Evaluation of the anti-nociceptive profile of essential oil from Melissa officinalis L. (lemon balm) in acute and chronic pain models.

ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Lamiaceae) is a medicinal plant native to Mediterranean regions and found in other parts of the world. Extracts and essential oil from this widely cultivated culinary medicinal herb are used in traditional medicine to manage a variety of disorders that include epilepsy and pain. AIM OF THE STUDY: To assess the anti-nociceptive potentials of Melissa officinalis essential oil (MO) and probe the involvement of adrenergic, opioidergic, serotonergic and potassium adenosine triphosphate (KATP) mechanisms in its anti-nociceptive effects. MATERIAL AND METHODS: We employed formalin-, acetic acid and hot plate-induced nociception to study the acute anti-nociceptive effects of MO. The sciatic nerve injury (CCI) model of neuropathic pain was utilized to study the anti-nociceptive effects of MO on chronic pain. Effects of MO on anxiety, cognitive deficits, oxidative stress and inflammation in the CCI rats were evaluated on elevated plus maze, open field test, novel object recognition, oxidative stress parameters and pro-inflammatory cytokines, respectively. The possible mechanism(s) of MO's anti-nociceptive effects were elucidated using prazosin, yohimbine, propranolol, glibenclimide, naloxone and metergoline, which are acknowledged antagonists for α1-, α2- and ß-adrenergic, potassium adenosine triphosphate (KATP), opioidergic and serotonergic systems, respectively. RESULTS: MO significantly attenuated acetic acid- and formalin-induced nociception; prolonged the mean reaction time of rats on hot plate before and following sciatic nerve chronic injury (CCI). MO ameliorated anxiety, cognitive deficits and oxidative stress, reduced pro-inflammatory cytokine levels and produced a near total restoration of injured sciatic nerves in CCI rats. Naloxone, metergoline and glibenclimide significantly blocked, while prazosin, yohimbine and popranolol failed to block the anti-nociceptive effects of MO in formalin-induced nociception. CONCLUSIONS: MO contains biologically active compounds with potential anti-nociceptive properties that modulate KATP, opioidergic and serotonergic pathways. These support the development of bioactive compounds from MO as anti-nociceptive agents.

Smart phone addiction and its mental health risks among university students in Jordan: a cross-sectional study.

BACKGROUND: Addiction to smart phones is classified clinically as behavioral addiction resulted from an excessive problematic usage of smart phones that effect the daily life of the users. Therefore, this study aims to explore the prevalence of smart phone addiction, its associated psychological distress risk, and its associated predictors among university students in Jordan. METHODS: Between November 2022 and January 2023, a cross-sectional online survey study was conducted in Jordan. In this study, we used previously developed questionnaire instruments, the psychological Distress scale of Kessler and the Smartphone Addiction Scale. A score of 30 was used to identify the dummy variable in the binary logistic regression analysis to identify predictors of severe psychological distress, and smartphone addiction score of 38.7 was used to to identify predictors of smartphone addiction. RESULTS: A total of 2337 university students participated in this study. The mean psychological distress score for the study participants was 30.0 (SD: 8.9). More than half of the study participants (59.1%) had a psychological distress score of 30 and above, which indicates a severe mental disorder state. More than half of the study participants (56.7%) had a smartphone addiction score of 30 and above, which reflects a smartphone addiction state. Females, divorced, those who feel that their mental abilities have been negatively affected by the use of smart phones, those who feel that using smartphones has affected their sleep and made it harder to fall asleep, and those feel that everything requires effort and fatigue, and they do not want to do any activity that requires effort were more likely to have severe psychological distress compared to others (p < 0.05). Females, those who feel that using smartphones has affected their sleep and made it harder to fall asleep, and those feel that everything requires effort and fatigue, and they do not want to do any activity that requires effort were more likely to be smartphone addicted compared to others (p < 0.05). CONCLUSION: Mental diseases are a major public health concern in Jordan, especially among university students. Females, those who thought smartphone usage hurt their mental capacities, and those who had trouble sleeping and fatigue were more likely to develop serious psychological discomfort and smartphone addiction. Smartphones are indispensable, but excessive use can lead to addiction and harm university students' mental health.

