Tag Archives: anti-inflammatory

Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrheic skin and acne treatment.

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“Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands.

We have previously shown that a non-psychotropic phytocannabinoid ((-)-cannabidiol [CBD]) exerted complex anti-acne effects by normalizing “pro-acne agents”-induced excessive sebaceous lipid production, reducing proliferation and alleviating inflammation in human SZ95 sebocytes.

Therefore, in the current study we aimed to explore the putative anti-acne effects of further non-psychotropic phytocannabinoids ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], (-)-cannabigerol [CBG], (-)-cannabigerovarin [CBGV] and (-)-Δ9 -tetrahydrocannabivarin [THCV]).

Viability and proliferation of human SZ95 sebocytes were investigated by MTT- and CyQUANT-assays; cell death and lipid synthesis were monitored by DilC1 (5)-SYTOX Green labelling and Nile Red staining, respectively. Inflammatory responses were investigated by monitoring expressions of selected cytokines upon lipopolysaccharide treatment (RT-qPCR, ELISA). Up to 10 μM, the phytocannabinoids only negligibly altered viability of the sebocytes, whereas high doses (≥50 μM) induced apoptosis.

Interestingly, basal sebaceous lipid synthesis was differentially modulated by the substances: CBC and THCV suppressed it, CBDV had only minor effects, whereas CBG and CBGV increased it.

Importantly, CBC, CBDV and THCV significantly reduced arachidonic acid (AA)-induced “acne-like” lipogenesis.

Moreover, THCV suppressed proliferation, and all phytocannabinoids exerted remarkable anti-inflammatory actions.

Our data suggest that CBG and CBGV may have potential in the treatment of dry-skin syndrome, whereas CBC, CBDV and especially THCV show promise to become highly efficient, novel anti-acne agents.

Moreover, based on their remarkable anti-inflammatory actions, phytocannabinoids could be efficient, yet safe novel tools in the management of cutaneous inflammations.”

http://www.ncbi.nlm.nih.gov/pubmed/27094344

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

The multiplicity of action of cannabinoids: implications for treating neurodegeneration.

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“The cannabinoid (CB) system is widespread in the central nervous system and is crucial for controlling a range of neurophysiological processes such as pain, appetite, and cognition. The endogenous CB molecules, anandamide, and 2-arachidonoyl glycerol, interact with the G-protein coupled CB receptors, CB(1) and CB(2).

These receptors are also targets for the phytocannabinoids isolated from the cannabis plant and synthetic CB receptor ligands.

The CB system is emerging as a key regulator of neuronal cell fate and is capable of conferring neuroprotection by the direct engagement of prosurvival pathways and the control of neurogenesis.

Many neurological conditions feature a neurodegenerative component that is associated with excitotoxicity, oxidative stress, and neuroinflammation, and certain CB molecules have been demonstrated to inhibit these events to halt the progression of neurodegeneration.

Such properties are attractive in the development of new strategies to treat neurodegenerative conditions of diverse etiology, such as Alzheimer’s disease, multiple sclerosis, and cerebral ischemia.

This article will discuss the experimental and clinical evidence supporting a potential role for CB-based therapies in the treatment of certain neurological diseases that feature a neurodegenerative component.”

http://www.ncbi.nlm.nih.gov/pubmed/20875047

An update on peroxisome proliferator-activated receptor (PPAR) activation by cannabinoids.

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“Some cannabinoids activate the different isoforms of peroxisome proliferator-activated receptors (PPARs; α, β and γ), as shown through the use of reporter gene assays, binding studies, selective antagonists and knockout studies.

Activation of all isoforms, but primarily PPARα and γ, mediate some (but not all) of the analgesic, neuroprotective, neuronal function modulation, anti-inflammatory, metabolic, anti-tumoral, gastrointestinal and cardiovascular effects of some cannabinoids, often in conjunction with activation of the more traditional target sites of action such as CB1 , CB2 and TRPV1.

PPARs also mediate some of the effects of inhibitors of endocannabinoid degradation or transport. Cannabinoids may be chaperoned to the PPARs by fatty acid binding proteins (FABPs).

The aim of this review is to update the evidence supporting PPAR activation by cannabinoids, and review the physiological responses to cannabinoids that are mediated, and not mediated, by PPAR activation.”

http://www.ncbi.nlm.nih.gov/pubmed/27077495

Synthesis and pharmacological evaluation of new biphenylic derivatives as CB2 receptor ligands.

