“Cannabinoid 1 receptor (CB1R) regulates the neuro-inflammatory and neurodegenerative damages of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R inhibition exerts inflammatory effects is still unclear. Here, we explored the cellular and molecular mechanisms of CB1R in the treatment of EAE by using a specific and selective CB1R antagonist SR141716A. Our study demonstrated that SR141716A accelerated the clinical onset and development of EAE, accompanied by body weight loss. SR141716A significantly up-regulated the expression of toll like receptor-4 (TLR-4) and nuclear factor-kappaB/p65 (NF-κB/p65) on microglia/macrophages of EAE mice as well as levels of inflammatory factors (TNF-α, IL-1β, IL-6) and chemokines (MCP-1, CX3CL1), accompanied by the shifts of cytokines from Th2 (IL-4, IL-10) to Th1 (IFN-γ)/Th17 (IL-17) in the spinal cords of EAE mice. Similar changes happened on splenic mononuclear cells (MNCs) except chemokine CX3CL1. Consistently, SR141716A promoted BV-2 microglia to release inflammatory factors (TNF-α, IL-1β, IL-6) while inhibited the production of IL-10 and chemokines (MCP-1, CX3CL1). Furthermore, when splenic CD4+ T cells co-cultured with SR141716A-administered BV-2 microglia, the levels of IL-4 and IL-10 were decreased while production of IL-17 and IFN-γ increased significantly. Our research indicated that inhibition of CB1R induced M1 phenotype-Th17 axis changed of microglia/macrophages through TLR-4 and NF-κB/p65 which accelerated the onset and development of EAE. Therefore, CB1R may be a promising target for the treatment of MS/EAE, but its complexity remains to be carefully considered and studied in further clinical application.” https://www.ncbi.nlm.nih.gov/pubmed/29501084 http://www.jni-journal.com/article/S0165-5728(17)30467-8/fulltext]]>
Tag Archives: anti-inflammatory
β-Amyrin, the cannabinoid receptors agonist, abrogates mice brain microglial cells inflammation induced by lipopolysaccharide/interferon-γ and regulates Mφ1/Mφ2 balances.
“Inflammation is a primary response to infection that can pathologically lead to various diseases including neurodegenerative diseases. The purpose of this study was to evaluate the effect of β-Amyrin, a naturally occurring pentacyclic triterpenoid compound, on inflammation induced by lipopolysaccharide (LPS) and interferone-γ (IFN-γ) in rat microglial cells.
CONCLUSION:
β-Amyrin reduces inflammation in microglial cells and can be used as a potential anti-inflammatory agent in central nervous system neurodegenerative diseases such as Alzheimer and multiple sclerosis, by affecting the inflammatory cytokine and differentiation of microglia as resident CNS macrophages.” https://www.ncbi.nlm.nih.gov/pubmed/29501766 “Amyrin and the endocannabinoid system. The canonical triterpene amyrin was recently suggested to bind to CB1 receptors and to significantly mediate cannabimimetic effects in animal models of pain.” http://gertschgroup.com/blog/entry/3188293/amyrin-and-the-endocannabinoid-system“The antinociceptive triterpene β-amyrin inhibits 2-arachidonoylglycerol (2-AG) hydrolysis without directly targeting CB receptors” https://www.researchgate.net/publication/225079976_The_antinociceptive_triterpene_b-amyrin_inhibits_2-arachidonoylglycerol_2-AG_hydrolysis_without_directly_targeting_CB_receptors
“Finally, pentacyclic triterpenes such as β-amyrin and cycloartenol have been shown to possess numerous biological activities including anti-bacterial, anti-fungal, anti-inflammatory and anti-cancer properties.” https://www.linkedin.com/pulse/cannabis-has-terpenes-say-what-pure-hempnotics
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Absence of cannabinoid 1 receptor in beta cells protects against high-fat/high-sugar diet-induced beta cell dysfunction and inflammation in murine islets.
“The cannabinoid 1 receptor (CB1R) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1R is expressed on pancreatic beta cells and is coupled to the G protein Gαi, suggesting a negative regulation of endogenous signalling in the beta cell. To assess the direct contribution of beta cell CB1R to metabolism, we designed a mouse model that allows us to determine the role of CB1R specifically in beta cells in the context of whole-body metabolism.
CONCLUSIONS/INTERPRETATION:
Our data demonstrate CB1R to be a negative regulator of beta cell function and a mediator of islet inflammation under conditions of metabolic stress. Our findings point to beta cell CB1R as a therapeutic target, and broaden its potential to include anti-inflammatory effects in both major forms of diabetes.” https://www.ncbi.nlm.nih.gov/pubmed/29497784 https://link.springer.com/article/10.1007%2Fs00125-018-4576-4]]>Hypoxia mimetic activity of VCE-004.8, a cannabidiol quinone derivative: implications for multiple sclerosis therapy.
