Chemical Composition, Antioxidant, and Antibacterial Activity of Ruta chalepensis L. Ethanolic Extract.

Ruta chalepensis L. is a versatile herb used in culinary arts and traditional medicine. The study aimed to determine the chemical composition of an ethanolic extract from R. chalepensis and the total phenolic and flavonoid content. Additionally, the extracts' antimicrobial and antioxidant activities were tested. The disc diffusion method and minimum inhibitory concentration (MIC) were used to test the antibacterial properties on four types of bacteria: Escherichia coli, Proteus penneri, Bacillus cereus, and Staphylococcus aureus. A colorimetric assay was used to evaluate the total phenolic and flavonoid content, and the DPPH method was used to assess the antioxidant activity. The phytochemical constituents were determined using LC-MS/MS. The results indicated that R. chalepensis ethanolic extract had 34 compounds, and the predominant compounds were quercetin (9.2 %), myricetin (8.8 %), and camphene (8.0 %). Moreover, the extract had a good level of polyphenols and flavonoids, as demonstrated by inhibiting free radicals (DPPH) (IC50 was 41.2±0.1). Also, the extract exhibited robust antimicrobial activity against P. penneri and S. aureus with an MIC of 12.5 and 25.0 µg/mL, respectively. In conclusion, the results suggest that the R. chalepensis ethanolic extract has good antioxidant and antibacterial properties that could be utilized to develop new antibacterial agents.

The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology.

The need to identify effective therapies for the treatment of psychiatric disorders is a particularly important issue in modern societies. In addition, difficulties in finding new drugs have led pharmacologists to review and re-evaluate some past molecules, including psychedelics. For several years there has been growing interest among psychotherapists in psilocybin or lysergic acid diethylamide for the treatment of obsessive-compulsive disorder, of depression, or of post-traumatic stress disorder, although results are not always clear and definitive. In fact, the mechanisms of action of psychedelics are not yet fully understood and some molecular aspects have yet to be well defined. Thus, this review aims to summarize the ethnobotanical uses of the best-known psychedelic plants and the pharmacological mechanisms of the main active ingredients they contain. Furthermore, an up-to-date overview of structural and computational studies performed to evaluate the affinity and binding modes to biologically relevant receptors of ibogaine, mescaline, N,N-dimethyltryptamine, psilocin, and lysergic acid diethylamide is presented. Finally, the most recent clinical studies evaluating the efficacy of psychedelic molecules in some psychiatric disorders are discussed and compared with drugs already used in therapy.

Different Seasonal Collections of Ficus carica L. Leaves Diversely Modulate Lipid Metabolism and Adipogenesis in 3T3-L1 Adipocytes.

Due to the high prevalence of obesity and type 2 diabetes, adipogenesis dysfunction and metabolic disorders are common features in the elderly population. Thus, the identification of novel compounds with anti-adipogenic and lipolytic effects is highly desirable to reduce diabetes complications. Plants represent an important source of bioactive compounds. To date, the antidiabetic potential of several traditional plants has been reported, among which Ficus carica L. is one of the most promising. Considering that plant metabolome changes in response to a number of factors including seasonality, the aim of this study was to evaluate whether Ficus carica leaves extracts collected in autumn (FCa) and spring (FCs) differently modulate lipid metabolism and adipogenesis in 3T3-L1 adipocytes. The 1H-NMR profile of the extracts showed that FCs have a higher content of caffeic acid derivatives, glucose, and sucrose than FCa. In contrast, FCa showed a higher concentration of malic acid and furanocoumarins, identified as psoralen and bergapten. In vitro testing showed that only FCa treatments were able to significantly decrease the lipid content (Ctrl vs. FCa 25 µg/mL, 50 µg/mL and 80 µg/mL; p < 0.05, p < 0.01 and p < 0.001, respectively). Furthermore, FCa treatments were able to downregulate the transcriptional pathway of adipogenesis and insulin sensitivity in 3T3-L1 adipocytes. In more detail, FCa 80 µg/mL significantly decreased the gene expression of PPARγ (p < 0.05), C/EBPα (p < 0.05), Leptin (p < 0.0001), adiponectin (p < 0.05) and GLUT4 (p < 0.01). In conclusion, this study further supports an in-depth investigation of F. carica leaves extracts as a promising source of active compounds useful for targeting obesity and diabetes.

Biochemical and Botanical Aspects of Allium sativum L. Sowing.

