS male pups. Moreover, rat pups that both parents experienced MS during infancy, showed normal cognitive behavior. Our data support the idea that MS-induced cognitive impairments could be transmitted across generations. Considerably, the experiences of one's parents could be inherited in the following generation in a sex-dependent manner.
... Phytochemical analysis of the aqueous extract of E. cardamomum fruit shows the presence of alkaloids, flavonoids, tannins, terpenoids, reducing sugars, steroids and phenols. 29 The results of this study are in agreement with the work of Masoumi-Ardakania 21 , who showed that the methanolic extract of cardamum seeds contains high concentrations of kaempferol, rutin and quercetin. ...
... A video camera on the top of the field recorded these elements and the animals' performance was recorded by the Noldus Ethovision system, version 7.1. The number of rearing behavior was recorded by the experimenter (Masoumi et al., 2017). ...
Rodents are highly dependent on maternal care after birth. Maternal separation (MS) is an animal model for studying neglect and abuse. Depriving the pup of such care renders the animal with Hypothalamic–Pituitary–adrenal (HPA) dysfunction and these animals are more susceptible to anxiety and stress as well as poor cognition. These effects are due to abnormal brain development in these animals. We have tried to investigate how maternal separation can affect pain sensation and whether a non‐pharmacological intervention such as enriched environment (EE) can restore an abnormal pain sensation. Animals were put into four groups MS, control (CTRL) and MS+EE and CTRL+EE groups that underwent EE after weaning until adulthood. These groups were tested for pain sensitivity with hotplate and tail flick for sensory pain and formalin for affect pain. The results showed that MS rats are more sensitive to pain in the hotplate test and formalin test, however, no significant difference was seen between groups for tail flick test. When MS rats experience EE their pain sensitivity is restored at the behavioral level. Further research is required to see how EE restores pain sensation in MS rats.
... According to Abu-Taweel, cardamom added to the rations of pregnant mice improved both memory and learning, and even brought perinatal benefits since the compounds can be transported via the placenta and/or during lactation [62]. Also, anxiolytic effects have been reported in the literature for cardamom [63]. Analysis of the chemical composition of E. cardamomum essential oil (ECEO) by GC/MS identified 93.5% of the constituents; 1,8-cineole (45.6%), α-terpinyl acetate (33.7%), terpinen-4-ol (2.4%), and myrcene (2.2%) [64]. ...
Epilepsy is a most disabling neurological disorder affecting all age groups. Among the various mechanisms that may result in epilepsy, neuronal hyperexcitability and oxidative injury produced by an excessive formation of free radicals may play a role in the development of this pathology. Therefore, new treatment approaches are needed to address resistant conditions that do not respond fully to current antiepileptic drugs. This paper reviews studies on the anticonvulsant activities of essential oils and their chemical constituents. Data from studies published from January 2011 to December 2018 was selected from the PubMed database for examination. The bioactivity of 19 essential oils and 16 constituents is described. Apiaceae and Lamiaceae were the most promising botanical families due to the largest number of reports about plant species from these families that produce anticonvulsant essential oils. Among the evaluated compounds, β-caryophyllene, borneol, eugenol and nerolidol were the constituents that presented antioxidant properties related to anticonvulsant action. These data show the potential of these natural products as health promoting agents and use against various types of seizure disorders. Their properties on oxidative stress may contribute to the control of this neurological condition. However, further studies on the toxicological profile and mechanism of action of essential oils are needed.
... The use of substances that diminish anxiety patterns makes the animal feel calmer and consider the environment less threatening. [14][15][16][17] However, our results with the use of EM did not significantly differ from the control group. ...
... The use of substances that diminish anxiety patterns makes the animal feel calmer and consider the environment less threatening. [14][15][16][17] However, our results with the use of EM did not significantly differ from the control group. ...
... The tight junction of endothelial cells i.e. blood brain barrier which merely allows free passage of lipid soluble drugs [16] . [18] . ...
Background: In traditional ayurved science, BrahmiGhrita [BG] is prescribed in the management of Unmada [depressive disorder]. It comprises of Brahmi, Ela and Puranghrita (10 years old clarified butter). However, generally Fresh Goghrita [Cow ghee] is utilized to prepare medicated ghee formulations. Till date antidepressant activity of BG in stress induced depression is not yet documented. Aims: Thus present study was conducted to assess antidepressant activity of two samples of BrahmiGhritaviz BG I and BG II in Chronic Unpredictable Mild Stress (CUMS) animal model.
Methods and material: Puran Ghrita, fresh Goghrita, BG I and BG II were administered orally at therapeutic dose [3.6gm/kg] along with application of specified stressors for 28 days. Animals were tested before and after treatment with Sucrose Preference and Force Swim test [FST]. Statistical test applied: ANOVA followed by Tuke’s test. Results: CUMS exposed animals showed depressive like behavior, with significant decrease in sucrose consumption and number of rotations in FST. Animals from standard drug [Imiprimine], BG I and BG II have shown significant increase in rotations in FST [p≤0.0001] as compared to CUMS group. BG I and BG II demonstrated significant behavioral changes in animals as compared to Puranghrita and fresh Goghrita respectively [p≤0.05]. Despite that, the role of Puran Ghrita in preparation of Brahmi Ghrita couldn’t be evaluated as against Brahmi Ghrita of fresh Goghrita in CUMS induced depressive rats.
Conclusions: BrahmiGhrita prepared from ten years old and fresh cow ghee have confirmed antidepressant like effect in CUMS study.
... The tight junction of endothelial cells i.e. blood brain barrier which merely allows free passage of lipid soluble drugs [16] . [18] . ...
ABSTRACT
Background: In traditional ayurved science, BrahmiGhrita [BG] is prescribed in the management of Unmada [depressive disorder]. It comprises of Brahmi, Ela and Puranghrita (10 years old clarified butter). However, generally Fresh Goghrita [Cow ghee] is utilized to prepare medicated ghee formulations. Till date antidepressant activity of BG in stress induced depression is not yet documented. Aims: Thus present study was conducted to assess antidepressant activity of two samples of Brahmi Ghrita viz BG I and BG II in Chronic Unpredictable Mild Stress (CUMS) animal model.
Methods and material: Puran Ghrita, fresh Goghrita, BG I and BG II were administered orally at therapeutic dose [3.6gm/kg] along with application of specified stressors for 28 days. Animals were tested before and after treatment with Sucrose Preference and Force Swim test [FST]. Statistical test applied: ANOVA followed by Tuke’s test. Results: CUMS exposed animals showed depressive like behavior, with significant decrease in sucrose consumption and number of rotations in FST. Animals from standard drug [Imiprimine], BG I and BG II have shown significant increase in rotations in FST [p≤0.0001] as compared to CUMS group. BG I and BG II demonstrated significant behavioral changes in animals as compared to Puranghrita and fresh Goghrita respectively [p≤0.05]. Despite that, the role of Puran Ghrita in preparation of Brahmi Ghrita couldn’t be evaluated as against Brahmi Ghrita of fresh Goghrita in CUMS induced depressive rats.
Conclusions: Brahmi Ghrita prepared from ten years old and fresh cow ghee have confirmed antidepressant like effect in CUMS study.
... These results provided a novel insight into the opioidergic system involvement in the negative effects of the psychostimulant METH on cognition. Animal's studies are more important for cognitive and behavioral interventions [23][24][25][26][27][28]. The findings of this research are in line with those of the previous animal's studies regarding METH adverse effects on memory [4,29,30]. ...
Background:
Methamphetamine (METH) as a synthetic psychostimulant is being increasingly recognized as a worldwide problem, which may induce memory impairment. On the other hand, it is well established that naloxone, an opiate antagonist, has some beneficial effects on learning and memory. The present research aimed at evaluating naloxone effects on spatial learning and memory impairment triggered by a neurotoxic regimen of METH in male rats.
Materials and methods:
The animals received the subcutaneous (sc) regimen of METH (4×6 mg/kg at 2-h intervals), intraperitoneal (ip) naloxone (4×1 mg/kg at 2-h intervals), or normal saline at four events. The Nal-METH group of rats received four naloxone injections (1 mg/ kg, ip) 30 min before each METH injection (6 mg/kg, sc) at 2-h intervals. Seven days later, they were evaluated for spatial learning and memory in the Morris Water Maze (MWM) task.
Results:
METH regimen induced hyperthermia, as well as a poor performance, in the acquisition and retention phases of the task, indicating spatial learning and memory impairment compared to the controls. Naloxone administration (1 mg/kg, ip) before each METH injection led to significant attenuations of both hyperthermia and METH adverse effects on the rat performance in the MWM task.
Conclusion:
The results revealed that pretreatment with the opiate antagonist naloxone could prevent METH adverse effects on body temperature and memory performance. It seems that the opioidergic system and hyperthermia may, at least partially, be involved in METH effects on spatial memory.
... Valeriana wallichii as anti depressant 61 , improves sleep 62 and neuroprotective 63 , Rubia cordifolia as having anti stress and nootropic action 64 , Punica granatum as Antidepressant and having Anti-Anxiety Effect 65 , Embelia ribes having antidepressant-like activity 66 , Elettaria cardamomum having Antidepressant and Anti-Anxiety Effect 53,67 , Jasminum sambac having anti stress effect 68 and Santalum album is sedative and neuro protective. 56,69 ...
Aim: This review article is an attempt to analyse the probable mode of action of Kalyanaka ghrita in psychiatric conditions.
... These results provided a novel insight into the opioidergic system involvement in the negative effects of the psychostimulant METH on cognition. Animal's studies are more important for cognitive and behavioral interventions [23][24][25][26][27][28]. The findings of this research are in line with those of the previous animal's studies regarding METH adverse effects on memory [4, 29,30]. ...
