Hempseed ( Cannabis sativa) lipid fractions alleviate high-fat diet-induced fatty liver disease through regulation of inflammation and oxidative stress

 Heliyon (@HeliyonJournal) | Twitter“Diet and lifestyle-induced dysregulated lipid metabolism have been implicated in fatty liver disease. Chronic redox modulation and hepatic inflammation are key pathological mediators and hallmarks of fatty liver disease associated liver steatosis and steatohepatitis.

In this context, owing to the beneficial phytochemical properties such as optimal omega-6: omega-3 PUFA ratio of hempseed, we aimed to explore its potential anti-inflammatory and antioxidant properties against high-fat diet (HFD)-induced experimental model of fatty liver disease.

The hempseed lipid fractions (HEMP) were prepared and their ameliorating effects on HFD induced morphological changes, lipid profiles, liver function markers (LFT), markers of oxidative stress and inflammation were studied.

Results indicated that HEMP administration to hypercholesterolemic rats resolved the morphological, histopathological, and biochemical indicators of fatty liver diseases. Further, the mechanistic evidence revealed that these hepatoprotective effects of HEMP are mediated through inhibition of oxidative stress and inflammatory mediators such as Cox-2, hPGDS, mPGES, IL-4, TNF-α and sEH.

In conclusion, current study suggests the plausible antioxidant and anti-inflammatory role of HEMP in alleviating pathophysiological conditions including fatty liver disease, where oxidative stress and inflammation are key mediators.”

https://pubmed.ncbi.nlm.nih.gov/32685737/

https://www.cell.com/heliyon/pdf/S2405-8440(20)31266-4.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844020312664%3Fshowall%3Dtrue

Patient Perception Regarding Potential Effectiveness of Cannabis for Pain Management

Home Page: The Journal of ArthroplastySelf-reported cannabis use has increased since its recent legalization in many states.

The primary objective of this study is to describe patients’ beliefs regarding the potential effectiveness of cannabis and gauge patient acceptance of these compounds if prescribed by a physician.

Patients strongly agree or agree that cannabis can help with sleep or anxiety.

Patients believe that cannabis may be helpful for pain management after total joint arthroplasty (TJA) and are willing to use if prescribed by their orthopedic provider.”

https://pubmed.ncbi.nlm.nih.gov/32684396/

https://www.arthroplastyjournal.org/article/S0883-5403(20)30716-6/pdf

Enhancing ovarian cancer conventional chemotherapy through the combination with cannabidiol loaded microparticles

 European Journal of Pharmaceutics and Biopharmaceutics“In this work, we evaluated, for the first time, the antitumor effect of cannabidiol (CBD) as monotherapy and in combination with conventional chemotherapeutics in ovarian cancer and developed PLGA-microparticles as CBD carriers to optimize its anticancer activity.

Spherical microparticles, with a mean particle size around 25 µm and high entrapment efficiency were obtained. Microparticles elaborated with a CBD:polymer ratio of 10:100 were selected due to the most suitable release profile with a zero-order CBD release (14.13±0.17 μg/day/10 mg Mps) for 40 days.

The single administration of this formulation showed an in vitro extended antitumor activity for at least 10 days and an in ovo antitumor efficacy comparable to that of CBD in solution after daily topical administration (≈1.5-fold reduction in tumor growth vs control). The use of CBD in combination with paclitaxel (PTX) was really effective.

The best treatment schedule was the pre+co-administration of CBD (10µM) with PTX. Using this protocol, the single administration of microparticles was even more effective than the daily administration of CBD in solution, achieving a ≈10- and 8- fold reduction in PTX IC50 respectively. This protocol was also effective in ovo. While PTX conducted to a 1.5-fold tumor growth inhibition, its combination with both CBD in solution (daily administered) and 10-Mps (single administration) showed a 2-fold decrease.

These results show the promising potential of CBD-Mps administered in combination with PTX for ovarian cancer treatment, since it would allow to reduce the administered dose of this antineoplastic drug maintaining the same efficacy and, as a consequence, reducing PTX adverse effects.”

https://pubmed.ncbi.nlm.nih.gov/32682943/

https://www.sciencedirect.com/science/article/abs/pii/S0939641120302113?via%3Dihub

Naturally Occurring Cannabinoids and their Role in Modulation of Cardiovascular Health

 Publication Cover“In recent years, the role of the endocannabinoid system (ECS) in various cardiovascular conditions has been a subject of great interest. The ECS is composed of cannabinoid receptors, their endogenous ligands, also known as endocannabinoids, and enzymes responsible for the synthesis and degradation of endocannabinoids.

Several lines of evidence suggest that the ECS plays a complex role in cardiac and vascular systems; however, under normal physiological conditions the functions of the ECS are limited. Overactivation of components of the ECS has been associated with various cardiovascular conditions.