The main aim of this study was to evaluate the yield and compliance of selected Iranian garlic (Allium sativum L.) cultivars, including Tuyserkan (TSN), Heydareh (HDH), Mouien (MUN), and Taroom (TRM), during two growing seasons. The TRM cultivar germination rate is higher than the other cultivars studied. The TRM cultivars have quite remarkable values for the dry weight, fresh weight, stem diameter, and the number of leaves present. The fresh weight and dry weight of the TRM cultivar for the second year are 33.8 t/ha and 16.7 t/ha, respectively. However, on average, the HDH cultivar is the tallest plant in the experiments. Average pyruvic acid content in fresh samples of the TRM and HDH cultivars is 78 µm/gfw and 69.3 µm/gfw, respectively. It is observed that there are remarkable differences in the level of pyruvic acid between the different cultivars. The growth, development, and yield of plants are highly dependent on their genetic characteristics; in this experiment, the TRM cultivar shows a good yield (16.7 t/ha), and the evaluated characteristics improve compared to the other cultivars studied, which could be due to the high compatibility of this cultivar to the environmental conditions of the study. The excellent performance on the yield of TRM makes this cultivar more appreciable on a commercial level.

Role of melatonin in autism spectrum disorders in a male murine transgenic model: Study in the prefrontal cortex.

Autism spectrum disorders (ASDs) are a group of clinically heterogeneous neurodevelopmental disorders sharing common features related to impaired social and communication abilities in addition to stereotyped behaviors. ASD patients present encephalic morphological, physiological, and biomolecular alterations with low levels of melatonin due to alterations in its pathways. Therefore, even if ASDs have traditionally been framed as behavioral disorders, several lines of evidence are accumulating that ASDs are characterized by certain anatomical and physiological abnormalities, including oxidative stress and inflammation in peripheral biomarkers, but likewise present in human brain tissue also characterized by alterations in synaptic remodeling and neuromodulation. Melatonin has also protective and antioxidant properties, so we can therefore hypothesize that alterations in melatonin's pathways may be one of the causes of the symptomatology of autism. The aim of the present study was to analyze the beneficial effect induced by melatonin administration and its possible mechanism of action in a transgenic mouse model of autism, immediately after weaning. The male mice were daily treated per os with melatonin (10 mg/Kg/day) or vehicle for 8 weeks starting from the sixth week of life. The antioxidant modulation, the GABAergic/glutamatergic impairment, and the synaptic remodeling in the prefrontal cortex have been evaluated. Social and repetitive behaviors were also evaluated. The behavioral results showed no statistical evidences, instead the immunohistochemical results indicated the ability of melatonin to promote the activity of antioxidant system, the GABAergic/glutamatergic equilibrium, and the synaptic remodeling. The results show that melatonin may be a possible adjuvant therapeutic strategy in ASDs.

Prosocial Effects of Nonpsychotropic Cannabis sativa in Mice.

Introduction:Cannabis sativa L. (C. sativa) is used since ancient times to produce fabrics, baskets, and cords. Later, different ethnic groups used to burn the leaves and flowers of psychotropic cultivars with high Δ9-tetrahydrocannabinol (D9-THC) levels, during the religious or propitiatory rites to alter the state of consciousness. To date, it is not known whether also nonpsychotropic cultivars of C. sativa were used during these rites, and whether these varieties could have an effect on human behavior. This study aimed to evaluate the behavioral effects of an extract of nonpsychotropic C. sativa (NP-CS) in mice. Materials and Methods: An extract of a nonpsychotropic cultivar of C. sativa dissolved in medium-chain triglyceride oil was used and the different phytochemical components were evaluated. The relative composition in terms of phytocannabinoid content was assessed by reverse phase high-performance liquid chromatography coupled to UV detection (RP-HPLC-UV), and the volatile components were analyzed by gas chromatography-mass spectrometry (GC-MS). In addition, the behavioral effect of NP-CS was assessed on a wild-type mouse model. The animals were treated for 14 days (oral gavage) and motility, anxiety, and social effects were assessed. Results: RP-HPLC-UV analysis demonstrated that D9-THC was present in lower concentration with respect to other cannabinoids, like cannabidiol. Furthermore, the GC-MS analysis revealed the presence of several terpenoids. Concerning in vivo studies, chronic treatment with NP-CS did not alter body weight, motility, and anxiety and increased social interaction. Conclusions: This study highlighted the prosocial effects of NP-CS.

