Tag Archives: anti-inflammatory

Regulation of neuroinflammation by herbal medicine and its implications for neurodegenerative diseases. A focus on traditional medicines and flavonoids.

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“Herbal medicine has long been used to treat neural symptoms. Although the precise mechanisms of action of herbal drugs have yet to be determined, some of them have been shown to exert anti-inflammatory and/or anti-oxidant effects in a variety of peripheral systems.

 Now, as increasing evidence indicates that neuroglia-derived chronic inflammatory responses play a pathological role in the central nervous system, anti-inflammatory herbal medicine and its constituents are being proved to be a potent neuroprotector against various brain pathologies.

 Structural diversity of medicinal herbs makes them valuable source of novel lead compounds against therapeutic targets that are newly discovered by genomics, proteomics, and high-throughput screening.”

http://www.ncbi.nlm.nih.gov/pubmed/15956812

Anti-inflammatory property of the cannabinoid receptor-2-selective agonist JWH-133 in a rodent model of autoimmune uveoretinitis.

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“Previous studies have shown that cannabinoids have anti-inflammatory and immune-modulating effects, but the precise mechanisms of action remain to be elucidated.

In this study, we investigated the effect of JWH 133, a selective agonist for cannabinoid receptor 2, the main receptor expressed on immune cells, in a model of autoimmune disease, experimental autoimmune uveoretinitis (EAU).

JWH 133 suppressed EAU in a dose-dependent manner (0.015-15 mg/kg), and the suppressive effect could be achieved in the disease-induction stage and the effector stage. Leukocytes from mice, which had been treated with JWH 133, had diminished responses to retinal peptide and mitogen Con A stimulation in vitro. In vivo JWH 133 treatment also abrogated leukocyte cytokine/chemokine production. Further in vitro studies indicated that JWH 133 down-regulated the TLR4 via Myd88 signal transduction, which may be responsible for its moderate, suppressive effect on antigen presentation. In vivo JWH 133 treatment (1 mg/kg) also suppressed leukocyte trafficking (rolling and infiltration) in inflamed retina as a result of an effect on reducing adhesion molecules CD162 (P-selectin glycoprotein ligand 1) and CD11a (LFA-1) expression on T cells.

In conclusion, the cannabinoid agonist JWH 133 has a high in vivo, anti-inflammatory property and may exert its effect via inhibiting the activation and function of autoreactive T cells and preventing leukocyte trafficking into the inflamed tissue.”

Full text: http://www.jleukbio.org/content/82/3/532.long

1′,1′-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties.

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“Chemical structures of Δ-9-THC (dronabinol), nabilone, and CT-3”

Figure 1

“1′,1′-Dimethylheptyl-Delta-8-tetrahydrocannabinol-11-oic acid (CT-3) is a novel cannabinoid that is under development by Atlantic Pharmaceuticals as an anti-inflammatory and analgesic drug.

The objective of the study was to investigate the effects of CT-3 on overt symptom complex (Irwin’s test), nociception, gastrointestinal (GI) ulceration, and pharmacological availability after intragastric (i.g.) and intraperitoneal (i.p.) administration.

  The evidence indicates that CT-3 exhibits a large dissociation between its anti-inflammatory/analgesic effects and its ulcerogenic actions. CT-3 warrants clinical development as a novel anti-inflammatory and analgesic drug.”

Full text: http://jpet.aspetjournals.org/content/291/1/31.long

WIN55212-2 attenuates amyloid-beta-induced neuroinflammation in rats through activation of cannabinoid receptors and PPAR-γ pathway.

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“Cannabinoids have been shown to exert neuroprotective effects in a plethora of neurodegenerative conditions.

Over the past decade, some studies demonstrate that cannabinoids can interact with nuclear peroxisome proliferator-activated receptors (PPARs).We investigated protective properties of WIN55212-2 (WIN, a non-selective cannabinoid receptor agonist) in beta-amyloid (Aβ)-induced neurodegeneration in rat hippocampus and possible involvement of PPAR-gamma (PPAR-γ). Aβ (1-42) was injected into the hippocampus of male rats. Animals were administered by intracerebroventricular rout the following treatments on days 1, 3, 5, 7: vehicle, WIN, GW9662 (selective PPAR-γ antagonist) plus WIN, AM251 (selective CB₁ receptor antagonist) plus WIN, SR144528 (selective CB₂ receptor antagonist) plus WIN, each of antagonists alone. Injection of Aβ-induced spatial memory impairment and a dramatic rise in hippocampal TNF-α, active caspase 3, nuclear NF-kB levels and TUNEL-positive neurons. WIN administration significantly improved memory function and diminished the elevated levels of these markers, while antagonizing either CB₁ or CB₂ receptor subtype partially attenuated the protective effects. Intriguingly, WIN significantly increased PPAR-γ level and transcriptional activity, the latter being partially inhibited with AM251 but not with SR144528. The enhancing effect on PPAR-γ pathway was crucial to WIN-induced neuroprotection since GW9662 partially reversed the beneficial actions of WIN. Co-administration of the three antagonists led to the complete abrogation of WIN effects.

