cannabinoid receptor 2
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In Vivo ◽  
2021 ◽  
Vol 36 (1) ◽  
pp. 227-232
Author(s):  
TAKASHI TANIKAWA ◽  
MASASHI KITAMURA ◽  
YASUHIRO HAYASHI ◽  
TAKAMI YOKOGAWA ◽  
YUTAKA INOUE

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6679
Author(s):  
Mukuo Wang ◽  
Shujing Hou ◽  
Ye Liu ◽  
Dongmei Li ◽  
Jianping Lin

The endocannabinoid system plays an essential role in the regulation of analgesia and human immunity, and Cannabinoid Receptor 2 (CB2) has been proved to be an ideal target for the treatment of liver diseases and some cancers. In this study, we identified CB2 antagonists using a three-step “deep learning–pharmacophore–molecular docking” virtual screening approach. From the ChemDiv database (1,178,506 compounds), 15 hits were selected and tested by radioligand binding assays and cAMP functional assays. A total of 7 out of the 15 hits were found to exhibit binding affinities in the radioligand binding assays against CB2 receptor, with a pKi of 5.15-6.66, among which five compounds showed antagonistic activities with pIC50 of 5.25–6.93 in the cAMP functional assays. Among these hits, Compound 8 with the 4H-pyrido[1,2-a]pyrimidin-4-one scaffold showed the best binding affinity and antagonistic activity with a pKi of 6.66 and pIC50 of 6.93, respectively. The new scaffold could serve as a lead for further development of CB2 drugs. Additionally, we hope that the model in this study could be further utilized to identify more novel CB2 receptor antagonists, and the developed approach could also be used to design potent ligands for other therapeutic targets.


2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Houyi Sun ◽  
Weicheng Zhang ◽  
Ning Yang ◽  
Yi Xue ◽  
Tianhao Wang ◽  
...  

AbstractIn glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH), downregulated osteogenic ability and damaged blood supply are two key pathogenic mechanisms. Studies suggested that cannabinoid receptor 2 (CB2) is expressed in bone tissue and it plays a positive role in osteogenesis. However, whether CB2 could enhance bone formation and blood supply in GC-induced ONFH remains unknown. In this study, we focused on the effect of CB2 in GC-induced ONFH and possible mechanisms in vitro and in vivo. By using GC-induced ONFH rat model, rat-bone mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) to address the interaction of CB2 in vitro and in vivo, we evaluate the osteogenic and angiogenic effect variation and possible mechanisms. Micro-CT, histological staining, angiography, calcein labeling, Alizarin red staining (ARS), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) staining, TUNEL staining, migration assay, scratch assay, and tube formation were applied in this study. Our results showed that selective activation of CB2 alleviates GC-induced ONFH. The activation of CB2 strengthened the osteogenic activity of BMSCs under the influence of GCs by promotion of GSK-3β/β-catenin signaling pathway. Furthermore, CB2 promoted HUVECs migration and tube-forming capacities. Our findings indicated that CB2 may serve as a rational new treatment strategy against GC-induced ONFH by osteogenesis activation and maintenance of blood supply.


2021 ◽  
Vol 8 (10) ◽  
pp. 229
Author(s):  
Francesca Gobbo ◽  
Giuseppe Sarli ◽  
Margherita De De Silva ◽  
Giorgia Galiazzo ◽  
Roberto Chiocchetti ◽  
...  

Immunohistochemistry (IHC) is a widely used technique in diagnostic pathology, but the simultaneous analysis of more than one antibody at a time with different chromogens is rather complex, time-consuming, and quite expensive. In order to facilitate the identification of mast cells (MCs) during immunohistochemical analysis of membrane and/or nuclear markers, we propose a new staining method that includes the association of IHC and toluidine blue as a counterstain. To achieve this goal, we tested c-kit, Ki67, and cannabinoid receptor 2 on several cases of cutaneous canine mast cell tumors (MCTs), cutaneous mastocytosis, and atopic dermatitis. The results obtained show how this double staining technique, although limited to non-cytoplasmic markers and of little use in poorly differentiated MCTs in which MC metachromasia is hard to see, can be used during the evaluation of nuclear and/or membranous immunohistochemical markers in all canine cutaneous disorders, especially if characterized by the presence of a low number of MCs. It can help to evaluate those MCTs in which neoplastic MCs must be clearly distinguished from inflammatory cells that can infiltrate the tumor itself, in facilitating the calculation of the Ki67 index. Moreover, it can be used to study the expression of new markers in both animal and human tissues containing MCs and in MC disorders.


Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5984
Author(s):  
Joanna Agnieszka Komorowska-Müller ◽  
Tanushka Rana ◽  
Bolanle Fatimat Olabiyi ◽  
Andreas Zimmer ◽  
Anne-Caroline Schmöle

Physiological brain aging is characterized by gradual, substantial changes in cognitive ability, accompanied by chronic activation of the neural immune system. This form of inflammation, termed inflammaging, in the central nervous system is primarily enacted through microglia, the resident immune cells. The endocannabinoid system, and particularly the cannabinoid receptor 2 (CB2R), is a major regulator of the activity of microglia and is upregulated under inflammatory conditions. Here, we elucidated the role of the CB2R in physiological brain aging. We used CB2R−/− mice of progressive ages in a behavioral test battery to assess social and spatial learning and memory. This was followed by detailed immunohistochemical analysis of microglial activity and morphology, and of the expression of pro-inflammatory cytokines in the hippocampus. CB2R deletion decreased social memory in young mice, but did not affect spatial memory. In fact, old CB2R−/− mice had a slightly improved social memory, whereas in WT mice we detected an age-related cognitive decline. On a cellular level, CB2R deletion increased lipofuscin accumulation in microglia, but not in neurons. CB2R−/− microglia showed an increase of activity markers Iba1 and CD68, and minor upregulation in tnfa and il6 expression and downregulation of ccl2 with age. This was accompanied by a change in morphology as CB2R−/− microglia had smaller somas and lower polarity, with increased branching, cell volume, and tree length. We present that CB2Rs are involved in cognition and age-induced microglial activity, but may also be important for microglial activation itself.


2021 ◽  
Author(s):  
wenjing du ◽  
Ting Zhang ◽  
Fangyong Yang ◽  
Zhao Tang ◽  
Qiuping Li ◽  
...  

Abstract Background: Idiopathic pulmonary fibrosis (IPF) a chronic, progressive, and lung fibrosis disease of unknown etiology with less effective treatment. It is important to discover new biomarker and therapeutic target for the diagnosis and cure of IPF. Method: Differential metabolic profiles may be useful for the diagnosis of IPF and provide additional insight into the molecular mechanisms underlying IPF. Plasma samples from IPF, COPD and normal controls were investigated using liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) and these datasets were analyzed using multiple pattern performance methods. Multivariate statistical methods, pathway enrichment analysis and univariate receiver operating characteristic (ROC) curve analysis were performed. Results: OPLS-DA results showed that it exhibited significant separation between any two groups. ROC curve analyses revealed that 8 metabolites with high AUC above 0.7 between three groups in the plasma samples. Pathway analysis revealed that 3 metabolites are involved in endogenous cannabinoids/cannabinoid receptor 2 (CB2) signaling. Moreover, we found that the specific elevation of CB2 could be a signature of PF(Pulmonary Fibrosis) lung tissues in rat model. Conclusions: LC-MS-based plasma metabolomics provides a important tool to identify the potential biomarkers for IPF. Taken together, we performed quantitative chemoproteomic profiling and identified endogenous cannabinoids/CB2 as the key target of ICA in bleomycin-induced pulmonary fibrosis. Trial Registration: The study was approved by the the Ethics Committee of Huashan Hospital, Fudan University (KY2021-453)


2021 ◽  
Author(s):  
Maya Petgrave ◽  
Praveen Nekkar Rao ◽  
Subha Kalyaanamoorthy ◽  
Aravindhan Ganesan

Glia ◽  
2021 ◽  
Author(s):  
Nico Reusch ◽  
Kishore Aravind Ravichandran ◽  
Bolanle Fatimat Olabiyi ◽  
Joanna Agnieszka Komorowska‐Müller ◽  
Jan N. Hansen ◽  
...  

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