Hospitalisations related to nervous-system diseases in Australia, 1998-2019: a secular trend analysis.

OBJECTIVE: The burden of neurological disease-related disabilities and deaths is one of the most serious issues globally. We aimed to examine the hospitalisation profile related to nervous system diseases in Australia for the duration between 1998 and 2019. DESIGN: A secular trend analysis using a population-based dataset. SETTING: This analysis used a population-based study of hospitalised patients in Australia. Hospitalisation data were extracted from the National Hospital Morbidity Database, which collects sets of episode-level information for Australian patients admitted to all private and public hospitals. PARTICIPANTS: All patients who were hospitalised in all private and public hospitalisations. PRIMARY OUTCOME MEASURE: Hospitalisation rates related to nervous system diseases. RESULTS: Hospitalisation rates increased by 1.04 times (from 650.36 (95% CI 646.73 to 654.00) in 1998 to 1328.90 (95% CI 1324.44 to 1333.35) in 2019 per 100 000 persons, p<0.01). Overnight-stay episodes accounted for 57.0% of the total number of hospitalisations. Rates of the same-day hospitalisation for diseases of the nervous system increased by 2.10-fold (from 219.74 (95% CI 217.63 to 221.86) in 1998 to 680.23 (95% CI 677.03 to 683.43) in 2019 per 100 000 persons). Rates of overnight-stay hospital admission increased by 42.7% (from 430.62 (95% CI 427.66 to 433.58) in 1998 to 614.70 (95% CI 611.66 to 617.75) in 2019 per 100 000 persons). 'Episodic and paroxysmal disorders' were the most prevalent reason for hospitalisation, which accounted for 49.0% of the total number of episodes. Female hospitalisation rates increased by 1.13-fold (from 618.23 (95% CI 613.24 to 623.22) in 1998 to 1316.33 (95% CI 1310.07 to 1322.58) in 2019 per 100 000 persons). Male hospitalisation rates increased by 86.4% (from 682.95 (95% CI 677.67 to 688.23) in 1998 to 1273.18 (95% CI 1266.98 to 1279.37) in 2019 per 100 000 persons). CONCLUSION: Hospitalisation rates for neurological disorders in Australia are high, potentially owing to the ageing of the population. Males had greater rates of hospitalisation than females.

The Jordanian Population's Knowledge, Attitudes, and Willingness to Help People with Autism: A Cross-Sectional Study.

Objective: To assess the knowledge and attitudes of the general public in Jordan towards autism. In addition, we aimed to assess their awareness of various treatment options for autism, and their attentiveness and willingness to assist. Methods: A cross-sectional survey was conducted in Jordan for the period between April and May 2022 using an online questionnaire developed based on a literature review. A total of 833 individuals in Amman city completed the questionnaires assessing participant demographics, knowledge of and attitude towards ADS, awareness of management options, perception, and ability to help. Using logistic regression, the odds ratios (ORs) and 95% confidence intervals (CIs) for those who are more likely to be informed about autism were determined. Results: The participants' overall understanding of autism spectrum disorder was poor, with a mean score of 6.2 (SD: 3.1) out of 17, or 36.5%. The participants showed a moderately positive attitude towards autism, with an average agreement of 60.9% for government support for ADS children. The items about management options auditory integration training therapy had the highest level (50.1%). Additionally, the participants showed a moderate to high level of attention and ability to help people with autism. The majority confirmed that they see the need to implement changes in public facilities to meet the needs of autistic patients (71.8%). When compared to others, females, aged below 30, single, with family income less than 500 JD, holding a bachelor's degree, and working outside the healthcare field had a higher likelihood of knowing more about the autism spectrum condition (p ≤ 0.05). Conclusion: Our research illustrates the lack of awareness and knowledge among the Jordanian population regarding autism. To fill this gap, educational awareness programs should be conducted to promote Jordanian knowledge regarding autism and find ways in which communities, organisations, and governments can support so as to allow for early diagnoses and an appropriate treatment plan and therapy for autistic children.