Background: Methamphetamine (METH) as a synthetic psychostimulant is being increasingly recognized as a worldwide problem, which may induce memory impairment. On the other hand, it is well established that naloxone, an opiate antagonist, has some beneficial effects on learning and memory. The present research aimed at evaluating naloxone effects on spatial learning and memory impairment triggered by a neurotoxic regimen of METH in male rats. Materials and Methods: The animals received the subcutaneous (sc) regimen of METH (4×6 mg/kg at 2-h intervals), intraperitoneal (ip) naloxone (4×1 mg/kg at 2-h intervals), or normal saline at four events. The Nal-METH group of rats received four naloxone injections (1 mg/kg, ip) 30 min before each METH injection (6 mg/kg, sc) at 2-h intervals. Seven days later, they were evaluated for spatial learning and memory in the Morris Water Maze (MWM) task. Result: METH regimen induced hyperthermia, as well as a poor performance, in the acquisition and retention phases of the task, indicating spatial learning and memory impairment compared to the controls. Naloxone administration (1 mg/kg, ip) before each METH injection led to significant attenuations of both hyperthermia and METH adverse effects on the rat performance in the MWM task. Conclusion: The results revealed that pretreatment with the opiate antagonist naloxone could prevent METH adverse effects on body temperature and memory performance. It seems that the opioidergic system and hyperthermia may, at least partially, be involved in METH effects on spatial memory. [GMJ. 2019;8:e1182]
... Some studies suggested that Elettaria cardamomum methanolic extract significantly recovered anxiety-like behaviors in a rat model of PTSD conducted by the OFT, EPM, and rotarod tests [38]. Also, administering berberine, an isoquinoline alkaloid derived from Korean traditional medicinal herbs, such as Coptidis Rhizoma after SPS procedure, significantly increased the time spent in the open arms in the EPM and prevented reduction in brain level of dopamine [39]. ...
Posttraumatic stress disorder (PTSD) is a trauma-induced psychiatric disease characterized by impaired hyperarousal, fear extermination, depression, anxiety, and amnesic symptoms that may include the release of monoamines in the dread circuit. Curcumin (CUR), a major diarylheptanoid and polyphenolic component of Curcuma longa , reportedly possesses several pharmacological features, including antidiabetic, antiatherosclerotic, anticancer, and neuropsychiatric actions. But the anxiolytic-like effects of CUR and its mechanism of action in PTSD are unclear. The current research measured some anxiety-related behavioral responses to examine the effects of CUR on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) dysfunction. Rats received CUR (20, 50, or 100 mg/kg, i.p., once daily) for 14 days after SPS exposure. Administration of CUR significantly increased the number of central zone crossings in the open field test and reduced grooming behavior in the elevated plus maze (EPM) test and increased the number of open-arm visits on the EPM test. CUR administration significantly reduced freezing response to contextual fear conditioning. CUR recovered neurochemical abnormalities and SPS-induced decreased 5-HT tissue levels in the hippocampus, amygdala, and striatum. These results suggested that CUR has anxiolytic-like effects on biochemical and behavioral symptoms associated with anxiety. Thus, CUR may be a useful agent to alleviate or treat psychiatric disorders similar to those observed in patients with PTSD.
... Coffee arabica (Qahwa) is flavor-rich with cardamom. Cardamom (Elettaria cardamomum) contained α terpineol, myrcene, limonene, menthone, βphellandrene, 1,8-cineol, sabinene and heptane and borneol (Farooq et al. 2015) found to possess anxiolytic (Masoumi-Ardakani et al. 2017) and it enhance learning and memory retention as compared to control (Abu-Taweel 2018). ...
The comparative effects of coffee robusta and coffee arabica (Qahwa) on different attention and memory related assignments were measured in a double-blind study of 300 healthy young adult women who were randomly assigned to one of three different drinks: Group I (coffee robusta sachet dissolved in 100 ml of hot water): Group II (coffee arabica): and group III (100 ml water only). Cognitive function was assessed by standardized tests. Several monitoring cognitive tests and tasks were specifically chosen and performed to investigate the comparative effects of coffee robusta (CR) and coffee arabica (Qahwa; AC) on sleepiness (sleep and clear headed scale), attention (trail A & B, symbol digit, letter cancellation), general cognitive ability (stroop test) and memory (card test). Data was interpreted by analysis of variance (ANOVA). The present study revealed that coffee robusta has beneficial effects on attention, general cognitive ability and memory. Higher though non-significant cognitive scores were associated with coffee robusta consumption. Although, consumption of coffee arabica (Qahwa) has significant effects (P < 0.05) on sleepiness, attention, general cognitive ability and memory and it significantly improve reaction time and correct responses. Since different tasks were related to the sustained attention and working memory processes, results would suggest that coffee arabica (qahwa) could increase the memory and efficiency of the attentional system might be due to the presence of chlorogenic acids (CGA) which are found in less quantity in coffee robusta. However, more studies using larger samples and different tasks are necessary to better understand the effects of coffee robusta and arabica (Qahwa) on attention and memory.
... The most recent papers demonstrated anxiolytic effects of Lippia graveolens L. [129], Lavandula officinalis L. [130], Trigonella foenumgraecum L. seeds [131], Tanacetum parthenium L. [132], Elettaria cardamomum L. [133], Caesalpinia digyna Rottler L. roots [134], Xiao Yao San [135] or Cocos nucifera L. [136] in preclinical research. There are also several recent clinical evaluations focusing on anxiolytic effects of plant extracts. ...
... Other authors have shown that the noise may increase the anxiety patterns indicating it work as a stress condition. [21][22][23] Haider et al. [17] showed that 15 days of exposure to noise stress resulted in deficits in working and recognition memory in rats and related this condition to changes in dopamine and in the hydroxy-tryptamine. ...
... Closed areas work as a safe place to the animal for example, to avoid the presence of predators. The use of substances that diminish anxiety patterns makes the animal feel calmer and consider the environment less threatening.[14][15][16][17]However, our results with the use of EM did not significantly differ from the control group. ...
... Usually an animal without any treatment tends to remain for a longer time in the closed arms that represents an exposition to naturally threatening situations, which in the The presence of substances that reduce anxiety makes the animal feel calmer and consider the environment less threatening. [23][24] Usually the animal is observed in the EPM for 5 minutes and is allowed to explore the structure freely in this period of time. Exploring the open arms occurs only in 20 to 25% of the time, indicating a behavior to avoid exploring these arms. ...
Ethnopharmacological relevance:
Depression is a public health problem. Despite the availability of treatment options, its prevalence is increasing. A high rate of treatment failure is often reported, along with considerable side effects associated with synthetic antidepressants. Therefore, developing effective and safe antidepressants from traditional herbs or natural products as an alternative strategy is warranted to avoid side effects and increase drug efficacy. In traditional medicine, cardamom has traditionally been used to treat conditions like asthma, tooth and gum infections, cataracts, nausea, diarrhea, and even depression and anxiety as well as some problems with the heart, kidneys, and digestive system.
Aim of the study:
The current study aimed to evaluate the antidepressant activity of cardamom oil in a rat model of depression induced by reserpine and compare it with the activity of the antidepressant drug fluoxetine.
Materials and methods:
Depression-like symptoms were induced in male rats by daily i.p. injection of reserpine (0.2 mg/kg/d for 15 d followed by 0.1 mg/kg/d for 21 d to maintain the depressive state), and the rats were treated with cardamom oil (oral dose = 200 mg/kg/d) for 21 d along with the maintenance dose of reserpine. We performed behavioral tests (forced swimming test and open-field test) and evaluated biochemical markers of depression.
Results:
Our findings revealed that cardamom oil attenuated depression-like symptoms in reserpine-injected rats by improving the behavioral changes measured by the forced swimming test and the locomotor activities measured by the open-field test. In reserpine-injected rats, cardamom oil exerted antidepressant-like effects by modulating lower levels of brain monoamine neurotransmitters (serotonin, norepinephrine, and dopamine), GSH, and higher oxido-nitrosative stress parameters (malondialdehyde and nitric oxide). Moreover, cardamom oil alleviated depression-like behaviors by lowering monoamine oxidase activity and raising the activities of Na+/K+-ATPase and acetylcholinesterase and levels of a brain-derived neurotrophic factor in the cortex and hippocampus.
Conclusion:
We recommend the use of cardamom oil as a safe and reliable treatment or an adjuvant for preventing depression-like symptoms in patients suffering from depression.
We aimed to investigate the in vitro and ex vivo anti-helminthic effects of Astragalus ecbatanus chloroform extract (AECE) as well as its cellular mechanisms against Echinococcus granulosus protoscoleces. In vitro and ex vivo anti-helminthic effects of AECE on E. granulosus protoscoleces were evaluated through eosin exclusion test. Effects of AECE on induction of the caspase-3 like activity, the permeability of plasma membrane were also determined. The effects of AECE against the human hepatocyte carcinoma (HepG2) and human embryonic kidney (HEK293T) cells were determined by MTT ([3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyl tetrazolium bromide)]) test. The findings revealed that AECE especially at 45 mg/mL displayed potent in vitro and ex vivo anti-helminthic effects against E. granulosus protoscoleces (p < 0.001). After treatment of protoscoleces with AECE, the caspase-3 enzyme activity and the rate of permeability of plasma membrane was dose dependently (P < 0.001) increased. The 50% cytotoxic concentration (CC50) value of AECE for normal and cancer cells lines 4.62 mg/mL and 1.89 mg/mL, respectively. The findings of the current study revealed the favorable in vitro and ex vivo anti-helminthic effects of AECE against protoscoleces of E. granulosus. However, further surveys in animal model are required to elucidate different aspects of this extract before use in clinical phases.
