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Activation of the apoptotic pathway has been associated with promoting neuronal cell death in the pathophysiology of Parkinson disease (PD). Nonetheless, the mechanisms by which it may occurs remain unclear. It has been suggested that stress-induced oxidation and potentially apoptosis may play a major role in the progression of PD. Thus, in this study, we aimed to investigate the effect of subchronic restraint stress on striatal dopaminergic activity, iron, p53, caspase-3, and plasmatic acetylcholinesterase (AChE) levels in an animal model of PD induced by administration of 6-hydroxydopamine(6-OHDA) in the medial forebrain bundle (MFB). The obtained results showed that restraint stress exacerbates motor coordination deficits and anxiety in animals treated with 6-OHDA in comparison to animals receiving saline, and it had no effect on object recognition memory. On another hand, 6-OHDA decreased dopamine(DA) levels, increased iron accumulation, and induced overexpression of the pro-apoptotic factors caspase-3, p53, and AChE. More interestingly, post-lesion restraint stress exacerbated the expression of caspase-3 and AChE without affecting p53 expression. These findings suggest that subchronic stress may accentuate apoptosis and may contribute to DA neuronal loss in the striatal regions and possibly exacerbate the progression of PD.

Cerebral metabolic abnormalities are common in neurodegenerative diseases. Previous studies have shown that mitochondrial damage alters ATP production and increases Reactive Oxygen Species (ROS) release which may contribute to neurodegeneration. In the present study, we investigated the neuroprotective effects of cannabidiol (CBD), a non-psychoactive component derived from marijuana (Cannabis sativa L.), on astrocytic bioenergetic balance; in a primary cell culture model of lipopolysaccharide (LPS)-induced neurotoxicity. Astrocytic metabolic profiling using an extracellular flux analyzer demonstrated that CBD decreases mitochondrial proton leak, increased spare respiratory capacity and coupling efficiency in LPS-stimulated astrocytes. Simultaneously CBD increased astrocytic glycolytic capacity and glycolysis reserve in a cannabinoid receptor type 1 (CB1) dependent manner. CBD-restored metabolic changes were correlated with a significant decrease in the pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) concentration, and a reduction of ROS production in LPS-stimulated astrocytes. These results suggest that CBD may inhibit LPS-induced metabolic impairments and inflammation by enhancing astrocytic metabolic glycolysis versus oxidative phosphorylation through its action on CB1 receptors. The present findings suggest CBD as a potential anti-inflammatory treatment in metabolic pathologies and highlight a possible role for the cannabinoidergic system in the modulation of mitochondrial oxidative stress.

Chronic exposure to cocaine alters inflammatory signalling pathways in the brain, activates microglia and induces cognitive and motivational behavioural impairments. The endocannabinoid system may mediate cocaine’s effects. In the present study, we investigated the modulatory effects of the cannabinoid CB2 receptor agonist JWH-133 on cocaine-induced inflammation and motivational behavioural changes in vivo, and the possible effects of fractalkine (CX3CL1) on primary microglia metabolic activity and its subsequent contribution to cocaine-induced neurotoxicity. Our findings show that the CB2-specific receptor agonist, JWH-133, significantly attenuated the reinstatement of cocaine-induced CPP, increased Δ-FOSB expression in the nucleus accumbens (Nac), increased CX3CL1 levels in the ventral tegmental area (VTA) and prefrontal cortex (PFC), and decreased IL-1β in the PFC and NAc of cocaine treated animals. On the other hand, stimulation of the cortical primary microglial cells with CX3CL1 induced a biphasic effect. At a low concentration of 50 nM, CX3CL1 decreased mitochondrial oxidative metabolism vs glycolysis, and decreased the release of the proinflammatory cytokine, IL-1β, but did not affect TNFα. However, a dose of 100 nM of CX3CL1 increased mitochondrial oxidative metabolism, and both, IL-1β and TNFα release. These findings demonstrate that CB2 cannabinoid receptor modulation alters cocaine-induced reward-seeking behaviour and related neurobiological changes and highlights a potential role for CX3CL1 in the modulation of microglial metabolic and inflammatory-mediated activities.

Strawberry tree (Arbutus Unedo L.) is one of the evergreen trees that grow spontaneously in Moroccan forests. This tall shrub is traditionally used in grazing zones of some Moroccan areas, especially during the dry season, but its value in Morocco has still been underestimated. In this paper, the nutritional composition of A. unedo leaves sample collected from seven Moroccan regions has been assessed. For this, the leaves were dried, crushed, and chemically analyzed for their proximate composition, energetic value, total and reducing sugar, and mineral composition. Results of this study suggested that samples from BniAarouse (BA) region showed the highest contents of essential nutrients such as proteins, dietary fiber, ashes, and fat with average values of 7.53, 17.89, 4.14, and 8.05 g/ 100 g of dry weight, respectively, which positively influences its consumption by small ruminants. Cluster analysis based on surveyed parameters separated the strawberries individuals into four distinct groups, providing a high variability among and within studied locations. That could be related to the diversity of the edaphoclimatic conditions between regions and to the genetic effect. The results of the present study highlighted the potential use of leaves as livestock feed, with intermediate quality, and promotes their optimal cultivation and subsequent domestication in Morocco.

