Tag Archives: anti-inflammatory

Potential new therapies against a toxic relationship: neuroinflammation and Parkinson’s disease.

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 Image result for ovid journal“Parkinson’s disease (PD) is a neurodegenerative disorder classically associated with motor symptoms, but several nonmotor disturbances appear decades before the clinical diagnosis of the disease.

A variety of hypotheses exist to explain the onset of PD, and neuroinflammation is one of the most investigated processes. In fact, strong evidence suggests that PD begins with an inflammatory process; currently, however, no anti-inflammatory therapy is clinically employed to alleviate the typical motor and the prodromal disturbances such as olfactory loss, cognitive impairments, depression and anxiety, sleep disturbances, and autonomic disorders.

In fact, the classical dopaminergic therapies are not effective in alleviating these symptoms and there is no other specific therapy for these outcomes. Therefore, in this review, we will discuss novel potential pharmacological therapeutic strategies focusing on cannabinoids, caffeine, melatonin, and dietary compounds, which could act as adjuvants to regular PD therapy.

These described chemicals have been extensively investigated as anti-inflammatory agents possibly promoting beneficial effects on nonmotor symptoms of PD. The investigation of the inflammatory process at different stages of PD progression should give us a better view of the therapeutic scenario and could improve our understanding of the mechanisms of this disease.”

https://www.ncbi.nlm.nih.gov/pubmed/31703030

https://insights.ovid.com/crossref?an=00008877-201912000-00008

Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced dyskinesia.

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Neurobiology of Disease“L-dopa induced dyskinesia (LID) is a debilitating side-effect of the primary treatment used in Parkinson’s disease (PD), l-dopa. Here we investigate the effect of HU-308, a cannabinoid CB2 receptor agonist, on LIDs.

Utilizing a mouse model of PD and LIDs, induced by 6-OHDA and subsequent l-dopa treatment, we show that HU-308 reduced LIDs as effectively as amantadine, the current frontline treatment. Furthermore, treatment with HU-308 plus amantadine resulted in a greater anti-dyskinetic effect than maximally achieved with HU-308 alone, potentially suggesting a synergistic effect of these two treatments. Lastly, we demonstrated that treatment with HU-308 and amantadine either alone, or in combination, decreased striatal neuroinflammation, a mechanism which has been suggested to contribute to LIDs.

Taken together, our results suggest pharmacological treatments with CB2 agonists merit further investigation as therapies for LIDs in PD patients. Furthermore, since CB2 receptors are thought to be primarily expressed on, and signal through, glia, our data provide weight to suggestion that neuroinflammation, or more specifically, altered glial function, plays a role in development of LIDs.”

https://www.ncbi.nlm.nih.gov/pubmed/31669673

“Collectively, our findings suggest CB2 agonists offer a putative target to treat LIDs, with efficacy comparable to the frontline treatment amantadine. Our study suggests that targeting glial function may be an important strategy for developing therapies for treating LIDs, a major unmet need for PD patients.”

https://www.sciencedirect.com/science/article/pii/S0969996119303213?via%3Dihub

Cannabidiol Regulates Gene Expression in Encephalitogenic T cells Using Histone Methylation and noncoding RNA during Experimental Autoimmune Encephalomyelitis.

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 Scientific Reports“Cannabidiol (CBD) has been shown by our laboratory to attenuate experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).

In this study, we used microarray and next generation sequencing (NGS)-based approaches to determine whether CBD would alter genome-wide histone modification and gene expression in MOG sensitized lymphocytes.

In summary, this study demonstrates that CBD suppresses inflammation through multiple mechanisms, from histone methylation to miRNA to lncRNA.”

https://www.ncbi.nlm.nih.gov/pubmed/31673072

“Marijuana (Cannabis sativa) has many biologically active compounds and its medicinal value has been known for centuries. CBD has been shown to have an anti-inflammatory effect in several animal models. In immune system, studies from our lab as well as those from others have shown that both THC and CBD have anti-inflammatory properties. ”

https://www.nature.com/articles/s41598-019-52362-8

Ameliorative effects of hempseed (Cannabis sativa) against hypercholesterolemia associated cardiovascular changes.

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Nutrition, Metabolism and Cardiovascular Diseases“Hypercholesterolemia (HC) is a major risk factor for cardiovascular (CV) diseases, that are the major cause of mortality worldwide.

