scholarly journals Anti-Inflammatory Activity of a CB2 Selective Cannabinoid Receptor Agonist: Signaling and Cytokines Release in Blood Mononuclear Cells

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 64
Author(s):  
Antonella Capozzi ◽  
Daniela Caissutti ◽  
Vincenzo Mattei ◽  
Francesca Gado ◽  
Stefano Martellucci ◽  
...  

The endocannabinoid system (ECS) exerts immunosuppressive effects, which are mostly mediated by cannabinoid receptor 2 (CBR2), whose expression on leukocytes is higher than CBR1, mainly localized in the brain. Targeted CBR2 activation could limit inflammation, avoiding CBR1-related psychoactive effects. Herein, we evaluated in vitro the biological activity of a novel, selective and high-affinity CBR2 agonist, called JT11, studying its potential CBR2-mediated anti-inflammatory effect. Trypan Blue and MTT assays were used to test the cytotoxic and anti-proliferative effect of JT11 in Jurkat cells. Its pro-apoptotic activity was investigated analyzing both cell cycle and poly PARP cleavage. Finally, we evaluated its impact on LPS-induced ERK1/2 and NF-kB-p65 activation, TNF-α, IL-1β, IL-6 and IL-8 release in peripheral blood mononuclear cells (PBMCs) from healthy donors. Selective CB2R antagonist SR144528 and CBR2 knockdown were used to further verify the selectivity of JT11. We confirmed selective CBR2 activation by JT11. JT11 regulated cell viability and proliferation through a CBR2-dependent mechanism in Jurkat cells, exhibiting a mild pro-apoptotic activity. Finally, it reduced LPS-induced ERK1/2 and NF-kB-p65 phosphorylation and pro-inflammatory cytokines release in human PBMCs, proving to possess in vitro anti-inflammatory properties. JT11 as CBR2 ligands could enhance ECS immunoregulatory activity and our results support the view that therapeutic strategies targeting CBR2 signaling could be promising for the treatment of chronic inflammatory diseases.

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2022
Author(s):  
Enrico Gugliandolo ◽  
Rosalia Crupi ◽  
Vito Biondi ◽  
Patrizia Licata ◽  
Salvatore Cuzzocrea ◽  
...  

Although inflammation is an important physiological response, it plays a prominent role in several diseases across the mammalian species. In horses, in particular, inflammation secondary to bacterial infection or translocation is one of the most frequent causes of morbidity and mortality. Research in new molecules with anti-inflammatory and immunomodulatory proprieties and safe use profile is constantly an active field; natural compounds are an important source of molecules with peculiar properties such as antioxidants, anti-inflammatory and immune modulating. Silibinin, a natural polyphenolic flavonoid, extracted from plant milk thistle, Silybum marianum, has been reported to have actions such as antioxidant immunomodulatory and anti-inflammatory. The aim of this study was to test the effect of silibinin on lipopolysaccharide (LPS)-induced inflammatory response in equine peripheral blood mononuclear cells (PBMCs). Our results showed the protective effect of silibinin 10 μM and 50 μM in equine PBMCs stimulated with LPS. Silibilinin was able to prevent the LPS induced increased levels of TNF-α, IL-1β, IL-6 and IL-8. The results from this study on LPS-stimulated equine PBMCs showed that silibinin could be a useful pharmacological approach in treatment or prevention of several inflammatory conditions in horse.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Rosanna W Chung ◽  
Per Leanderson ◽  
Anna K Lundberg ◽  
Lena Jonasson