Knowledge of and Attitude towards Epilepsy among the Jordanian Community.

BACKGROUND: Epilepsy is a disorder characterized by recurring seizures that do not have an immediate identifiable cause. It is a disorder with complex symptoms and a wide range of risk factors, with age, genetics, and origin being the most prevalent variations. This study aimed to evaluate the knowledge of and attitude towards epilepsy among the Jordanian community. METHOD: An online cross-sectional study using a self-administered questionnaire was conducted between 29 March and 15 May 2022 in Jordan. In this study, three previously validated questionnaire items were adapted and employed. Binary logistic regression was applied to identify predictors of good knowledge and a positive attitude. RESULTS: A total of 689 participants were involved in this study. A weak level of knowledge about epilepsy was observed among the study participants (35.3%). The participants showed a moderately positive attitude towards epilepsy (63.3%). Being female, holding a bachelor's degree, knowing anyone who had epilepsy and seeing anyone having an epileptic seizure were factors that positively affected participants' knowledge about epilepsy. Being aged between 24 and 29 years or being divorced were factors that affected the participants' attitudes negatively towards epilepsy. CONCLUSION: The study's participants had limited knowledge of epilepsy and a favorable attitude toward it. The community's understanding of epilepsy and attitude toward epilepsy patients should be improved by an informed educational effort on the part of various media platforms. All facets of the community, including parents, should be the focus of these initiatives.

Circulating Ubiquitin Carboxyl Terminal Hydrolase L1 and Neuroglobin Levels in Traumatic Spinal Cord Injuries: Relation to Severity and Outcomes.

Introduction: Traumatic spinal cord injury (TSCI) is a life-threatening neurological disorder and there is a lack of biomarker research, particularly human studies that could help to categorize the severity and predict the outcome. We aimed to assess the role of serum Ubiquitin C-terminal hydrolase L1 (UCH-L1) and Neuroglobin (NGB) in predicting severity and outcome of TSCI. Methods: This prospective study included 63 participants categorized into 33 patients with various types of TSCI and 30 unrelated healthy volunteers. Neurosurgical [American spinal injury association (ASIA) impairment score (AIS)] and radiological [using spine computed tomography (CT) and magnetic resonance imaging (MRI)] assessments were performed on the included patients to determine the severity and the level of injury with neurological follow-up of patients within 6 months post-injury. Serum UCH-L1 and NGB were measured for all participants using commercially available ELISA assay kits. Results: Of the included patients, 20 (60.60%) had partial SCI and the remaining 13 patients (39.39%) had complete SCI. On follow-up, 19 patients (57.57%) showed improved AIS, while 14 cases (42.42%) did not show any improvement in their AIS scores. There was significantly higher median serum UCHL1 value among cases compared to controls (1723 pg/mL and 657 pg/mL, respectively), p ˂ 0.05. There was an insignificant rise of serum NGB levels among cases in comparison with the controls (15.2pg/mL and 7.52pg/mL, respectively, p ˃ 0.05). Significantly lower initial median serum UCHL1 levels (pg/mL) were observed in patients with improved AIS during the neurological follow-up compared with those who did not show any improvement in their AIS score (1723, and 4700 respectively, p ˂ 0.05), with lack of significant difference in the initial median serum NGB levels, p ˃ 0.05. Conclusion: Initial serum UCHL1 assay could be a helpful marker in reflecting the degree of TSCI and predicting its outcome, though NGB needs further assessment.

Expression Patterns of Macrophage Migration Inhibitory Factor and Its Gene Variants (MIF-173 G˃C) in Verruca Vulgaris.