“Multiple sclerosis (MS) is characterized by a combination of inflammatory and neurodegenerative processes variously dominant in different stages of the disease. Thus, immunosuppression is the goal standard for the inflammatory stage, and novel remyelination therapies are pursued to restore lost function.
Cannabinoids such as 9Δ-THC and CBD are multi-target compounds already introduced in the clinical practice for multiple sclerosis (MS). Semisynthetic cannabinoids are designed to improve bioactivities and druggability of their natural precursors. VCE-004.8, an aminoquinone derivative of cannabidiol (CBD), is a dual PPARγ and CB2agonist with potent anti-inflammatory activity.
Activation of the hypoxia-inducible factor (HIF) can have a beneficial role in MS by modulating the immune response and favoring neuroprotection and axonal regeneration.
We investigated the effects of VCE-004.8 on the HIF pathway in different cell types. CONCLUSIONS: This study provides new significant insights about the potential role of VCE-004.8 for MS treatment by ameliorating neuroinflammation and demyelination.” https://www.ncbi.nlm.nih.gov/pubmed/29495967 https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-018-1103-y]]>2-AG limits Theiler's virus induced acute neuroinflammation by modulating microglia and promoting MDSCs.
“The innate immune response is mediated by primary immune modulators such as cytokines and chemokines that together with immune cells and resident glia orchestrate CNS immunity and inflammation. Growing evidence supports that the endocannabinoid 2-arachidonoylglycerol (2-AG) exerts protective actions in CNS injury models. Here, we used the acute phase of Theiler’s virus induced demyelination disease (TMEV-IDD) as a model of acute neuroinflammation to investigate whether 2-AG modifies the brain innate immune responses to TMEV and CNS leukocyte trafficking. 2-AG or the inhibition of its hydrolysis diminished the reactivity and number of microglia at the TMEV injection site reducing their morphological complexity and modulating them towards an anti-inflammatory state via CB2 receptors. Indeed, 2-AG dampened the infiltration of immune cells into the CNS and inhibited their egress from the spleen, resulting in long-term beneficial effects at the chronic phase of the disease. Intriguingly, it is not a generalized action over leukocytes since 2-AG increased the presence and suppressive potency of myeloid derived suppressor cells (MDSCs) in the brain resulting in higher apoptotic CD4+ T cells at the injection site. Together, these data suggest a robust modulatory effect in the peripheral and central immunity by 2-AG and highlight the interest of modulating endogenous cannabinoids to regulate CNS inflammatory conditions.”
https://www.ncbi.nlm.nih.gov/pubmed/29484707
http://onlinelibrary.wiley.com/doi/10.1002/glia.23317/abstract
Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice.
“Cannabis extracts and several cannabinoids have been shown to exert broad anti-inflammatory activities in experimental models of inflammatory CNS degenerative diseases. Clinical use of many cannabinoids is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), devoid of psychoactive activity, are, potentially, safe and effective alternatives for alleviating neuroinflammation and neurodegeneration.
Treatment with CBD during disease onset ameliorated the severity of the clinical signs of EAE.
CBD, a non-psychoactive cannabinoid, ameliorates clinical signs of EAE in mice, immunized against MOG. Suppression of microglial activity and T-cell proliferation by CBD appeared to contribute to these beneficial effects.”
https://www.ncbi.nlm.nih.gov/pubmed/21449980 “In summary, we have shown that CBD administered to MOG-immunized C57BL/6 mice, at the onset of EAE disease, reduced the severity of the clinical signs of EAE. CBD treatment was accompanied by diminished axonal loss and inflammation (infiltration of T cells and microglial activation). Moreover, CBD prevented proliferation of myelin-specific T cells in vitro. These observations suggest that CBD may have potential for alleviating MS-like pathology.” http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01379.x/full“Study Shows Cannabidiol (CBD) Improves MS-Like Symptoms” http://www.prohealth.com/library/showarticle.cfm?libid=31211
]]>The Role of Cannabinoid Receptor 1 in the Immunopathology of Respiratory Syncytial Virus.
“Endocannabinoid system plays an important role in pathophysiologic processes such as immune functions and impacts on disease severity.
Our previous study showed that cannabinoid receptor 2 (CB2) affects clinical course of respiratory syncytial virus (RSV) infection. In this study, we investigated the role of cannabinoid receptor 1 (CB1) in RSV immunopathology and its therapeutic potential in mice model.
This study and our previous finding indicated that endocannabinoid signaling regulates the inflammatory response to RSV infection, and is a potential therapeutic candidate for alleviation of RSV-associated immunopathology.”
https://www.ncbi.nlm.nih.gov/pubmed/29461930
http://online.liebertpub.com/doi/10.1089/vim.2017.0098
“Cannabis is a widely used drug in the United States, and the frequency of cannabis use in the human immunodeficiency virus (HIV)–infected population is disproportionately high. Previous human and macaque studies suggest that cannabis may have an impact on plasma viral load; however, the relationship between cannabis use and HIV-associated systemic inflammation and immune activation has not been well defined.
“Grossamide, a representative lignanamide in