Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury.

Posted on July 24, 2015 by David

“Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts.

Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury.

Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is the active components of marijuana.

In this study we examined the role of ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults.

CONCLUSION:

A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury.

THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma.”

http://www.ncbi.nlm.nih.gov/pubmed/26202357

Cannabisin B induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arrest in HepG2 cells.

Posted on June 2, 2015 by David

“This study investigates the anticancer properties of cannabisin B, purified from hempseed hull, in HepG2 human hepatoblastoma cells.

The results indicate that cannabisin B significantly inhibited cell proliferation by inducing autophagic cell death rather than typical apoptosis.

Cell viability transiently increased upon the addition of a low concentration of cannabisin B but decreased upon the addition of high concentrations.

Cannabisin B-induced changes in cell viability were completely inhibited by pre-treatment with 3-methyladenine (3-MA), indicating that the induction of autophagy by cannabisin B caused cell death.

Additionally, cannabisin B induced S phase cell cycle arrest in a dose-dependent manner.

Moreover, cannabisin B was found to inhibit survival signaling by blocking the activation of AKT and down-stream targets of the mammalian target of rapamycin (mTOR).

These findings suggest that cannabisin B possesses considerable antiproliferative activity and that it may be utilised as a promising chemopreventive agent against hepatoblastoma disease.”

http://www.ncbi.nlm.nih.gov/pubmed/23411211

http://www.thctotalhealthcare.com/category/liver-cancer-2/

The effect of endocannabinoid system in ischemia-reperfusion injury: a friend or a foe?

Posted on May 6, 2015 by David

“In recent years, the endocannabinoid system has emerged as a new therapeutic target in variety of disorders associated with inflammation and tissue injury, including those of the neuronal, liver, renal and cardiovascular system.

The aim of the present review is to elucidate the effect of endocannabinoid system on ischemia reperfusion injury (IRI) in different organs and systems.

Expert opinion: CB2 receptors may play an important compensatory role in controlling tissue inflammation and injury in cells of the neuronal, cardiovascular, liver and renal systems, as well as in infiltrating monocytes/macrophages and leukocytes during various pathological conditions of the systems (atherosclerosis, restenosis, stroke, myocardial infarction, heart, liver and renal failure).

These receptors limit inflammation and associated tissue injury.

On the basis of preclinical results, pharmacological modulation of CB2 receptors may hold a unique therapeutic potential in stroke, myocardial infarction, atherosclerosis, IRI and liver disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25936364

Protective Role of CB2 Receptor Activation in Galactosamine/LPS-induced Acute Liver Failure Through Regulation of Macrophage Polarization and miRNAs.

Posted on March 11, 2015 by David

“Acute liver failure (ALF) is a potentially life threatening disorder without any effective treatment strategies. D-Galactosamine/LPS (GalN/LPS)-induced ALF is a widely used animal model to identify novel hepato-protective agents.

In the present study, we investigated the potential of a Cannabinoid receptor 2 (CB2) agonist, in the amelioration of GalN/LPS induced ALF…

Together, these data demonstrate for the first time that CB2 activation attenuates GalN/LPS-induced ALF by inducing an M1 to M2 shift in macrophages and by regulating the expression of unique miRs that target key molecules involved in TLR4 pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/25749929

Cannabinoid signaling and liver therapeutics.

Posted on February 19, 2015 by David

Journal of Hepatology Home

“Over the last decade, the endocannabinoid system has emerged as a pivotal mediator of acute and chronic liver injury, with the description of the role of CB1 and CB2 receptors and their endogenous lipidic ligands in various aspects of liver pathophysiology.

A large number of studies have demonstrated that CB1 receptor antagonists represent an important therapeutic target, owing to beneficial effects on lipid metabolism and in light of its antifibrogenic properties.

Unfortunately, the brain-penetrant CB1 antagonist rimonabant, initially approved for the management of overweight and related cardiometabolic risks, was withdrawn because of an alarming rate of mood adverse effects.

However, the efficacy of peripherally-restricted CB1 antagonists with limited brain penetrance has now been validated in preclinical models of NAFLD, and beneficial effects on fibrosis and its complications are anticipated.

CB2 receptor is currently considered as a promising anti-inflammatory and antifibrogenic target, although clinical development of CB2 agonists is still awaited.

In this review, we highlight the latest advances on the impact of the endocannabinoid system on the key steps of chronic liver disease progression and discuss the therapeutic potential of molecules targeting cannabinoid receptors…

Overwhelming evidence supports the therapeutic potential of peripherally-restricted CB1 antagonists and CB2 agonists in the management of chronic liver diseases.”

http://www.journal-of-hepatology.eu/article/S0168-8278(13)00212-2/fulltext

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

Cannabinoid CB2 receptors protect against alcoholic liver disease by regulating Kupffer cell polarization in mice.