Introduction: Verruca vulgaris is a benign hyperkeratotic proliferation of the epidermis. Few studies look at the differences in serum and tissue macrophage migration inhibitory factor (MIF) levels in verruca vulgaris, as well as its gene polymorphisms that have yet to be explored. The current study provided in-depth evaluation of MIF in serum and tissues of patients with verruca vulgaris, and establishes for the first time the possible association of MIF gene polymorphisms with common warts. Methods: This case-control study included 50 patients who were diagnosed clinically as common warts in comparison with 50 age and sex-matched controls. Clinical examination was done on all included cases. Serum MIF was measured using enzyme-linked immunosorbent assay (ELISA), while its tissue expression was analyzed using Western blotting and immunohistochemical techniques for the included participants. Analysis of MIF-173 G˃C single nucleotide polymorphism was performed by polymerase chain reaction (PCR) using restriction fragment length polymorphism (RFLP) technique. Results: The overall results revealed significantly lower MIF tissue expression in lesional and perilesional skin biopsies from cases compared to the controls using Western blot and immunohistochemical analysis. Yet, the difference in the serum MIF levels between cases and controls was not significant (p ˃ 0.05). GC genotype of the studied MIF rs755622 G>C SNP could be considered as a protective genetic factor against the occurrence of verruca vulgaris among Egyptians with OR (95% CI) equal 0.444 (0.199-0.989). Conclusion: MIF and its genetic variants are thought to play a pathogenic role in verruca vulgaris development and recurrence.

New Insights Into the Anticonvulsant Effects of Essential Oil From Melissa officinalis L. (Lemon Balm).

Melissa officinalis L. is used in traditional European and Iranian folk medicines to treat a plethora of neurological diseases including epilepsy. We utilized the in vitro and in vivo models of epilepsy to probe the anticonvulsant potentials of essential oil from M. officinalis (MO) to gain insight into the scientific basis for its applications in traditional medicine for the management of convulsive disorders. MO was evaluated for effects on maximal electroshock (MES) and pentylenetetrazole (PTZ) -induced seizures in mice, on 4-aminopyridine (4-AP)-brain slice model of epilepsy and sustained repetitive firing of current clamped neurons; and its ameliorative effects were examined on seizure severity, anxiety, depression, cognitive dysfunction, oxidative stress and neuronal cell loss in PTZ-kindled rats. MO reversibly blocked spontaneous ictal-like discharges in the 4-AP-brain slice model of epilepsy and secondary spikes from sustained repetitive firing, suggesting anticonvulsant effects and voltage-gated sodium channel blockade. MO protected mice from PTZ- and MES-induced seizures and mortality, and ameliorated seizure severity, fear-avoidance, depressive-like behavior, cognitive deficits, oxidative stress and neuronal cell loss in PTZ-kindled rats. The findings warrant further study for the potential use of MO and/or its constituent(s) as adjunctive therapy for epileptic patients.

The Prevalence of Mental Distress and Social Support among University Students in Jordan: A Cross-Sectional Study.

OBJECTIVES: To examine the prevalence of mental distress among university students in Jordan. METHODS: An online cross-sectional study using a self-administered questionnaire was conducted between 12th of June and the 4th of August 2021 in Jordan to measure student mental stress using Self-Reporting Questionnaire-20 (SRQ-20). RESULTS: A total of 1063 university students participated in the study. One-third of the participating students reported that they had a history of COVID-19 infection. More than half of the participating university students (65.7%) were found to have mental distress (measured symptomatically by the SRQ-20 with a score of eight or more). The average mental distress score was 9.8 (SD: 5.5) out of 20. Female students, students from non-medical colleges, students in their last years of study, students with chronic diseases and those with low income were associated with high levels of mental distress (p < 0.05). With regards to social support, a moderate level of social support was received from three sources: persons considered as significant others, family members, and friends. The average social support score for the participating university students was 41.9 (SD: 10.3) out of 60 (equivalent to 69.8%). CONCLUSIONS: Mental distress is prevalent among university students in Jordan. There is a need for evidence-based governmental strategies and interventions that provide social support at universities such as self-help measures and professional mental health services as part of student health services that would be helpful to reduce the burden of mental distress of students and promote the mission of the integration of mental health in all university policies.

