Tag Archives: anti-inflammatory

Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC).

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“During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role.

For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages.

Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC).

Our results show a differential effect of alcohol and cannabinoids, which may provide insights into the divergent inflammatory role of alcohol and cannabinoids to modulate MDDC function in the context of HIV infection.”

http://www.ncbi.nlm.nih.gov/pubmed/26733986

http://www.thctotalhealthcare.com/category/hivaids/

Cannabinoid receptor-specific mechanisms to ameliorate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation.

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“Sickle cell anaemia is a manifestation of a single point mutation in haemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life.

Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice.

Morphine is the common analgesic treatment but also remains a major challenge due to the side effects and ability to activate mast cells. Therefore, we examined the cannabinoid receptor-specific mechanisms to ameliorate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor 2 deleted sickle mice.

We show that cannabinoids ameliorate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2.

Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice.

This study provides a “proof of principle” for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anaemia.”

Oxyradical Stress, Endocannabinoids, and Atherosclerosis.

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“Atherosclerosis is responsible for most cardiovascular disease (CVD) and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation.

Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression.

Overactive NADPH oxidase (Nox) produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS) have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress.

In addition to inflammation and ROS, the endocannabinoid system (eCB) is also important in atherogenesis.

Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis.

For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects.

The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ) is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG).

Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress.

This review will highlight the role of reactive oxygen species (ROS) in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis.

In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis.

We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology.”

http://www.ncbi.nlm.nih.gov/pubmed/26702404

http://www.thctotalhealthcare.com/category/atherosclerosis-2/

GPR55 – a putative “type 3” cannabinoid receptor in inflammation.

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“G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor.

Therefore, GPR55 has emerged as a putative “type 3″ cannabinoid receptor, establishing a novel class of cannabinoid receptor.

Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.”

 http://www.ncbi.nlm.nih.gov/pubmed/26669245

The endocannabinoid system as a target for the treatment of neuronal damage.

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“Cannabinoids have been proposed as clinically promising neuroprotective molecules, based on their capability to normalize glutamate homeostasis, reducing excitotoxicity, to inhibit calcium influx, lowering intracellular levels and the subsequent activation of calcium-dependent destructive pathways, and to reduce the generation of reactive oxygen intermediates or to limit their toxicity, decreasing oxidative injury.

Cannabinoids are also able to decrease local inflammatory events by acting on glial processes that regulate neuronal survival, and to restore blood supply by reducing vasocontriction produced by several endothelium-derived factors.

Treatment of neurodegenerative disorders is a challenge for neuroscientists and neurologists. Unhappily, the efficacy of available medicines is still poor and there is an urgent need for novel neuroprotective agents. Cannabinoids can serve this purpose given their recognized antiexcitotoxic, antioxidant and anti-inflammatory properties.”

http://www.ncbi.nlm.nih.gov/pubmed/20230193

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

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“Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques.

Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques.

Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques.

This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group.”

The disease-modifying effects of a Sativex-like combination of phytocannabinoids in mice with experimental autoimmune encephalomyelitis are preferentially due to Δ9-tetrahydrocannabinol acting through CB1 receptors.

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“Sativex®, an equimolecular combination of Δ9-tetrahydrocannabinol-botanical drug substance (Δ9-THC-BDS) and cannabidiol-botanical drug substance (CBD-BDS), is a licensed medicine that may be prescribed for alleviating specific symptoms of multiple sclerosis (MS) such as spasticity and pain.

However, further evidence suggest that it could be also active as disease-modifying therapy given the immunomodulatory, anti-inflammatory and cytoprotective properties of their two major components.

In this study, we investigated this potential in the experimental autoimmune encephalitis (EAE) model of MS in mice.

We compared the effect of a Sativex-like combination of Δ9-THC-BDS (10mg/kg) and CBD-BDS (10mg/kg) with Δ9-THC-BDS (20mg/kg) or CBD-BDS (20mg/kg) administered separately by intraperitoneal administration to EAE mice.

Treatments were initiated at the time that symptoms appear and continued up to the first relapse of the disease.

The results show that the treatment with a Sativex-like combination significantly improved the neurological deficits typical of EAE mice, in parallel with a reduction in the number and extent of cell aggregates present in the spinal cord which derived from cell infiltration to the CNS.

These effects were completely reproduced by the treatment with Δ9-THC-BDS alone, but not by CBD-BDS alone which only delayed the onset of the disease without improving disease progression and reducing the cell infiltrates in the spinal cord.

Next, we investigated the potential targets involved in the effects of Δ9-THC-BDS by selectively blocking CB1 or PPAR-γ receptors, and we found a complete reversion of neurological benefits and the reduction in cell aggregates only with rimonabant, a selective CB1 receptor antagonist.

Collectively, our data support the therapeutic potential of Sativex as a phytocannabinoid formulation capable of attenuating EAE progression, and that the active compound was Δ9-THC-BDS acting through CB1 receptors.”

Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative Colitis.

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“Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease are chronic relapsing and remitting chronic diseases for which there is no cure.

The treatment of IBD frequently requires immunosuppressive and biologic therapies which carry an increased risk of infections and possible malignancy.

There is a continued search for safer and more natural therapies in the treatment of IBD.

This review aims to summarize the most current literature on the use of dietary supplements for the treatment of IBD. Specifically, the efficacy and adverse effects of vitamin D, fish oil, probiotics, prebiotics, curcumin, Boswellia serrata, aloe vera and cannabis sativa are reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/26561079

Seeing over the horizon – targeting the endocannabinoid system for the treatment of ocular disease.

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“The observation that marijuana reduces intraocular pressure was made by Hepler and Frank in the 1970s. Since then, there has been a significant body of work investigating cannabinoids for their potential use as therapeutics.

To date, no endocannabinoid system (ECS)-modulating drug has been approved for clinical use in the eye; however, recent advances in our understanding of the ECS, as well as new pharmacological tools, has renewed interest in the development of ocular ECS-based therapeutics.

This review summarizes the current state-of-affairs for the use of ECS-modulating drugs for the treatment of glaucoma and ocular inflammatory and ischemic disease.”

http://www.ncbi.nlm.nih.gov/pubmed/26565550

The neuroprotection of cannabidiol against MPP+-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson’s disease.

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“Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa with potential to treat neurodegenerative diseases.

Its neuroprotection has been mainly associated with anti-inflammatory and antioxidant events; however, other mechanisms might be involved.

We investigated the involvement of neuritogenesis, NGF receptors (trkA), NGF, and neuronal proteins in the mechanism of neuroprotection of CBD against MPP+ toxicity in PC12 cells…

This is the first study to report the involvement of neuronal proteins and trkA in the neuroprotection of CBD.

Our findings suggest that CBD has a neurorestorative potential independent of NGF that might contribute to its neuroprotection against MPP+, a neurotoxin relevant to Parkinson’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/26556726