Free radicals mediated oxidative stress is a critical player in HC-associated pathophysiological insults including atherosclerosis. Unwanted side effects associated with statins, COX-2 inhibitors, and other synthetic drugs limit their use. Thus, modulation of oxidative stress during HC using green pharmaceuticals seems an appropriate approach against deleterious CV consequences without noticeable side-effect.

In this regard, owing to an abundance of proteins, fiber and optimal ratios of omega 6 PUFA: omega-3 PUFA in Hempseed (HS), we aim to exploit its anti-inflammatory and antioxidant properties to ameliorate HC- associated CV effects.

CONCLUSIONS:

Current study evidently demonstrates that the anti-hypercholesterolemic effects of HS are mediated through redox-sensitive modulation of inflammatory pathways.”

https://www.ncbi.nlm.nih.gov/pubmed/31668458

“Hypercholesterolemia (HC) associated oxidative stress is central to cardiovascular (CV) diseases. Unwanted side effects associated with statins and other synthetic drugs limits their use. Modulation of HC associated oxidative stress by Hempseed (HS) was based on its anti-inflammatory/antioxidant properties. HS exhibited intense anti-inflammatory and anti-atherosclerotic effect via redox modulation of PG biosynthetic pathway. The multipronged approach to characterize HC associated CV effects and its modulation by HS is novel.”

https://www.nmcd-journal.com/article/S0939-4753(19)30345-X/fulltext

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Roles of the Hepatic Endocannabinoid and Apelin Systems in the Pathogenesis of Liver Fibrosis.

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cells-logo“Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms. The hepatic endocannabinoid and apelin systems are two signalling pathways with a substantial role in the liver fibrosis pathophysiology-both are upregulated in patients with advanced liver disease. Endogenous cannabinoids are lipid-signalling molecules derived from arachidonic acid involved in the pathogenesis of cardiovascular dysfunction, portal hypertension, liver fibrosis, and other processes associated with hepatic disease through their interactions with the CB1 and CB2 receptors. Apelin is a peptide that participates in cardiovascular and renal functions, inflammation, angiogenesis, and hepatic fibrosis through its interaction with the APJ receptor. The endocannabinoid and apelin systems are two of the multiple cell-signalling pathways involved in the transformation of quiescent hepatic stellate cells into myofibroblast like cells, the main matrix-producing cells in liver fibrosis. The mechanisms underlying the control of hepatic stellate cell activity are coincident despite the marked dissimilarities between the endocannabinoid and apelin signalling pathways. This review discusses the current understanding of the molecular and cellular mechanisms by which the hepatic endocannabinoid and apelin systems play a significant role in the pathophysiology of liver fibrosis.”

https://www.ncbi.nlm.nih.gov/pubmed/31653030

https://www.mdpi.com/2073-4409/8/11/1311

Effects of Cannabis and Its Components on the Retina: A Systematic Review.

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 Publication Cover“Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesizing the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardized, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina.

RESULTS:

We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects.

CONCLUSIONS:

This review suggests that cannabinoids may have an important role in retinal processing and function.”

https://www.ncbi.nlm.nih.gov/pubmed/31648567

https://www.tandfonline.com/doi/abs/10.1080/15569527.2019.1685534?journalCode=icot20

Cannabinoids in the treatment of rheumatic diseases: Pros and cons.

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Autoimmunity Reviews“Medical cannabis is being increasingly used in the treatment of rheumatic diseases because, despite the paucity of evidence regarding its safety and efficacy, a growing number of countries are legalising its use for medical purposes in response to social pressure.

Cannabinoids may be useful in the management of rheumatic disorders for two broad reasons: their anti-inflammatory and immunomodulatory activity, and their effects on pain and associated symptoms.

It is interesting to note that, although a wide range of medications are available for the treatment of inflammation, including an ever-lengthening list of biological medications, the same is not true of the treatment of chronic pain, a cardinal symptom of many rheumatological disorders.

The publication of systematic reviews (SR) concerning the use of cannabis-based medicines for chronic pain (with and without meta-analyses) is outpacing that of randomised controlled trials. Furthermore, narrative reviews of public institution are largely based on these SRs, which often reach different conclusions regarding the efficacy and safety of cannabis-based medicines because of the lack of high-quality evidence of efficacy and the presence of indications that they may be harmful for patients.