Phytochemical Analysis and Anti-Inflammatory Activity of Different Ethanolic Phyto-Extracts of Artemisia annua L.

Artemisia annua L. (AA) has shown for many centuries important therapeutic virtues associated with the presence of artemisinin (ART). The aim of this study was to identify and quantify ART and other secondary metabolites in ethanolic extracts of AA and evaluate the biological activity in the presence of an inflammatory stimulus. In this work, after the extraction of the aerial parts of AA with different concentrations of ethanol, ART was quantified by HPLC and HPLC-MS. In addition, anthocyanins, flavanols, flavanones, flavonols, lignans, low-molecular-weight phenolics, phenolic acids, stilbenes, and terpenes were identified and semi-quantitatively determined by UHPLC-QTOF-MS untargeted metabolomics. Finally, the viability of human neuroblastoma cells (SH-SY5Y) was evaluated in the presence of the different ethanolic extracts and in the presence of lipopolysaccharide (LPS). The results show that ART is more concentrated in AA samples extracted with 90% ethanol. Regarding the other metabolites, only the anthocyanins are more concentrated in the samples extracted with 90% ethanol. Finally, ART and all AA samples showed a protective action towards the pro-inflammatory stimulus of LPS. In particular, the anti-inflammatory effect of the leaf extract of AA with 90% ethanol was also confirmed at the molecular level since a reduction in TNF-α mRNA gene expression was observed in SH-SY5Y treated with LPS.

Biological Response of Lallemantia iberica to Brassinolide Treatment under Different Watering Conditions.

Lallemantia iberica (L. iberica) is an important dry season medicinal plant. Drought, an important abiotic stress, adversely affects the plant's metabolism, which can be alleviated by plant growth regulators like brassinolides. A two-year field experiment was conducted in 2017-2018 to determine the effects of three different irrigation regimes and four brassinolide concentrations on the L. iberica biochemical properties. A split-plot based on a completely randomized block design in three replicates was used as an experimental design with the following irrigation regimes: full watering, watering until flowering and watering until branching. These were the main plots, and 0, 0.5, 1 and 1.5 µM brassinolide concentrations were applied as the subplots. The results showed that many antioxidant enzymes and some biochemical parameters were affected by brassinolide treatment. Furthermore, the highest membrane stability and grain yield were produced in full watering treatment in the second year, and these treatments were not affected by brassinolide application. Several concentrations of brassinolide differently affected the studied treatments, and our study suggests that the amelioration of the effects of the drought stress on L. iberica could possibly be achieved through brassinolide-induced elevation of reactive oxygen species (ROS) scavenging defense systems. There is a need for complementary research to prove the effectiveness of foliar application of this growth regulator to improve the growth and yield of L. iberica under water shortage conditions.

Protective Effects of Gynostemma pentaphyllum (var. Ginpent) against Lipopolysaccharide-Induced Inflammation and Motor Alteration in Mice.

Gynostemma pentaphyllum (var. Ginpent) (GP) is a variety of Cucurbit with anti-inflammatory and antioxidant effects in patients. In this manuscript, the main components present in the dry extract of GP have been identified using Ultra High Performance Liquid Chromatography quadrupole-time-of-flight mass spectrometry (UHPLC/Q-TOF-MS). In addition, the anti-inflammatory action of GP was evaluated in animal models with acute peripheral inflammation and motor alteration induced by lipopolysaccharide. The results showed that GP dry extract is rich in secondary metabolites with potential antioxidant and anti-inflammatory properties. We found that the treatment with GP induced a recovery of motor function measured with the rotarod test and pole test, and a reduction in inflammatory cytokines such as interleukin-1ß and interleukin-6 measured with the ELISA test. The data collected in this study on the effects of GP in in vivo models may help integrate the therapeutic strategies of inflammatory-based disorders.

Artocarpus lakoocha Roxb. and Artocarpus heterophyllus Lam. Flowers: New Sources of Bioactive Compounds.