BACKGROUND Wound healing is among the frequent illnesses that affects the skin, and therefore, the screening of natural preparation to treat skin burn is important. In Morocco, Cynara humilis is a Moroccan medicinal plant widely used for the treatment of skin burn. OBJECTIVES The aim of this study was to investigate the safety of C. humilis and its wound healing potential against skin burn. METHODS In this work, C. humilis was selected based on an ethnopharmacological survey. As revealed by traditional medicine, C. humilis powder extract (CHPE) was used to test wound healing effects. Furthermore, to assure the safety of this powder, acute and subchronic dermal toxicities were investigated on animal models. RESULTS The oral acute toxicity test of CHPE did not show mortality in treated rats (LD50 >2000 mg/kg). Moreover, in the acute dermal toxicity, CHPE at 5 g/kg did not induce clinical signs observed during the observation period of 48 h. In the subchronic toxicity test, CHPE did not cause significant abnormalities in the physiological parameters and pathological changes in the major organs of the rats. Body weight evolution and macroscopic analysis of skin burn showed CHPE exhibited important wound healing effects in a time-dependent manner. CHPE reduced significantly wound surface (6.93 ± 0.25 cm2 ) compared with the SDA group (8.30 ± 0.37 cm2 ) and the no-treated group (10.05 ± 0.28 cm2 ). Moreover, the retention rate was increased importantly after the treatment with CHPE (61.66 ± 1.42%) compared with the SDA-treated group (53.57% ± 2.83%) and the no-treated group control animals (43.34% ± 1.27%). CONCLUSION These results were confirmed by a histological evaluation, which showed that CHPE increased the neovascularization, the collagen deposition, and the re-epithelialization. The findings of this work suggest that CHPE could be a promising source for developing drugs against skin burn.

Background: Cancer is a multifactorial disease involving individual, behavioral and environmental factors that can contribute to its onset. More than 40% of cancers are estimated to be attributable to avoidable risk factors, particularly diet, physical activity, weight status, and alcohol consumption. Aim: To provide insight into the role of weight status, diet, and physical activity in cancer causation and prevention, and to highlight evidence-based recommendations. Material and methods: A literature review of published studies, particularly recent systematic reviews, meta-analyses, and large prospective studies was conducted using PubMed/Medline, ScienceDirect, and Google Scholar databases. Results: There is evidence that diets high in red and processed meats, fat and refined carbohydrates, and low in plant foods such as vegetables, fruits, and whole grains, high consumption of alcohol, overweight/obesity, and physical inactivity are associated with increased risk of tumor development and progression. Therefore, the current recommendations for cancer prevention are based on: (1) eating at least five portions (400g) of vegetables (3 portions) and fruits (2 portions); (2) limiting the consumption of alcohol and unhealthy foods such as red and processed meats, energy-dense foods, and trans-fatty acids; (3) maintaining a healthy weight status; and (4) being at least moderately physically active. Conclusion: While a balanced diet, as defined by the recommendations, can help reduce the risk of certain cancers, no single food can prevent the development of this pathology. The term "anticancer" associated with diet is therefore misleading. Several nutritional factors are associated with an increase or a decrease in the risk of certain cancers. Adopting a healthy and plant-based diets, avoiding overweight/obesity, and being physically active are considered as cornerstones of preventive strategies against cancer. Further studies are needed to elucidate the associations between dietary and lifestyle patterns and cancer. Keywords: Cancer, Diet, Weight status, Overweight, Obesity, Physical activity.

Background: University life is a crucial period when dietary habits and lifestyle behaviours are formed and may have long-lasting effects on the development of obesity and related chronic diseases. Aim: To investigate the association of overweight/obesity with dietary habits, physical activity, screen time and sleep duration among university students. Methods: A total of 438 students aged 18–26 years were recruited from Mohammed V University in Rabat, Morocco. Anthropometric measurements were assessed using standardized equipment. Data regarding dietary habits, physical and sedentary activities were collected via a self-administered questionnaire. Results: The prevalence of overweight and obesity was 14.8% and 1.6%, respectively. Students who reported frequent consumption (>3 times/week) of fast food, fried potatoes and sugary drinks were more likely to be overweight/obese than peers who did not. Similarly, odds of being overweight/obese were slightly higher among females who reported non-daily intake of fruits and milk or dairy products and among males who ate vegetables less frequently (Conclusions: Overall, unhealthy dietary habits were associated with an increased risk of overweight/obesity. A similar trend was also observed between abnormal sleep duration and overweight/obesity in males. Interventions to promote healthy dietary and lifestyle habits and prevent overweight/obesity in this population are needed.

Celiac disease (CD) is a chronic inflammatory enteropathy caused by gluten (protein from wheat, rye and, barley) in genetically predisposed individuals carrying the HLA-DQ2/HLA-DQ8 genotype. This pathology has a multifactorial etiology in which HLA genes, the microbiome, gluten and, other environmental factors are involved in the development of the disease. Its pathogenesis involves both innate and adaptive immunity as well as upregulation of IL-15. The objective of this review is to examine the results of current studies on genetic and environmental variables to better understand the pathogenesis of this enteropathy. The complex etiology of celiac disease makes our understanding of the pathogenesis of the disease incomplete, and a better knowledge of the many genetic and environmental components would help us better understand the pathophysiology of celiac disease.

