Sedative Action Research Articles

Neuropharmacological Effects of the Dichloromethane Extract from the Stems of Argemone ochroleuca Sweet (Papaveraceae) and Its Active Compound Dihydrosanguinarine.

Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography-mass spectrometry (GC-MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1-50 mg/kg p.o.) and DHS (0.1-10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED50) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED50 = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED50 = 3 mg/kg) and the tail suspension test (ED50 = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED50 = 2 mg/kg) in the hole board test. The AOE (1-50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABAA receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS.

To investigate phytochemical parameter, Pharmacognostical evaluation, pharmacological (anti-bacterial) activity of the extract of Euphorbia pulcherrima

Introduction: Euphorbia pulcherrima is member of Euphorbiaceae family of medicinal plants, and it is used to cure variety of ailments which includes toothache, vomiting, fractures, severe bleeding, bruising, and hypermenorrhoea. Euphorbia pulcherrima has been found to possess a variety of chemicals, including alkaloids, steroids, terpenoids, flavonoids and reducing sugars. The review analyses its pharmacological profile, chemical component, and phytochemistry, with an emphasis on antioxidant activity, antimicrobial activity, Osteoclast activity, analgesic activity, anti-inflammatory activity, sedative activity, muscle relaxant activity, anticonvulsant activity and toxicological profile, in order to better assess the plants medicinal potential. Traditionally the latex has been employed as an anti-vomiting and toothache treatment. Aches and pains have been treated with leaf poultices. In traditional Chinese medicine it has been used it to treat fractures, severe bleeding, bruising, and hypermenorrhoea. 
 Methods: Due to extensive research on the pharmacological effects and active compounds of Euphorbia pulcherrima, it has a great deal of potential in modern medicine. Phyto, physicochemical standardization of dried, matured root of Euphorbia pulcherrima has been carried out in the present study. The study includes organoleptic characters along with estimation of its physicochemical parameters such as loss on drying, ash values, extractability in water and methanol. Preliminary phytochemical screening and anti-bacterial assay has been conducted.
 Conclusion: As there is not enough evidence for detailed physicochemical and phytochemical evaluation on root of Euphorbia pulcherrima is reported. The present study reveals that the selected plant extract produces antimicrobial activity with dose dependent manner. However, it needs further evaluation in clinical settings before consideration for the treatment of different diseases.
 Keywords: Euphorbia pulcherrima, Phytochemicals, pharmacological activity, Physicochemical.

Advances in pharmacological effects of jujuboside B

Ziziphi Spinosae Semen(ZSS) is an edible TCM derived from the dried ripe seeds of Ziziphus jujube Mill. var. spinosa(Bunge)Hu ex H. F. Chou(Rhamnaceae), which has the effects of nourishing the heart, tonifying the liver, calming the heart, tranquilizing the mind, arresting sweating, and promoting fluid production, and is widely used in the treatment and health care of diseases related to cardiovascular, nervous, and immune systems. Jujuboside B(JuB), one of the main active ingredients of ZSS, possesses various pharmacological effects with application values. This paper reviewed the chemical structure and pharmacological effects of JuB. JuB has sedative, hypnotic, antitumor, anti-platelet, anti-inflammatory, and other biological activities, which shows the potential thera-peutic effects on insomnia, tumors, coronary artery disease, airway inflammation, and liver injury. However, there are some limitations to the results of current studies. More comprehensive studies, including basic research and clinical trials, need to be carried out to provide more reliable evidence.

Behavioural, Sedative and Anticonvulsant Activities of Ethanol Extract of the Leaf of <i>Lagenaria breviflora</i> (Benth) in Mice

