Tag Archives: anti-inflammatory

Cannabinoid Modulation of Cutaneous Aδ Nociceptors During Inflammation

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“Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB1 and CB2).

These results suggest that attenuation of mechanically evoked responses of Aδ nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB1 receptors during inflammation.

Several studies have demonstrated that locally administered cannabinoids produce antinociception in animal models of both acute and persistent pain through peripheral mechanisms.

Taken together, our data suggest that peripherally acting cannabinoids could be a potential therapeutic treatment for chronic inflammatory pain.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585399/

 

Cannabinoid receptors in microglia of the central nervous system: immune functional relevance.

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“Microglia, resident macrophages of the brain, function as immune effector and accessory cells. Paradoxically, they not only play a role in host defense and tissue repair but also have been implicated in a variety of neuropathological processes.

Microglia, in addition to exhibiting phenotypic markers for macrophages, express CB1 and CB2 cannabinoid receptors. Recent studies suggest the existence of a third, yet-to-be cloned, non-CB1, non-CB2 cannabinoid receptor.

These receptors appear to be functionally relevant within defined windows of microglial activation state and have been implicated as linked to cannabinoid modulation of chemokine and cytokine expression.

The recognition that microglia express cannabinoid receptors and that their activation results in modulation of select cellular activities suggests that they may be amenable to therapeutic manipulation for ablating untoward inflammatory responses in the central nervous system.”  http://www.ncbi.nlm.nih.gov/pubmed/16204639

http://www.jleukbio.org/content/78/6/1192.long

 

Role of CB1 and CB2 receptors in the inhibitory effects of cannabinoids on lipopolysaccharide-induced nitric oxide release in astrocyte cultures.

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“The purpose of this study was to investigate the role of the central cannabinoid receptor (CB(1)) in mediating the actions of the endogenous cannabinoid agonist anandamide and the synthetic cannabinoid CP-55940.

Activation of primary mouse astrocyte cultures by exposure to bacterial lipopolysaccharide (LPS) caused a marked (approximately tenfold) increase in nitric oxide (NO) release.

Coincubation with the cannabinoid agonists anandamide or CP-55940 markedly inhibited release of NO (-12% to -55%).

We also showed that endogenous or synthetic cannabinoids inhibit LPS-induced inducible NO synthase expression (mRNA and protein) in astrocyte cultures.

These results indicate that CB1 receptors may promote antiinflammatory responses in astrocytes.”

http://www.ncbi.nlm.nih.gov/pubmed/11891798

Cannabinoid-mediated inhibition of inducible nitric oxide production by rat microglial cells: evidence for CB1 receptor participation.

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“Activated brain microglial cells release inflammatory mediators such as nitric oxide (NO) that may play important roles in central nervous system antibacterial, antiviral, and antitumor activities. However, excessive release of these factors has been postulated to elicit immune-mediated neurodegenerative inflammatory processes and to cause brain injury.

Recent studies using the rat animal model indicate that select cannabinoids may modulate production of these inflammatory factors.

Collectively, these results indicate that the cannabinoid analog CP55940 selectively inhibits inducible NO production by microglial cells and that this inhibition is effected, at least in part, through the CB1 receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/11727767

The central cannabinoid receptor (CB1) mediates inhibition of nitric oxide production by rat microglial cells.

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Journal of Pharmacology and Experimental Therapeutics

“Upon activation, brain microglial cells release proinflammatory mediators, such as nitric oxide (NO), which may play an important role in the central nervous system antibacterial, antiviral, and antitumor activities. However, excessive release of NO has been postulated to elicit immune-mediated neurodegenerative inflammatory processes and to cause brain injury.

In the present study, the effect of cannabinoids on the release of NO from endotoxin/cytokine-activated rat cortical microglial cells was evaluated.

Collectively, these results indicate a functional linkage between the CB1 receptor and cannabinoid-mediated inhibition of NO production by rat microglial cells.”

http://www.ncbi.nlm.nih.gov/pubmed/10027878

“In summary, this study reports on CB1 receptor expression in a primary immune cell type in the context of functional relevance. That is, the data support a linkage between the CB1 receptor as expressed in brain microglial cells and the inhibition of NO.
These results expand on our current knowledge concerning the role of cannabinoid receptors in the modulation of immune cell function as, to date, the CB2 receptor has been the only cannabinoid receptor subtype implicated in cannabinoid-mediated immune modulation.
These data suggest also that select cannabinoid agonists have the potential to ablate the elicitation of proinflammatory mediators especially under conditions of chronic neuropathological disease.”
http://jpet.aspetjournals.org/content/288/3/1357.long

Cannabinoids ablate release of TNFalpha in rat microglial cells stimulated with lypopolysaccharide.

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“Upon activation, brain microglial cells release proinflammatory mediators, such as TNFalpha, which may play an important role in eliciting neuroinflammatory processes causing brain damage.

As cannabinoids have been reported to exert anti-inflammatory and neuroprotective actions in the brain, we here examined the effect of both synthetic and endogenous cannabinoids on TNFalpha release elicited by bacterial endotoxin lypopolysaccharide (LPS) in cultured microglia.

In summary, our data indicate that both synthetic and endogenous cannabinoids inhibit LPS-induced release of TNFalpha from microglial cells.