Paving Luteolin Therapeutic Potentialities and Agro-Food-Pharma Applications: Emphasis on In Vivo Pharmacological Effects and Bioavailability Traits.

Luteolin is a naturally occurring secondary metabolite belonging to the class of flavones. As many other natural flavonoids, it is often found in combination with glycosides in many fruits, vegetables, and plants, contributing to their biological and pharmacological value. Many preclinical studies report that luteolin present excellent antioxidant, anticancer, antimicrobial, neuroprotective, cardioprotective, antiviral, and anti-inflammatory effects, and as a consequence, various clinical trials have been designed to investigate the therapeutic potential of luteolin in humans. However, luteolin has a very limited bioavailability, which consequently affects its biological properties and efficacy. Several drug delivery strategies have been developed to raise its bioavailability, with nanoformulations and lipid carriers, such as liposomes, being the most intensively explored. Pharmacological potential of luteolin in various disorders has also been underlined, but to some of them, the exact mechanism is still poorly understood. Given the great potential of this natural antioxidant in health, this review is aimed at providing an extensive overview on the in vivo pharmacological action of luteolin and at stressing the main features related to its bioavailability, absorption, and metabolism, while essential steps determine its absolute health benefits and safety profiles. In addition, despite the scarcity of studies on luteolin bioavailability, the different drug delivery formulations developed to increase its bioavailability are also listed here.

Gephyrin and CYP2C9 Genetic Polymorphisms in Patients with Pharmacoresistant Epilepsy.

PURPOSE: Gephyrin (GPHN) is an essential protein in the regulation of inhibitory postsynaptic density and polymorphism in the corresponding gene may have a role in the development of pharmacoresistant epilepsy (PRE). For the first time, we aimed to evaluate the association of rs928553T/C variants with PRE susceptibility. Moreover, we have analyzed the genetic polymorphism affecting CYP2C9 "rs12782374G/A" in the same population to detect the effect of SNP on the drug-metabolizing ability of patients with PRE. PATIENTS AND METHODS: This case-control study enrolled 100 patients (group A) and 100 healthy, age and sex-matched controls, unrelated to patients (group B). TaqMan™ assays using real-time PCR were run for genotyping of rs928553T/C and rs12782374G/A in all participants. RESULTS: GPHN T>C polymorphism revealed significant risk association with occurrence of PRE using dominant, recessive and codominant models as follows: TT vs (TC+CC): OR 0.23, 95%CI: 0.13-0.43, P<0.001. In addition, (TT+TC vs CC): OR 0.38, 95%CI: 0.18-0.77, P<0.001. Also, T vs C (OR 0.34, 95%CI: 0.22-0.51, P=<0.001). Similarly, CYP2C9 G>A polymorphism showed a significant increased risk of PRE (GG vs (GA+AA): OR 0.11, 95%CI: 0.05-0.23, P<0.001). Furthermore, (GG+GA vs AA): OR 0.18, 95%CI: 0.084-0.39, P<0.001. Also, G vs A (OR 0.24, 95%CI: 0.15-0.366, P=<0.001). CONCLUSION: Mutation of both GPHN (rs928553) and CYP2C9 (rs1278237) genes may be implicated as a genetic mediators of resistance in patients with PRE.

Protective effect of caffeine and/or taurine on the 6-hydroxydopamine-induced rat model of Parkinson's disease: Behavioral and neurochemical evidence.