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“Targeting type-2 cannabinoid receptor (CB2) is considered a feasible strategy to develop new drugs for the treatment of diseases like neuropathic pain, chronic inflammation, neurodegenerative disorders and cancer.

Such drugs are devoid of the undesired central side effects that are typically mediated by the CB1 receptor.

In this work we synthesized 18 biphenylic carboxamides as new CB2-selective ligands and evaluated their pharmacological profiles. The functional activity of these compounds is strongly influenced by the nature of the substituent at position 4′ and 5 of the biphenyl scaffold.

Position 5 seems to be responsible for the agonist or inverse agonist behaviour independently of the substituent in position 4′, with the exception of the methoxyl group which transforms both full agonists and inverse agonists into neutral antagonists.

This study provides a novel complete toolbox of CB2 functional modulators that derive from the same chemical scaffold. Such probes may be useful to investigate the biological role of CB2 receptors in cellular assays.”

http://www.ncbi.nlm.nih.gov/pubmed/27078864

Production of endocannabinoids by activated T cells and B cells modulates inflammation associated with delayed type hypersensitivity.

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“Endocannabinoids are endogenous ligands for the cannabinoid (CB) receptors which include anandamide (AEA) and (2-AG). 2-AG has been linked to inflammation due to its elevated expression in animal models of autoimmunity and hypersensitivity.

However, administration of exogenous 2-AG has been shown to suppress inflammation making its precise role unclear. In the current study, we investigated the role of 2-AG following immunization of C57BL/6 (BL6) mice with methylated BSA (mBSA) antigen, which triggers both delayed type hypersensitivity (DTH) and antibody response.

Together, these data show for the first time that activated T and B cells produce 2-AG, which plays a negative regulatory role to decrease DTH via inhibition of T-cell activation and proliferation.

Moreover, these findings suggest that exogenous 2-AG treatment can be used therapeutically in Th1- or Th17-driven disease.”  http://www.ncbi.nlm.nih.gov/pubmed/27064137

“∆9-Tetrahydrocannabinol (THC) is one of the major bioactive cannabinoids derived from the Cannabis sativa plant and is known for its anti-inflammatory properties. Delayed-type hypersensitivity (DTH) is driven by proinflammatory T helper cells including the classic inflammatory Th1 lineage as well as the more recently discovered Th17 lineage. In the current study, we investigated whether THC can alter the induction of Th1/Th17 cells involved in mBSA-induced DTH response… In summary, the current study suggests that THC treatment during DTH response can simultaneously inhibit Th1/Th17 activation via regulation of microRNA (miRNA) expression.• THC treatment inhibits simultaneous Th1/Th17 driven inflammation. • THC treatment corrects DTH-mediated microRNA dysregulation. • THC treatment regulates proinflammatory cytokines and transcription factors.” http://www.ncbi.nlm.nih.gov/pubmed/27038180

http://www.thctotalhealthcare.com/tag/anti-inflammatory/

Immunohistochemical analysis of cannabinoid receptor 1 expression in steatotic rat livers.

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“The primary aim of the present study was to determine the expression levels of cannabinoid receptor type 1 (CB1) in steatotic rat livers.  The secondary aim was to clarify whether steatosis and inflammation are more marked in areas with increased CB1 overexpression.

The expression of CB1 and the number of cells overexpressing CB1 were determined. Steatosis was scored according to the Dixon scoring system.

CB1 overexpression and steatosis were detected in hepatocytes from all 38 livers sampled. The expression of CB1 was more marked in hepatocytes localized next to portal triads. Near the central veins, the expression was significantly weaker. Steatosis was more marked in areas of increased CB1 overexpression. Lymphocyte infiltration was more commonly observed in areas of increased CB1 overexpression.

Therefore, the present results indicate that CB1 receptors are overexpressed in areas with steatosis, and indicate that CB1 in hepatocytes contributes to the formation of steatosis in rats, even prior to its progression to steatohepatitis.

These results are consistent with publications reporting that CB1 in hepatocytes increases lipogenesis and contributes to inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/27073427

http://www.thctotalhealthcare.com/category/liver-disease/

Analysis of endocannabinoid signaling elements and related proteins in lymphocytes of patients with Dravet syndrome.

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“Cannabidiol (CBD) reduces seizures in childhood epilepsy syndromes including Dravet syndrome (DS).

A formulation of CBD has obtained orphan drug designation for these syndromes and clinical trials are currently underway.