Societal safety concerns about medical cannabis (e.g. driving risks, workplace safety and pediatric intoxication) must always be borne in mind, and will probably not be addressed by clinical studies. Medical cannabis and cannabis-based medicines have often been legalised as therapeutic products by legislative bodies without going through the usual process of regulatory approval founded on the results of traditional evidence-based studies. This review discusses the advantages and limitations of using cannabis to treat rheumatic conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31648042

https://www.sciencedirect.com/science/article/abs/pii/S1568997219302162?via%3Dihub

Cannabidiol prevents LPS-induced microglial inflammation by inhibiting ROS/NF-κB-dependent signaling and glucose consumption.

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Publication cover image“We used mouse microglial cells in culture activated by lipopolysaccharide (LPS, 10 ng/ml) to study the anti-inflammatory potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis.

Under LPS stimulation, CBD (1-10 μM) potently inhibited the release of prototypical proinflammatory cytokines (TNF-α and IL-1β) and that of glutamate, a noncytokine mediator of inflammation. The effects of CBD were predominantly receptor-independent and only marginally blunted by blockade of CB2 receptors.

We established that CBD inhibited a mechanism involving, sequentially, NADPH oxidase-mediated ROS production and NF-κB-dependent signaling events. In line with these observations, active concentrations of CBD demonstrated an intrinsic free-radical scavenging capacity in the cell-free DPPH assay.

Of interest, CBD also prevented the rise in glucose uptake observed in microglial cells challenged with LPS, as did the inhibitor of NADPH oxidase apocynin and the inhibitor of IκB kinase-2, TPCA-1. This indicated that the capacity of CBD to prevent glucose uptake also contributed to its anti-inflammatory activity.

Supporting this view, the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) mimicked the antioxidant/immunosuppressive effects of CBD. Interestingly, CBD and 2-DG, as well as apocynin and TPCA-1 caused a reduction in glucose-derived NADPH, a cofactor required for NADPH oxidase activation and ROS generation.

These different observations suggest that CBD exerts its anti-inflammatory effects towards microglia through an intrinsic antioxidant effect, which is amplified through inhibition of glucose-dependent NADPH synthesis.

These results also further confirm that CBD may have therapeutic utility in conditions where neuroinflammatory processes are prominent.”

https://www.ncbi.nlm.nih.gov/pubmed/31647138

https://onlinelibrary.wiley.com/doi/abs/10.1002/glia.23738

Cannabidiol and Cannabinoid Compounds as Potential Strategies for Treating Parkinson’s Disease and L-DOPA-Induced Dyskinesia.

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 “Parkinson’s disease (PD) and L-DOPA-induced dyskinesia (LID) are motor disorders with significant impact on the patient’s quality of life. Unfortunately, pharmacological treatments that improve these disorders without causing severe side effects are not yet available. Delay in initiating L-DOPA is no longer recommended as LID development is a function of disease duration rather than cumulative L-DOPA exposure.

Manipulation of the endocannabinoid system could be a promising therapy to control PD and LID symptoms.

In this way, phytocannabinoids and synthetic cannabinoids, such as cannabidiol (CBD), the principal non-psychotomimetic constituent of the Cannabis sativa plant, have received considerable attention in the last decade.

In this review, we present clinical and preclinical evidence suggesting CBD and other cannabinoids have therapeutic effects in PD and LID. Here, we discuss CBD pharmacology, as well as its neuroprotective effects and those of other cannabinoids.

Finally, we discuss the modulation of several pro- or anti-inflammatory factors as possible mechanisms responsible for the therapeutic/neuroprotective potential of Cannabis-derived/cannabinoid synthetic compounds in motor disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31637586

https://link.springer.com/article/10.1007%2Fs12640-019-00109-8

Cannabidiol As A Novel Therapeutic Strategy For Oral Inflammatory Diseases: A Review Of Current Knowledge And Future Perspectives.

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Image result for altern ther health med “The high frequency and painful profile of inflammatory oral lesions and the lack of an effective drug protocol for their management stimulate the search for pharmacological alternatives for the treatment of these conditions. Cannabidiol is the major non-psychotropic constituent of Cannabis sativa, receiving lately scientific interest because of its potential in the treatment of inflammatory disorders such as asthma, colitis and arthritis. There is little published in the current literature about the use of cannabidiol in oral health. Among its many protective functions, the ability to attenuate inflammation through the modulation of cytokines and its antiedema and analgesic effects may be important features in the treatment of oral lesions. In this review, we suggest that cannabidiol can be useful in the management of oral inflammatory disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31634872