Objective
To analyze the effects of cluster needling at scalp acupoints (CNSA) on behavioral performance and expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the hippocampus of rats with schizophrenia, and therefore, to shed light on the mechanism of action of CNSA in attenuating schizophrenia.
Methods
Thirty-six Wistar rats were randomly divided into the control, model, risperidone, and CNSA groups (9 rats per group). The schizophrenia model was prepared by injecting 0.1 mg/mL dizocilpine maleate (MK-801) for 14 consecutive days. Subsequently, rats in the risperidone and CNSA groups were subjected to the following therapy for 14 consecutive days: (1) Risperidone group: intragastric administration of risperidone suspension (0.4 mg/kg); (2) CNSA group: the “GV 20” “Qiándĭng (前顶GV 21) ” “Shéntíng (神庭GV 24) ” “Xìnhuì (囟会 GV 22) ” “Tōngtiān (通天BL 7) ” “Luòquè (络却BL 8) ” “Qūchā (曲差BL 4) ” and “Wŭchù (五处 BL 5) ” acupoints were selected for needle positioning. Following 14-day intervention period, the Morris water maze experiment and open field experiment were performed. Finally, hippocampal tissue specimens were collected and SOD, CAT, and GSH-Px expression levels were measured by ELISA. Results: (1) Morris water maze experiment: Following the 14-day model construction period, the model, risperidone, and CNSA groups showed a significant increase in escape latency (all P<0.05) and a significant decrease in the number of platform crossings (all P<0.05) compared with the control group, indicating successful induction of schizophrenia in the rat model. At the end of the intervention period (28d), the risperidone and CNSA groups showed a significant decrease in escape latency (both P<0.05), and the CNSA group showed a significant increase in the number of platform crossings (P<0.05) compared with the model group. (2) Open field experiment: At 14d, the model, risperidone and CNSA groups exhibited a significant decrease in the travelled distance and amount of time spent in the central zone (all P<0.05) compared with the control group (all P<0.05). At 28d, the risperidone and CNSA groups showed a significant increase in the travelled distance and percentage of time spent in the central zone (P<0.05 or P<0.01). (3) Antioxidant enzyme expression: At 28d, the model group exhibited significant decreases in the hippocampal SOD, CAT, and GSH-Px levels, compared with the control group (P<0.01 or P<0.001).
Conclusion
CNSA enabled the attenuation of cognitive impairment and enhancement of memory and learning abilities in the rat model of schizophrenia, plausibly through inhibition of the expression of oxidative stress factors in the hippocampus.
Anxiety is a disorder with known etiology and clinical symptoms which is managed by combination therapy or the use of complementary and alternative medicine (CAM), such as psychopharmacotherapy, cognitive behavioral therapy, and herbal medicine. The approach of scientists is to identify natural anxiolytics, based on their active components and their mechanism of action. So far, several medicinal plants have been identified and their effective components have been isolated and characterized as having cellular and molecular targets to the central nervous system (CNS). Despite the progress made in identification, application and drug interaction issues of such products, further studies should be planned to minimize their side effects and enhance their efficiency and specificity for a given health condition. The use of natural anxiolytics, either alone or in combination with other remedies can be improved by managing the preparation protocols, the route and the form of administration. In this context, natural drinks such as coffee with high levels of caffeine may exacerbate the clinical symptoms of anxiety. On the other hands, theanine (present in tea leaves) can alleviate the symptoms of the disorder. The current information available on traditional medicine and pharmacognosy is promising for formulation of nutraceuticals more specifically, with highest efficiency for prevention and treatment of anxiety. This review article attempts to introduce major herbs/plants recognized for their anti-anxiety effects and explain the feasibility for their specific application. The methods for the extract preparation and optimum condition for using such materials as traditional medicine or for their use in new formulations as nutraceuticals is suggested. The review also includes information about anxiety disorders, etiology, symptoms, types, neurobiology and different approaches to ameliorate anxiety conditions.
Consideration and improvement for anxiety and depression are important during global pandemic diseases. Appropriate healthcare can be obtained by paying more attention to traditional medicinal sciences. The adverse effects of stress with its various symptoms can be managed by introducing plants that boost mental health. The most relevant psychological reactions in the general population related to global pandemic are pervasice anxiety, frustration and boredom, aspecific and uncontrolled fear, disabling loneliness, significant lifestyle changes, and psychiatric conditions. Ginseng, chamomile, passionflower, herbal tea, lavender, saffron, kava, rose, cardamom, Chinese date and some chief formula like yokukansan, Dan-zhi-xiao-yao-san, so-ochim-tang-gamiband, and saikokaryukotsuboreito are notable herbal treatments for mental health problems. The most common medicinal plants which have been used in Iran for the cure of stress and anxiety are Viper,s-buglosses, Dracocephalum, valerian, chamomile, common hop, Hawhorns, and Lavender. Medicinal plants and herbs can be used for treatment and alleviating negative effects of stress, anger and depression during the global pandemic.
The spice cardamom, also known historically as the “queen of spices,” is produced from the seeds of the plant Elettaria cardamomum, which is cultivated commercially on plantations in the south of India, Sri Lanka, Central America, and Southeast Asia. It enhances both sweet and savory dishes in many regions around the world. In ancient traditional medicines, cardamom was used to alleviate digestive disorders and obesity, and even today, it is used in local cultures for individuals with ailments such as bronchitis, depression, dysentery, influenza, and infections. This narrative review discusses human investigations of cardamom's effects on blood glucose and lipid regulation, inflammation and hypertension, and gastrointestinal discomfort of pregnancy. To date, the limited and inconsistent outcomes from these trials are insufficient to support recommendations for human use. Related animal studies are also summarized, and recommendations for future research are highlighted.
The Elettaria Maton genera belonging to the Zingiberaceae family is native to South India to West Malesia. From ancient times this genus has been largely explored for its biological properties. Various pharmacological properties such as anti-inflammatory, analgesic, antioxidant, and antimicrobial effects have been related to this genus. E. cardamomum also acts as an Ayurvedic aphrodisiac and remedy in case of digestive problems, asthma, bronchitis, and urinary complaints, and several other human ailments; this review aims to provide a critical and comprehensive evaluation of the traditional and current medical uses of E. cardamomum, and compare these applications with modern research studies. Cardamom contains various chemical constituents such as proteins, minerals, lipids, carbohydrates, terpenoids and carotenoids, flavonoids, and essential oils, and its capsules is widely used as a spice and flavoring ingredient in foods. This critical review also discusses the botanical distribution, phytochemical constituents, and biological activities of its extracts and essential oil.
Objective:
Separation of pups from their dam during the infancy not only has detrimental effects on the pups' brain but also affects dams' behavior. Postpartum stress may affect mothers' cognitive functions. In the present study, by using a 180 min/day maternal separation (MS) paradigm, we assessed anxiety- like behavior and locomotor activity of rat dams which experienced separation from postnatal day (PND) 1 until weaning. We tried for the first time to clarify whether such separation impairs dam's performance in the Morris water maze.
Method:
We assessed dams' behavior at three time points; 24 hours, 1 week and 1 month after weaning. Therefore, the six groups consisted of control (CTRL); 24h, 1week and 1month and MS; 24h, 1week and 1month was allocated in this study.
Results:
Our results revealed that although MS-24h and MS-1week groups had intact locomotor activity, MS-1month group showed less locomotor activity in the open field. Moreover, MS induced anxiety-like behavior was more pronounced in MS-1week and MS-1month dams. Spatial learning and memory was also impaired only in MS-1month dams.
Conclusion:
We can conclude that MS induces cognitive impairments in dam that may appear not immediately after the separation, but a few weeks after such stressful event.
Alzheimer’s disease (AD) is one of the most important causes of dementia, especially in the elderlies. Due to the failures of recent clinical trials in finding effective medications, it appears the use of complementary therapies such as Traditional Persian Medicine (TPM) and the rich sources of effective herbs as well as their constituents for improving memory function could be beneficial. The aim of this study was to evaluate the recommended natural remedies in the TPM and examine their pharmacological properties. For this purpose, the data were collected by searching the recommended prescriptions of the seminal TPM textbooks. Then, the names of the most freuqently mentioned plants were extracted from the natural remedies and evaluated for their pharmacological properties. The sources included recently published articles cited in the major scientific databases. A total of 262 plants were identified in 96 evaluated prescriptions; 20 plants were identified with the most frequency of report (i.e. more than 10 times). Their neuroprotective effects, antioxidant features, and anti-AD properties were discussed. Based on our results, TPM has introduced many effective treatments for AD. Hence, more clinical studies are warranted to verify their efficacy and safety.