Our findings indicate that WIN exerts neuroprotective and anti-inflammatory actions against Aβ damage through both CB₁ and CB₂ receptors. Of great note, both direct and CB₁-mediated increase in PPAR-γ signaling also contributes to WIN-induced neuroprotection.”

http://www.ncbi.nlm.nih.gov/pubmed/22634229

The role of CB1 in immune modulation by cannabinoids.

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“There is clear evidence that CB(2), historically referred to as the peripheral cannabinoid receptor, mediates many of the immune modulatory effects of cannabinoids.

 However, cannabinoid receptors cannot be classified simply as central or peripheral since CB(2) has been shown to play a role in the central nervous system (CNS) and CB(1) mediates many immune system effects. Although Cnr1 mRNA and CB(1) protein expression is lower than Cnr2 mRNA or CB(2) protein expression in cells of the immune system, several studies have shown direct modulation of immune function via CB(1) by endogenous and exogenous cannabinoids in T cells, innate cells, and to a lesser extent, B cells.

In addition, indirect, but CB(1)-dependent, mechanisms of immune modulation exist. In fact, the mechanism by which cannabinoids attenuate neuroinflammation via CB(1) is likely a combination of immune suppression and neuroprotection.

 Although many studies demonstrate that agonists for CB(1) are immune suppressive and anti-inflammatory, CB(1) antagonists also exhibit anti-inflammatory properties. Overall, the data demonstrate that many of the immune modulatory effects of cannabinoids are mediated via CB(1).”

http://www.ncbi.nlm.nih.gov/pubmed/23261520

Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions.

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“Previous studies have shown that modulation of the receptor-mediated cannabinoid system during neuroinflammation can produce potent neuroprotective and anti-inflammatory effects

…Together, these results suggest that pharmacological CB2R ligands offer a new strategy for BBB protection during neuroinflammation.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325902/

Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation.

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“There is now a large body of data indicating that the cannabinoid receptor type 2 (CB2) is linked to a variety of immune events. This functional relevance appears to be most salient in the course of inflammation, a process during which there is an increased number of receptors that are available for activation. Studies aimed at elucidating signal transduction events resulting from CB2 interaction with its native ligands, and of the role of exogenous cannabinoids in modulating this process, are providing novel insights into the role of CB2 in maintaining a homeostatic immune balance within the host. Furthermore, these studies suggest that the CB2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses, including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768535/

HIV Infection Weakened By Marijuana: Study Shows Cannabis Helps Synthetic Anti-inflammatory Substances

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“Researchers discovered that the synthetic anti-inflammatory substances distantly related to the active ingredient of marijuana may be able to weaken the most common strain of HIV while inside one of its major hideouts, the immune cells known as macrophages.”

HIV REsearch

“Despite drug therapy, HIV is notorious for hiding within certain types of cells, where it reproduces at a slower rate and eventually gives rise to chronic inflammation.

A study done by researchers at Temple University School of Medicine’s Department of Pathology and Laboratory Medicine(TUSM) and Center for Substance Abuse Research discovered that the synthetic anti-inflammatory substances distantly related to the active ingredient of marijuana may be able to weaken the most common strain of HIV while inside one of its major hideouts, the immune cells known as macrophages.”

More: http://www.beautyworldnews.com/articles/3589/20130502/hiv-infection-weakened-marijuana-study-shows-cannabis-helps-synthetic-anti.htm

Researchers Have Discovered Synthetic Agents Used To Treat HIV Inflammation – Medical News Today

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“HIV can cause serious inflammation, regardless of drug therapy, as it develops slowly in immune cells called macrophages. However, new research conducted at the Temple University School of Medicine’s Department of Pathology and Laboratory Medicine and Center for Substance Abuse Research (CSAR) has just found that there are synthetic agents with anti-inflammatory properties, related to the active ingredient in cannabis, THC (tetrahydrocannabinol) which could limit and treat the chronic inflammation.

These findings suggest that CB2 agonists could be used along with antiretroviral drugs which could lead to a new form of therapy for HIV/AIDS.

It also suggests that the human immune system itself could be used to fight off the HIV infection.

According to Persidsky: “Our study suggests that the body’s own natural defenses can be made more powerful to fight some of the worst symptoms of HIV.”

Stimulating CB2 receptors could also be applied for treating other infections.”

More: http://www.medicalnewstoday.com/articles/260152.php

Acute Δ9-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice.

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“Nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most widely used analgesics in the world, cause gastrointestinal inflammation that is potentially life-threatening.

Although inhibitors of endocannabinoid catabolic enzymes protect against gastropathy in fasted NSAID-treated mice, the gastroprotective effects of Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, have yet to be investigated…

 These data indicate that the phytocannabinoid Δ9-THC protects against diclofenac-induced gastric inflammatory tissue damage at doses insufficient to cause common cannabinoid side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/23769745