Several lines of evidence suggest that chronic exposure to cannabinoids during adolescence may increase the risk of schizophrenia. Studies of the disorder have identified altered cortical dopaminergic neurotransmission. In this study, we hypothesised that heightened endocannabinoid system activation via chronic exposure to a highly potent cannabinoid receptors agonist in adolescent rats would cause long-lasting neurobiological changes that may dramatically alter expression and functions of dopamine metabolising enzymes, comethyl-o-transferase (COMT) and monoamine oxidases MAO-A and MAO-B. To test this hypothesis, adult male rats (70 PND) undergoing chronic treatment of the highly potent and non-selective CB agonist WIN55,212-2 (1.2 mg/kg) during adolescence (PND 30-50) were subjected after 20 days washout period to prepulse inhibition of acoustic startle test (PPI) to confirm cannabinoid-induced sensorimotor-gating impairments and afterwards examined for COMT, MAO-A and MAO-B expression and activity in the prefrontal cortex. Chronic WIN55,212-2 exposure during adolescence caused disruption of PPI, increased cortical dopamine level, decreased COMT mRNA expression and decreased MAO-A and MAO-B enzymatic activities. These results indicate that chronic exposure to cannabinoids during adolescence induces sensorimotor-gating alterations which likely result from changes in the prefrontal cortex dopaminergic signalling. This has important implications for developing methods of targeting dopamine metabolising enzymes and/or sequelae of its dysregulation in cannabinoid-induced schizoaffective-like behaviour.

Background:Cotula cinerea belongs to the Asteraceae family and grows in desert areas such as Moroccan Sahara. The use of this plant in Moroccan traditional medicine prompted us to investigate its chemical composition, its acute oral toxicity, its analgesic and antioxidative activities.Methods:Extraction was conducted by steam distillation for essential oil and by maceration using solvents (hexane, ethyl acetate, n-butanol) for other non-volatile compounds. Quantitative analysis of total polyphenols, procyanidins and flavonoids was conducted through spectrophotometric assays. Qualitative phytochemical composition of the essential oil was investigated by GC/MS analysis. Acute oral toxicity was tested at a dose of 2000 mg/kg in mice. Central analgesic effect was assessed in rat using tail flick and hot plate models and the obtained results were compared to morphine. Antioxidant activity of the essential oil and the obtained extracts was evaluated through 2,2-diphenyl-1- picrylhydrazyl (DPPH°) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and the obtained results were compared to TROLOX.Results:The obtained results showed that the studied extracts contained significant amounts of total polyphenols, flavonoids and condensed tannins. The phytochemical composition of the essential oil was predominated by thujone, eucalyptol and santolinatriene. The results of the acute oral toxicity showed that the tested essential oil and extracts were not toxic even at the highest dose of 2000 mg/kg. Experiments on analgesic activity showed that the administered extracts have a central analgesic effect. The highest effect was observed with the n-butanol and ethyl acetate extracts for both tail-flick and hot plate tests. The antioxidant activity of the explored extracts showed higher scavenging activities of the studied samples compared to TROLOX.Conclusion:Our results indicate thus that C. cinerea could be considered as a source of various secondary metabolites including terpenoids and polyphenols. Exploration of its biological activities showed that the plant essential oil and extracts possessed antioxidant and analgesic effects. Based on the results of this study, it is likely that extracts of C. cinerea could open perspectives for its use for pain relief.

The acute and subchronic toxicological effects of Salvia verbenaca extracts in hexane, ethyl acetate, n-butanol, were investigated. The extracts were not toxic at 2000 mg Kg−1. A normal body weight...

The purpose of this study was to determine the chemical composition and to evaluate the antioxidant and antibacterial effects of the Moroccan Artemisia herba-alba Asso essential oil against foodborne pathogens. The essential oil of Artemisia herba-alba was analyzed by gas chromatography coupled with mass spectroscopy. The antibacterial activity was assessed against three bacterial strains isolated from foodstuff and three bacterial strains referenced by the ATCC (American Type Culture Collection) using the disk diffusion assay and the macrodilution method. The antioxidant activity was evaluated using the DPPH (2, 2-diphenyl-1- picrylhydrazyl) method. The fourteen compounds of the Artemisia herba-alba essential oil were identified; the main components were identified as β-thujone, chrysanthenone, α-terpineol, α-thujone, α-pinene, and bornyl acetate. The results of the antibacterial activity obtained showed a sensitivity of the different strains to Artemisia herba-alba essential oil with an inhibition diameter of 8.50 to 17.00 mm. Concerning the MICs (minimum inhibitory concentrations), the essential oil exhibited much higher antibacterial activity with MIC values of 2.5 μl/ml against Bacillus subtilis ATCC and Lactobacillus sp. The essential oil was found to be active by inhibiting free radicals with an IC50 (concentration of an inhibitor where the response is reduced by half) value of 2.9 μg/ml. These results indicate the possible use of the essential oil on food systems as an effective inhibitor of foodborne pathogens, as a natural antioxidant, and for potential pharmaceutical applications. However, further research is needed in order to determine the toxicity, antibacterial, and antioxidant effects in edible products.