Background: Lagenaria breviflora Benth is used in West Africa as a traditional remedy for the treatment of gastrointestinal disorders, the treatment of human measles, digestive disorders, and as a wound antiseptic.
 Objectives: This study investigated the behavioural, sedative, and anticonvulsant activities of the ethanol extract of Lagenaria breviflora (EOLB) in mice, and its possible mechanism(s) of action.
 Materials and Methods: The CNS activities of EOLB (100, 200, and 400 mg/kg, i.p., n=6) were evaluated using animal models of novelty- induced behaviours (NIB), sedation (ketamine-induced hypnosis), and anticonvulsion (maximal electroshock (MES), pentylenetetrazole (PTZ), and strychnine). Probable mechanism(s) were evaluated using an antagonist (flumazenil, 2 mg/ml, i.p.) and an agonist (amphetamine (2 mg/kg, i.p.) on NIB.
 Results: LD50 values obtained were 1225 mg/kg and greater than 5000 mg/kg for the intraperitoneal and oral routes respectively. The EOLB at all doses tested significantly (p<0.01) inhibited the NIB. The EOLB (400 mg/kg) significantly (p<0.01) shortened sleep latency and significantly (p<0.05) prolonged the total sleeping time induced by ketamine (100 mg/kg, i.p.). EOLB at 400 mg/kg gave 33.3 % protection against HLTE caused by the MES-induced convulsion, significantly (p<0.01) prolonged the time of death, and offered 83.3 % protection against convulsion caused by PTZ. Flumazenil and amphetamine (2 mg/kg, i.p. respectively) significantly (p<0.001) reversed the effects of the EOLB on NIB.
 Conclusions: The study concluded that the ethanol leaf extract of Lagenaria breviflora is safe orally and mildly toxic intraperitoneally. The extract showed significant depressive activity on the central nervous system, sedative and anticonvulsant activities which may be mediated through augmentation of GABAergic or inhibition of the dopaminergic neural pathways, thus supporting some of the tradomedicinal claims of the uses of Lagenaria breviflora.

Novel H2S-Releasing Bifunctional Antihistamine Molecules with Improved Antipruritic and Reduced Sedative Actions.

Hydrogen sulfide (H2S) is an endogenous gasotransmitter with anti-inflammatory actions that also reduces itching. To test whether a combination of an antihistamine with a H2S donor has improved antipruritic efficacy, bifunctional molecules with antihistamine and H2S-releasing pharmacophores were synthesized and tested in vitro and in vivo. H2S release from the hybrid molecules was evaluated with the methylene blue and lead acetate methods, and H1-blocking activity was assessed by determining tissue factor expression inhibition. All new compounds released H2S in a dose-dependent manner and retained histamine blocking activity. Two compounds with the highest potency were evaluated in vivo for their antipruritic as well as sedative action; they proved to possess higher efficacy in inhibiting histamine-induced pruritus and decreased sedative effects compared to the parent compounds (hydroxyzine and cetirizine), suggesting that they exhibit superior antipruritic action and limited side effects that likely arise from the H2S-releasing moiety.

Molecular Descriptors and QSAR Models for Sedative Activity of Sesquiterpenes Administered to Mice via Inhalation.

Essential oils are often utilized for therapeutic purposes and are composed of complex structural molecules, including sesquiterpenes, with high molecular weight and potential for stereochemistry. A detailed study on the properties of selected sesquiterpenes was conducted as part of a broader investigation on the effects of sesquiterpenes on the central nervous system. A set of 18 sesquiterpenes, rigorously selected from an original list of 114, was divided into 2 groups i.e., the training and test sets, with each containing 9 compounds. The training set was evaluated for the sedative activity in mice through inhalation, and all compounds were sedatives at any dose in the range of 4 × 10-4-4 × 10-2 mg/cage, except for curzerene. Molecular determinants of the sedative activities of sesquiterpenes were evaluated using quantitative structure-activity relationship (QSAR) and structure-activity relationship (SAR) analyses. An additional test set of six compounds obtained from the literature was utilized for validating the QSAR model. The parental carbonyl cation and an oxygen-containing groups are possible determinants of sedative activity. The QSAR study using multiple regression models could reasonably predict the sedative activity of sesquiterpenes with statistical parameters such as the correlation coefficient r2 = 0.82 > 0.6 and q2 LOO = 0.71 > 0.5 obtained using the leave-one-out cross-validation technique. Molar refractivity and the number of hydrogen bond acceptors were statistically important in predicting the activities. The present study could help predict the sedative activity of additional sesquiterpenes, thus accelerating the process of drug development.