CITATIONS 2 READS 98 7 authors, including: Some of the authors of this publication are also working on these related projects: Ethnopharmacological survey and evaluation of the therapeutic index of some plants used in the treatment of female infertility in Morocco and evaluation of their therapeutic indexes. View project Abstract Depression and anxiety represent a major mental health problem in the world. The majority of Moroccan people use traditional medicine for their health needs, including various forms of depression and anxiety. The aim of this work is to make an inventory of plant species used in folk medicine for the management of depression and anxiety in Fez-Meknes regions. Established questionnaires were administered to 243 interviews in 4 communities within Fez-Meknes region. With traditional health practitioners, herbalists and consumer. Plant species belonging to 31 families were reported. The most frequently cited families are Lamiaceae followed by Asteraceae, Apiaceae and Verbena-ceae. Leaves were the major plant parts used forming 58% solely and 73 mixed with other parts. This was followed by seeds (17%), flowers (6%), roots (2%) and fruits and bark (1% each). The current survey represents a useful documentation , which can use to preserve knowledge on the use of medicinal plants in this region and to explore the phyto-chemical and pharmacological potential of medicinal plants. Résumé La dépression et l'anxiété constituent un problème majeur de santé mentale dans le monde. La majorité des Mar-ocains utilisent la médecine traditionnelle pour répondre à leurs besoins en matière de santé, y compris pour diverses formes de dépression et d'anxiété. Le but de ce travail est de faire un inventaire des espèces de plantes utilisées en méde-cine traditionnelle pour soigner la dépression et l'anxiété dans les régions de Fès-Meknès. Des questionnaires établis ont été administrés lors de 243 entretiens dans quatre communautés de cette région, avec les guérisseurs, les herboristes et les con-sommateurs. Cinquante-cinq espèces de plantes appartenant à 31 familles ont été rapportées. Les familles les plus citées sont les Lamiaceae, suivies des Asteraceae, des Apiaceae et des Verbenaceae. Les feuilles constituent la principale partie uti-lisée de la plante, seules (58 %) ou mélangées à d'autres parties (73 %) ; viennent ensuite les graines (17 %), les fleurs (6 %), les racines (2 %) et les fruits et l'écorce (1 % chacun). L'enquête actuelle constitue une documentation utile qui peut servir à préserver les connaissances sur l'utilisation des plantes médicinales dans cette région et à explorer le potentiel phytochimique et pharmacologique des plantes médicinales.
Background: Separation of pups from their dam during the infancy not only has detrimental effects on the pups’ brain but also affects dams’ behavior. Postpartum stress may affect mothers’ cognitive functions. In the present study, by using a 180 min/day maternal separation (MS) paradigm, we assessed anxiety- like behavior (in the elevated plus maze) and locomotor activity (in the open field) of rat dams which experienced separation from postnatal day (PND) 1 until weaning. Since no study has ever investigated MS effects on spatial learning and memory of dams in the Morris water maze, we tried for the first time to clarify whether such separation impairs dam’s performance in the Morris water maze.
Methods:We assessed dams’ behavior at three time points; 24 hours, 1 week and 1 month after weaning. Therefore, the six groups consisted of control (CTRL); 24h, 1week and 1month and MS; 24h, 1week and 1month was allocated in this study.
Results: Our results revealed that although MS-24h and MS-1week groups had intact locomotor activity, MS-1month group showed less locomotor activity in the open field. Moreover, MS induced anxiety–like behavior was more pronounced in MS-1week and MS-1month dams. Spatial learning and memory was also impaired only in MS-1month dams.
Conclusions: We can conclude that MS induces cognitive impairments in dam that may appear not immediately after the separation, but a few weeks after such stressful event.
Background
In Nepal, traditional treatment using medicinal plants is popular. Whereas medication-overuse headache is, by definition, caused by excessive use of acute headache medication, we hypothesized that medicinal plants, being pharmacologically active, were as likely a cause.
Methods
We used data from a cross-sectional, nationwide population-based study, which enquired into headache and use of medicinal plants and allopathic medications. We searched the literature for pharmacodynamic actions of the medicinal plants.
Results
Of 2100 participants, 1794 (85.4%) reported headache in the preceding year; 161 (7.7%) reported headache on ≥15 days/month, of whom 28 (17.4%) had used medicinal plants and 117 (72.7%) allopathic medication(s). Of 46 with probable medication-overuse headache, 87.0% (40/46) were using allopathic medication(s) and 13.0% (6/46) medicinal plants, a ratio of 6.7:1, higher than the overall ratio among those with headache of 4.9:1 (912/185). Of 60 plant species identified, 49 were pharmacodynamically active on the central nervous system, with various effects of likely relevance in medication-overuse headache causation.
Conclusions
MPs are potentially a cause of medication-overuse headache, and not to be seen as innocent in this regard. Numbers presumptively affected in Nepal are low but not negligible. This pioneering project provides a starting point for further research to provide needed guidance on use of medicinal plants for headache.
Mental health condition is including depression and anxiety, and they may impact wellbeing, personal relationships and productivity of both genders. Herbal medicines have been used to treatment of anxiety and depression symptoms for centuries. SARS, MERS and COVID‐19 are related to coronavirus types. SARS (sever acute respiratory syndrome, China, 2002), MERS (Middle East respiratory syndrome, Saudi Arabia, 2012), and SARS‐CoV‐2 (2019–2020) are the main coronavirus outbreaks. Both anxiety and depression are more serious to be considered and improved for all general public during fight with these diseases. In this mini‐review article, we have mentioned the key role some of the most important plants and herbs for treatment of stress and anxiety and improve mental health against SARS and SARS‐CoV‐2 on the basis of traditional Asian medicine, especially traditional Chinese and Persian medicine.
Este libro está diseñado como un texto de apoyo para los estudiantes de pregrado en química y carreras relacionadas, para introducirse en el campo extenso de la química de los productos naturales, específicamente en lo relacionado al conocimiento químico de los denominados metabolitos secundarios como: Compuestos aromáticos como los flavonoides, compuestos no-aromáticos como los terpenoides, compuestos nitrogenados como los alcaloides, compuestos azufrados, etc. Además del enfoque químico se menciona el uso o potencial farmacéutico de estas sustancias. Se describen las técnicas experimentales que se utilizan para la obtención, el aislamiento, la identificación y la caracterización química de estas sustancias. Se plantean problemas para retar a los estudiantes en la caracterización de los metabolitos secundarios, especialmente mediante la Espectrometría de Resonancia Magnética Nuclear.
Depression and anxiety represent a major mental health problem in the world. The majority of Moroccan people use traditional medicine for their health needs, including various forms of depression and anxiety. The aim of this work is to make an inventory of plant species used in folk medicine for the management of depression and anxiety in Fez-Meknes regions. Established questionnaires were administered to 243 interviews in 4 communities within Fez-Meknes region. With traditional health practitioners, herbalists and consumer. Plant species belonging to 31 families were reported. The most frequently cited families are Lamiaceae followed by Asteraceae , Apiaceae and Verbenaceae . Leaves were the major plant parts used forming 58% solely and 73 mixed with other parts. This was followed by seeds (17%), flowers (6%), roots (2%) and fruits and bark (1% each). The current survey represents a useful documentation, which can use to preserve knowledge on the use of medicinal plants in this region and to explore the phytochemical and pharmacological potential of medicinal plants.
Neonatal administration of MK-801 (NMDA receptor antagonist) results in schizophrenia-like behaviors in rodents. Berberine (BBR) is a herbal alkaloid, which shows many neuroprotective properties in neurodegenerative diseases. The present study was designed to clarify whether systemic administration of BBR improves motor and cognitive disturbances induced by MK-801 treatment. Male Wistar rat pups were treated with intraperitoneal administration of saline (1 ml/kg) as a control group, MK-801 (1 mg/kg), BBR (20 mg/kg) and BBR (20 mg/kg) plus MK- 801 (1 mg/kg). Treatments were administered on postnatal day (P) 6–10 for once daily. To assess motor learning, coordination as well as spatial learning and memory, behavioral evaluation was performed at P55–60, using the rotarod, open field, and Morris water maze paradigm. MK-801 injection led to motor perturbations in both the open field and accelerating rotarod tests, which were restored by BBR. Also, BBR improved learning impairments, although it had no significant effect on the Probe test. Taken together, it can be concluded that BBR produces a neuroprotective effect in rats with MK-801-associated behavioral deficits. Given that the MK-801 exposure demonstrates an animal model of schizophrenia, we suggest that timely BBR administration may act as a potential treatment in schizophrenic patients.
Acetylcholinesterase (AChE) is an enzyme involved in the progression of Alzheimer's disease (AD). Cardamom oil (CO) has been reported to have acetylcholinesterase inhibitory, antioxidant and anti-anxiety effects. Hence, we studied the effect of cardamom oil in aluminum chloride induced neurotoxicity in rats. AD like symptoms were induced in Wistar rats with aluminum chloride (100 mg/kg, p.o.). Cardamom oil was administered concomitantly by oral route at doses of 100 and 200 mg/kg for 42 days. Behavioral parameters like Morris water maze, elevated plus maze, passive avoidance test and locomotor activity were evaluated on day 21 and 42. AChE activity, oxidative stress parameters, histopathological studies and immunohistochemistry studies were carried out in hippocampus and cortex. Cardamom oil treatment showed significant improvement in behavioral parameters, inhibition of AChE activity (p < 0.001) and reduction in oxidative stress in the brain. Histopathological studies of hippocampus and cortex by hematoxylin & eosin (H. & E.) and congo red stain showed inhibition of neuronal damage and amyloid β plaque formation with cardamom oil treatment. Immunohistochemistry showed, CO treatment inhibited amyloid β expression and upregulated brain-derived neurotrophic factor (BDNF). The present study showed that, cardamom oil has neuroprotective effect in aluminum chloride induced neurotoxicity linked with inhibition of AChE activity and reduction in oxidative damage. This effect of cardamom oil may be useful in management of Alzheimer's disease.
Individuals with posttraumatic stress disorder (PTSD) are characterized by fear memory problems and hypocortisolemia of which traumatic stress-induced monoaminergic disruption over infralimbic (IL) cortex is considered the key mechanism. Hyperbaric oxygen therapy (HBOT) has recently proven its utility in treating several mental disorders but remains unexplored for PTSD. The present study aimed to examine the effects of 5-day HBO paradigm on traumatic stress (single prolonged stress, SPS, an animal model of PTSD)-induced dysregulation of fear memory/anxiety profiles and related abnormalities in IL monoamines and plasma corticosterone. Rats were randomly assigned to four groups (CON-sham, CON-HBOT, SPS-sham, and SPS-HBOT) and received Pavlovian fear conditioning test or elevated-T maze (ETM). The extracellular and tissue levels of monoamines over the IL cortex and the activity of the hypothalamus-pituitary-adrenal axis (i.e., the plasma corticosterone level and expression of the glucocorticoid receptor (GR) in the IL, hippocampus, amygdala, and hypothalamus) were measured. The results demonstrated that HBOT restored behaviorally the SPS-impaired fear extinction retrieval ability and SPS-induced conditioned anxiety, and neurochemically the SPS-reduced IL monoamines efflux level, and the corticosterone profiles. The present study shows some positive effects of HBOT in both behavioral and neurochemical profiles of PTSD outcomes.
