The Critical Role of Cannabinoid Receptor 2 in URB602-induced Protective Effects Against Renal Ischemia-Reperfusion Injury in the Rat.

 Image result for shock journal“Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage.

Accumulating proofs demonstrates that the endocannabinoid system (ECS) may provide a promising access for treatment strategy of renal IRI associated AKI.

In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation.

Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.”

https://www.ncbi.nlm.nih.gov/pubmed/32004183

 

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Antioxidative and Anti-Inflammatory Properties of Cannabidiol.

antioxidants-logo“Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31881765

https://www.mdpi.com/2076-3921/9/1/21

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Agitation, Oxidative Stress, and Cytokines in Alzheimer Disease: Biomarker Analyses From a Clinical Trial With Nabilone for Agitation.

 Image result for journal of geriatric psychiatry and neurology

“The endocannabinoid system has been a target of interest for agitation in Alzheimer disease (AD) because of potential behavioral effects and its potential impact on mechanisms implicated in AD such as oxidative stress (OS) and neuroinflammation.

We explored whether serum markers of OS and neuroinflammation were associated with response to the cannabinoid nabilone in agitated patients with AD (N = 38).

These findings suggest that OS and neuroinflammation may be associated with agitation severity, while nabilone may have anti-inflammatory effects.”

https://www.ncbi.nlm.nih.gov/pubmed/31547752

https://journals.sagepub.com/doi/abs/10.1177/0891988719874118?journalCode=jgpb

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Activation of cannabinoid type 2 receptor protects skeletal muscle from ischemia-reperfusion injury partly via Nrf2 signaling.

Life Sciences“Cannabinoid type 2 (CB2) receptor activation has been shown to attenuate IRI in various organs. NF-E2-related factor (Nrf2) is an anti-oxidative factor that plays multiple roles in regulating cellular redox homeostasis and modulating cell proliferation and differentiation. The protective effects of CB2 receptor activation on skeletal muscle IRI and the underlying mechanism that involves Nrf2 signaling remain unknown.

Our results showed that CB2 receptor activation reduced IR-induced histopathological lesions, edema, and oxidative stress 1 day post-injury and accelerated early myogenesis 4 days post-injury in mice. Nrf2 knockout mice that were treated with AM1241 exhibited deteriorative skeletal muscle oxidative damage and myogenesis. In vitro, pretreatment with AM1241 significantly increased the expression of Nrf2 and its nuclear translocation, attenuated the decrease in H2O2-induced C2C12 cell viability, and decreased reactive oxygen species generation and apoptosis. CB2 receptor activation also significantly enhanced C2C12 myoblasts differentiation, which was impaired by silencing Nrf2.

Overall, CB2 receptor activation protected skeletal muscle against IRI by ameliorating oxidative damage and promoting early skeletal muscle myogenesis, which was partly via Nrf2 signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/31128135

https://www.sciencedirect.com/science/article/abs/pii/S0024320519304126?via%3Dihub

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabisin F from Hemp (Cannabis sativa) Seed Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia as SIRT1 Modulator.

ijms-logo

“Hemp seed (Fructus cannabis) is rich in lignanamides, and initial biological screening tests showed their potential anti-inflammatory and anti-oxidative capacity.

This study investigated the possible effects and underlying mechanism of cannabisin F, a hempseed lignanamide, against inflammatory response and oxidative stress in lipopolysaccharide (LPS)-stimulated BV2 microglia cells.

