Insulinotropic and antidiabetic effects of β-caryophyllene with l-arginine in type 2 diabetic rats.

Journal of Food Biochemistry banner“Beta-caryophyllene (BCP) is a flavoring agent, whereas l-arginine (LA) is used as a food supplement.

They possess insulinotropic and β cell regeneration activities, respectively.

We assessed the antidiabetic potential of BCP, LA, and its combination in RIN-5F cell lines and diabetic rats.

The results indicated that the combination of BCP with LA showed a significant decrease in glucose absorption and an increase in its uptake in tissues and also an increase in insulin secretion in RIN-5F cells. The combination treatment of BCP with LA showed a significant reduction in glucose, lipid levels, and oxidative stress in pancreatic tissue when compared with the diabetic group. Furthermore, the combination of BCP with LA normalized glucose tolerance and pancreatic cell damage in diabetic rats.

In conclusion, the combinational treatment showed significant potentials in the treatment of type 2 diabetes mellitus.

PRACTICAL APPLICATIONS:

Type 2 diabetes mellitus is the most prevalent chronic metabolic disorder affecting a large population.

Beta-caryophyllene is a CB2 receptor agonist shown to have insulinotropic activity.

l-Arginine is a food supplement that possesses beta-cell regeneration property.

The combination of BCP with LA could work as a potential therapeutic intervention, considering the individual pharmacological activities of each.

We evaluated the antidiabetic activity of the combination of BCP with LA in diabetic rats using ex vivo and in vitro experimentations.

Results from the study revealed that the combination of BCP with LA showed a significant (p < .001) reduction in glucose and lipid levels as compared to individual treatment. In vitro study also supports the diabetic potential of the combination of BCP with LA in the glucose-induced insulin secretion in RIN-5F cell lines.

The study indicates a therapeutic approach to treat T2DM by BCP and LA combination as food and dietary supplement.”

https://www.ncbi.nlm.nih.gov/pubmed/31997410

https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.13156

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Activation of CB2R with AM1241 ameliorates neurodegeneration via the Xist/miR-133b-3p/Pitx3 axis.

Publication cover image“Activation of cannabinoid receptor type II (CB2R) by AM1241 has been demonstrated to protect dopaminergic neurons in Parkinson’s disease (PD) animals.

However, the specific mechanisms of the action of the CB2R agonist AM1241 for PD treatment have not been characterized.

The CB2 receptor agonist AM1241 alleviated PD via regulation of the Xist/miR-133b-3p/Pitx3 axis, and revealed a new approach for PD treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/31989652

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.29530

The Critical Role of Cannabinoid Receptor 2 in URB602-induced Protective Effects Against Renal Ischemia-Reperfusion Injury in the Rat.

 Image result for shock journal“Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage.

Accumulating proofs demonstrates that the endocannabinoid system (ECS) may provide a promising access for treatment strategy of renal IRI associated AKI.

In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation.

Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.”

https://www.ncbi.nlm.nih.gov/pubmed/32004183

 

Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex.

Image result for cell journal“Drugs selectively targeting CB2 hold promise for treating neurodegenerative disorders, inflammation, and pain while avoiding psychotropic side effects mediated by CB1. The mechanisms underlying CB2 activation and signaling are poorly understood but critical for drug design. Here we report the cryo-EM structure of the human CB2-Gi signaling complex bound to the agonist WIN 55,212-2. The 3D structure reveals the binding mode of WIN 55,212-2 and structural determinants for distinguishing CB2 agonists from antagonists, which are supported by a pair of rationally designed agonist and antagonist. Further structural analyses with computational docking results uncover the differences between CB2 and CB1 in receptor activation, ligand recognition, and Gi coupling. These findings are expected to facilitate rational structure-based discovery of drugs targeting the cannabinoid system.”

https://www.ncbi.nlm.nih.gov/pubmed/32004460

https://www.cell.com/cell/fulltext/S0092-8674(20)30054-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420300544%3Fshowall%3Dtrue

Cannabinoids CB2 Receptors, One New Promising Drug Target for Chronic and Degenerative Pain Conditions in Equine Veterinary Patients.