There are conflicting reports concerning the association of Toxoplasma gondii infection with increased risk of mental disorders. This investigation will provide a good understanding about defining the possible association between T. gondii exposure and risk of anxiety and cognitive alterations. Besides, a secondary objective of this study was to determine the effect of pioglitazone administration on the possible alterations induced by T. gondii exposure. Male BALB/c mice were used for this study. The animal model of Toxoplasma infection was established by the intraperitoneal inoculation of 20–25 tissue cysts from Tehran strain of T. gondii. Pioglitazone (20 mg/kg, i.p.1/day) was administered to the animals for 2 weeks before behavioural tests. Behavioural tests including open-field, elevated plus-maze and passive avoidance learning were evaluated in the groups. Since cytokines were implicated as a contributing factor for mood disorders, the mRNA levels of TNF-α, IL-1β, IL-6 as well as inducible nitric oxide synthase (iNOs) were examined by real-time PCR. Findings demonstrated that T. gondii caused anxiety-like symptoms and impaired cognitive functions of the infected BALB/c mice, whereas pioglitazone, a peroxisome proliferator-activated receptor agonist, showed a promising effect against the cognitive impairments induced by Toxoplasma infection. The results also revealed that the mRNA levels of the aforementioned cytokines were significantly (p < 0.05) increased in the infected mice compared to the uninfected BALB/c ones. Pioglitazone can be offered as a potential neuroprotective agent in the treatment of patients with T. gondii infection that manifests anxiety and cognitive impairments; however, further studies are needed to clarify the exact mechanisms.
There are conflicting reports concerning the association of Toxoplasma gondii infection with increased risk of mental disorders. This investigation will provide a good understanding about defining the possible association between T. gondii exposure and risk of anxiety and cognitive alterations. Besides, a secondary objective of this study was to determine the effect of pioglitazone administration on the possible alterations induced by T. gondii exposure. Male BALB/c mice were used for this study. The animal model of Toxoplasma infection was established by the intraperitoneal inoculation of 20-25 tissue cysts from Tehran strain of T. gondii. Pioglitazone (20 mg/kg, i.p.1/day) was administered to the animals for 2 weeks before behavioural tests. Behavioural tests including open-field, elevated plus-maze and passive avoidance learning were evaluated in the groups. Since cytokines were implicated as a contributing factor for mood disorders, the mRNA levels of TNF-α, IL-1β, IL-6 as well as inducible nitric oxide synthase (iNOs) were examined by real-time PCR. Findings demonstrated that T. gondii caused anxiety-like symptoms and impaired cognitive functions of the infected BALB/c mice, whereas pioglitazone, a peroxisome proliferator-activated receptor agonist, showed a promising effect against the cognitive impairments induced by Toxoplasma infection. The results also revealed that the mRNA levels of the aforementioned cytokines were significantly (p < 0.05) increased in the infected mice compared to the uninfected BALB/c ones. Pioglitazone can be offered as a potential neuroprotective agent in the treatment of patients with T. gondii infection that manifests anxiety and cognitive impairments; however, further studies are needed to clarify the exact mechanisms.
There are several scolicidal agents for inactivation of hydatid cyst protoscolices during surgery, but most of them are associated with adverse side effects such as sclerosing cholangitis and liver necrosis. The present study was aimed to evaluate scolicidal effects of various extracts of Nigella sativa seeds against protoscoleces of hydatid cyst in an in vitro model.
Protoscoleces were aseptically aspirated from naturally infected livers of sheep and goats. Various concentrations of the different extracts of N. sativa (5 to 50 mg/ml) were used for 5 to 60 min. Viability of protoscoleces was confirmed by 0.1% eosin staining.
The findings exhibited that methanolic extract at the concentration of 50 mg/ml after 10 min of incubation, and aqueous extract at the concentration of 50 mg/ml after 30 min of incubation can kill 100% of protoscoleces. In addition, all of experiments revealed dose-dependent and also time-dependent scolicidal effect of various extracts of N. sativa on the protoscoleces of hydatid cyst.
The results of the present study demonstrated that N. sativa may be a natural source for the production of new scolicidal agent for use in hydatid cyst surgery. However, further studies will be required to evaluate scolicidal effects of N. sativa in the in vivo model.
Hepatic encephalopathy (HE) is a serious consequence of hepatic cirrhosis (HC). Previous studies have demonstrated cognitive impairments in both clinical and animal experiments of HC. Some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of HC. In the current study, the possible effect of erythropoietin (ERY) as a potent neuroprotective agent on motor and cognitive impairments induced by HC has been studied. Male Wistar rats (180-200 g) underwent bile duct ligation (BDL) or sham surgery. Administration of ERY (5,000 IU/kg, i.p., daily for three days) was initiated 2 weeks after surgery and lasted for the next 28 days. Open field, rotarod, Morris water maze and passive avoidance learning was used to evaluate the motor and cognitive function of the animals. ANOVA and repeated measures ANOVA were used to analyze the data. p < 0.05 was considered statistically significant. BDL rats had an increased level of hepatic enzymes and bilirubin. Impairment of balance function by BDL was reversed by ERY. Spatial and passive avoidance learning impairments observed in BDL rats were also reversed by chronic administration of ERY. ERY can be offered as a potential neuroprotective agent in the treatment of patients with HC that manifest mental dysfunctions. Though further studies are needed to clarify the exact mechanisms, the neuroprotective properties of ERY against BDL impairments were demonstrated in the current study.
Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. Thus, our aim was to provide a comprehensive narrative review of plant-based medicines that have clinical and/or preclinical evidence of anxiolytic activity. We present the article in two parts. In part one, we reviewed herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In this current article (part two), we review herbal medicines for which there have been both preclinical and clinical investigations of anxiolytic activity. A search of MEDLINE (PubMed), CINAHL, Scopus and the Cochrane Library databases was conducted (up to 28 October 2012) for English language papers using the search terms ‘anxiety’ OR ‘anxiety disorder’ OR ‘generalized anxiety disorder’ OR ‘social phobia’ OR ‘post-traumatic stress disorder’ OR ‘panic disorder’ OR ‘agoraphobia’ OR ‘obsessive compulsive disorder’ in combination with the search terms ‘Herb*’ OR ‘Medicinal Plants’ OR ‘Botanical Medicine’ OR ‘Chinese herb*’, in addition to individual herbal medicines. This search of the literature revealed 1,525 papers, of which 53 plants were included in the review (having at least one study using the whole plant extract). Of these plants, 21 had human clinical trial evidence (reviewed here in part two), with the other 32 having solely preclinical evidence (reviewed in part one). Support for efficacy was found for chronic use (i.e. greater than one day) of the following herbs in treating a range of anxiety disorders in human clinical trials: Piper methysticum, Matricaria recutita, Ginkgo biloba, Scutellaria lateriflora, Silybum marianum, Passiflora incarnata, Withania somniferum, Galphimia glauca, Centella asiatica, Rhodiola rosea, Echinacea spp., Melissa officinalis and Echium amoenum. For several of the plants studied, conclusions need to be tempered due to methodological issues such as small sample sizes, brief intervention durations and non-replication. Current evidence does not support Hypericum perforatum or Valeriana spp. for any anxiety disorder. Acute anxiolytic activity was found for Centella asiatica, Salvia spp., Melissa officinalis, Passiflora incarnata and Citrus aurantium.
Bacopa monnieri has shown anxiolytic effects in people with cognitive decline. The therapeutic application of psychotropic plant-based treatments for anxiety disorders is also discussed, specifically Psychotria viridis and Banisteriopsis caarti (ayahuasca), Psilocybe spp. and cannabidiol-enriched (low tetrahydrocannabinol (Δ9-THC)) Cannabis spp.
Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. This article (part 1) reviews herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In part 2, we review herbal medicines for which there have been clinical investigations for anxiolytic activity. An open-ended, language-restricted (English) search of MEDLINE (PubMed), CINAHL, Scopus and the Cochrane Library databases was conducted (up to 28 October 2012) using specific search criteria to identify herbal medicines that have been investigated for anxiolytic activity. This search of the literature revealed 1,525 papers, from which 53 herbal medicines were included in the full review (having at least one study using the whole plant extract). Of these plants, 21 had human clinical trial evidence (reviewed in part 2), with another 32 having solely preclinical studies (reviewed here in part 1). Preclinical evidence of anxiolytic activity (without human clinical trials) was found for Albizia julibrissin, Sonchus oleraceus, Uncaria rhynchophylla, Stachys lavandulifolia, Cecropia glazioui, Magnolia spp., Eschscholzia californica, Erythrina spp., Annona spp., Rubus brasiliensis, Apocynum venetum, Nauclea latifolia, Equisetum arvense, Tilia spp., Securidaca longepedunculata, Achillea millefolium, Leea indica, Juncus effusus, Coriandrum sativum, Eurycoma longifolia, Turnera diffusa, Euphorbia hirta, Justicia spp., Crocus sativus, Aloysia polystachya, Albies pindrow, Casimiroa edulis, Davilla rugosa, Gastrodia elata, Sphaerathus indicus, Zizyphus jujuba and Panax ginseng. Common mechanisms of action for the majority of botanicals reviewed primarily involve GABA, either via direct receptor binding or ionic channel or cell membrane modulation; GABA transaminase or glutamic acid decarboxylase inhibition; a range of monoaminergic effects; and potential cannabinoid receptor modulation. Future research should focus on conducting human clinical trials on the plants reviewed with promising anxiolytic activity.