Drug burden index in people living with HIV over 50 years of age in a real clinical practice cohort

ObjectivesTo determine DBI and its relationship with polypharmacy and pharmacotherapeutic complexity (PC) in a cohort of PLWH over 50 years of age at follow-up of pharmacotherapy in a tertiary hospital. MethodsObservational and retrospective study that included PLWH in active antiretroviral treatment over 50 years of age who have been followed up in outpatient pharmacy services. Pharmacotherapeutic complexity was estimated through Medication Regimen Complexity Index (MRCI). Collected variables included comorbidities, current prescriptions and its classification according to anticholinergic and sedative activity and associated risk of falls. ResultsStudied population included 251 patients (85.7% men; median age: 58 years, interquartile range: 54–61). There was a high prevalence of high DBI scores (49.2%). High DBI was significantly correlated with a high PC, polypharmacy, psychiatric comorbidity and substances abuse (p<0.05). Among sedative drugs, the most prescribed were anxiolytic drugs (N05B) (n=85), antidepressant drugs (N06A) (n=41) and antiepileptic drugs (N03A) (n=29). For anticholinergic drugs, alpha-adrenergic antagonist drugs (G04C) were the most prescribed (n=18). Most frequent drugs associated with risk of falls were anxiolytics (N05B) (n=85), angiotensin-converting enzyme inhibitors (C09A) (n=61) and antidepressants (N06A) (n=41). ConclusionThe DBI score in older PLWH is high and it is related to PC, polypharmacy, mental diseases and substance abuse as is the prevalence of fall-related drugs. Control of these parameters as well as the reduction of the sedative and anticholinergic load should be included in the lines of work in the pharmaceutical care of people living with HIV+.

Acmella calva (DC.) R.K. Jansen Flower: A Comprehensive In vivo Study of its Central and Peripheral Analgesic, Hypoglycemic, Antidepressant, and Anti-Diarrheal Properties

Acmella calva (DC.) R.K. Jansen (Local name “Surzo konna”) is a Southeast Asian perennial herb mostly used in rural areas as an ailment of dental disorders. This study involved the evaluation of peripheral and central analgesic activities, hypoglycemic, anti-diarrheal and anti-depressant activities of the methanolic extract of A. calva flower at different doses- (200 mg/kg, 400 mg/kg and 600 mg/kg of body weight) on Swiss Albino mice models. The sample exhibited moderate central analgesic activity at all doses whereas the acetic acid-induced writhing test in mice revealed 67.69% reduction in peripheral pain response for both 400 and 600 mg/kg doses (69.23% for standard diclofenac sodium). Reduction in diarrheal faeces was found to be 41.03% and 46.46% at dose of 200 mg/kg and 400 mg/kg respectively compared to the standard loperamide 53.85%. Hypoglycemic activity in diabetic mice showed statistically significant data depending on increasing doses and thiopental induced sleeping test revealed the sedative activity (P&lt;0.05) compared to diazepam. The in-vivo bioactivities suggest that this plant part can be a potential source of active lead compounds. Dhaka Univ. J. Pharm. Sci. 22(1): 65-71, 2023 (June)

Chemical composition and comparative analysis of lavender essential oil samples from Bulgaria in relation to the pharmacological effects

Lavender essential oil is economically important and widely used in aromatherapy perfumery, food industry and pharmacy. Bulgaria is a global leader in lavender cultivation overtaking countries such as France, UK, China, India, and Spain during the last few years. The aim of this research is: 1) to characterize a lavender essential oil sample obtained from agricultural plantation near Pomorie, Bulgaria; 2) to perform descriptive statistical test based on a data set of 13 samples available in 4 publications, 3) to compare the varieties regarding the quantity of the most important components such as linalool and linalyl acetate 4) to summarize the pharmacological effects of the main components. As a result of GS/MS analysis of the essential oil sample obtained from agricultural plantation near Pomorie, we identified 44 compounds. The major constituents were linalyl acetate (27.5%) linalool (24.1%),E-β-ocimene (7.0%), terpinen-4-ol (5.1%) caryophyllene (4.5%), carvacrol (4.4%), lavandulyl acetate (3.5%),Z-β-farnesene (3.3%), and -Z-β-ocimene (3.2%). Linalool and linalyl acetate are the main ingredients based on which the quality of the essential oil is evaluated. In the studied samples they fluctuated between varieties depending on the year of extraction and the locations of origin in Bulgaria. Some varieties were characterized by a more stable ratio of linalool – linalyl acetate, compared to others. The main other components of our sample as well as the other examined Bulgarian samples fit the standards according to the requirements of ISO (2002) and the of European Pharmacopoeia (10thedn., Council of Europe 2020) with few exceptions. Lavender oil has numerous pharmacological applications based on its anxiolytic, sedative, antioxidant, anti-inflammatory, antitumor and antimicrobial activities. Although linalool and linalyl acetate largely contribute to these effects, the overall efficacy of lavender oil is proven to be due synergistic relationships between the components.