Intriguingly, activation of the ECS may also reflect a cardioprotective compensatory mechanism. With this knowledge, a range of naturally occurring and synthetic cannabinoid receptor agonists and antagonists, as well as inhibitors of endocannabinoid metabolic enzymes have emerged as promising approaches for the treatment or management of cardiovascular health.

This review will first focus on the known role of the ECS in regulating the cardiovascular system. Secondly, we discuss emerging data highlighting the therapeutic potential of naturally occurring non-psychoactive ECS modulators within the cardiovascular system, including phytocannabinoids, terpenes, and the endocannabinoid-like molecule palmitoylethanolamide.”

https://pubmed.ncbi.nlm.nih.gov/32677481/

“Several approaches discussed here, including administration of eCB-related molecules such as PEA, or supplementing with various phytocannabinoids can be promising candidates for the management of cardiovascular risk factors and CVD.”

https://www.tandfonline.com/doi/full/10.1080/19390211.2020.1790708

The Pro-neurogenic Effects of Cannabidiol and Its Potential Therapeutic Implications in Psychiatric Disorders

Archive of "Frontiers in Behavioral Neuroscience". “During the last decades, researchers have investigated the functional relevance of adult hippocampal neurogenesis in normal brain function as well as in the pathogenesis of diverse psychiatric conditions.

Although the underlying mechanisms of newborn neuron differentiation and circuit integration have yet to be fully elucidated, considerable evidence suggests that the endocannabinoid system plays a pivotal role throughout the processes of adult neurogenesis. Thus, synthetic, and natural cannabinoid compounds targeting the endocannabinoid system have been utilized to modulate the proliferation and survival of neural progenitor cells and immature neurons.

Cannabidiol (CBD), a constituent of the Cannabis Sativa plant, interacts with the endocannabinoid system by inhibiting fatty acid amide hydrolase (FAAH) activity (the rate-limiting enzyme for anandamide hydrolysis), allosterically modulating CB1 and CB2 receptors, and activating components of the “extended endocannabinoid system.” Congruently, CBD has shown prominent pro-neurogenic effects, and, unlike Δ9-tetrahydrocannabinol, it has the advantage of being devoid of psychotomimetic effects.

Here, we first review pre-clinical studies supporting the facilitating effects of CBD on adult hippocampal neurogenesis and available data disclosing cannabinoid mechanisms by which CBD can induce neural proliferation and differentiation. We then review the respective implications for its neuroprotective, anxiolytic, anti-depressant, and anti-reward actions.

In conclusion, accumulating evidence reveals that, in rodents, adult neurogenesis is key to understand the behavioral manifestation of symptomatology related to different mental disorders. Hence, understanding how CBD promotes adult neurogenesis in rodents could shed light upon translational therapeutic strategies aimed to ameliorate psychiatric symptomatology dependent on hippocampal function in humans.”

https://pubmed.ncbi.nlm.nih.gov/32676014/

https://www.frontiersin.org/articles/10.3389/fnbeh.2020.00109/full

Hydroxycinnamic acid derivatives isolated from hempseed and their effects on central nervous system enzymes

 Publication Cover“New neuroprotective treatments of natural origin are being investigated. Both, plant extracts and isolated compounds have shown bioactive effects.

Hempseed is known for its composition of fatty acids, proteins, fibre, vitamins, as well as a large number of phytochemical compounds. After a defatting process of the seeds, hydroxycinnamic acids and its amine derivatives are the majoritarian compounds in an ethyl acetate fraction (EAF).

In the present study, we investigated in vitro effect on neuronal enzymes: MAO-A, MAO-B, tyrosinase and acetylcholinesterase. Besides, the effect of EAF on striatal biogenic amines in mice was evaluated. Both, EAF and isolated compounds (N-trans-caffeoyltyramine and N-trans-coumaroyltyramine), showed inhibitory action on MAO-A, MAO-B and tyrosinase. Furthermore, an increasing of biogenic amines was observed in the corpus striatum of the mice, after administration of EAF.

These findings show that EAF and the hydroxycinnamic acid derivatives may represent a potential treatment in degenerative neuronal diseases.”

https://pubmed.ncbi.nlm.nih.gov/32664762/

https://www.tandfonline.com/doi/abs/10.1080/09637486.2020.1793305?journalCode=iijf20