Artocarpus heterophyllus Lam. (AH) and Artocarpus lakoocha Roxb. (AL) are two endemic plants that grow on the Asian continent. To date, their applications have been aimed at using their fruit as a food source or for some of their therapeutic virtues. In this study, attention was given to the flowers of AH and AL. Initially, the cytotoxicity of the phytoextracts was assessed, and the content of minerals, phenols, and flavonoids was determined. Furthermore, some antioxidant components were identified by HPLC. Furthermore, the ability of AH and AL extracts to modulate the gene expression of some targets involved in the antioxidant response was studied. The results obtained highlighted the nutritional and antioxidant value of the AH and AL flower extracts. This study will contribute to enhancing the use of AH and AL flowers as potential supplements in human nutrition.

Variation in Terpene Profiles of Thymus vulgaris in Water Deficit Stress Response.

Thyme (Thymus spp.) volatiles predominantly consisting of monoterpenes and sesquiterpenes, serve as antimicrobial, antiseptic and antioxidant in phytomedicine. They also play a key role in plants as secondary metabolites via their potential role against herbivores, attracting pollinators and abiotic stress tolerance. Plant volatiles are affected by different environmental factors including drought. Here, the effect of prolonged water deficit stress on volatile composition was studied on the sensitive and tolerant thyme plant cultivars (T. vulgaris Var. Wagner and T. vulgaris Var. Varico3, respectively). Volatile sampling along with morpho-physiological parameters such as soil moisture, water potential, shoot dry weight, photosynthetic rate and water content measurements were performed on one-month-old plants subsequent to water withholding at 4-day intervals until the plants wilted. The tolerant and sensitive plants had clearly different responses at physiological and volatile levels. The most stress-induced changes on the plants' physiological traits occurred in the photosynthetic rates, where the tolerant plants maintained their photosynthesis similar to the control ones until the 8th day of the drought stress period. While the analysis of the volatile compounds (VOCs) of the sensitive thyme plants displayed the same pattern for almost all of them, in the tolerant plants, the comparison of the pattern of changes in the tolerant plants revealed that the changes could be classified into three separate groups. Our experimental and theoretical studies totally revealed that the most determinant compounds involved in drought stress adaptation included α-phellandrene, O-cymene, γ-terpinene and ß-caryophyelene. Overall, it can be concluded that in the sensitive plants trade-off between growth and defense, the tolerant ones simultaneously activate their stress response mechanism and continue their growth.

Zeolite Clinoptilolite: Therapeutic Virtues of an Ancient Mineral.

Zeolites are porous minerals with high absorbency and ion-exchange capacity. Their molecular structure is a dense network of AlO4 and SiO4 that generates cavities where water and other polar molecules or ions are inserted/exchanged. Even though there are several synthetic or natural occurring species of zeolites, the most widespread and studied is the naturally occurring zeolite clinoptilolite (ZC). ZC is an excellent detoxifying, antioxidant and anti-inflammatory agent. As a result, it is been used in many industrial applications ranging from environmental remediation to oral applications/supplementation in vivo in humans as food supplements or medical devices. Moreover, the modification as micronization of ZC (M-ZC) or tribomechanically activated zeolite clinoptilolite (TMAZ) or furthermore as double tribomechanically activated zeolite clinoptilolite (PMA-ZC) allows improving its benefits in preclinical and clinical models. Despite its extensive use, many underlying action mechanisms of ZC in its natural or modified forms are still unclear, especially in humans. The main aim of this review is to shed light on the geochemical aspects and therapeutic potentials of ZC with a vision of endorsing further preclinical and clinical research on zeolites, in specific on the ZC and its modified forms as a potential agent for promoting human brain health and overall well-being.

Cannabidiol: Recent advances and new insights for neuropsychiatric disorders treatment.

The pharmacological research on the Cannabis sativa-derived compounds has never terminated. Among the phytocannabinoids without psychotropic effects, the prevalent one in Cannabis is cannabidiol (CBD). Although CBD was initially considered a type 2 cannabinoid receptor (CB2R) antagonist, it did not show a good cannabinoidergic activity. Furthermore, heterogeneous results were obtained in experimental animal models of anxiety disorders, psychotic stages and neurodegenerative diseases. Recently, CBD has been authorized by the FDA to treat some rare forms of epilepsy and many trials have begun for the treatment of autism spectrum disorders. This review aims to clarify the pharmacological activity of CBD and its multiple therapeutic applications. Furthermore, critical and conflicting results of the research on CBD are discussed with a focus on promising future prospects.

Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history.