Coronaridine congeners induce sedative and anxiolytic-like activity in naïve and stressed/anxious mice by allosteric mechanisms involving increased GABAA receptor affinity for GABA

The sedative and anxiolytic-like activity of two coronaridine congeners, (+)-catharanthine and (−)-18-methoxycoronaridine (18-MC), was studied in male and female mice. The underlying molecular mechanism was subsequently determined by fluorescence imaging and radioligand binding experiments. The loss of righting reflex and locomotor activity results showed that both (+)-catharanthine and (−)-18-MC induce sedative effects at doses of 63 and 72 mg/kg in a sex-independent manner. At a lower dose (40 mg/kg), only (−)-18-MC induced anxiolytic-like activity in naïve mice (elevated O-maze test), whereas both congeners were effective in mice under stressful/anxiogenic conditions (light/dark transition test) and in stressed/anxious mice (novelty-suppressed feeding test), where the latter effect lasted for 24 h. Coronaridine congeners did not block pentylenetetrazole-induced anxiogenic-like activity in mice. Considering that pentylenetetrazole inhibits GABAA receptors, this result supports a role for this receptor in the activity mediated by coronaridine congeners. Functional and radioligand binding results showed that coronaridine congeners interact with a site different from that for benzodiazepines, increasing GABAA receptor affinity for GABA. Our study showed that coronaridine congeners induce sedative and anxiolytic-like activity in naïve and stressed/anxious mice in a sex-independent fashion, likely by a benzodiazepine-independent allosteric mechanism that increases GABAA receptor affinity for GABA.

Drug burden index in people living with HIV over 50 years of age in a real clinical practice cohort

ObjectivesTo determine DBI and its relationship with polypharmacy and pharmacotherapeutic complexity (PC) in a cohort of PLWH over 50 years of age at follow-up of pharmacotherapy in a tertiary hospital. MethodsObservational and retrospective study that included PLWH in active antiretroviral treatment over 50 years of age who have been followed up in outpatient pharmacy services. Pharmacotherapeutic complexity was estimated through Medication Regimen Complexity Index (MRCI). Collected variables included comorbidities, current prescriptions and its classification according to anticholinergic and sedative activity and associated risk of falls. ResultsStudied population included 251 patients (85.7% men; median age: 58 years, interquartile range: 54–61). There was a high prevalence of high DBI scores (49.2%). High DBI was significantly correlated with a high PC, polypharmacy, psychiatric comorbidity and substances abuse (p<0.05). Among sedative drugs, the most prescribed were anxiolytic drugs (N05B) (n=85), antidepressant drugs (N06A) (n=41) and antiepileptic drugs (N03A) (n=29). For anticholinergic drugs, alpha-adrenergic antagonist drugs (G04C) were the most prescribed (n=18). Most frequent drugs associated with risk of falls were anxiolytics (N05B) (n=85), angiotensin-converting enzyme inhibitors (C09A) (n=61) and antidepressants (N06A) (n=41). ConclusionThe DBI score in older PLWH is high and it is related to PC, polypharmacy, mental diseases and substance abuse as is the prevalence of fall-related drugs. Control of these parameters as well as the reduction of the sedative and anticholinergic load should be included in the lines of work in the pharmaceutical care of people living with HIV+.

Effect of Gabapentin-Fluoxetine Derivative GBP1F in a Murine Model of Depression, Anxiety and Cognition.