By showing that such effect does not appear to be mediated by either CB receptor type 1 or 2, we provide evidence suggestive of the existence of yet unidentified cannabinoid receptor(s) in brain microglia.”

http://www.ncbi.nlm.nih.gov/pubmed/12509806

Cannabinoids, inflammation, and fibrosis.

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“Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs).

As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis.

A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ9-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented.

Mention is also made of the noncannabinoid plant components and pyrolysis products, followed by a discussion of 3 synthetic preparations-Cesamet (nabilone; Meda Pharmaceuticals, Somerset, NJ, USA), Marinol (THC; AbbVie, Inc., North Chicago, IL, USA), and Sativex (Cannabis extract; GW Pharmaceuticals, Cambridge United Kingdom)-that have anti-inflammatory effects. A fourth synthetic cannabinoid, ajulemic acid (CT-3, AJA; Resunab; Corbus Pharmaceuticals, Norwood, MA, USA), is discussed in greater detail because it represents the most recent advance in this area and is currently undergoing 3 phase 2 clinical trials by Corbus Pharmaceuticals.

The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed. The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances.

Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents. Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.”

http://www.ncbi.nlm.nih.gov/pubmed/27435265

Protective effect of cannabidiol on hydrogen peroxide‑induced apoptosis, inflammation and oxidative stress in nucleus pulposus cells.

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“Cannabidiol, a major component of marijuana, protects nerves, and exerts antispasmodic, anti-inflammatory and anti‑anxiety effects.

In the current study, the protective effect of cannabidiol was observed to prevent hydrogen peroxide (H2O2)‑induced apoptosis, inflammation and oxidative stress in nucleus pulposus cells.

Taken together, these results suggest that cannabidiol potentially exerts its protective effect on LDH via the suppression of anti‑apoptosis, anti‑inflammation and anti‑oxidative activities in nucleus pulposus cells.”

http://www.ncbi.nlm.nih.gov/pubmed/27430346

VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease.

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“Cannabinoids have shown to exert neuroprotective actions in animal models by acting at different targets including canonical cannabinoid receptors and PPARγ.

We previously showed that VCE-003, a cannabigerol (CBG) quinone derivative, is a novel neuroprotective and anti-inflammatory cannabinoid acting through PPARγ. We have now generated a non-thiophilic VCE-003 derivative named VCE-003.2 that preserves the ability to activate PPARγ and analyzed its neuroprotective activity.

This compound exerted a prosurvival action in progenitor cells during neuronal differentiation, which was prevented by a PPARγ antagonist, without affecting neural progenitor cell proliferation. In addition, VCE-003.2 attenuated quinolinic acid (QA)-induced cell death and caspase-3 activation and also reduced mutant huntingtin aggregates in striatal cells.

The neuroprotective profile of VCE-003.2 was analyzed using in vivo models of striatal neurodegeneration induced by QA and 3-nitropropionic acid (3NP) administration. VCE-003.2 prevented medium spiny DARPP32(+) neuronal loss in these Huntington’s-like disease mice models improving motor deficits, reactive astrogliosis and microglial activation. In the 3NP model VCE-003.2 inhibited the upregulation of proinflammatory markers and improved antioxidant defenses in the brain.

These data lead us to consider VCE-003.2 to have high potential for the treatment of Huntington’s disease (HD) and other neurodegenerative diseases with neuroinflammatory traits.”

http://www.ncbi.nlm.nih.gov/pubmed/27430371

Expression of the Endocannabinoid Receptor 1 in Human Stroke: An Autoptic Study.

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“Stroke is one of the leading causes of disability and death in the world.

The endocannabinoid (eCB) system is upregulated in several neurological diseases including stroke. A previous animal study demonstrated an increased expression of the endocannabinoid receptor 1 (CB1R) in the penumbra area surrounding the ischemic core, suggesting a crucial role in inflammation/reperfusion after stroke. Regarding the localization of CB1/CB2 receptors, animal studies showed that cortical neurons, activated microglia, and astroglia are involved. Our aim was to evaluate the cerebral expression of CB1R in the ischemic brain areas of 9 patients who died due to acute cerebral infarction in the middle cerebral artery territory.

METHODS:

The cerebral autoptic tissue was collected within 48 hours since death. Ischemic and contralateral normal-appearing areas were identified. After tissue preprocessing, 4-µm-thick cerebral sections were incubated with the primary CB1R antibodies (Cayman Chemical Company, Ann Arbor, MI). Thereafter, all cerebral sections were hematoxylin treated. In each section, the total cell number and CB1R-positive cells were counted and the CB1R-positive cell count ratio was calculated. For statistical analysis, Student’s t-test was used.

RESULTS:

In normal tissue, CB1R-positive neurons were the majority; a few non-neuronal cells expressed CB1R. In the ischemic areas, a few neurons were detectable. A significant increase in total CB1R staining was found in the ischemic regions compared to contralateral areas.

CONCLUSIONS:

We found an increase in CB1R expression in the ischemic region (neuronal and non-neuronal cell staining), suggesting the inflammatory reaction to the ischemic insult. Whether such response might mediate neuroprotective actions or excitotoxicity-related detrimental effects is still unclear.”

http://www.ncbi.nlm.nih.gov/pubmed/27425766