Cannabisin F suppressed the production and the mRNA levels of pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in a concentration-dependent manner in LPS-stimulated BV2 microglia cell. Furthermore, cannabisin F enhanced SIRT1 expression and blocked LPS-induced NF-κB (Nuclear factor kappa B) signaling pathway activation by inhibiting phosphorylation of IκBα (Inhibit proteins of nuclear factor kappaB) and NF-κB p65. And the SIRT1 inhibitor EX527 significantly inhibited the effect of cannabisin F on pro-inflammatory cytokines production, suggesting that the anti-inflammatory effects of cannabisin F are SIRT1-dependent. In addition, cannabisin F reduced the production of cellular reactive oxygen species (ROS) and promoted the expression of Nrf2 (Nuclear factor erythroid-2 related factor 2) and HO-1 (Heme Oxygenase-1), suggesting that the anti-oxidative effects of cannabisin F are related to Nrf2 signaling pathway.

Collectively, these results suggest that the neuro-protection effect of cannabisin F against LPS-induced inflammatory response and oxidative stress in BV2 microglia cells involves the SIRT1/NF-κB and Nrf2 pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/30691004

https://www.mdpi.com/1422-0067/20/3/507

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

The protective effects of Δ9 -tetrahydrocannabinol against inflammation and oxidative stress in rat liver with fructose-induced hyperinsulinemia.

Journal of Pharmacy and Pharmacology banner

“A large amount of fructose is metabolized in the liver and causes hepatic functional damage. Δ9 -tetrahydrocannabinol (THC) is known as a therapeutic agent for clinical and experimental applications.

 

The study aims to investigate the effects of THC treatment on inflammation, lipid profiles and oxidative stress in rat liver with hyperinsulinemia.

 

According to the result, long-term and low-dose THC administration may reduce hyperinsulinemia and inflammation in rats to some extent.”

 

https://www.ncbi.nlm.nih.gov/pubmed/30427077

https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.13042

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabidiol restores differentiation capacity of LPS exposed adipose tissue mesenchymal stromal cells.

Experimental Cell Research

“Multipotent mesenchymal stromal cells (MSCs) support wound healing processes. These cells express toll-like receptors (TLRs). TLRs perform important key functions when the immune system is confronted with danger signals. TLR ligation by lipopolysaccharides (LPS) activates MSCs and induces intracellular signaling cascades, which affect their differentiation profile, increase the release of inflammatory cytokines and the production of reactive oxygen species. Continuing exposure to LPS triggers prolonged inflammatory reactions, which may lead to deleterious conditions, e.g. non-healing wounds.

Cannabidiol (CBD) exerts anti-inflammatory processes through cannabinoid receptor dependent and independent mechanisms. In the present study, we examined whether CBD could influence the inflammatory MSC phenotype.

Exposure to LPS increased the release of IL-6, as well as other soluble factors, and elevated levels of oxidized macromolecules found in cell homogenisates. While the amount of IL-6 was unaffected, co-treatment with CBD reduced the oxidative stress acting on the cells. LPS inhibited adipogenic as well as chondrogenic differentiation, which was attenuated by CBD treatment. In the case of adipogenesis, the disinhibitory effect probably depended on CBD interaction with the peroxisome proliferator-activated receptor-γ.

CBD could exert mild immunosuppressive properties on MSCs, while it most effectively acted anti-oxidatively and by restoring the differentiation capacity upon LPS treatment.” https://www.ncbi.nlm.nih.gov/pubmed/30036540

“Cannabidiol (CBD) reduces oxidative stress and restores adipogenesis and chondrogenesis of mesenchymal stromal cells (MSCs) upon lipopolysaccharides (LPS)  exposure.” https://linkinghub.elsevier.com/retrieve/pii/S0014482718304312

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Brain endocannabinoid signaling exhibits remarkable complexity.

Image result for Brain Res Bull.