Opuntia ficus-indica var. saboten. is widely cultivated in Jeju Island (South Korea) for use in manufacture of health foods. This study described antidepressant effect of two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. The expression of the hypothalamic POMC mRNA or plasma β-endorphin levels were increased by extract of Opuntia ficus-indica var. saboten or its flavoniods administered orally. In addition, antidepressant activity was studied using tail suspension test (TST), forced swimming test (FST) and rota-rod test in chronically restraint immobilization stress group in mice. After restraint stress (2 hrs/day for 14 days), animals were kept in cage for 14 days without any further stress, bet with drugs. Mice were fed with a diet supplemented for 14 days and during the behavioral test period with kaempferol or quercitrin (30 mg/kg/day). POMC mRNA or plasma β-endorphin level was increased by extract of Opuntia ficus-indica var. saboten and its flavoniods. In addition, immobility time in TST and FST was significantly reduced by kaempferol or quercitrin. In rota-rod test, the time of permanence was maintained to the semblance of control group in turning at 15 rpm. Our results suggest that two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. show a potent antidepressant effect.
Research in the area of herbal psychopharmacology has increased markedly over the past decades. To date however, a comprehensive review of herbal antidepressant, anxiolytic and hypnotic psychopharmacology and applications in depression, anxiety and insomnia has been absent. A search of MEDLINE (PubMed), CINAHL, PsycINFO, and the Cochrane Library databases was conducted (up to February 21st 2011) on commonly used psychotropic herbal medicines. A review of the literature was conducted to ascertain mechanisms of action of these botanicals, in addition to a systematic review of controlled clinical trials for treatment of mood, anxiety and sleep disorders, which are common comorbid psychiatric disorders. Specific emphasis was given to emerging phytomedicines. Analysis of evidence levels was conducted, as were effect sizes (Cohen's d) where data were available. Results provided evidence of a range of neurochemical, endocrinological, and epigenetic effects for 21 individual phytomedicines, which are detailed in this paper. Sixty six controlled studies were located involving eleven phytomedicines. Several of these provide a high level of evidence, such as Hypericum perforatum for major depression, and Piper methysticum for anxiety disorders. Several human clinical trials provide preliminary positive evidence of antidepressant effects (Echium amoenum, Crocus sativus, and Rhodiola rosea) and anxiolytic activity (Matricaria recutita, Ginkgo biloba, Passiflora incanata, E. amoenum, and Scutellaria lateriflora). Caution should however be taken when interpreting the results as many studies have not been replicated. Several herbal medicines with in vitro and in vivo evidence are currently unexplored in human studies, and along with use of emerging genetic technologies "herbomics", are areas of potential future research.
Data were obtained on the general population epidemiology of DSM-III-R posttraumatic stress disorder (PTSD), including information on estimated life-time prevalence, the kinds of traumas most often associated with PTSD, sociodemographic correlates, the comorbidity of PTSD with other lifetime psychiatric disorders, and the duration of an index episode.
Modified versions of the DSM-III-R PTSD module from the Diagnostic Interview Schedule and of the Composite International Diagnostic Interview were administered to a representative national sample of 5877 persons aged 15 to 54 years in the part II subsample of the National Comorbidity Survey.
The estimated lifetime prevalence of PTSD is 7.8%. Prevalence is elevated among women and the previously married. The traumas most commonly associated with PTSD are combat exposure and witnessing among men and rape and sexual molestation among women. Posttraumatic stress disorder is strongly comorbid with other lifetime DSM-III-R disorders. Survival analysis shows that more than one third of people with an index episode of PTSD fail to recover even after many years.
Posttraumatic stress disorder is more prevalent than previously believed, and is often persistent. Progress in estimating age-at-onset distributions, cohort effects, and the conditional probabilities of PTSD from different types of trauma will require future epidemiologic studies to assess PTSD for all lifetime traumas rather than for only a small number of retrospectively reported "most serious" traumas.
Preliminary unpublished studies in our laboratory suggested that the behaviour of Sprague-Dawley (SD) and Dark Agouti (DA) rats was markedly different on both the elevated plus maze and in the open-field apparatus. We wished to confirm and extend this initial finding.
The study was designed to examine the behaviour of SD and DA rats in the elevated plus maze, open-field apparatus and automated activity meters. The response of both strains on the elevated plus maze following diazepam (1 mg/kg and 1.5 mg/kg) administration was subsequently investigated.
DA rats showed markedly greater anxiety-like behaviour than SD rats in both the plus maze and open field, with fewer percentage open/total arm entries and percentage time spent on open/total arms in the plus maze and fewer crossings in the open field. Acute handling plus administration of vehicle abolished this difference in anxiety levels, with DA rats showing similar open-arm behaviour to that of SD rats. Both strains demonstrated a clear anxiolytic response to diazepam (1 mg/kg) in terms of percentage time spent on the open arms, but only SD rats had a statistically significant increase in percentage open-arm entries compared with vehicle-injected control animals.
While the high level of anxiety-like behaviour of DA rats versus SD rats could prove useful in future ethological studies on anxiety, the fact that acute handling decreased the anxiety-like behaviour on the elevated plus maze may limit the value of this strain for the study of putative anxiolytic drugs.
Natural products, either as pure compounds or as standardized plant extracts, provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. To secure this, a number of pivotal quality standards need to be set at the level of extract processing and primary evaluation in pharmacological screening models. This review provides a number of recommendations that will help to define a more sound 'proof-of-concept' for antibacterial, antifungal, antiviral and antiparasitic potential in natural products. An integrated panel of pathogens is proposed for antimicrobial profiling, using accessible standard in vitro experimental procedures, endpoint parameters and efficacy criteria. Primary requirements include: (1) use of reference strains or fully characterized clinical isolates, (2) in vitro models on the whole organism and if possible cell-based, (3) evaluation of selectivity by parallel cytotoxicity testing and/or integrated profiling against unrelated micro-organisms, (4) adequately broad dose range, enabling dose-response curves, (5) stringent endpoint criteria with IC(50)-values generally below 100microug/ml for extracts and below 25microM for pure compounds, (6) proper preparation, storage and in-test processing of extracts, (7) inclusion of appropriate controls in each in vitro test replicate (blanks, infected and reference controls) and (8) follow-up of in vitro activity ('hit'-status) in matching animal models ('lead'-status).
Major depression is a common, disabling, and often difficult-to-treat illness. Decades of research into the neurobiology and treatment of depression have greatly advanced our ability to manage this disorder. However, a number of challenges remain. A substantial number of depressed patients do not achieve full remission despite optimized treatment. For patients who do achieve resolution of symptoms, depression remains a highly recurrent illness, and repeated episodes are common. Finally, little is known about how depression might be prevented, especially in individuals at increased risk. In the face of these challenges, a number of exciting research efforts are currently under way and promise to greatly expand our knowledge of the etiology, pathophysiology, and treatment of depression. This review highlights these future prospects for depression research with a specific focus on lines of investigation likely to generate novel, more effective treatment options.
Quercetin, an effective flavonol used as an antioxidant, was investigated for its anxiolytic and cognitive activities in male Wistar rats. Oral quercetin (300 mg/kg body weight/day) was compared with oral and intranasal quercetin liposomes (20 microg/day). Quercetin liposomes, in a mixture of egg phosphatidylcholine, cholesterol, and quercetin (2:1:1) and dispersed in 50% polyethylene glycol in water, were approximately 200 nm in mean particle diameter and negative surface charge with a range of encapsulation efficiency of 60% to 80%. Anxiolytic and cognitive-enhancing effects of quercetin, conventional and liposomal, were subjected to elevated plus maze and Morris water maze tests, respectively. Both conventional and quercetin liposomes showed anxiolytic and cognitive-enhancing effects. A lower dose and a faster rate were observed with intranasal quercetin liposomes when compared with oral quercetin, conventional and liposomal. The intranasal quercetin liposomes are effective in the delivery of quercetin to the central nervous system.
Anxiolytic-like effects of some short-acting benzodiazepine hypnotics were examined with experimental paradigms of anxiety using an elevated plus-maze in male ICR mice. Diazepam was used as a positive control. The drug at a dose of 1 mg/kg significantly increased the percentage of time spent in the open arms and percentage of the number of open arm entries in the elevated plus-maze. Triazolam, brotizolam, rilmazafone, and lormetazepam also showed an anxiolytic-like effect as indicated by the significant increase in the percentage of time spent in the open arms and percentage of the number of open arm entries. Effects of short-acting benzodiazepine hypnotics used in the study were more potent than those of diazepam. In addition, the doses affecting the elevated plus-maze by benzodiazepine hypnotics were much smaller than those that showed muscle-relaxant activity measured by the rotarod test, indicating that anxiolytic-like effects of benzodiazepine hypnotics had high specificity and selectivity.
