Remote Ischemia Preconditioning Attenuates Blood-Spinal Cord Barrier Breakdown in Rats Undergoing Spinal Cord Ischemia Reperfusion Injury: Associated with Activation and Upregulation of CB1 and CB2 Receptors.

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“Remote ischemic preconditioning (RIPC) has protective effects on spinal cord ischemia reperfusion (I/R) injury, but the potential mechanisms remain unclear. In our study, the effects and underlying mechanisms of RIPC on blood-spinal cord barrier (BSCB) breakdown following I/R injury were investigated.

RIPC attenuated the motor dysfunction, BSCB disruption and downregulation of occludin after I/R injury, which were impaired by blocking CB1 and CB2 receptors. Moreover, RIPC upregulated the elevated perivascular expression of CB1 and CB2 receptors following I/R injury.

CONCLUSIONS:

These results indicated that RIPC, through activation and upregulation of CB1 and CB2 receptors, was involved in preserving the integrity of BSCB after spinal cord I/R injury.”

https://www.ncbi.nlm.nih.gov/pubmed/29130941

https://www.karger.com/Article/FullText/484460

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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

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Inverse association of marijuana use with nonalcoholic fatty liver disease among adults in the United States.

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“The impact of marijuana on nonalcoholic fatty liver disease (NAFLD) is largely unknown. We studied the association between marijuana and NAFLD utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005-2014 and NHANES III (1988-1994).

RESULTS:

Of the 14,080 (NHANES 2005-2014) and 8,286 (NHANES III) participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed NAFLD were inversely associated with marijuana use (p < 0.001). Compared to marijuana-naïve participants, marijuana users were less likely to have suspected NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82-0.99 for past user; OR: 0.68, 95% CI: 0.58-0.80 for current user) and ultrasonographically-diagnosed NAFLD (OR: 0.75, 95% CI: 0.57-0.98 for current user) in the age, gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58-0.98) and 0.70 (95% CI 0.56-0.89), respectively (P for trend = 0.001) with similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59-1.00 for current user; OR: 0.71, 95% CI: 0.51-0.97 for current light user). In insulin resistance-adjusted model, marijuana use remained an independent predictor of lower risk of suspected NAFLD.

CONCLUSIONS:

In this nationally representative sample, active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. The pathophysiology is unclear and warrants further investigation.”

https://www.ncbi.nlm.nih.gov/pubmed/29049354

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186702

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Potential of plant-sourced phenols for inflammatory bowel disease.

“Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics.

In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota.

In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help the further development of new preventive/adjuvant regimens for IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/28990509

http://www.eurekaselect.com/156267/article

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Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus co-infected patients (ANRS CO13-HEPAVIH).

Journal of Viral Hepatitis

“Liver steatosis is common in Human Immunodeficiency Virus (HIV) – Hepatitis C Virus (HCV) co-infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV-HCV co-infected patients.

Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis.

Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination.

The ANRS CO13-HEPAVIH cohort is a French nationwide multicenter of HIV-HCV co-infected patients. Medical and socio-behavioral data from clinical follow-up visits and annual self-administered questionnaires were prospectively collected. A cross-sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n=838), 40.1% had steatosis. Fourteen percent reported daily cannabis use, 11.7% regular use, and 74.7% no use or occasional use (“never or sometimes”).

Daily cannabisuse was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95%]=0.64 [0.42;0.99]; p=0.046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabisuse may be a protective factor against steatosis in HIV-HCV co-infected patients. These findings confirm the need for a clinical evaluation of cannabis-based pharmacotherapies in this population.”

https://www.ncbi.nlm.nih.gov/pubmed/28984055

http://onlinelibrary.wiley.com/doi/10.1111/jvh.12797/abstract

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Activation of type 2 cannabinoid receptor (CB2R) by selective agonists regulates the deposition and remodelling of the extracellular matrix.

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“Remodelling of the extracellular matrix and accumulation of fibronectin and collagen type I play critical roles in scar formation following glaucoma filtration surgery. The transforming growth factor β1 (TGF-β1) signal transduction pathway is involved in this process in human Tenon’s fibroblasts (HTFs).

The type 2 cannabinoid receptor (CB2R) is an important member of the cannabinoidreceptor family of G protein-coupled receptors. In this study, we investigated the effects of the CB2R agonists HU308 and JWH133 on the deposition of newly formed extracellular matrix (ECM) and the contractility of HTFs.