We believe of interest to investigate whether these potential targets are altered in DS, in particular whether the endocannabinoid system is dysregulated. To this end, lymphocytes from patients and controls were used for analysis of gene expression of transmitter receptors and transporters, ion channels, and enzymes associated with CBD effects, as well as endocannabinoid genes.

In conclusion, together with changes in the voltage-dependent calcium channel α-1h subunit, we found an upregulation of CB 2 receptors, associated with an activation of lymphocytes and changes in inflammation-related genes, in DS patients. Such changes were also reported in inflammatory disorders and may indirectly support the occurrence of a potential dysregulation of the endocannabinoid system in the brain.”

http://www.ncbi.nlm.nih.gov/pubmed/27069631

http://www.thctotalhealthcare.com/category/dravet-syndome/

Endocannabinoids and immune regulation

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“Cannabinoid pharmacology has made important advances in recent years after the discovery of the cannabinoid receptors.

These discoveries have added to our understanding of exogenous and endogenous cannabinoid signaling along with exploring the various pathways of their biosynthesis, molecular structure, inactivation, and anatomical distribution of their receptors throughout the body.

The endocannabinoid system is involved in immunoregulation and neuroprotection.

The discovery of cannabinoid receptors occurring naturally throughout the vertebrate body and the availability of highly selective and potent canabimimetics led to the identification of a naturally occurring lipid signaling system termed the endocannabinoid system.

Interestingly, the endocannabinoid system dates back very long in the evolution because it exists as an ancient plant signaling system regulating the plant immunity-related genes in response to infection and stress.

The main pharmacological functions of the endocannabinoid system include neuromodulation, controlling motor functions, cognition, emotional responses, homeostasis and motivation. However, in the periphery, this system is an important modulator of autonomic nervous system, the immune system and microcirculation.

There have been a number of recent studies which have demonstrated that the endocannabinoids have both inhibitory effects and stimulatory impact on the immune system and may be actually important in homeostasis or control of the immune reactions.

 The image of endocannabinoid system now appears to be of a modulatory complex which affects the physiological functions in peripheral tissues and can thus be considered as a potential therapeutic target in the future.
Thus, manipulation of endocannabinoids in vivo may constitute a novel treatment modality against inflammatory disorders.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044336/

Marijuana-derived Δ-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated delayed-type hypersensitivity through microRNA regulation.

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“∆9-Tetrahydrocannabinol (THC) is one of the major bioactive cannabinoids derived from the Cannabis sativa plant and is known for its anti-inflammatory properties. Delayed-type hypersensitivity (DTH) is driven by proinflammatory T helper cells including the classic inflammatory Th1 lineage as well as the more recently discovered Th17 lineage. In the current study, we investigated whether THC can alter the induction of Th1/Th17 cells involved in mBSA-induced DTH response. THC treatment (20 mg/kg) of C57BL/6 mice with DTH caused decreased swelling and infiltration of immune cells at the site of antigen rechallenge. Additionally, THC treatment decreased lymphocyte activation as well as Th1/Th17 lineage commitment, including reduced lineage-specific transcription factors and cytokines. Interestingly, while DTH caused an overexpression of miR-21, which increases Th17 differentiation via SMAD7 inhibition, and downregulation of miR-29b, an IFN-γ inhibitor, THC treatment reversed this microRNA (miR) dysregulation. Furthermore, when we transfected primary cells from DTH mice with miR-21 inhibitor or miR-29b mimic, as seen with THC treatment, the expression of target gene message was directly impacted increasing SMAD7 and decreasing IFN-γ expression, respectively. In summary, the current study suggests that THC treatment during DTH response can simultaneously inhibit Th1/Th17 activation via regulation of microRNA (miRNA) expression.

KEY MESSAGES:

• THC treatment inhibits simultaneous Th1/Th17 driven inflammation. • THC treatment corrects DTH-mediated microRNA dysregulation. • THC treatment regulates proinflammatory cytokines and transcription factors.”

http://www.ncbi.nlm.nih.gov/pubmed/27038180

Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices.

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“In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is now considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND).

Endocannabinoids exhibit neuroprotective and anti-inflammatory properties in several central nervous system (CNS) disease models, but their effects in HAND are poorly understood.

Results indicated a Tat-induced decrease in GABAergic neurotransmission, which was occluded by cannabinoids via a CB1R-related mechanism.

Understanding the relationship between Tat toxicity and endocannabinoid signaling has the potential to identify novel therapeutic interventions to benefit individuals suffering from HAND and other cognitive impairments.”

http://www.ncbi.nlm.nih.gov/pubmed/26993829

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