Posted on February 19, 2015 by David

“Activation of Kupffer cells plays a central role in the pathogenesis of alcoholic liver disease.

Because cannabinoid CB2 receptors (CB2) display potent anti-inflammatory properties, we investigated their role in the pathogenesis of alcoholic liver disease, focusing on the impact of CB2 on Kupffer cell polarization and the consequences on liver steatosis.

Altogether, these findings demonstrate that CB2 receptors display beneficial effects on alcohol-induced inflammation by regulating M1/M2 balance in Kupffer cells, thereby reducing hepatocyte steatosis via paracrine interactions between Kupffer cells and hepatocytes.

These data identify CB2 agonists as potential therapeutic agents for the management of alcoholic liver disease.”

http://www.ncbi.nlm.nih.gov/pubmed/21735467

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

Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects.

Posted on February 19, 2015 by David

“A multitude of physiological effects and putative pathophysiological roles have been proposed for the endogenous cannabinoid system in the gastrointestinal tract, liver and pancreas.

These range from effects on epithelial growth and regeneration, immune function, motor function, appetite control, fibrogenesis and secretion.

Cannabinoids have the potential for therapeutic application in gut and liver diseases.

Two exciting therapeutic applications in the area of reversing hepatic fibrosis as well as antineoplastic effects may have a significant impact in these diseases.

This review critically appraises the experimental and clinical evidence supporting the clinical application of cannabinoid receptor-based drugs in gastrointestinal, liver and pancreatic diseases.

Application of modern pharmacological principles will most probably expand the selective modulation of the cannabinoid system peripherally in humans.

We anticipate that, in addition to the approval in several countries of the CB(1) antagonist, rimonabant, for the treatment of obesity and associated metabolic dysfunctions, other cannabinoid modulators are likely to have an impact on human disease in the future, including hepatic fibrosis and neoplasia.”

http://www.ncbi.nlm.nih.gov/pubmed/18397936

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

Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration.

Posted on February 19, 2015 by David

“Accumulating data indicate that the cannabinoid system is a crucial mediator in the pathogenesis of a variety of liver diseases.

In the present study we show that CB2 receptors reduce liver injury and accelerate liver regeneration via distinct pathways.

CB2 receptors reduce liver injury and promote liver regeneration following acute insult, via distinct paracrine mechanisms involving hepatic myofibroblasts.

These results suggest that CB2 agonists display potent hepatoprotective properties, in addition to their antifibrogenic effects.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246453/
“Association of the cannabinoid receptor 2 (CB2) Gln63Arg polymorphism with indices of liver damage in obese children: an alternative way to highlight the CB2 hepatoprotective properties.” http://www.ncbi.nlm.nih.gov/pubmed/21608006

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

Hyperactivation of anandamide synthesis and regulation of cell-cycle progression via cannabinoid type 1 (CB1) receptors in the regenerating liver.

Posted on February 19, 2015 by David

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“The mammalian liver regenerates upon tissue loss, which induces quiescent hepatocytes to enter the cell cycle and undergo limited replication under the control of multiple hormones, growth factors, and cytokines.

Endocannabinoids acting via cannabinoid type 1 receptors (CB(1)R) promote neural progenitor cell proliferation, and in the liver they promote lipogenesis.

These findings suggest the involvement of CB(1)R in the control of liver regeneration…

We conclude that activation of hepatic CB(1)R by newly synthesized anandamide promotes liver regeneration by controlling the expression of cell-cycle regulators that drive M phase progression.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076854/

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

Anandamide Drives Cell Cycle Progression through CB1 Receptors in a Rat Model of Synchronized Liver Regeneration.

Posted on February 18, 2015 by David

“The endocannabinoid system, through cannabinoid receptor signaling by endocannabinoids, is involved in a wide range of functions and physiopathological conditions.

… liver regeneration, a useful in vivo model of synchronized cell proliferation, is characterized by a peak of anandamide that elicits through CB1 receptor the expression of critical mitosis genes. The aim of this study was to focus on the timing of endocannabinoid signaling changes during the different phases of the cell cycle, exploiting the rat liver regeneration model following partial hepatectomy…

These results support the notion that the signaling mediated by anandamide through CB1 receptor may be important for the entry and progression of cells into the cell cycle and hence for their proliferation under mitogenic signals.”

http://www.ncbi.nlm.nih.gov/pubmed/25684344

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