Alcohol abuse is a widespread cause of aggressive and impulsive behaviors that impact the users as well as their entourage. However, only a few medications are effective. Recently, cannabidiol has been reported to improve mood disorders and recovery from substance abuse, yet the psychopharmacologic effects of cannabidiol in ethanol-induced drug reward and aggressivity remain unexplored. In the present study, we investigated the effects of cannabidiol on ethanol-induced place preference and aggressivity in individually and group-housed male rats using the conditioned place preference test, and intruder evoc aggression test, respectively. The obtained results showed that ethanol significantly increased locomotor activity, induced conditioned place preference in all animals, and, specifically, increased aggressivity in individually housed rats. These behavioural impairments induced by ethanol were associated with decreased glucocorticoid and mineralocorticoid receptors transcription in the prefrontal cortex. Notwithstanding, cannabidiol at a dose of 10 mg/kg significantly inhibited Et-OH-induced place preference in group-housed, but not in individually housed rats, and markedly inhibited the aggressive behaviour. These findings suggest that ethanol-induced behavioural impairments are dependent on the housing condition that may affect corticosterone receptors expression and subsequently the animal responsivity to cannabidiol treatment.

Almond oil, a rich source of macronutrients and micronutrients, is extracted for food flavorings and the cosmetics industry. In recent years, the need for high-quality and high-quantity production of almond oil for human consumption has been increased. The present review examines the chemical composition of almond oil, storage conditions, and clinical evidence supporting the health benefits of almond oil. From the reviewed studies, it appears that almond oil contains a significant proportion of poly and monounsaturated fatty acids, with oleic acid as the main compound, and an important amount of tocopherol and phytosterol content. Some variations in almond oil composition can be found depending on the kernel's origin and the extraction system used. Some new technologies such as ultrasonic-assisted extraction, supercritical fluid extraction, subcritical fluid extraction, and salt-assisted aqueous extraction have emerged as the most promising extraction techniques that allow eco-friendly and effective recovery of almond oil. This safe oil was reported by several clinical studies to have potential roles in cardiovascular risk management, glucose homeostasis, oxidative stress reduction, neuroprotection, and many dermatologic and cosmetic applications. However, the anticarcinogenic and fertility benefits of almond oil have yet to be experimentally verified.

The Culex pipiens mosquito (Diptera: Culicidae) is highly suspected to be the vector responsible for the spread of several parasitic and viral diseases. The use of synthetic insecticides is generally the preferred method of controlling these mosquitoes’ proliferation. However, it has led to resistance problems in target mosquitoes and environmental damage. Hence, diverse plant extracts could be considered as an alternative and potential source as mosquito control agents. In this study, essential oils of Lavandula angustifolia subsp. angustifolia and Lavandula dentata spp. dentata that are growing in Morocco were examined for their insecticidal effects on Culex pipiens larvae. The bioassay was performed according to a methodology inspired by the standard protocol of the World Health Organization. The mortality rate was determined after 24 hours of exposure, and probit regression analysis was used to calculate LC50 and LC90. The chemical analysis revealed that the principal compounds of L. angustifolia subsp. essential oils include linalool, linalyl acetate, geraniol, lavandulyl acetate, camphor, β-caryophyllene, terpinen-4-ol, β-myrcene, and 1,8-cineole, while the essential oil of L. dentata spp. was mainly composed of 1,8-cineole, camphor, α-pinene, trans-pinocarveol, linalool, and borneol. These volatile compounds have shown a toxic effect against Culex pipiens larvae, with lethal concentrations LC50 and LC90 being, respectively, 140 µg/ml and 450 µg/ml, for the L. angustifolia subsp. essential oil. Meanwhile, they were estimated at 2670 µg/ml and 7400 µg/ml, respectively, for the L. dentata spp. essential oil. These results suggest using essential oils of two species of Lavandula to control the Culex pipiens mosquito. It could be useful for the study of new natural larvicidal compounds.

Background: Cancer is a multifactorial disease involving individual, behavioral and environmental factors that can contribute to its onset. More than 40% of cancers are estimated to be attributable to avoidable risk factors, particularly diet, physical activity, weight status, and alcohol consumption. Aim: To provide insight into the role of weight status, diet, and physical activity in cancer causation and prevention, and to highlight evidence-based recommendations. Material and methods: A literature review of published studies, particularly recent systematic reviews, meta-analyses, and large prospective studies was conducted using PubMed/Medline, ScienceDirect, and Google Scholar databases. Results: There is evidence that diets high in red and processed meats, fat and refined carbohydrates, and low in plant foods such as vegetables, fruits, and whole grains, high consumption of alcohol, overweight/obesity, and physical inactivity are associated with increased risk of tumor development and progression. Therefore, the current recommendations for cancer prevention are based on: (1) eating at least five portions (400g) of vegetables (3 portions) and fruits (2 portions); (2) limiting the consumption of alcohol and unhealthy foods such as red and processed meats, energy-dense foods, and trans-fatty acids; (3) maintaining a healthy weight status; and (4) being at least moderately physically active. Conclusion: While a balanced diet, as defined by the recommendations, can help reduce the risk of certain cancers, no single food can prevent the development of this pathology. The term "anticancer" associated with diet is therefore misleading. Several nutritional factors are associated with an increase or a decrease in the risk of certain cancers. Adopting a healthy and plant-based diets, avoiding overweight/obesity, and being physically active are considered as cornerstones of preventive strategies against cancer. Further studies are needed to elucidate the associations between dietary and lifestyle patterns and cancer.