Gabapentin is a commonly prescribed antiepileptic agent for seizures, which is also used for pain and addiction management. Due to growing evidence of its abuse liability, there has been an incentive to synthesise potentially useful gabapentin derivatives devoid of adverse effects. A gabapentin adduct with a fluoxetine moiety, GBP1F, was assessed for any sedative, cognitive, anxiolytic, or antidepressant-like actions in murine behavioral models. Selected groups of mice were used for each behavioral paradigm, and the effect of GBP1F (5, 10, and 15 mg/kg) was assessed using spontaneous locomotor activity, the tail suspension test, elevated plus maze test, and the Y maze test models. Immediately following behavioral experiments, postmortem striatal and hippocampal tissues were evaluated for the effect of GBP1F on concentrations of dopamine, DOPAC, HVA, serotonin, 5-HIAA, vitamin C, and noradrenaline using high performance liquid chromatography with electrochemical detection. GBP1F induced a mild suppression of locomotor activity, ameliorated anxiety and depression-like behavior, did not alter cognitive behavior, and raised serotonin and 5-HIAA concentrations in the hippocampus and striatum. GBP1F also positively enhanced dopamine and vitamin C tissue levels in the striatum. Thus, GBP1F represents a compound with anxiolytic- and antidepressant-like effects though further studies are warranted at the molecular level to focus on the precise mechanism(s) of action.

Strategy for the management and prevention of psycho-emotional disorders in the GP’s practice

Psycho-emotional disorders, such as anxiety disorders, acute and chronic stress, are significant risk factors for the development and complicated course of both major cardiovascular and other common chronic non-communicable diseases. The psycho-emotional disorders significantly reduce patients’ motivation and adherence to lifestyle changes and drug therapy, significantly worse quality of life, increase the risk of disability and healthcare system expenditures. The topicality of the issues of diagnosis and management of psycho-emotional disorders in the general practitioner’s practice is caused, on the one hand, by high rates of these disorders in patients with cardiovascular and other chronic diseases, deterioration in quality of life and an increase in adverse outcomes, and on the other hand, inadequate awareness of the risks associated with the sphere of psycho-emotional status in patients. The management of psycho-emotional disorders includes both pharmacological and non-pharmacological treatments. Antidepressants that fall into the class of selective serotonin or serotonin and norepinephrine reuptake inhibitors are the first-line drugs used for the treatment of most of the disorders discussed. However, prescription of these drugs requires to take into account a wide range of possible side effects in patients with chronic diseases, including CVDs. Drugs that have fast onsets of sedative and anti-anxiety action, also known as tranquilizers, are more widely used in real-world clinical practice. Tofisopam is the most promising from this group of drugs in therapeutic and cardiological practice. The efficacy and safety of tofisopam have been studied in numerous studies in patients with chronic non-communicable diseases and a wide range of anxiety disorders, including the long-term use of the drug.

L-Theanine and Immunity: A Review.

L-theanine (N-ethyl-γ-glutamine) is the main amino acid in tea leaves. It not only contributes to tea flavor but also possesses several health benefits. Compared with its sedative and calming activities, the immunomodulatory effects of L-theanine have received less attention. Clinical and epidemiological studies have shown that L-theanine reduces immunosuppression caused by strenuous exercise and prevents colds and influenza by improving immunity. Numerous cell and animal studies have proven that theanine plays an immunoregulatory role in inflammation, nerve damage, the intestinal tract, and tumors by regulating γδT lymphocyte function, glutathione (GSH) synthesis, and the secretion of cytokines and neurotransmitters. In addition, theanine can be used as an immunomodulator in animal production. This article reviews the research progress of L-theanine on immunoregulation and related mechanisms, as well as its application in poultry and animal husbandry. It is hoped that this work will be beneficial to future related research.

Eye Movement and Coma Recovery after Cardiac Arrest (P1-7.006)