CB2R was expressed in HTFs. Notably, the CB2R agonists HU308 and JWH133 ameliorated TGF-β1-induced generation of fibronectin, types I and III collagen, and the expression of matrix metalloproteinase 1 (MMP-1) and MMP-3. In addition, the CB2R agonists HU308 and JWH133 ameliorated TGF-β1-induced matrix contraction and remodelling in a dose- and time-dependent manner, respectively. HU308 and JWH133 also suppressed the TGF-β1-induced activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK).

Based on our results, agonistic activation of CB2R exerts a protective effect on scarring during the healing of wounds from glaucoma filtration surgery.”

https://www.ncbi.nlm.nih.gov/pubmed/28958132

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Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids.

“The beta amyloid (Aβ) and other aggregating proteins in the brain increase with age and are frequently found within neurons. The mechanistic relationship between intracellular amyloid, aging and neurodegeneration is not, however, well understood.

We use a proteotoxicity model based upon the inducible expression of Aβ in a human central nervous system nerve cell line to characterize a distinct form of nerve cell death caused by intracellular Aβ. It is shown that intracellular Aβ initiates a toxic inflammatory response leading to the cell’s demise. Aβ induces the expression of multiple proinflammatory genes and an increase in both arachidonic acid and eicosanoids, including prostaglandins that are neuroprotective and leukotrienes that potentiate death.

Cannabinoids such as tetrahydrocannabinol stimulate the removal of intraneuronal Aβ, block the inflammatory response, and are protective.

Altogether these data show that there is a complex and likely autocatalytic inflammatory response within nerve cells caused by the accumulation of intracellular Aβ, and that this early form of proteotoxicity can be blocked by the activation of cannabinoid receptors.”

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Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK.

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“Melanogenesis plays a critical role in the protection of skin against external stresses such as ultraviolet irradiation and oxidative stressors. This study was aimed to investigate the effects of cannabidiol on melanogenesis and its mechanisms of action in human epidermal melanocytes. We found that cannabidiol increased both melanin content and tryrosinase activity. The mRNA levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP) 1, and TRP2 were increased following cannabidiol treatment. Likewise, cannabidiol increased the protein levels of MITF, TRP 1, TRP 2, and tyrosinase. Mechanistically, we found that cannabidiol regulated melanogenesis by upregulating MITF through phosphorylation of p38 mitogen-activated protein kinase (MAPK) and p42/44 MAPK, independent of cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling. In addition, the melanogenic effect of cannabidiol was found to be mediated by cannabinoid CB1 receptor, not by CB2receptor. Taken together, these findings indicate that cannabidiol-induced melanogenesis is cannabinoid CB1 receptor-dependent, and cannabidiol induces melanogenesis through increasing MITF gene expression which is mediated by activation of p38 MAPK and p42/44 MAPK. Our results suggest that cannabidiol might be useful as a protective agent against external stresses.”

https://www.ncbi.nlm.nih.gov/pubmed/28601556

http://www.sciencedirect.com/science/article/pii/S0009279716304343

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Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy.

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“The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders.” https://www.ncbi.nlm.nih.gov/pubmed/28367124

“This study showed that CBD treatment reduces the behavioral severity and oscillatory electrographic changes of SE, the post-ictal lethargy, and the neuronal loss associated with the pilocarpine-induced SE rat model. More studies are needed to understand the specific mechanisms of action related to the neuroprotective and anticonvulsant effects of CBD in epilepsy.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355474/

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Acetylcholinesterase inhibitors in Alzheimer’s disease

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“Alzheimer’s Disease (AD) is the most common single cause of dementia in our ageing society. On full assessment and diagnosis of AD, initiation of an AChe inhibitor is recommended as early as possible, it is important that AChe inhibitor therapy is considered for patients with mild to moderate AD.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014378/

“Characterization of Lignanamides from Hemp (Cannabis sativa L.) Seed and Their Antioxidant and Acetylcholinesterase Inhibitory Activities. Hempseed is known for its content in fatty acids, proteins and fiber, which contribute to its nutritional value. Lignanamides 2, 7, 9-14 showed good antioxidant activity among which 7, 10 and 13 also inhibited acetylcholinesterase in vitro. The new identified compounds in this study added to the diversity of hempseed composition and the bioassays implied that hempseed, with lignanamides as nutrients, may be a good source of bioactive and protective compounds.” http://www.ncbi.nlm.nih.gov/pubmed/26585089

“The Effects of Hempseed Meal Intake and Linoleic Acid on Drosophila Models of Neurodegenerative Diseases and Hypercholesterolemia. Our results indicate that hempseed meal (HSM) and linoleic acid are potential candidates for the treatment of Alzheimer’s disease (AD) and cardiovascular disease. These results show that HSM may prove of great utility as a health food, with potential for the prevention of AD and cardiovascular disease.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933972/

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