Aristolochia longa L. (Aristolochiaceae) is an herbaceous plant recognized in alternative medicine for its many therapeutic virtues. The aim of this study was to determine the pharmacotoxicological effects of this plant in order to ensure safe clinical use. The oral toxicity of the aqueous extract of A. longa roots was performed in vivo on Wistar rats at doses of 0.8, 1.25, 2, 2.5, and 5 g/kg/day for 21 days. Clinical signs were observed throughout the experimental period, followed by measurement of body weight change, while selected biochemical parameters, as well as relative organ weights and the histology of liver, kidney, and intestinal tissues, were evaluated after 6, 11, and 16 days and then at the end of 21 days of daily administration. At repeated doses for 21 days, the extract contributed to significant weight gain, in both control and treated rats. The global analysis of hepatic and renal biomarkers showed a significant increase between control and different doses of the extract, from the first to the third week of treatment, indicating the likely toxic effect of the extract on liver and kidney function. Organ toxicity was confirmed by histopathological examination, which revealed greater renal and hepatic parenchymal changes in animals treated with a high dose beyond the 16th day. At the end of the treatment, relatively small size of intestinal villi was also observed. It was concluded that ALAE has a low toxicity potential in nonprolonged oral administrations. However, at high chronic oral doses, A. longa appears to have significant toxicity on the organs tested.

Current therapeutic for the treatment of anxiety is associated with a wild variety of prominent side effects. The traditional use of plant extract to health care can indicate an important source of new pharmaceuticals. In Morocco traditional medicine, the use of Mercurialis annua is commonly recommended for relief of anxiety. Nevertheless, despite its popular use there are no studies related to its possible neuropharmacological effect. Here, we investigated the possible anxiolytic effect of the extract of M.annua after acute treatment in mice. The methanolic extract from the aerial parts of M.annua (100, 200 or 400 mg/kg) was orally administered, and its anxiolytic effect was evaluated in hole board test, the light–dark box test, and motor coordination with the rota rod test. Diazepam was employed as standard drug 1mg/kg. The methanolic extract of Ma 100 mg/kg increased the time spent in the brightly-lit chamber of the light/dark box, as well as in the number of times the animal crossed from one compartment to the other. Performance on the rota rod was unaffected. In the hole board test, the extract significantly increased head-dip counts. These results provides support for anxiolytic activity of Mercurialis annua, in line with its medicinal traditional use, and may also suggest a better side-effect profile of Mercurialis annua relative to diazepam.

Rationale Cotula cinerea of the Asteraceae family is a traditional Moroccan plant with various biological activities such as analgesic, cytotoxic and antioxidant effects which are often related to the presence of secondary metabolites. The present work aims to screen and identify the main phytochemicals compounds of Cotula cinerea extracts. Methods A method was developed that coupled a rapid and simple ultra-high-performance liquid chromatography system with both photodiode array and high-resolution time-of-flight mass spectrometry detectors (UHPLC-PDA/TOF-HRMS) for the identification of the main secondary metabolites of three investigated extracts (hexane, AcOEt and n-BuOH). Results A total of 30 phytocomponents pertaining to phenolic compounds and terpenoids have been detected, identified and quantified. Among these were previously reported free and conjugated coumaric and caffeic acids along with free and conjugated flavones and flavonols with kaempferol, quercetin, luteolin and apigenin aglycones. In addition, sulfated flavonoids were identified in the investigated extracts and are reported in this work for the first time in Cotula cinerea. The obtained results have been discussed in relation to the biological activities of the corresponding extracts. Conclusions This study proposed a practical strategy for rapidly screening and identifying secondary metabolites of Cotula cinerea and provided new information on the phytochemicals of this Saharan plant. This work has therefore provided useful results for further pharmacological studies and the design of new drugs based on this species and will facilitate the utilization of Cotula cinerea in the clinic and its safety evaluation. It is also hoped that the information presented here might stimulate further studies that will possibly lead to development of therapeutic agents from this plant.

The objective of this work was to investigate the cytotoxicological effect of the extracts (hexane, ethyl acetate, and n-butanol) of Cotula cinerea and Salvia verbenaca in addition to the essential oil of Cotula cinerea. These plants are widely used in the Moroccan traditional folk medicine. The cytotoxic effect was explored against two cancer cell lines, Vero and RD, using the colorimetric MTT assay. The obtained results showed that the cytotoxicity differed according to the used extract with an efficient effect of Cotula cinerea extracts compared to Salvia verbenaca. A potent cytotoxicity was thus observed for the Cotula cinerea hexane extract which inhibited the growth of RD cell line at the lowest IC50 value (57.21±3.43 µg/mL). This was followed by the ethyl acetate extract and the essential oil with moderate effects against RD cell line and showed IC50 values of 187.52±6.27 µg/mL and 173.05±4.46 µg/mL, respectively. On the other hand, different results were obtained and Cotula cinerea essential oil was the most cytotoxic with the lowest IC50 value (72.72±2.18 µg/mL) against Vero cell line. In the same conditions, higher concentrations were needed in the case of Salvia verbenaca extracts. The results of this study showed thus that Cotula cinerea essential oil and hexane extract showed significant cytotoxic effects against RD and Vero cell lines, respectively, and could be considered as novel source of antitumor agents. This study is expected to be beneficial for clinical and traditional applications for Cotula cinerea as a remedy against cancer and opens new perspectives for further investigations on other types of cancer cell lines.

