Tag Archives: anti-inflammatory

Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells.

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“Apart from their effects on mood and reward, cannabinoids exert beneficial actions such as neuroprotection and attenuation of inflammation. The immunosuppressive activity of cannabinoids has been well established. We previously showed that the psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signalling pathways.

CONCLUSIONS AND IMPLICATIONS:

These observations indicated that CBD, but much less than THC, induced a cellular stress response in microglial cells and suggested that this effect could underlie its anti-inflammatory activity.”

http://www.ncbi.nlm.nih.gov/pubmed/21542829

Cannabinoids Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells

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“Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. Δ9-Tetrahydrocannabinol (THC)is a major constituent of Cannabis and serves as an agonist of the cannabinoid receptors CB1 and CB2.

The second major constituent of Cannabis extract is cannabidiol (CBD). CBD lacks the psychoactive effects that accompany the use of THC. Moreover, CBD was demonstrated to antagonize some undesirable effects of THC, including intoxication, sedation, and tachycardia, while sharing neuroprotective, anti-oxidative, anti-emetic, and anti-carcinogenic properties. Both THC and CBD have been shown to exert anti-inflammatory properties and to modulate the function of immune cells…

In summary, our results show that although both THC and CBD exert anti-inflammatory effects, the two compounds engage different, although to some extent overlapping, intracellular pathways. Both THC and CBD decrease the activation of proinflammatory signaling…

 The cannabinoids by moderating or disrupting these signaling networks may show promise as anti-inflammatory agents.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804319/

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

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“The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress.

 Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

CB1 receptor is a useful pharmacological target for treating PD and other disorders associated with neuroinflammation and microglia-derived oxidative damage. ”

http://www.jimmunol.org/content/187/12/6508.long

Alzheimer’s disease and inflammation: a review of cellular and therapeutic mechanisms.

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“1. Of the neurodegenerative diseases that cause dementia, Alzheimer’s disease (AD) is the most common. Three major pathologies characterize the disease: senile plaques, neurofibrillary tangles and inflammation. We review the literature on events contributing to the inflammation and the treatments thought to target this pathology. 2. The senile plaques of AD consist primarily of complexes of the beta-amyloid protein. This protein is central to the pathogenesis of the disease. 3. Inflammatory microglia are consistently associated with senile plaques in AD, although the classic inflammatory response (immunoglobulin and leucocyte infiltration) is absent. beta-Amyloid fragments appear to mediate such inflammatory mechanisms by activating the complement pathway in a similar fashion to immunoglobulin. 4. Epidemiological studies have identified a reduced risk of AD in patients with arthritis and in leprosy patients treated with anti-inflammatory drugs. Longitudinal studies have shown that the consumption of anti-inflammatory medications reduces the risk of AD only in younger patients (< 75 years). 5. There is a considerable body of in vitro evidence indicating that the inflammatory response of microglial cells is reduced by non-steroidal anti-inflammatory drugs (NSAID). However, no published data are available concerning the effects of these medications on brain pathology in AD. 6. Cyclo-oxygenase 2 enzyme is constitutively expressed in neurons and is up-regulated in degenerative brain regions in AD. Non-steroidal anti-inflammatory drugs may reduce this expression. 7. Platelets are a source of beta-amyloid and increased platelet activation and increased circulating beta-amyloid have been identified in AD. Anti-platelet medication (including NSAID) would prevent such activation and its potentially harmful consequences. 8. Increased levels of luminal beta-amyloid permeabilizes the blood-brain barrier (BBB) and increases vasoconstriction of arterial vessels, paralleling the alterations observed with infection and inflammation. Cerebral amyloidosis is highly prevalent in AD, compromising the BBB and vasoactivity.

Anti-inflammatory medications may alleviate these problems.”

http://www.ncbi.nlm.nih.gov/pubmed/10696521

Distribution patterns of cannabinoid CB1 receptors in the hippocampus of APPswe/PS1ΔE9 double transgenic mice.

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Abstract

“Cannabinoids have neuroprotective effects that are exerted primarily through cannabinoid CB1 receptors in the brain. This study characterized CB1 receptor distribution in the double transgenic (dtg) APP(swe)/PS1(ΔE9) mouse model for Alzheimer’s disease. Immunohistochemical labeling of CB1 protein in non-transgenic mice revealed that CB1 was highly expressed in the hippocampus, with the greatest density of CB1 protein observed in the combined hippocampal subregions CA2 and CA3 (CA2/3). CB1 immunoreactivity in the CA1 and CA2/3 hippocampal regions was significantly decreased in the dtg APP(swe)/PS1(ΔE9) mice compared to non-transgenic littermates. Reduced CB1 expression in dtg APP(swe)/PS1(ΔE9) mice was associated with astroglial proliferation and elevated expression of the cytokines inducible nitric oxide synthase and tumor necrosis factor alpha. This finding suggests an anti-inflammatory effect of cannabinoids that is mediated by CB1 receptor, particularly in the CA2/3 region of the hippocampus. Furthermore, the study suggests a decreased CB1 receptor expression may result in diminished anti-inflammatory processes, exacerbating the neuropathology associated with Alzheimer’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/21192920

Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity

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“Creutzfeldt–Jakob disease (CJD) in humans belongs to a group of fatal neurodegenerative disorders called transmissible spongiform encephalopathies (TSEs) or prion diseases. No therapeutic treatments against TSEs are currently available. The urgent need to find effective anti-prion therapies has been strengthened by the emergence of variant CJD (vCJD) caused by contaminated beef consumption …

Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection. When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug.

Overall, CBD is a promising therapeutic drug against the TSEs because it combines several crucial characteristics. It has a low toxicity and lack of psychotropic side effects as well as in vivo neuroprotective, anti-inflammatory, and anti-PrPres properties. Because CBD easily crosses the BBB, it also has the potential to be effective after prion infection has reached the CNS. Finally, prolonged treatments with CBD do not induce tolerance, a phenomenon frequently observed with THC. Additional investigations should be performed to define the optimal dose, route, frequency, and duration of the in vivo CBD treatment necessary to prevent TSE infection…”

http://www.jneurosci.org/content/27/36/9537.full

The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells.

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“Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. A massive accumulation of beta-amyloid (Abeta) peptide aggregates has been proposed as pivotal event in AD. Abeta-induced toxicity is accompanied by a variegated combination of events including oxidative stress… Cannabidiol, a non-psychoactive marijuana component, has been recently proposed as an antioxidant neuroprotective agent in neurodegenerative diseases. Moreover, it has been shown to rescue PC12 cells from toxicity induced by Abeta peptide. Here, we report that cannabidiol inhibits hyperphosphorylation of tau protein in Abeta-stimulated PC12 neuronal cells, which is one of the most representative hallmarks in AD… These results provide new molecular insight regarding the neuroprotective effect of cannabidiol and suggest its possible role in the pharmacological management of AD, especially in view of its low toxicity in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/16389547

 

Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement.

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“In view of the pro-inflammatory scenario observed in Alzheimer’s disease, in the recent years anti-inflammatory drugs have been proposed as potential therapeutic agents. We have previously shown that cannabidiol, the main non-psychotropic component from Cannabis sativa, possess a variegate combination of anti-oxidant and anti-apoptotic effects that protect PC12 cells from Abeta toxicity. In parallel, cannabidiol has been described to have anti-inflammatory properties in acute models of inflammation …

The here reported data increases our knowledge about the possible neuroprotective mechanism of cannabidiol, highlighting the importance of this compound to inhibit beta-amyloid induced neurodegeneration, in view of its low toxicity in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/16490313

Effects of cannabinoids on the immune system and central nervous system: therapeutic implications.

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“Cannabinoids possess immunomodulatory activity, are neuroprotective in vivo and in vitro and can modify the production of inflammatory mediators… Cannabinoid-induced immunosuppression may have implications for the treatment of neurological disorders that are associated with excess immunological activity, such as multiple sclerosis and Alzheimer’s disease. There is anecdotal evidence that cannabis use improves the symptoms of multiple sclerosis, and studies with animal models are beginning to provide evidence for the mechanism of such effects. The development of nonpsychotropic cannabinoid analogues and modulators of the metabolism of endogenous cannabinoid ligands may lead to novel approaches to the treatment of neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/18031185

Microglial interaction with beta-amyloid: implications for the pathogenesis of Alzheimer’s disease.

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Abstract

“The etiology of Alzheimer’s disease (AD) involves a significant inflammatory component as evidenced by the presence of elevated levels of a diverse range of proinflammatory molecules in the AD brain. These inflammatory molecules are produced principally by activated microglia, which are found to be clustered within and adjacent to the senile plaque. Moreover, long-term treatment of patients with non-steroidal anti-inflammatory drugs has been shown to reduce risk and incidence of AD and delay disease progression. The microglia respond to beta-amyloid (Abeta) deposition in the brain through the interaction of fibrillar forms of amyloid with cell surface receptors, leading to the activation of intracellular signal transduction cascades. The activation of multiple independent signaling pathways ultimately leads to the induction of proinflammatory gene expression and production of reactive oxygen and nitrogen species. These microglial inflammatory products act in concert to produce neuronal toxicity and death. Therapeutic approaches focused on inhibition of the microglial-mediated local inflammatory response in the AD brain offer new opportunities to intervene in the disease.”

http://www.ncbi.nlm.nih.gov/pubmed/11455613