BACKGROUND: Caffeine and taurine, which possess neuro-modulatory activity happen to be consumed together as part of the constituents of energy drinks, could have beneficial effects and prevent neuronal deterioration in Parkinson's disease (PD). OBJECTIVE: This study aimed to investigate behavioral and neurochemical effects of these two agents in an animal model of PD at two time points to evaluate possible neuro-protective or neuro-modulatory effects. METHODS: Stereotaxic injection of 6-hydroxydopamine (6-OHDA) in rat striatum was used to model PD-like behavior in animals. Motor behavior was assessed by a characteristic rotation behavior response to the apomorphine challenge and dopamine levels in the striatum were quantified using HPLC-ED. RESULTS: A reduction in apomorphine induced rotations following administration of caffeine and/or taurine as compared to the untreated lesioned group (controls) was shown. Significant decreases in dopamine levels were also seen in the ipsilateral side of 6-OHDA group, this effect was not significantly reversed in caffeine and taurine treated groups. Treatments partially restored the content of DA levels in the lesioned striatum. CONCLUSIONS: Current results demonstrated beneficial effects for the combination of caffeine and taurine in PD animal model, suggesting that consumption of both agents could be a new added therapeutic target for Parkinson's disease prevention and treatment.

Circulating and local nuclear expression of survivin and fibulin-3 genes in discriminating benign from malignant respiratory diseases: correlation analysis.

Survivin is an inhibitor of apoptosis as well as a promoter of cell proliferation. Fibulin-3 is a matrix glycoprotein that displays potential for tumor suppression or propagation. The present study aimed to validate the expression levels of survivin and fibulin-3 in benign and malignant respiratory diseases. This case-control study included 219 patients categorized into five groups. Group A included 63 patients with lung cancer, group B included 63 patients with various benign lung diseases, group D included 45 patients with malignant pleural mesothelioma (MPM), and group E included 48 patients with various benign pleural diseases. Group C included 60 healthy individuals (control group). Serum survivin and fibulin-3 levels were measured by ELISA, whereas their nuclear expressions in the lung and pleura were assessed via Western blot analysis. The results showed significantly higher survivin serum levels and significantly lower fibulin-3 levels in group A compared with in group B and controls (P<0.001). There were significantly higher serum levels of survivin and fibulin-3 in group D compared with in group E and controls (P<0.001), consistent with observed nuclear survivin and fibulin-3 expression levels. Fibulin-3 was determined to have higher value than survivin in discriminating lung cancer from MPM (P<0.05). Survivin and fibulin-3 could be useful diagnostic markers for lung and pleural cancers, and fibulin-3 expression was particularly useful in differentiating lung cancer from MPM.

Herbal medicines: a cross-sectional study to evaluate the prevalence and predictors of use among Jordanian adults.

INTRODUCTION: Understanding why adults resort to herbal medicine can help in planning interventions aimed at increasing awareness regarding herbal use. This study sought to investigate the prevalence and to determine factors for predicting the use of herbal medicine among Jordanian adults. METHODS: A cross-sectional study was conducted involving 378 older adults who were randomly selected from two different areas of Jordan. A questionnaire was used to gather data and validation criteria for validity and reliability of the content were tested by content and face validity in a panel of experts. RESULTS: From a total of 500 invited participants, 378 completed the questionnaire. The prevalence of the use of of herbal products in this study was high at 80.2%. Herbal medicines use was not associated with any demographic factors other than age (p < 0.05). Moreover, the only associated health-related characteristic was the patient's disease state including, notably, hypertension (p < 0.05). Reasons for not using herbal medicines as reported by nonusers included mainly a lack of belief in their efficacy (52.2%). Another two important reasons were that the individuals believed themselves to healthy and have no need for their use (31.3%) and the unavailability of enough information about the herbal medicines (29.7%). Finally, the most common side effects as reported by patients in this study were nausea and vomiting (9.3%), and, to a lesser extent, skin rash (2.1%). CONCLUSION: There is a high rate of use of herbal medicines in Jordan, especially among hypertensive patients. Therefore, there is a need to establish effective herbal medicine policies and health education programs to discuss the benefits and risks of herbal medicine use, with the aim of maximizing patient-desired therapeutic outcomes.