Chronic cannabinoid exposure during adolescence in male rats induces chronic cognitive and emotional impairments. However, the impact of this form of exposure on offspring vulnerability to stress is unknown. The aim of this study was to evaluate the behavioural and epigenetic effects of stress in the offspring of male rats whose fathers were exposed to cannabinoids during adolescence. Male adolescent offspring of Win55,212-2 (1.2 mg/kg) treated rats were exposed during one week to variable stressors and subjected to behavioural tests of anxiety and episodic-like memory, followed by an assessment of global DNA methylation and expression of DNA methyltransferases enzymes DNMT1 and DNMT3a mRNA in the prefrontal cortex. Stress exposure induced a significant anxiogenic-like effect but did not affect the episodic-like memory in the offspring of Win55,212-2 exposed fathers in comparison to the offspring of non-exposed fathers. These behavioural changes were subsequent to a significant increase in global DNA methylation and DNMT1 and DNMTa3 transcription in the prefrontal cortex. These data suggest that the deleterious effect of chronic exposure to cannabinoids during adolescence are not limited to the exposed individuals but may increase the vulnerability to stress-induced anxiety in the offspring and alter their epigenetic programming.

The objective of our work is to make a pharmacological study of molecules derived from 4-phenyl-1,5-benzodiazepin-2-one carrying long chains so that they have a structure similar to surfactants, with the benzodiazepine as a hydrophilic head and a carbon chain as a hydrophobic tail. First, we studied the acute toxicity of the above mentioned 4-phenyl-1,5-benzodiazepin-2-one derivatives. This study was conducted according to OECD 423 guidelines in female mice and revealed that these compounds are nontoxic. We then assessed the psychotropic effects of our products on the central nervous system (CNS). The results obtained show that 4-phenyl-1,5-benzodiazepin-2-one has no sedative effect at therapeutic doses of 100 and 200 mg/kg. On the other hand, its long-chain derivatives possess them. Moreover, all these products have no cataleptic and hypnotic effects at the doses studied. But at 100 mg/kg, these compounds all have the ability to significantly prolong the hypnotic effect of thiopental sodium.

Une etude ethnobotanique a ete menee au Maroc en vue de recenser a l’echelle nationale les plantes medicinales utilisees en medecine traditionnelle marocaine dans le traitement de l’anxiete. 70 herboristes ont ete interroges individuellement et ont livre chacun les especes vegetales utilisees pour combattre les troubles anxieux. 77 especes medicinales reparties sur 43 familles ont ete ainsi signalees et identifiees. L’analyse statistique des donnees de l’enquete ethnobotanique a permis d’inventorier une vingtaine de plantes citees majoritairement. Les feuilles constituent la partie la plus utilisee, generalement sous forme d’infusion. Ont ete egalement analysees les donnees concernant le niveau de connaissances des herboristes, qui ont une de moyenne d’âge entre 35 et 55 ans. 69% d’entre eux ont accepte de discuter de leur profil, 79% ont une experience de plus d’une decennie, 46% sont bacheliers, 65% suivent des formations continues et 37% se soignent et soignent leurs familles uniquement par les plantes.

Nepeta amethystina est une plante utilisee en medecine traditionnelle marocaine comme analgesique, sedative et en application sur les « abces » pour accelerer la cicatrisation. Notre objectif est d’etudier la toxicite aigue et l’action analgesique de l’extrait global (EG) de N.amethystina, en comparaison avec les resultats anterieurement publies, au terme des etudes realisees auMaroc sur la toxicite aigue et l’action analgesique des EG de Nepeta atlantica Ball et Nepeta tuberosa. L.ssp.reticulata (Desf.) Maire. L’etude de la toxicite aigue montre une DL50 de cet EG de 1000 mg/kg IP. Les resultats des etudes sur les activites analgesiques conferent a cette espece un fort pouvoir analgesique peripherique superieur a celui de l’acide acetylsalicylique (200 mg/kg IP) a partir de 25 mg/kg IP, tandis que l’action analgesique centrale de type morphinique apparait a la dose de 25 mg/kg IP, et est maximale a 50 mg/kg IP.

Background: Anxiety is a serious disorder affecting the world population. The most widely prescribed medications for anxiety disorders are the Benzodiazepines; however, they have prominent side effects. Thus, interest in alternative medicine that affects the ‘mind’ is growing. Among medicinal plants, Urtica urens has been recommended for relief of anxiety in Morocco folk medicine. Methods: The anxiolytic activity was evaluated with the adult mice by the elevated plus maze (EPM) and Open Field (OF) models of anxiety. The efficacy of the plant extract (100-600 mg/kg) was compared with the standard anxiolytic drug diazepam (1 mg/kg i.p.) Results: In the EPM, aqueous extract at 400mg/kg showed an anxiolytic effect by increasing the time spent on open arms and the percentage of open arm entries compared to control group. In an open field test aqueous extract of U. urens (400 mg/kg) increased the central area crossing, the time spent and number of rearing in the center of arena. Conclusions: These results provides support for anxiolytic activity of Urtica urens, in line with its medicinal traditional use, and may also suggest a better side-effect profile of Urtica urens relative to diazepam.