Journal of Equine Veterinary Science“Osteoarticular equine disease is a common cause of malady; in general, its therapy is supported on steroids and nonsteroidal anti-inflammatories. Nevertheless, many side effects may develop when these drugs are administered. Nowadays, the use of new alternatives for this pathology attention is demanded; in that sense, cannabinoid CB2 agonists may represent a novel alternative.

Cannabinoid belongs to a group of molecules known by their psychoactive properties; they are synthetized by the Cannabis sativa plant, better known as marijuana.

The aim of this study was to contribute to understand the pharmacology of cannabinoid CB2 receptors and its potential utilization on equine veterinary patients with a chronic degenerative painful condition. In animals, two main receptors for cannabinoids are recognized, the cannabinoid receptor type 1 and the cannabinoid receptor type 2. Once they are activated, both receptors exert a wide range of physiological responses, as nociception modulation.

Recently, it has been proposed the use of synthetic cannabinoid type 2 receptor agonists; those receptors looks to confer antinociceptive properties but without the undesired psychoactive side effects; for that reason, veterinary patients, whit chronical degenerative diseases as osteoarthritis may alleviate one of the most common symptom, the pain, which in some cases for several reasons, as patient individualities, or side effects produced for more conventional treatments cannot be attended in the best way.”

https://www.ncbi.nlm.nih.gov/pubmed/31952645

https://www.sciencedirect.com/science/article/abs/pii/S073708061930629X?via%3Dihub

Cannabinoid Receptor 2 Modulates Maturation of Dendritic Cells and Their Capacity to Induce Hapten-Induced Contact Hypersensitivity.

ijms-logo“Contact hypersensitivity (CHS) is an established animal model for allergic contact dermatitis. Dendritic cells (DCs) play an important role in the sensitization phase of CHS by initiating T cell responses to topically applied haptens. The cannabinoid receptors 1 (CB1) and 2 (CB2) modulate DC functions and inflammatory skin responses, but their influence on the capacity of haptenized DCs to induce CHS is still unknown. We found lower CHS responses to 2,4-dinitro-1-fluorobenzene (DNFB) in wild type (WT) mice after adoptive transfer of haptenized Cnr2-/- and Cnr1-/-/Cnr2-/- bone marrow (BM) DCs as compared to transfer of WT DCs. In contrast, induction of CHS was not affected in WT recipients after transfer of Cnr1-/- DCs. In vitro stimulated Cnr2-/- DCs showed lower CCR7 and CXCR4 expression when compared to WT cells, while in vitro migration towards the chemokine ligands was not affected by CB2. Upregulation of MHC class II and co-stimulatory molecules was also reduced in Cnr2-/- DCs. This study demonstrates that CB2 modulates the maturation phenotype of DCs but not their chemotactic capacities in vitro. These findings and the fact that CHS responses mediated by Cnr2-/- DCs are reduced suggest that CB2 is a promising target for the treatment of inflammatory skin conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31940843

https://www.mdpi.com/1422-0067/21/2/475

Activation of cannabinoid receptor type 2 reduces lung ischemia reperfusion injury through PI3K/Akt pathway.

Image result for int j clin exp pathol“Cannabinoid receptor-2 activation plays a protective role against ischemic reperfusion injury (IRI) in various organs, and exerts a protective effect against paraquat-induced acute lung injury, while the role of CB2 in lung IRI remains unclear.

Hence, the present study was designed to explore the role of CB2 in lung IRI, and whether the PI3K pathway was involved.

The study suggested that activation of CB2 receptor plays a protective role against IR-induced lung injury through reducing inflammation in mice.