“The endocannabinoid (eCB) signaling system is one of the most extensive of the mammalian brain. Despite the involvement of only few specific ligands and receptors, the system encompasses a vast diversity of triggered mechanisms and driven effects. It mediates a wide range of phenomena, including the regulation of transmitter release, neural excitability, synaptic plasticity, impulse spread, long-term neuronal potentiation, neurogenesis, cell death, lineage segregation, cell migration, inflammation, oxidative stress, nociception and the sleep cycle. It is also known to be involved in the processes of learning and memory formation. This extensive scope of action is attained by combining numerous variables. In a properly functioning brain, the correlations of these variables are kept in a strictly controlled balance; however, this balance is disrupted in many pathological conditions. However, while this balance is known to be disrupted by drugs in the case of addicts, the stimuli and mechanisms influencing the neurodegenerating brain remain elusive. This review examines the multiple factors and phenomena affecting the eCB signaling system in the brain. It evaluates techniques of controlling the eCB system to identify the obstacles in their applications and highlights the crucial interdependent variables that may influence biomedical research outcomes.”

https://www.ncbi.nlm.nih.gov/pubmed/29953913

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabidiol to Improve Mobility in People with Multiple Sclerosis

Image result for frontiers in neurology

“Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that affects an estimated 2.3 million people worldwide. The symptoms of MS are highly varied but frequently include pain, muscle spasticity, fatigue, inflammation, and depression. These symptoms often lead to reduced physical activity, negatively impact functional mobility, and have a detrimental impact on patients’ quality of life.

Although recent years have seen significant advances in disease modifying therapy, none of the current treatments halts or cures MS related symptoms. As a consequence, many people with MS (PwMS) look for alternative and complementary therapies such as cannabis.

The cannabis plant contains many biologically active chemicals, including ~60 cannabinoids. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are typically the most concentrated chemical components of cannabis and believed to primarily drive therapeutic benefit.

There is evidence that CBD has a number of beneficial pharmacological effects. It is anti-inflammatory, antioxidative, antiemetic, antipsychotic, and neuroprotective. The review of 132 original studies by Bergamaschi et al. describes the safety profile of CBD by highlighting that catalepsy is not induced and physiological parameters (heart rate, blood pressure, and body temperature) are not altered. Moreover, psychomotor and psychological functions are not negatively affected. High doses of up to 1,500 mg per day and chronic use have been repeatedly shown to be well tolerated by humans.

Additionally, there is also evidence that CBD may reduce the negative psychotropic effects, memory impairment, and appetite stimulation, anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions.

 Anecdotal reports indicate that an increasing number of PwMS use cannabis (medical marijuana) as a supplement to improve their mobility.

Based on the following considerations, it is our opinion that CBD supplementation maybe advisable for PwMS to reduce fatigue, pain, spasticity, and ultimately improve mobility. “

https://www.frontiersin.org/articles/10.3389/fneur.2018.00183/full

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

N-Arachidonoyl Dopamine: A Novel Endocannabinoid and Endovanilloid with Widespread Physiological and Pharmacological Activities.

Mary Ann Liebert, Inc. publishers

“N-arachidonoyl dopamine (NADA) is a member of the family of endocannabinoids to which several other N-acyldopamines belong as well. Their activity is mediated through various targets that include cannabinoid receptors or transient receptor potential vanilloid (TRPV)1. Synthesis and degradation of NADA are not yet fully understood. Nonetheless, there is evidence that NADA plays an important role in nociception and inflammation in the central and peripheral nervous system. The TRPV1 receptor, for which NADA is a potent agonist, was shown to be an endogenous transducer of noxious heat. Moreover, it has been demonstrated that NADA exerts protective and antioxidative properties in microglial cell cultures, cortical neurons, and organotypical hippocampal slice cultures. NADA is present in very low concentrations in the brain and is seemingly not involved in activation of the classical pathways. We believe that treatment with exogenous NADA during and after injury might be beneficial. This review summarizes the recent findings on biochemical properties of NADA and other N-acyldopamines and their role in physiological and pathological processes. These findings provide strong evidence that NADA is an effective agent to manage neuroinflammatory diseases or pain and can be useful in designing novel therapeutic strategies.”

https://www.ncbi.nlm.nih.gov/pubmed/29082315

http://online.liebertpub.com/doi/10.1089/can.2017.0015

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous