Beta-Caryophyllene Modifies Intracellular Lipid Composition in a Cell Model of Hepatic Steatosis by Acting through CB2 and PPAR Receptors.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease; however, no specific pharmacological therapy has yet been approved for this condition. Plant-derived extracts can be an important source for the development of new drugs. The aim of this study was to investigate the effects of (E)-β-caryophyllene (BCP), a phytocannabinoid recently found to be beneficial against metabolic diseases, on HepG2 steatotic hepatocytes.

Reproducibility of adipogenic responses to metabolism disrupting chemicals in the 3T3-L1 pre-adipocyte model system: An interlaboratory study.

The 3T3-L1 murine pre-adipocyte line is an established cell culture model for screening Metabolism Disrupting Chemicals (MDCs). Despite a need to accurately identify MDCs for further evaluation, relatively little research has been performed to comprehensively evaluate reproducibility across laboratories, assess factors that might contribute to varying degrees of differentiation between laboratories (media additives, plastics, cell source, etc.), or to standardize protocols.

Cannabinoid Receptor Modulation of Neurogenesis: ST14A Striatal Neural Progenitor Cells as a Simplified In Vitro Model.

The endocannabinoid system (ECS) is involved in the modulation of several basic biological processes, having widespread roles in neurodevelopment, neuromodulation, immune response, energy homeostasis and reproduction. In the adult central nervous system (CNS) the ECS mainly modulates neurotransmitter release, however, a substantial body of evidence has revealed a central role in regulating neurogenesis in developing and adult CNS, also under pathological conditions. Due to the complexity of investigating ECS functions in neural progenitors in vivo, we tested the suitability of the ST14A striatal neural progenitor cell line as a simplified in vitro model to dissect the role and the mechanisms of ECS-regulated neurogenesis, as well as to perform ECS-targeted pharmacological approaches.

Protective Effects of ()-β-Caryophyllene (BCP) in Chronic Inflammation.

()-β-caryophyllene (BCP) is a bicyclic sesquiterpene widely distributed in the plant kingdom, where it contributes a unique aroma to essential oils and has a pivotal role in the survival and evolution of higher plants. Recent studies provided evidence for protective roles of BCP in animal cells, highlighting its possible use as a novel therapeutic tool. Experimental results show the ability of BCP to reduce pro-inflammatory mediators such as tumor necrosis factor-alfa (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), thus ameliorating chronic pathologies characterized by inflammation and oxidative stress, in particular metabolic and neurological diseases.

PipeNig-FL, a Fluid Extract of Black Pepper ( L.) with a High Standardized Content of -β-Caryophyllene, Reduces Lipid Accumulation in 3T3-L1 Preadipocytes and Improves Glucose Uptake in C2C12 Myotubes.

-β-caryophyllene (BCP) is a natural sesquiterpene hydrocarbon with several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, and cardioprotective functions. These properties are mainly due to its selective interaction with the peripherally expressed cannabinoid receptor 2. In addition, BCP activates peroxisome proliferated activator receptors α and γ and inhibits the Toll-like receptor signaling pathway.

Bisphenol A Activates Calcium Influx in Immortalized GnRH Neurons.

Bisphenol A (BPA) is one of the most widely used chemicals worldwide, e.g., as a component of plastic containers for food and water.

Plasticizers used in food-contact materials affect adipogenesis in 3T3-L1 cells.

Recent studies suggest that exposure to some plasticizers, such as Bisphenol A (BPA), play a role in endocrine/metabolic dispruption and can affect lipid accumulation in adipocytes. Here, we investigated the adipogenic activity and nuclear receptor interactions of four plasticizers approved for the manufacturing of food-contact materials (FCMs) and currently considered safer alternatives. Differentiating 3T3-L1 mouse preadipocytes were exposed to scalar concentrations (0.

Endocannabinoids are Involved in Male Vertebrate Reproduction: Regulatory Mechanisms at Central and Gonadal Level.

Endocannabinoids (eCBs) are natural lipids regulating a large array of physiological functions and behaviors in vertebrates. The eCB system is highly conserved in evolution and comprises several specific receptors (type-1 and type-2 cannabinoid receptors), their endogenous ligands (e.g.

Role of the endocannabinoid system in the central regulation of nonmammalian vertebrate reproduction.

The endocannabinoid system (ECS) has a well-documented pivotal role in the control of mammalian reproductive functions, by acting at multiple levels, that is, central (CNS) and local (gonads) levels. Since studies performed in animal models other than mammals might provide further insight into the biology of these signalling molecules, in the present paper we review the comparative data pointing toward the endocannabinoid involvement in the reproductive control of non-mammalian vertebrates, focussing in particular on the central regulation of teleost and amphibian reproduction. The morphofunctional distribution of brain cannabinoid receptors will be discussed in relation to other crucial signalling molecules involved in the control of reproductive functions, such as GnRH, dopamine, aromatase, and pituitary gonadotropins.