ETHNOPHARMACOLOGICAL RELEVANCE: Cannabis sativa L. (C. sativa) is an annual dioecious plant, which shares its origins with the inception of the first agricultural human societies in Asia. Over the course of time different parts of the plant have been utilized for therapeutic and recreational purposes, for instance, extraction of healing oils from seed, or the use of inflorescences for their psychoactive effects. The key psychoactive constituent in C. sativa is called Δ-9-tetrahydrocannabinol (D9-THC). The endocannabinoid system seems to be phylogenetically ancient, as it was present in the most primitive vertebrates with a neuronal network. N-arachidonoylethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG) are the main endocannabinoids ligands present in the animal kingdom, and the main endocannabinoid receptors are cannabinoid type-1 (CB1) receptor and cannabinoid type-2 (CB2) receptor. AIM OF THE STUDY: The review aims to provide a critical and comprehensive evaluation, from the ancient times to our days, of the ethnological, botanical, chemical and pharmacological aspects of C. sativa, with a vision for promoting further pharmaceutical research to explore its complete potential as a therapeutic agent. MATERIALS AND METHODS: This study was performed by reviewing in extensive details the studies on historical significance and ethnopharmacological applications of C. sativa by using international scientific databases, books, Master's and Ph.D. dissertations and government reports. In addition, we also try to gather relevant information from large regional as well as global unpublished resources. In addition, the plant taxonomy was validated using certified databases such as Medicinal Plant Names Services (MPNS) and The Plant List. RESULTS AND CONCLUSIONS: A detailed comparative analysis of the available resources for C. sativa confirmed its origin and traditional spiritual, household and therapeutic uses and most importantly its popularity as a recreational drug. The result of several studies suggested a deeper involvement of phytocannabinoids (the key compounds in C. sativa) in several others central and peripheral pathophysiological mechanisms such as food intake, inflammation, pain, colitis, sleep disorders, neurological and psychiatric illness. However, despite their numerous medicinal benefits, they are still considered as a menace to the society and banned throughout the world, except for few countries. We believe that this review will help lay the foundation for promoting exhaustive pharmacological and pharmaceutical studies in order to better understand the clinical relevance and applications of non-psychoactive cannabinoids in the prevention and treatment of life-threatening diseases and help to improve the legal status of C. sativa.

Evaluation of selective cannabinoid CB(1) and CB(2) receptor agonists in a mouse model of lipopolysaccharide-induced interstitial cystitis.

Interstitial cystitis is a debilitating bladder inflammation disorder. To date, the understanding of the causes of interstitial cystitis remains largely fragmentary and there is no effective treatment available. Recent experimental results have shown a functional role of the endocannabinoid system in urinary bladder. In this study, we evaluated the anti-inflammatory effect of selective cannabinoid CB1 and CB2 receptor agonists in a mouse model of interstitial cystitis. Bladder inflammation was induced in mice by lipopolysaccharide (LPS) and whole bladders were removed 24h later. LPS induced a significant increase of the contractile amplitude in spontaneous activity and a hypersensitivity to exogenous acetylcholine-induced contraction of whole-isolated bladder. Next, we evaluated the anti-inflammatory activity of cannabinoidergic compounds by pretreating mice with CB1 or CB2 selective agonist compounds, respectively ACEA and JWH015. Interestingly, JWH015, but not ACEA, antagonized LPS-induced bladder inflammation. Additionally, anti-inflammatory activity was studied by evaluation, leukocytes mucosa infiltration, myeloperoxidase activity, and mRNA expression of pro-inflammatory interleukin (IL-1α and IL-1ß), tumor necrosis factor-alpha (TNF-α) and cannabinoid CB1 and CB2 receptors. JWH015 significantly decreased leukocytes infiltration in both submucosa and mucosa, as well as the myeloperoxydase activity, in LPS treated mice. JWH015 reduced mRNA expression of IL-1α, IL-1ß, and TNF-α. LPS treatment increased expression of bladder CB2 but not CB1 mRNA. Taken together, these findings strongly suggest that modulation of the cannabinoid CB2 receptors might be a promising therapeutic strategy for the treatment of bladder diseases and conditions characterized by inflammation, such as interstitial cystitis.

Synthesis and pharmacological evaluation of novel 4-alkyl-5-thien-2'-yl pyrazole carboxamides.