Elettaria cardamomum is an aromatic spice (cardamom) native to the humid Asian areas, which contains some compounds with a potential anticonvulsant activity. Various pharmacological properties such as anti-inflammatory, analgesic, antioxidant, and antimicrobial effects have been related to this plant. This research was conducted to examine the probable protective impact of the essential oil and methanolic extract of E. cardamomum against chemically (pentylentetrazole)- and electrically (maximal electroshock)-induced seizures in mice. In addition, neurotoxicity, acute lethality, and phytochemistry of the essential oil and methanolic extract were estimated. The TLC method showed the presence of kaempferol, rutin, and quercetin in the extract, and the concentration of quercetin in the extract was 0.5 µg/mL. The major compounds in the essential oil were 1,8-cineole (45.6 %), α-terpinyl acetate (33.7 %), sabinene (3.8 %), 4-terpinen-4-ol (2.4 %), and myrcene (2.2 %), respectively. The extract and essential oil showed significant neurotoxicity in the rotarod test at the doses of 1.5 g/kg and 0.75 mL/kg, respectively. No mortalities were observed up to the doses of 2 g/kg and 0.75 mL/kg for the extract and essential oil. The essential oil was effective in both the pentylentetrazole and maximal electroshock models; however, the extract was only effective in the pentylentetrazole model. The study suggested that E. cardamomum methanolic extract had no significant lethality in mice. Both the essential oil and methanolic extract showed movement toxicity. Anticonvulsant effects of E. cardamomum were negligible against the seizures induced by pentylentetrazole and maximal electroshock.
Georg Thieme Verlag KG Stuttgart · New York.
The original aroma compounds present in the cardamom were isolated by Amberlite XAD-2 column chromatography from fresh green cardamom and termed as OFFC (Original flavour of fresh cardamom), distilling fresh green cardamom DOFC (Distilled oil of fresh cardamom) and distilling commercial cardamom DOCC (Distilled oil of commercial cardamom). They were analysed by HRGC and GC-MS techniques. The major compounds did not show much variations in these samples viz., 1, 8 cineole and α-terpinyl acetate. Many sesquiterpene hydrocarbons were found to be present in the DOFC and not in OFFC. However, there were marked differences in the contents of other components. It was also observed that some new compounds were present in the oil of cardamom.
Background:
Data were obtained on the general population epidemiology of DSM-III-R posttraumatic stress disorder (PTSD), including information on estimated lifetime prevalence, the kinds of traumas most often associated with PTSD, sociodemographic correlates, the comorbidity of PTSD with other lifetime psychiatric disorders, and the duration of an index episode.Methods:
Modified versions of the DSM-III-R PTSD module from the Diagnostic Interview Schedule and of the Composite International Diagnostic Interview were administered to a representative national sample of 5877 persons aged 15 to 54 years in the part II subsample of the National Comorbidity Survey.Results:
The estimated lifetime prevalence of PTSD is 7.8%. Prevalence is elevated among women and the previously married. The traumas most commonly associated with PTSD are combat exposure and witnessing among men and rape and sexual molestation among women. Posttraumatic stress disorder is strongly comorbid with other lifetime DSM-III-R disorders. Survival analysis shows that more than one third of people with an index episode of PTSD fail to recover even after many years.Conclusions:
Posttraumatic stress disorder is more prevalent than previously believed, and is often persistent. Progress in estimating age-at-onset distributions, cohort effects, and the conditional probabilities of PTSD from different types of trauma will require future epidemiologic studies to assess PTSD for all lifetime traumas rather than for only a small number of retrospectively reported "most serious" traumas.
Chronic stress alters sensory and cognitive function of the mankind and animals. Sub-chronic swim stress is known to induce a prolonged hyperalgesia which is mediated through NMDA and opioid systems. Nitric oxide is a soluble gas which acts as a retrograde messenger that modulates the release of mentioned neurotransmitters. It is also involved in nociception and memory. The objective of the current study was to evaluate the role of NO pathway in nociception and memory impairments induced by sub-chronic swim stress.
A three session forced swimming stress protocol was administered to the rats. Pretreatment with L-NAME (10mg/kg, i.p.), L-Arginine (10mg/kg, i.p.) or saline was made before each swimming session. Anxiety-like behavior, nociception and passive avoidance (PA) learning was evaluated 24hours after last swim stress session.
Swim stress altered locomotion and anxiety-like behaviors in the open field test. Reduced thermal threshold was observed in the nociceptive measurement after swim stress. Pretreatment with L-NAME could reverse the reduced threshold. A decreased step through latency was observed in the PA paradigm after swim stress, which could be inhibited by pretreatment with L-NAME.
The results of this study indicate that sub-chronic swim stress impairs nociception and PA learning. NO pathway seems to have a modulatory role in these alterations. Further studies are suggested to examine the protective effect of NOS inhibitors on stress-induced impairments in sensory and cognitive function.
Walnut is extensively used in traditional medicine for treatment of various ailments. It is described as an anticancer, anti-inflammatory, blood purifier and antioxidant agent. In this study, we investigated whether or not Walnut could protect neurons against cisplatin-induced neurotoxicity in rats. Dietary walnut (6%) was assessed for its neuroprotective effects through the alteration in performance of hippocampus- and cerebellum-related behaviors following chronic cisplatin treatment (5mg/kg/week for 5 consecutive weeks) in male rats. We also evaluated the effect of cisplatin and walnut administration on nociception. We showed that exposure of adolescent rats to cisplatin resulted in significant decrease in explorative behaviors and memory retention. Walnut consumption improved memory and motor abilities in cisplatin treated rats, while walnut alone did not show any significant changes in these abilities compared to saline. Cisplatin increased latency of response to nociception, and walnut reversed this effect of cisplatin. We conclude that walnuts in the diet following anticancer drugs such as cisplatin might have a protective effect against cisplatin-induced disruptions in motor and cognitive function. However, further studies are needed to elucidate the exact mechanisms of this protective effect of walnut and to explore underlying mechanisms.
A new hyphenated extraction method composed of ultrasound assisted extraction (UAE)-optimized ultrasound assisted emulsification microextraction (USAEME) was developed for the extraction and preconcentration of the essential oil of Elettaria cardamomum Maton. The essential oil was analyzed by gas chromatography-mass spectrometry (GC-MS) and optimization was performed using gas chromatography-flame ionization detection (GC-FID). Ultrasound played two different roles in the extraction of the essential oil. First, as a source of sufficient energy to break the oil-containing glands in order to release the oil, and second as an emulsifier to disperse the organic phase within water. The effective parameters (factors) of USAEME including volume of extraction solvent (C(2)H(4)Cl(2)), extraction temperature and ultrasonic time were optimized by using a central composite design (CCD). The optimal conditions were 120 μL for extraction solvent volume, 32.5 °C for temperature and 10.5 min for ultrasonic time. The linear dynamic ranges (LDRs) were 0.01-50 mg L(-1) with the determination coefficients in the range of 0.9990-0.9999. The limits of detection (LODs) and the relative standard deviations (RSDs) were 0.001-0.007 mg L(-1) and 3.6-6.3%, respectively. The enrichment factors were 93-98. The main components of the extracted essential oil were α-terpenyl acetate (46.0%), 1,8-cineole (27.7%), linalool (5.3%), α-terpineol (4.0%), linalyl acetate (3.5%).
The biological underpinnings for participation of the immune system in the pathogenesis of Posttraumatic Stress Disorder (PTSD) include evidence for cross-talk between the stress and immune systems, as well as more recently discovered roles for immune system mediators in core behavioral functions such as adult neurogenesis, as well as in processes that underlay synaptic plasticity, such as learning and memory. This article reviews the expanding body of literature on immune system mediators in the periphery and the central nervous system (CNS) in chronic PTSD along with the evidence for increased peripheral inflammation, and excess morbidity and mortality. CNS inflammation has been implicated in the pathogenesis of depression. This literature is briefly reviewed, along with evidence for a possible role for CNS inflammation in PTSD symptoms, especially in individuals who have PTSD with co-morbid depression. Whether the immune system is involved in risk and resilience, or evolution of PTSD symptoms following a trauma event remains to be determined, although hypotheses have been advanced. This paper reviews the current evidence including the novel hypothesis that cellular immunity is implicated in PTSD risk and resilience. Potential research implications and directions are discussed. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
Quercetin is a bioflavonoid reported to produce variety of behavioral effects like anxiolytic, antidepressant, etc. Recent gathering evidences indicated that quercetin attenuates stress-induced behavioral and biochemical effects. It also decreases CRF expression in the brain. As CRF is commonly implicated in the high-anxiety and depression, we hypothesized that quercetin may involve CRF in its anxiolytic- and antidepressant-like effects. To support such possibility, we investigated the influence of quercetin on CRF or CRF antagonist (antalarmin) induced changes in social interaction time in social interaction test, and immobility time in forced swim test. Results indicated that quercetin (20-40 mg/kg, p.o.) or antalarmin (2-4 microg/mouse, i.c.v.) dose dependently increased social interaction time and decreased immobility time indicating anxiolytic- and antidepressant-like effect. These effects were comparable with the traditional anxiolytic (diazepam, 1-2mg/kg, i.p.) and antidepressant (fluoxetine, 10-20mg/kg, i.p.) agents. Administration of CRF (0.1 and 0.3 nmol/mouse, i.c.v.) produced just opposite effects to that of quercetin on these parameters. Further, it was seen that pretreatment with quercetin (20 or 40 mg/kg, p.o.) dose dependently antagonized the effects of CRF (0.1 or 0.3 nmol/mouse, i.c.v.) in social interaction and forced swim test. The sub-effective dose of antalarmin (1 microg/mouse) when administered along with the sub-effective dose of quercetin (10mg/kg) produced significant anxiolytic-and antidepressant-like effect. These observations suggest reciprocating role of quercetin on the CRF-induced anxiogenic and depressant-like effects.
An overview of ethologically-based animal models suitable for investigating the pharmacological treatment of anxiety disorders is presented. The DSM-IIIR classification provides a framework for the discussion. The limitations of the models in current use are considered. It is suggested that there is a need for a greater emphasis on animal models of anxiety with an etiological basis.