Introduction: Low plasma carotenoid levels are associated with increased cardiovascular risk factors. Carotenoids are anti-oxidants with potential anti-inflammatory properties. In this study, we measured different types of carotenoid in plasma and assessed their relationship with interleukin-6 (IL-6) in patients with acute coronary syndrome (ACS) or stable coronary artery disease (CAD). A sub-cohort was followed for 12 months. Moreover, we assessed the anti-inflammatory effects of lutein in peripheral blood mononuclear cells (PBMC) collected from CAD patients. Methods: We included 48 ACS and 109 stable CAD patients. Circulating levels of lutein+zeaxanthin, β-cryptoxanthin, lycopene, α- and β-carotene, and IL-6 were measured. Lutein and zeaxanthin are isomers and as such measured together. Lutein, however, is the major form of the isomers. PBMC were treated with lutein (1μM, 5μM and 25μM) for 24hr followed by 24hr incubation with or without LPS. Cytokines and matrix metalloproteinase-9 (MMP-9) in cell media were measured. Results: Levels of lutein+zeaxanthin and lycopene were inversely correlated to IL-6 in the whole cohort, p <0.001 and p <0.05, respectively. In stable CAD patients, only lutein+zeaxanthin were correlated to IL-6 ( p <0.001). In the sub-cohort (n=33), changes in IL-6 were inversely correlated to changes in lutein+zeaxanthin at the 3 rd month ( p <0.01) and 12 th month ( p <0.05). Changes in IL-6 were also inversely correlated to changes in lycopene levels at 12 th month ( p <0.05). Other carotenoids did not correlate to IL-6 in plasma. In vitro , spontaneous and LPS-induced secretion of cytokines (IL-6, IL-1β and TNF-α) and MMP-9 from PBMC were dose-dependently and significantly reduced by lutein. Conclusions: The clinical findings indicated that lutein+zeaxanthin might play a role in resolution of inflammation in CAD patients. In vitro , we were able to confirm that lutein exerted anti-inflammatory effects by suppressing secretion of inflammatory cytokines and MMP-9 from PBMC.


2012 ◽  
Vol 141 (1) ◽  
pp. 542-546 ◽  
Author(s):  
Damodharan Vijayalakshmi ◽  
Ramamurthy Dhandapani ◽  
Sivalingam Jayaveni ◽  
Panneer Selvam Jithendra ◽  
Chellan Rose ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jingying Sai ◽  
Lingxin Xiong ◽  
Jingtong Zheng ◽  
Chuangui Liu ◽  
Yanjiao Lu ◽  
...  

Yinhua Miyanling Tablet (YMT), the Chinese formula, has long been administrated in clinical practice for the treatment of acute pyelonephritis and acute urocystitis. In the current study, we aimed to investigate the anti-inflammatory effect of YMTin vitroand to evaluate the association between anti-inflammation and innate immune response. Human peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll density gradient centrifugation and then were stimulated by Lipopolysaccharide (LPS). The differential gene expression of inflammation-related genes after drug administration was assessed using PCR array, and the protein levels of differential genes were measured by ELISA and Western blot. The result showed that YMT significantly inhibited the expression of NLRP3, Caspase-1, and the downstream cytokine IL-1βand suppressed the production of inflammatory mediators TNF-α, IL-6, IL-10, and MCP-1 in a dose-dependent manner compared to the LPS groupP<0.01. The finding indicated that YMT exhibited anti-inflammatory effectin vitroby suppressing the NLRP3/Caspase-1 inflammasome, and that may have therapeutic potential for the treatment of inflammatory diseases.


Author(s):  
Katharina Schroecksnadel ◽  
Christiana Winkler ◽  
Barbara Wirleitner ◽  
Harald Schennach ◽  
Günter Weiss ◽  
...  

AbstractInflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10–100μM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses of compounds needed to reduce homocysteine levels to 50% of stimulated cells were always slightly lower than those necessary to achieve the same effect on neopterin concentrations. The influence of resveratrol and of all the other compounds on homocysteine production appears to be independent of any direct effect on homocysteine biochemistry.


Pteridines ◽  
2008 ◽  
Vol 19 (1) ◽  
pp. 101-106 ◽  
Author(s):  
Christiana Winkler ◽  
Katharina Schroecksnadel ◽  
Maximilian Ledochowski ◽  
Harald Schennach ◽  
Bakhouche Houcher ◽  
...  

AbstractNigella sativa, commonly known as black cumin seed, belongs to the botanical family of Ranunculaceae. The active antioxidant components of Nigella sativa display a remarkable array of biochemical, immunological and pharmacological actions, including bronchodilatory, anti-inflammatory, antibacterial, hypoglycaemic, antitumoural and immunopotentiating effects. Effects of Nigella sativa seeds extracts were investigated in freshly isolated human peripheral blood mononuclear cells stimulated with the mitogens phytohaemagglutinin and concanavalin A in vitro. Tryptophan degradation and neopterin production were monitored in culture supernatants, both these immunobiochemical pathways are induced by pro-inflammatory cytokine interferon-γ. Compared to unstimulated cells, the mitogens enhanced degradation of tryptophan and production of neopterin. Nigella sativa seeds extracts significantly suppressed both pathways in a dose-dependent way. Suppression of tryptophan degradation and neopterin formation by Nigella sativa seeds extracts demonstrates an inhibitory influence on activated T-cells and macrophages. Data are in line with an anti-inflammatory activity of the extracts.


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