<h3>Objective:</h3> To characterize eye movements in comatose patients after cardiac arrest (CA). <h3>Background:</h3> Most patients resuscitated from CA present with altered levels of consciousness due to brain injury. One potential marker of arousal recovery is evidence of eye movements. Brainstem pathways and thalamocortical projections responsible for eye movements share similar anatomic structures responsible for arousal. Our aim is to quantify eye movements using electro-oculography (EOG) data from patients presenting with CA. <h3>Design/Methods:</h3> We are conducting a retrospective study of patients presenting within 24 hours of CA. We identify eye movements on EOG over a period of up to 72 hours, excluding periods of clinical care, sedation, and epileptiform activity. We will study the association of eye movement frequency and the following outcomes by two weeks: 1. Present corneal or pupillary reflex; 2. Eye opening (to stimuli or spontaneously); 3. Command following. Patients are excluded if they have ophthalmoplegia, dementia, or traumatic brain injury. We will compare eye movement frequency in our comatose cohort to a separate cohort of non-comatose patients who underwent sleep studies. <h3>Results:</h3> Our preliminary data consists of 100 patients, mean (± SD) age of 60.2 (± 15.3) years and 38% were female. By 2 weeks, 85% had a pupillary reflex, 75% had a corneal reflex, 43% opened eyes to stimuli, and 21% followed commands. Of 151.5 hours of EOG time across four patients, we preliminarily found eye movements present in 0.56% of total time, with a median of 0.73% and range of 0% to 2.29%. This is comparable to our cohort of 47 patients who underwent sleep studies, with eye movements present in 3.2% of N2, 2.9% of N3, and 19.8% of REM. <h3>Conclusions:</h3> Eye movements in comatose patients may be indicative of recovery potential. Understanding these differences could have prognostic significance and help in triaging care and family discussions. <b>Disclosure:</b> The institution of Mr. Cronin has received research support from American Heart Association. Miss Hwang has nothing to disclose. The institution of an immediate family member of Miss Wack has received research support from Canon Medical Systems USA, Inc. Brian Pugsley has nothing to disclose. Mary Russo has nothing to disclose. Dr. Greer has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Thieme, Inc. Dr. Greer has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for multiple. The institution of Dr. Greer has received research support from Becton Dickenson, Inc. Dr. Greer has received publishing royalties from a publication relating to health care. Dr. Ong has nothing to disclose.

Antibacterial Activity and Anxiolytic Effect in Adult Zebrafish of Genus Lippia L. Species.

Species belonging to the genus Lippia are used worldwide as foods, beverages, and seasonings. Studies have demonstrated that these species have antioxidant, sedative, analgesic, anti-inflammatory, and antipyretic activities. This work aimed to evaluate the antibacterial activity and anxiolytic effect by different pathways of essential oils and ethanolic extracts of three species of Lippia (Lippia alba, Lippia sidoides, and Lippia gracilis). The ethanolic extracts were characterized by HPLC-DAD-ESI-MSn and their phenolics were quantified. The antibacterial activity was evaluated by determining the minimal inhibitory concentration and modulation of antibiotic activity, and toxic and anxiolytic effects were evaluated in the zebrafish model. The extracts showed compositions with a low ratio and shared compounds. L. alba and L. gracilis showed higher amounts of phenols and flavonoids, respectively. All extracts and essential oils presented antibacterial activity, especially those obtained from L. sidoides. On the other hand, L. alba extract presented the most significant antibiotic-enhancing effect. The samples were not toxic after 96 h of exposure, but showed an anxiolytic effect through modulation of the GABAA receptor, while L. alba extract acted via modulation of the 5-HT receptor. This new pharmacological evidence opens horizons for therapeutic approaches targeting anxiolytic and antibacterial therapies and food conservation using these species and their constituents.

Inhibitory effects of linalool, an essential oil component of lavender, on nociceptive TRPA1 and voltage-gated Ca2+ channels in mouse sensory neurons

Linalool, an essential oil component of lavender is commonly used in fragrances. It is known that linalool has anxiolytic, sedative, and analgesic actions. However, the mechanism of its analgesic action has not yet been fully clarified. Pain signals elicited by the activation of nociceptors on peripheral neurons are transmitted to the central nervous system. In the present study, we investigated the effects of linalool on transient receptor potential (TRP) channels and voltage-gated channels, both of which are important for pain signaling via nociceptors in somatosensory neurons. For detection of channel activity, the intracellular Ca2+ concentration ([Ca2+]i) was measured using a Ca2+-imaging system, and membrane currents were recorded using the whole-cell patch-clamp technique. Analgesic actions were also examined in vivo.In mouse sensory neurons linalool at concentrations that did not induce [Ca2+]i increases did not affect [Ca2+]i responses to capsaicin and acids, TRPV1 agonists, but suppressed those induced by allyl isothiocyanate (AITC) and carvacrol, TRPA1 agonists. Similar inhibitory effects of linalool were observed in cells that heterologously expressed TRPA1. Linalool attenuated the [Ca2+]i increases induced by KCl and voltage-gated Ca2+ currents but only slightly suppressed voltage-gated Na＋currents in mouse sensory neurons. Linalool diminished TRPA1-mediated nociceptive behaviors.The present data suggest that linalool exerts an analgesic action via the suppression of nociceptive TRPA1 and voltage-gated Ca2+ channels.