The endocannabinoid system

Essays in Biochemistry “Thirty years ago, the discovery of a cannabinoid (CB) receptor that interacts with the psychoactive compound in Cannabis led to the identification of anandamide, an endogenous receptor ligand or endocannabinoid. Research on endocannabinoids has since exploded, and additional receptors along with their lipid mediators and signaling pathways continue to be revealed. Specifically, in humans, the release of endocannabinoids from membrane lipids occurs on demand and the signaling process is rapidly attenuated by the breakdown of the ligand suggesting a tight regulation of the endocannabinoid system (ECS). Additionally, the varying distribution of CB receptors between the central nervous system and other tissues allows for the ECS to participate in a wide range of cognitive and physiological processes. Select plant-derived ‘phyto’cannabinoids such as Δ-9-tetrahydrocannabinol (Δ9-THC) bind to the CB receptors and trigger the ECS, and in the case of Δ9-THC, while it has therapeutic value, can also produce detrimental effects. Current research is aimed at the identification of additional phytocannabinoids with minimal psychotropic effects with potential for therapeutic development. Although decades of research on the ECS and its components have expanded our understanding of the mechanisms and implications of endocannabinoid signaling in mammals, it continues to evolve. Here, we provide a brief overview of the ECS and its overlap with other related lipid-mediated signaling pathways.”

https://pubmed.ncbi.nlm.nih.gov/32648908/

“Therapeutic intervention in the dysregulation of the ECS will no doubt involve new phytocannabinoids and various synthetic CBs with which to control an increasing list of ECS- related pathologies.”

https://portlandpress.com/essaysbiochem/article/doi/10.1042/EBC20190086/225762/The-endocannabinoid-system

Anandamide and 2-AG are the principal endogenous ligands that define the classical endocannabinoid signaling system (ECS).

Cannabidiol attenuates methamphetamine-induced conditioned place preference via the Sigma1R/AKT/GSK-3β/CREB signaling pathway in rats

 Issue Cover“Methamphetamine (METH) is a highly addictive psychostimulant.

Cannabidiol (CBD) is an exogenous cannabinoid without psychostimulating activity, which has potential therapeutic effects on opioid addiction. However, it is unclear whether CBD has therapeutic effects on METH-induced motivational effects.

The present study examines whether CBD has a protective effect on METH-induced conditioned place preference (CPP) in rats by regulating the Sigma1R and AKT-GSK3β-CREB signaling pathway.

The present study found that METH can induce CPP in rats. When a pretreatment of CBD is applied, the CBD can weaken CPP in METH-induced rats by regulating the SigmaR1/AKT/GSK-3β/CREB signaling pathway.

The results of this study indicate that CBD has a potential therapeutic effect on METH-induced rewarding effects.”

https://pubmed.ncbi.nlm.nih.gov/32670551/

https://academic.oup.com/toxres/article-abstract/9/3/202/5831937?redirectedFrom=fulltext

Understanding the basics of cannabidiol from cannabis to apply to therapeutics in epilepsy

Page Header“The compounds present in cannabis have been in use for both recreational and medicinal purposes for many centuries. Changes in the legislation in South Africa have led to an increase in the number of people interested in using these compounds for self-medication. Many of them may approach their general practitioner as the first source of information about possible therapeutic effects. It is important that medical professionals are able to give patients the correct information. Cannabidiol (CBD) is one of the main compounds in cannabis plants, and there is evidence that it can successfully treat certain patients with epilepsy. This review looks at the most recent evidence on the use of CBD in the treatment of epilepsy and explores the mechanisms behind these beneficial effects.”

https://pubmed.ncbi.nlm.nih.gov/32657678/

http://www.samj.org.za/index.php/samj/article/view/12839

Cannabidiol induces osteoblast differentiation via angiopoietin1 and p38 MAPK

Publication cover image“In this study, we report the potential of cannabidiol, one of the major cannabis constituents, for enhancing osteoblastic differentiation in U2OS and MG-63 cells.

Cannabidiol increased the expression of Angiopoietin1 and the enzyme activity of alkaline phosphatase in U2OS and MG-63. Invasion and migration assay results indicated that the cell mobility was activated by cannabidiol in U2OS and MG-63. Western blotting analysis showed that the expression of tight junction related proteins such as Claudin1, Claudin4, Occuludin1, and ZO1 was increased by cannabidiol in U2OS and MG-63.

Alizarin Red S staining analysis showed that calcium deposition and mineralization was enhanced by cannabidiol in U2OS and MG-63. Western blotting analysis indicated that the expression of osteoblast differentiation related proteins such as distal-less homeobox 5, bone sialoprotein, osteocalcin, type I collagen, Runt-related transcription factor 2 (RUNX2), osterix (OSX), and alkaline phosphatase was time dependently upregulated by cannabidiol in U2OS and MG-63. Mechanistically, cannabidiol-regulated osteoblastic differentiation in U2OS and MG-63 by strengthen the protein-protein interaction among RUNX2, OSX, or the phosphorylated p38 mitogen-activated protein kinase (MAPK).

In conclusion, cannabidiol increased Angiopoietin1 expression and p38 MAPK activation for osteoblastic differentiation in U2OS and MG-63 suggesting that cannabidiol might provide a novel therapeutic option for the bone regeneration.”

https://pubmed.ncbi.nlm.nih.gov/32656944/

https://onlinelibrary.wiley.com/doi/abs/10.1002/tox.22996