Cardamom seeds are widely used for flavouring purposes in food and as carminative. Little information has been reported on their pharmacological and toxicological properties or, for their volatile oil which constitutes about 5% of the seed's total weight. A comparative study of the anti-inflammatory activity of the oil extracted from commercial Elettaria cardamomum seeds, in doses of 175 and 280 microliters/kg and indomethacin in a dose of 30 mg/kg against acute carrageenan-induced planter oedema in male albino rats was performed, which proved to be marked. Moreover, investigation of the analgesic activity using p-benzoquinone as a chemical stimulus proved that a dose of 233 microliters/kg of the oil produced 50% protection against the writhing (stretching syndrome) induced by intraperitoneal administration of a 0.02% solution of p-benzoquinone in mice. In addition the antispasmodic activity was determined on a rabbit intestine preparation using acetylcholine as agonist, the results proving that cardamom oil exerts its antispasmodic action through muscarinic receptor blockage.
Rodent models of clinical anxiety are extensively used for evaluating putative anxiolytic activity. In the present review, the available methods which can be utilized by most laboratories, have been discussed. These methods have been categorized as methods involving conditioning techniques and those not involving conditioning. In most cases, the methodology has been briefly discussed in terms of experimental use and efficacy of benzodiazepine and the newer non-benzodiazepine anxiolytics.
The volatile oil of Elettaria cardamomum (L.) Maton seeds was obtained by supercritical CO(2) extraction (SC-CO(2)). The effect of the extraction conditions on the yield and composition of the resulting cardamom volatile oil was examined by testing two pressure values, 9.0 and 11.0 MPa; two temperatures, 40 and 50 degrees C; two flow rate values, 0.6 and 1.2 kg/h; and two particles size values, 250-425 and >850 microm. The extraction conditions that gave the highest yield, Y (grams of extract per gram of seeds), of 5.5%, were as follows: pressure, 9.0 MPa; temperature, 40 degrees C; carbon dioxide flow, phi = 1.2 kg/h; and particles sizes in the range of 250-425 microm. Waxes, recovered as traces, were entrapped in the first separator set at 9.0 MPa and -10 degrees C. The oil was recovered in the second separator working at 1.5 MPa and 10 degrees C. The main components were as follows: alpha-terpinyl acetate, 42.3%; 1,8-cineole, 21.4%; linalyl acetate, 8.2%; limonene, 5.6%; and linalool, 5.4%. A comparison with the hydrodistilled oil, obtained at a yield of 5.0%, did not reveal any consistent difference. In contrast, the extract obtained using hexane, Y = 7.6%, showed strong composition differences. Indeed, the volatile fraction of the extract was made up mainly of the following: limonene, 36.4%; 1,8-cineole, 23.5%; terpinolene, 8.6%; and myrcene, 6.6%.
Different experiential, psychophysiological, and neurobiological responses to traumatic symptom provocation in posttraumatic stress disorder (PTSD) have been reported in the literature. Two subtypes of trauma response have been hypothesized, one characterized predominantly by hyperarousal and the other primarily dissociative, each one representing unique pathways to chronic stress-related psychopathology. Recent PTSD neuroimaging findings in our own laboratory support this notion and are consistent with the view that grouping all PTSD subjects, regardless of their different symptom patterns, in the same diagnostic category may interfere with our understanding of posttrauma psychopathology. This review will integrate findings of different experiential, psychophysiological, and neurobiological responses to traumatic symptom provocation with the clinical symptomatology and the neurobiology of PTSD.
Cardamom, the fruits of Elettaria cardamomum Maton. (Zingiberaceae) commonly known as "Heel khurd" is used in Unani system of medicine to treat gastrointestinal disorders. A crude methanolic extract (TM), essential oil (EO), petroleum ether soluble (PS) and insoluble (PI) fractions of methanolic extract, were studied in rats at doses of 100-500, 12.5-50, 12.5-150 and 450 mg/kg, respectively for their ability to inhibit the gastric lesions induced by aspirin, ethanol and pylorous ligature. In addition their effects on wall mucus and gastric acid output were recorded. All fractions (TM, EO, PS, PI) significantly inhibited gastric lesions induced by ethanol and aspirin but not those induced by pylorus ligation. TM proved to be active reducing lesions by about 70% in the EtOH-induced ulcer model at 500 mg/kg. The PS fraction reduced the lesions by 50% at 50 and 100mg/kg (no dose response was observed) with similar effect than the PI fraction at 450 mg/kg. In the aspirin-induced gastric ulcer, the best gastroprotective effect was found in the PS fraction, which inhibited lesions by nearly 100% at 12.5mg/kg. In our experimental conditions, the PS extract at doses >or=12.5mg/kg proved to be more active than ranitidine at 50mg/kg.
Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experience, and presents with characteristic symptoms, such as intrusive memories, a state of hyperarousal, and avoidance, that endure for years. Single-prolonged stress (SPS) is one of the animal models proposed for PTSD. Rats exposed to SPS showed enhanced inhibition of the hypothalamo-pituitary-adrenal (HPA) axis, which has been reliably reproduced in patients with PTSD, and increased expression of glucocorticoid receptor (GR) in the hippocampus. In this study, we characterized further neuroendocrinologic, behavioral and electrophysiological alterations in SPS rats. Plasma corticosterone recovered from an initial increase within a week, and gross histological changes and neuronal cell death were not observed in the hippocampus of the SPS rats. Behavioral analyses revealed that the SPS rats presented enhanced acoustic startle and impaired spatial memory that paralleled the deficits in hippocampal long-term potentiation (LTP) and depression. Contextual fear memory was enhanced in the rats 1 week after SPS exposure, whereas LTP in the amygdala was blunted. Interestingly, blockade of GR activation by administering 17-beta-hydroxy-11-beta-/4-/[methyl]-[1-methylethyl]aminophenyl/-17-alpha-[prop-1-ynyl]estra-4-9-diene-3-one (RU40555), a GR antagonist, prior to SPS exposure prevented potentiation of fear conditioning and impairment of LTP in the CA1 region. Altogether, SPS caused a number of behavioral changes similar to those described in PTSD, which marks SPS as a putative PTSD model. The preventive effects of a GR antagonist suggested that GR activation might play a critical role in producing the altered behavior and neuronal function of SPS rats.
We have recently shown that the hexanic extract from leaves of Schinus molle produces antidepressant-like effects in the tail suspension test in mice. This study investigated the antidepressant-like effect of the ethanolic extract from aerial part of S. molle in the forced swimming test and tail suspension test in mice, two predictive models of depression. Moreover, we investigated the antidepressant potential of rutin, a flavonoid isolated from the ethanolic extract of this plant and the influence of the pretreatment with the inhibitors of serotonin or noradrenaline synthesis, p-chlorophenylalanine methyl ester (PCPA) and alpha-methyl-p-tyrosine (AMPT), respectively in the antidepressant-like effect of this flavonoid. The administration of the ethanolic extract produced a reduction in the immobility time in the tail suspension test (dose range 600-1000 mg/kg, p.o.), but not in the forced swimming test. It also produced a reduction in the ambulation in the open-field test in mice not previously habituated to the arena, but no effect in the locomotor activity in mice previously habituated to the open-field. The administration of rutin reduced the immobility time in the tail suspension test (0.3-3 mg/kg, p.o.), but not in the forced swimming test, without producing alteration in the locomotor activity. In addition, pretreatment of mice with PCPA (100 mg/kg, i.p., for 4 consecutive days) or AMPT (100 mg/kg, i.p.) prevented the anti-immobility effect of rutin (0.3 mg/kg, p.o.) in the tail suspension test. The results firstly indicated the antidepressant-like effect of the ethanolic extract of S. molle in the tail suspension test may be dependent on the presence of rutin that likely exerts its antidepressant-like effect by increasing the availability of serotonin and noradrenaline in the synaptic cleft.
The aerial parts of Tilia americana var. mexicana (Schltdl) Hardin (Tiliaceae) have been widely used in Mexican traditional medicine to relieve sleeplessness, headache, and nervous excitement. The anxiolytic effect of four extracts and several flavonoid fractions from the bracts of Tilia americana subsp.mexicana, var. mexicana (Schltdl) Hardin or Tilia mexicana (Tiliaceae) was studied. Administration of 100mg/kg of n-hexane, ethyl acetate, and aqueous extracts to elevated plus-maze (EPM)-exposed mice displayed no anxiolytic effect; however, identical doses of methanol extract was able to increase the time percentage that mice spent in the EPM's open arms, as well as the percentage of crossings in the EPM's arms. The dose-response curve produced by methanol extract showed anxiolytic activity since 25mg/kg; animals showed no motor activity alteration in the open field test (OFT). Methanol extract was subjected to a bioassay-guided fractionation to obtain four ascendant polarity fractions (F1-F4) which were administrated at 100mg/kg. Data results indicate that F1 displayed the main anxiolytic effect. The purification of F1 produced a rich flavonoid anxiolytic mixture (F1C). This fraction was purified by RP-18 open chromatographic column to obtain four polar descent fractions: F1C(1), F1C(2), F1C(3), and F1C(4), respectively. Tiliroside was the major ingredient from the active fraction. High performance liquid chromatography analysis indicated that F1C was constituted principally of tiliroside, quercetin, quercitrin, kaempherol, and their glycosides. These results supported the use of Tilia americana in Mexican traditional medicine as well as the anxiolytic effect of a rich flavonoid fraction without affect motor activity.
- W C Evans
- Evans Pharmacognosy
W.C. Evans, Trease and Evans Pharmacognosy, WB Saunders Company Ltd.,
1998, pp. 15-16 (14th ed.).
Experimental methods for evaluation of psychotropic agents in rodents: anti-anxiety agents
- Bhatacharya