Discovery of new butyrylcholinesterase inhibitors via structure-based virtual screening.

Butyrylcholinesterase (BChE) plays an important role in the progression of the Alzheimer's disease. In this study, we used a structure-based virtual screening (VS) approach to discover new BChE inhibitors. A ligand database was filtered and docked to the BChE protein using Glide program. The outcome from VS was filtered and the top ranked hits were thoroughly examined for their fitting into the protein active site. Consequently, the best 38 hits were selected for in vitro testing using Ellman's method, and six of which showed inhibition activity for BChE. Interestingly, the most potent hit (Compound 4) exhibited inhibitory activity against the BChE enzyme in the low micromolar level with an IC50 value of 8.3 µM. Hits obtained from this work can act as a starting point for future SAR studies to discover new BChE inhibitors as anti-Alzheimer agents.

Targeting Dopaminergic System for Treating Nicotine Dependence.

BACKGROUND: Smoking is the world's leading cause of preventable death among populations. Cigarette smoking increases the risk of numerous health problems, including heart diseases, stroke, atherosclerosis and many types of cancer, including lung, stomach and bladder cancers. OUTCOMES: Many individuals find it difficult to stop smoking because of the addictive effects of nicotine and the presence of several monoamine oxidase (MAO) inhibitors in the tobacco smoke extract. OBJECTIVE: The development of novel, safe and effective medications for smoking cessation is a high public health priority. RESULTS: The role of mesocorticolimbic dopaminergic pathways in withdrawal symptoms and general reinforcement processes clearly recommends dopaminergic system as a potential target for the treatment of nicotine addiction. CONCLUSION: This review article discusses the new pharmacological treatments of nicotine dependence, which are targeting dopaminergic neurotransmission. This includes blockade of dopamine transporter and inhibition of MAO as pharmacotherapy for the treatment of nicotine dependence.

Effects of ampicillin on cystine/glutamate antiporter and glutamate transporter 1 isoforms as well as ethanol drinking in male P rats.

Evidence demonstrated that glial cells, mainly astrocytes, regulate glutamate uptake through several glutamate transporters. Among these glutamate transporters, glutamate transporter 1 (GLT-1; its human homolog is excitatory amino acid transporter-2) is responsible for the majority of glutamate uptake. Cystine-glutamate antiporter (xCT) is another glial protein critical in regulating glutamate transmission. Several studies from our laboratory demonstrated that attenuation of ethanol intkae was associated in part with upregulation of xCT and GLT-1 expression suggesting the important role of these transporters in the treatment of ethanol dependence. We found recently that ß-lactam antibiotic, ampicillin, upregulated GLT-1 expression in the prefrontal cortex (PFC) and nucleus accumbens (NAc) and consequently reduced ethanol intake in alcohol-preferring (P) rats. In this study, we investigated the effects of ampicillin on the expression of xCT and GLT-1 isoforms (GLT-1a and GLT-1b) as well as on GLAST expression. We found that ampicillin reduced ethanol intake as compared to the saline (control)-treated group. In addition, we found that ampicillin induced upregulation of xCT, GLT-1a, and GLT-1b expression in both the PFC and NAc, but had no effect on GLAST expression. Our findings provide significant role of ampicillin on upregulating xCT and GLT-1 isoforms expression, might be suggested as possible targets for the attenuation of ethanol consumption.

Pharmacological and neuroprotective profile of an essential oil derived from leaves of Aloysia citrodora†Palau.

OBJECTIVES: The Jordanian 'Melissa', (Aloysia citrodora) has been poorly studied both pharmacologically and in the clinic. Essential oils (EO) derived from leaves of A. citrodora were obtained by hydrodistillation, analysed by gas chromatography-mass spectrometry (GC-MS) and were investigated for a range of neurobiological and pharmacological properties, as a basis for potential future use in drug discovery. METHODS: A selection of central nervous system (CNS) receptor-binding profiles was carried out. Antioxidant activity and ferrous iron-chelating assays were adopted, and the neuroprotective properties of A. citrodora EO assessed using hydrogen peroxide-induced and ß-amyloid-induced neurotoxicity with the CAD (Cath.-a-differentiated) neuroblastoma cell line. KEY FINDINGS: The major chemical components detected in the A. citrodora EOs, derived from dried and fresh leaves, included limonene, geranial, neral, 1, 8-cineole, curcumene, spathulenol and caryophyllene oxide, respectively. A. citrodora leaf EO inhibited [(3) H] nicotine binding to well washed rat forebrain membranes, and increased iron-chelation in vitro. A. citrodora EO displays effective antioxidant, radical-scavenging activities and significant protective properties vs both hydrogen peroxide- and ß-amyloid-induced neurotoxicity. CONCLUSIONS: A. citrodora EO displays a range of pharmacological properties worthy of further investigation to isolate the compounds responsible for the observed neuroactivities, to further analyse their mode of action and determine their clinical potential in neurodegenerative diseases.

Elaborate ligand-based modeling coupled with QSAR analysis and in silico screening reveal new potent acetylcholinesterase inhibitors.

Inhibition of the enzyme acetylcholinesterase (AChE) has been shown to alleviate neurodegenerative diseases prompting several attempts to discover and optimize new AChE inhibitors. In this direction, we explored the pharmacophoric space of 85 AChE inhibitors to identify high quality pharmacophores. Subsequently, we implemented genetic algorithm-based quantitative structure-activity relationship (QSAR) modeling to select optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of explaining bioactivity variation among training compounds (r2(68)=0.94, F-statistic=125.8, r2 LOO=0.92, r2 PRESS against 17 external test inhibitors = 0.84). Two orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least two binding modes accessible to ligands within AChE binding pocket. The successful pharmacophores were comparable with crystallographically resolved AChE binding pocket. We employed the pharmacophoric models and associated QSAR equation to screen the national cancer institute list of compounds. Twenty-four low micromolar AChE inhibitors were identified. The most potent gave IC50 value of 1.0 µM.

Pharmacological profile of essential oils derived from Lavandula angustifolia and Melissa officinalis with anti-agitation properties: focus on ligand-gated channels.

Both Melissa officinalis (Mo) and Lavandula angustifolia (La) essential oils have putative anti-agitation properties in humans, indicating common components with a depressant action in the central nervous system. A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically validated essential oil derived from La, which has shown clinical benefit in treating agitation. La inhibited [35S] TBPS binding to the rat forebrain gamma aminobutyric acid (GABA)(A) receptor channel (apparent IC50 = 0.040 +/- 0.001 mg mL(-1)), but had no effect on N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or nicotinic acetylcholine receptors. A 50:50 mixture of Mo and La essential oils inhibited [3H] flunitrazepam binding, whereas the individual oils had no significant effect. Electrophysiological analyses with rat cortical primary cultures demonstrated that La reversibly inhibited GABA-induced currents in a concentration-dependent manner (0.01-1 mg mL(-1)), whereas no inhibition of NMDA- or AMPA-induced currents was noted. La elicited a significant dose-dependent reduction in both inhibitory and excitatory transmission, with a net depressant effect on neurotransmission (in contrast to the classic GABA(A) antagonist picrotoxin which evoked profound epileptiform burst firing in these cells). These properties are similar to those recently reported for Mo. The anti-agitation effects in patients and the depressant effects of La we report in neural membranes in-vitro are unlikely to reflect a sedative interaction with any of the ionotropic receptors examined here. These data suggest that components common to the two oils are worthy of focus to identify the actives underlying the neuronal depressant and anti-agitation activities reported.