The synthesis of three series of novel 4-alkyl-5-(5'-chlorothiophen-2'-yl)-pyrazole-3-carbamoyl analogues of rimonabant with affinity for the CB1 cannabinoid receptor subtype is reported. Amongst the novel derivatives, compounds 21j, 22a, 22c, and 22f showed affinity values expressed as Ki ranging from 5.5 to 9.0 nM. Derivative 23e revealed a good CB1 affinity (K(i) = 11.7 nM) and the highest CB1 selectivity of the whole series (K(i)CB2/K(i)CB1 = 384.6). These new compounds appeared to be able to pass the blood brain barrier and to counteract the activity of cannabinoid agonist. According to the results of mice vas deferens assays, as in the case of rimonabant, derivatives 21a, 22a, and 22b showed inverse agonist activity. In contrast, as a preliminary result to be confirmed, compound 23a exhibited neutral antagonist profile. According to the data obtained through an acute animal model, selected compounds 21a, 22a, and 23a evidenced the capability to significantly reduce food intake. At specific conditions, the effect of the novel compounds were higher than that induced by rimonabant. Amongst the novel CB1 antagonist compounds, 23a may represent a useful candidate agent for the treatment of obesity and its metabolic complications, with reduced side effects relative to those instead observed with rimonabant.

NESS038C6, a novel selective CB1 antagonist agent with anti-obesity activity and improved molecular profile.

The present work aims to study the effects induced by a chronic treatment with a novel CB1 antagonist (NESS038C6) in C57BL/6N diet-induced obesity (DIO) mice. Mice treated with NESS038C6 and fed with a fat diet (NESS038C6 FD) were compared with the following three reference experimental groups: DIO mice fed with the same fat diet used for NESS038C6 and treated with vehicle or the reference CB1 antagonist/inverse agonist rimonabant, "VH FD" and "SR141716 FD", respectively; DIO mice treated with vehicle and switched to a normal diet (VH ND). NESS038C6 chronic treatment (30 mg/kg/day for 31 days) determined a significant reduction in DIO mice weight relative to that of VH FD. The entity of the effect was comparable to that detected in both SR141716 FD and VH ND groups. Moreover, if compared to VH FD, NESS038C6 FD evidenced: (i) improvement of cardiovascular risk factors; (ii) significant decrease in adipose tissue leptin expression; (iii) increase in mRNA expression of hypothalamic orexigenic peptides and a decrease of anorexigenic peptides; (iv) expression increase of metabolic enzymes and peroxisome proliferator-activated receptor-α in the liver; (v) normalization of monoaminergic transporters and neurotrophic expression in mesolimbic area. However, in contrast to the case of rimonabant, the novel CB1 antagonist improved the disrupted expression profile of genes linked to the hunger-satiety circuit, without altering monoaminergic transmission. In conclusion, the novel CB1 antagonist compound NESS038C6 may represent a useful candidate agent for the treatment of obesity and its metabolic complications, without or with reduced side effects relative to those instead observed with rimonabant.

Weight loss induced by rimonabant is associated with an altered leptin expression and hypothalamic leptin signaling in diet-induced obese mice.

This study investigates the molecular mechanisms and the center-periphery cross talk underlying the anti-obesity effect of the cannabinoid receptor 1 (CB(1)) antagonist/inverse agonist rimonabant in diet-induced obese (DIO) mice exposed to a 31 days chronic treatment with the drug. Present data showed a significant and stable weight loss both in animals treated with rimonabant 10mg/kg by oral gavage exposed to a high fat diet (SRFD) and in vehicle treated mice switched to a regular chow (VEND) with respect to vehicle fat diet fed mice (VEFD). Caloric intake was significantly lowered in SRFD and VEND during the first two and four days, respectively, then reaching the VEFD consume throughout the treatment. The drop of body weight was accompanied by leptin mRNA decrease in visceral fat tissue both in VEND and SRFD, as revealed by Real time PCR analysis. No difference in CB(1) mRNA receptor expression in hypothalamus and in visceral fat tissue among groups was observed. Leptin receptors were decreased in the hypothalamus of SRFD but not of VEND mice. Moreover, in SRFD and VEND mice the expression of orexigenic genes Neuropeptide Y and Agouti Related Protein (AGRP) was increased, while anorexigenic ones, Pro-OpioMelanoCortin (POMC) and Cocaine-and-Amphetamine-Regulated Transcript (CART) displayed no alteration in any group. This data contribute to clarify the molecular basis of the anti-obesity properties of rimonabant, underlying the role of the peripheral modulators which affect central circuits involved in the regulation of food intake and energy homeostasis.