Sedative-Hypnotic Effects of Glycine max Merr. Extract and Its Active Ingredient Genistein on Electric-Shock-Induced Sleep Disturbances in Rats.

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders.

Gymnadenia conopsea (L.) R. Br.: Comprehensive review of propagation and breeding, traditional uses, chemical composition, pharmacology, quality control, and processing.

Gymnadenia conopsea, a perennial herbaceous flowering plant that belongs to the family of Orchidaceae, sporadic distributed in the altitudes of 200-4700m across northern Europe and, temperate and subtropical Asia region. The dried tubers of G. conopsea have been used to treat cough, asthma, and their syndromes, and also as a tonic in China and surrounding countries for a long history. G. conopsea is often processed deeply processed before use to enhance its efficacy. In recent years, because of its remarkable pharmacological activity and health care function, G. conopsea has been used more and more widely. Due to its extensive application and bad growth environment, the wild distribution of G. conopsea is decreasing and it has been listed as an endangered plant. This review aims to summarize the propagation and breeding, traditional uses, chemical composition, pharmacology, quality control, and processing of G. conopsea. Moreover, it also provides suggestions for the future high-value utilization of G. conopsea. A literature search on Gymnadenia genus and G. conopsea was performed using scientific databases including SciFinder, ACS, Web of Science, Springer, ScienceDirect, PubMed, and CNKI. Information was also collected from classic books of Chinese herbal medicine, official websites, Ph.D. and M.Sc. Dissertations, and so on. Structures of chemical compounds were drawn by ChemDraw software. As of submission date of this manuscript, total 170 natural compounds have been isolated and characterized from G. conopsea, and all of the compounds were isolated from the tubers. The isolated compounds including benzylester glucosides, dihydrostilbenes, phenanthrenes, phenolic compounds, alkaloids, polysaccharide, lignans, flavones, triterpenoids, steroids, and other compounds. Some of these compounds and active extracts exhibited a wide range of pharmacological activities, in which, the tonifying, anti-fatigue, anti-oxidant, anti-viral, sedative and hypnotic activities are consistent with the traditional uses for the treatment of diseases. In addition, a variety of new pharmacological activities, such as preventing and treating gastric ulcers, immunoregulatory, anti-hyperlipidemia, anti-anaphylaxis, anti-silicosis, anti-cancer and neuroprotective activities have also been reported. However, the bioactive compounds responsible for most of the above pharmacological effects have not been well summarised till now. In this manuscript, analysis, speculation and summary of compounds that responsible for pharmacological effects were conducted. The chemical constituents and pharmacological activities studies of G. conopsea extract have been summarised in this context, the isolated compounds responsible for the pharmacological activities were also analyzed and deduced according to the publications, all above led to suggestions for the future high-value utilization of G. conopsea.

Cannabidiol as a Modulator of the Development of Alcohol Tolerance in Rats.

The study aimed to explore in vivo the influence of cannabidiol (CBD) on the development of alcohol tolerance in rats. Rats were treated with ethanol (3.0 g/kg, i.p.) and CBD (20 mg/kg, p.o.) for nine successive days, and rectal body temperature, sedation (sleeping time), and blood alcohol concentration (BAC) were measured. In the prefrontal cortex, hippocampus, and striatum, the cannabinoid (CB1R and CB2R) and dopaminergic (DRD1, DRD2, DRD4, DRD5) receptors' mRNA level changes were analyzed using the quantitative RT-PCR method. CBD inhibited the development of tolerance to the hypothermic and sedative action of alcohol, coupled with BAC elevation. On a molecular level, the most pronounced effects of the CBD + ethanol interaction in the striatum were observed, where CBD reversed the downregulation of CB2R gene transcription caused by ethanol. For CB1R, DRD1, and DRD2 mRNAs, the CBD + ethanol interaction produced opposite effects than for CB2R ones. In turn, for the transcription of genes encoding dopaminergic receptors, the most potent effect of alcohol as CBD occurred in the hippocampus. However, the combined CBD and alcohol administration showed the same effect for each substance administered separately. Since tolerance is considered a prelude to drug addiction, obtained results allow us to emphasize the thesis that CBD can inhibit the development of alcohol dependence in rats.