Background: Anxiety is an unpleasant state of inner turmoil often accompanied by cognitive, somatic, emotional, and behavioral components. There is some evidence in traditional medicine for the effectiveness of Urtica urens in the treatment of anxiety in humans. The present study was designed to study anxiolytic property of aqueous extracts of Urtica urens; an important and commonly used for its medicinal properties belongs to urticaceae family. Methods: The anxiolytic activity was evaluated with the adult mice by hole board test, and the light-dark box test, and motor coordination with the rota rod test. The efficacy of the plant extract (100–400 mg/kg) was compared with the standard anxiolytic drug diazepam (1 mg/kg i.p.). Results: The extract increased the time spent in the brightly-lit chamber of the light/dark box, as well as in the number of times the animal crossed from one compartment to the other. Performance on the rota rod was unaffected. In the hole board test, the extract significantly increased both head-dip counts and head-dip duration. Urtica urens, in contrast to diazepam, had no effect on locomotion. Conclusions: These results provides support for anxiolytic activity of Urtica urens, in line with its medicinal traditional use, and may also suggest a better side-effect profile of Urtica urens relative to diazepam.

Cannabis sativa preparations are some of the most widely used illicit recreational drugs. In addition to their direct addictive potential, cannabinoids may influence the sensitivity to other drugs. The aim of the present study was to determine if a cross-sensitization between Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and other drugs (amphetamine and heroin) could be demonstrated. We examined the effects of a chronic treatment with Delta(9)-THC (0.6, 3 and 15mg/kg, ip) on the locomotor response to amphetamine (1mg/kg, ip) and heroin (1mg/kg, ip). Chronic treatment with Delta(9)-THC resulted in tolerance to the initial hypothermic and anorexic effects. Pre-treatment with Delta(9)-THC increased the locomotor responses to amphetamine and heroin. This cross-sensitization was time-dependent as it was observed three days after the last injection of Delta(9)-THC for amphetamine, and a relatively long time after the end of chronic treatment (41 days) for heroin. Moreover, the enhanced response to amphetamine or heroin was noted in some individuals only: the high-responder rats (HR). These animals have previously been shown to be vulnerable to drug taking behaviors. It is hypothesised that repeated use of Cannabis derivates may facilitate progression to the consumption of other illicit drugs in vulnerable individuals.

Background: In common with other animal models of psychopathology, the forced-swimming test (FST) suffers from the fact that it involves normal animals. Moreover, powerful antidepressant drugs such as the selective serotonin reuptake inhibitors have been found to give false negatives in this behavioral test. Methods: To circumvent these theoretical and practical difficulties, we studied the interindividual variability of the behavioral reactivity of rats in the FST. The effects of fluoxetine treatment or of a stressful experience (repeated testing in the FST) were analyzed on various behavioral responses. Results: The following observations were made in replicated experiments: 1) a dimensional behavioral response from passivity to high reactivity in the FST; 2) an antidepressant-like effect of fluoxetine only in a subgroup of animals categorized as low responders on the dimension of passivity–reactivity; and 3) a switch toward passive responses following a past experience of stress, which was corrected by fluoxetine treatment. Conclusions: It is concluded that a dimensional approach could improve the screening of antidepressant drugs and could aid the development of new ones by identifying the biobehavioral characteristics of responder and nonresponder subjects.

Introduction: Damage to the Septum or to the Prefrontal cortex impairs learning and the flexibility of the early attention-related stages of information porocessing. These brain regions are the goals, respectively, of the dopaminergic (DA) mesolimbic and mesocortical pathways emanating from the ventral tegmental A 10 nuclei (VTA). These areas are represented in the "convergent nodes" and "circuit systems" we have described as a basis for the functional influence of DA on integrative function, see Figure 1 and 2, and Oades and Halliday, 1987 Here we elaborate the use of the measurement of a search strategy (for 4 food-holes in a 16 hole board) in rodents as a measure of the influences affecting attention to cues and the establishment of a working memory: in particular we examined the effects of local VTA injections of a DA agonist and antagonist on the stability of the normally consistent sequence of hole visits, and concentrate on the mesolimbic system. We also present preliminary results of the effect of septal 6-OHDA lesions on the conditioned blocking measure of selective attention in a shuttle avoidance task. Methods: Animals were given 10 trials/session, 2 sessions/day for 5 days on a 16-hole board in a closed arena. A food pellet was placed in the same 4 holes on each occasion. Prior to session 4 and 7 the rats received either the DA D2 antagonist spiroperidol (2µg/0.5µl) or the DA agonist apomorphine (2 µg/0.5µl) or the vehicle (saline or pH adjusted tartarate) into the VTA. (Diffusion was restricted to within 1.5 mm.) It would be predicted that local neuroleptic treatment would block local, inhibitory autoreceptors and thus lead to increased DA activity in the terminal regions. Monoamines and their metabolites in the N. accumbens were measured with HPLC. Results: 1/ Neuroleptic, but not other VTA-treatments, increased rearing (3-4 fold), non-food-hole visits / errors (50-100%) and the number of switches away from the preferred hole-visit sequence established on the first 3 sessions. 2/ An increase of DA utilization in the nucleus accumbens was demonstrated in selected animals sacrificed after session 7. 3/ There was a significant correlation for increased DA utilization with the number of errors (of working- and reference-memory type), the amount of rearing, but not with switches away from the preferred search sequence. 4/ Septal-6-OHDA damage did not alter conditioned blocking considered across all test trials - but this masked an initial mild attenuation followed by exaggerated blocking at the end of testing (see Oades et al., 1987 for a full report). Conclusions: On the basis of the disruption of holeboard search by increased DA activity it is postulated that mesolimbic DA is important for the evaluation and temporal coordination of response feedback for the pursuance of task-solving strategies. The changeover from reduced to enhanced conditioned blocking after septal-6-OHDA treatment is discussed in the context of where septal damage induces 'changeovers' in other situations, and seen to be consistent with the interpretation that mesolimbic DA modulates the evaluation of attended stimuli and the formation of working memory templates. (The holeboard work started with investigation of hippocampal lesions and haloperidol treatment as an animal model for schizophrenia, Oades and Isaacson, 1978; Oades, 1981 and continued with studies of the role of the VTA A 10 DA system in Oades, 1981a, 1981b and 1982 ).