The PI3K/Akt pathway might be involved in the protective effect of CB2 receptors in lung IRI.”

https://www.ncbi.nlm.nih.gov/pubmed/31933805

CB2R orchestrates neuronal autophagy through regulation of the mTOR signaling pathway in the hippocampus of developing rats with status epilepticus.

 Journal Cover“Neuronal loss and gliosis are the major pathological changes after status epilepticus (SE).

The authors’ previous study revealed the time‑dependent changes of cannabinoid receptor type 2 (CB2R) in hippocampal neurons of developing rats after SE, which were accompanied by a decrease in the number of neurons. Meanwhile, growing evidence indicates that CB2R stimulation exerts anti‑convulsant properties in seizure models. However, the activation of CB2R in neuronal repair in response to the damage after SE is still unclear.

In this experiment, a highly‑selective CB2R agonist JWH133 and antagonist AM630 were administered to determine the activity of CB2R in neuronal autophagy and apoptosis of the post‑SE repair in developing rats. The present results revealed that activation of CB2R by JWH133, not only obviously lowered the success rate, 24‑h death rate and the Racine stage in the model, but also extended the latency period to SE. In addition, compared with the vehicle control group, CB2R activation increased neuronal autophagy and the expression of phosphorylated‑mammalian target of rapamycin (p‑mTOR)/mTOR, Beclin‑1, and LC3II/LC3I while decreasing the expression of p‑Unc‑51‑like autophagy‑activating kinase 1 (ULK‑1)/ULK1, p62, and cleaved caspase‑3.

These results were dose‑dependent and were especially evident in the high‑dose group, and interestingly the opposite results were obtained in the AM630 group. Thus, CB2R orchestrates neuronal autophagy through regulation of the mTOR signaling pathway in the hippocampus of developing rats with SE. These findings might provide an important basis for further investigation of the therapeutic role of CB2R in ameliorating epilepsy‑related neuronal damage.”

https://www.ncbi.nlm.nih.gov/pubmed/31894322

https://www.spandidos-publications.com/10.3892/ijmm.2019.4439

β-Caryophyllene, a CB2-Receptor-Selective Phytocannabinoid, Suppresses Mechanical Allodynia in a Mouse Model of Antiretroviral-Induced Neuropathic Pain.

molecules-logo “Neuropathic pain associated with nucleoside reverse transcriptase inhibitors (NRTIs), therapeutic agents for human immunodeficiency virus (HIV), responds poorly to available drugs.

Smoked cannabis was reported to relieve HIV-associated neuropathic pain in clinical trials. Some constituents of cannabis (Cannabis sativa) activate cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors. However, activation of the CB1 receptor is associated with side effects such as psychosis and physical dependence.

Therefore, we investigated the effect of β-caryophyllene (BCP), a CB2-selective phytocannabinoid, in a model of NRTI-induced neuropathic pain.

BCP prevents NRTI-induced mechanical allodynia, possibly via reducing the inflammatory response, and attenuates mechanical allodynia through CB2 receptor activation. Therefore, BCP could be useful for prevention and treatment of antiretroviral-induced neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31892132

https://www.mdpi.com/1420-3049/25/1/106

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Beta‐caryophyllene, a dietary terpenoid, inhibits nicotine‐taking and nicotine‐seeking in rodents

British Journal of Pharmacology banner“Beta-caryophyllene (BCP) is a dietary plant-derived terpenoid that has been used as a food additive for many decades.

Recent studies indicate that BCP is a cannabinoid CB2 receptor (CB2R) agonist with medical benefits for a number of human diseases. However, little is known about its therapeutic potential for drug abuse and addiction.

The present findings suggest that BCP has significant anti-nicotine effects via both CB2 and non-CB2 receptor mechanisms, and therefore, deserves further study as a potential new pharmacotherapy for cigarette smoking cessation.”

https://www.ncbi.nlm.nih.gov/pubmed/31883107

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14969

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142