Cannabinoid receptors are widely expressed in goldfish: molecular cloning of a CB2-like receptor and evaluation of CB1 and CB2 mRNA expression profiles in different organs.

Cannabinoids, the bioactive constituents of Cannabis sativa, and endocannabinoids, among which the most important are anandamide and 2-arachidonoylglycerol, control various biological processes by binding to specific G protein-coupled receptors, namely CB1 and CB2 cannabinoid receptors. While a vast amount of information on the mammalian endocannabinoid system does exist, few data have been reported on bony fish. In the goldfish, Carassius auratus, the CB1 receptor has been cloned and its distribution has been analyzed in the retina, brain and gonads, while CB2 had not yet been isolated.

Xenoestrogens elicit a modulation of endocannabinoid system and estrogen receptors in 4NP treated goldfish, Carassius auratus.

Based on pharmacological, behavioral and neuroanatomical studies, the endocannabinoids appear to be pivotal in some important neuroendocrine regulations of both vertebrates and invertebrates. Interestingly, a well developed endocannabinoid system was recently demonstrated by us in different bonyfish brain areas which control reproduction, energy balance and stress. Fish in particular are very sensitive to different types of stressors which can heavily affect their reproductive activity and negatively reverberate on aquaculture.

Involvement of endocannabinoid CB1 receptor in the modulation of stress responses related to xenoestrogen exposure.

The endocannabinoid system, through the cannabinoid receptor CB1, is involved in the modulation of adaptive responses to environmental conditions. However, little is known about the role of the cannabinergic system, particularly CB1 receptor expression, in relation to the effects induced by xenoestrogens concerning the reproductive axis. Our results demonstrate that only 10(-8) mol/L of 17beta-estradiol was able to induce significantly higher levels of CB1A mRNA, while no effects were found after treatment with 4-nonylphenol (10(-8) or 10(-6) mol/L); moreover, mRNA expression titers of CB1B did not show any significant change.

Interplay of the endocannabinoid system with neuropeptide Y and corticotropin-releasing factor in the goldfish forebrain.

Based on pharmacological, behavioral, and neuroanatomical studies, the endocannabinoid system appears to be pivotal in some neuroendocrine mechanisms, such as modulation of vertebrate reproduction, stress, and food intake. The present study aimed to investigate the involvement of the endocannabinoid system in the control of the feeding response in the goldfish. By means of immunohistochemistry techniques, using anti-CB1 cannabinoid receptor, anti-corticotropin-releasing factor (CRF), and anti-neuropeptide Y (NPY) antisera on brain sections of Carassius auratus, we found a topographical co-distribution of the three signaling molecules through the preoptic area and posterior lobes of the hypothalamus and even a co-localization of CB1 and NPY in the telencephalon.

Goldfish CB1 mRNA expression is affected by fasting and anandamide administration.

The endocannabinoid system has a well-documented pivotal role in the control of mammalian feeding response; nevertheless, some evidence is available regarding a similar role in nonmammalian vertebrates and invertebrates. As in the bonyfish Carassius auratus, CB1 cannabinoid receptors are abundant in brain regions involved in the control of food intake, and fasting affects endocannabinoid levels, in this study the effects of food deprivation and anandamide administration on CB1 expression were evaluated. Fasting led to a time-dependent increase of CB1 mRNA levels in the forebrain, an effect reversed by refeeding.

Are the cannabinoids involved in bony fish reproduction?

Following the discovery of two CB1 genes in the fish Fugu rubripes, investigations on the phylogeny of endocannabinoids have indicated that this system is highly conserved. Our study demonstrated that CB1 receptors are expressed in the CNS and gonads of two teleosts, Carassius auratus and Pelvicachromis pulcher, and they show a high percentage of sequence identity with Fugu rubripes CB(1A) and Danio rerio CB1. By means of immunohistochemistry for CB1, sGnRH, and TH, we found a codistribution of these signaling molecules in the basal telencephalon/preoptic area, which are key centers for gonadotropic regulation.

Activator protein-2gamma (AP-2gamma) expression is specifically induced by oestrogens through binding of the oestrogen receptor to a canonical element within the 5'-untranslated region.

The activator protein 2 (AP-2) transcription factors are essential proteins for oestrogenic repression of the ERBB2 proto-oncogene in breast cancer cells. In the present study, we have examined the possible oestrogenic regulation of AP-2 genes themselves in breast-tumour-derived lines. As early as 1 h after oestrogen treatment, AP-2gamma mRNA was markedly increased, whereas AP-2alpha was down-regulated, but with slower kinetics, and AP-2beta was not affected at all.

Xenopus laevis CB1 cannabinoid receptor: molecular cloning and mRNA distribution in the central nervous system.

In the present research we isolated and characterized Xenopus laevis CB1 cannabinoid receptor mRNA. The CB1 coding sequence shows a high degree of identity with those of other vertebrates, mammals included, confirming that CB1 receptor is conserved over the course of vertebrate evolution. Notably, the similarity between the X.