Introduction: The frequency of spontaneous alternation in a Y-maze (visiting each arm in turn at p>50%) depends on the influence of the attention given to intra- and extra-maze cues. We examined the observing responses shown by rats (collateral rearing and head-turning behaviour), the habituation to the novelty and alternation responses over 15 minutes/day, four days in a row - in a Y-maze under enhanced and reduced dopamine (DA) activity (amphetamine- and haloperidol treatment). Methods: Prior to placement in a Y-maze for 15 minutes observation on 4 successive days animals were treated with either amphetamine (0.5 or 2.5 mg/kg) or pre-treated with a low dose of haloperidol (0.08 mg/kg, ip). Results: 1/ Amphetamine treated animals chose the arms at random on day 1, but after the higher dose on day 2-4 they perseverated their choice. The controls maintained their alternation over this period. 2/ The amphetamine-induced effects on alternation were prevented by prior treatment with the neuroleptic haloperidol. 3/ Amphetamine treatment increased the frequency of rearing in the middle at the choice point of the Y-maze. Haloperidol pre-treatment blocked this increase at the midpoint on day 1, and blocked the rearing behavior at the end of an arm on day 2. 4/ Amphetamine also increased the frequency of head turning and "looking", - an effect that was also prevented by haloperidol. (day 2 onwards). 5/ Haloperidol increased the duration of" looking" and of rearing at the end of an arm later in testing. Conclusions: Two effects are postulated to have occurred. a) a conflict on day 1 between the novelty-controlled sensory or attentional effects, that leads to an alternation of arm-choice, and amphetamine-induced DA activity that facilitates an alternation of behavioural responses: -- the result was random choice and increased rearing at the choice point. b) On days 2-4 the drug-induced effects on switching motor responses came to control behaviour (cf. Oades, 1985 review on the role of DA activity in switching between alternative sources of information).

The effects of early undernutrition on behavior and brain biochemistry were examined in rats. At weaning, rats were provided either an ad lib diet (control group) or maintained at 80% of the weight of their control littermates (undernourished group). Three weeks into the diet they were tested in an open field. After 6 weeks of diet, HPLC analyses were conducted on sample brains from each group to assess levels of dopamine and metabolites, respectively dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. At seven weeks of diet, remaining rats were trained in an 8-arm radial maze, and a retention test conducted 72 h after attaining the learning criterion. At fourteen weeks of diet, sensory reactivity was measured by tail-immersion in a water bath maintained at constant temperature 50 +/- 1 degrees C. Undernourished rats exhibited hyperactivity and increased exploratory behavior in the open field, as well as increased sensory reactivity in the tail flick test. In the radial maze, however, undernourished rats did not differ from controls in either learning or retention. Haloperidol (i. p. injection) impaired retention by control but not undernourished animals. HPLC analyses showed an increase in dopamine turnover in the striatum of undernourished rats. Our results suggest that, unlike its effects when induced immediately at birth or in adulthood, undernutrition at weaning does not appear to influence learning and retention but induced an hyperactivity and alterations in striatal DA turnover which was associated with a decrease in responsiveness to i. p. haloperidol injection.

Mesencephalic dopaminergic neurons appear to be involved in the organization of the behavioral response. They seem to facilitate the functioning of the integrative structures they innervate and to hav

Male Sprague-Dawley rats received bilateral ibotenic acid lesions of the central amygdaloid nucleus (CeA) and were compared to sham-lesioned rats in their response to different concentrations of saccharin and quinine solutions. In two-bottle choice test situation, the lesioned rats exhibited a lower saccharin preference at concentrations of 2.5; 7.5 and 25 mM, while their aversion towards quinine and the highest concentration of saccharin (50 mM) was increased. In a one-bottle test, the lesioned rats showed consistent decreases in their consumption of 2.5 and 7.5 mM saccharin solutions whereas their intake of 0.9 mM solution of saccharin was equal to that of the sham-lesioned rats. The lesion of the CeA had no significant effects on the acquisition of conditioned taste aversion. There was less postoperative weight gain in lesioned rats as compared to sham-lesioned animals but the lesion had no significant effect on daily water intake. These findings suggest that the CeA plays an important role in the normal response to exteroceptive food stimuli via modulation of the aversive value of taste stimuli. The results are discussed in the context of an interaction between the CeA and the lateral hypothalamus (LH) in the modulation of palatability and feeding behavior.