Category Archives: Uncategorized

Targeting of Protein’s Messenger RNA for Viral Replication, Assembly and Release in SARS-CoV-2 Using Whole Genomic Data From South Africa: Therapeutic Potentials of Cannabis Sativa L

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frontiers in pharmacology – Retraction Watch“The possible evolutionary trend of COVID-19 in South Africa was investigated by comparing the genome of SARS-CoV-2 isolated from a patient in KwaZulu-Natal, South Africa with those isolated from China, Spain, Italy, and United States, as well as the genomes of Bat SARS CoV, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Mouse Hepatitis Virus (MHV), and Infectious Bronchitis Virus (IBV). Phylogenetic analysis revealed a strong homology (96%) between the genomes of SARS-CoV-2 isolated from KwaZulu-Natal, South Africa and those isolated from the study countries as well as those isolated from bat SARS CoV, MERS-CoV, MHV and IBV.

The ability of phytocannabinoids from Cannabis sativa infusion to interact with gene segments (mRNAs) coding for proteins implicated in viral replication, assembly and release were also investiagted using computational tools. Hot water infusion of C. sativa leaves was freeze-dried and subjected to Gas Chromatography-Mass Spectroscopy analysis which revealed the presence of tetrahydrocannabivarin, cannabispiran, cannabidiol tetrahydrocannabinol, cannabigerol, and cannabinol. Molecular docking analysis revealed strong binding affinities and interactions between the phytocannabinoids and codon mRNAs for ORF1ab, Surface glycoprotein, Envelope protein and Nucleocapsid phosphoprotein from SARS-CoV-2 whole genome which may be due to chemico-biological interactions as a result of nucleophilic/electrophilic attacks between viral nucleotides and cannabinoids.

These results depict the spread of SARS-CoV-2 is intercontinental and might have evolved from other coronaviruses. The results also portray the phytocannabinoids of C. sativa infusion as potential therapies against COVID-19 as depicted by their ability to molecularly interact with codon mRNAs of proteins implicated in the replication, translation, assembly, and release of SARS-CoV-2. However, further studies are needed to verify these activities in pre-clinical and clinical studies.”

https://pubmed.ncbi.nlm.nih.gov/34539415/

“Taken together, the results from this study indicates a homology between the genome of SARS-CoV-2 isolated from KwaZulu-Natal, South Africa and those isolated from Europe, Asia and North America, as well as those isolated from bat SARS COV, MERS-CoV, MHV and IBV. Thus, depicting the spread of the virus is intercontinental and might have evolved from other coronaviruses. The results also indicate the phytocannabinoids of C. sativa infusion as potential therapies against COVID-19 as depicted by their ability to molecularly interact with codon mRNAs of proteins implicated in the replication, translation, assembly, and release of SARS-CoV-2.”

https://www.frontiersin.org/articles/10.3389/fphar.2021.736511/full

Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults

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Scientific Reports“Aged skeletal muscle undergoes metabolic and structural alterations eventually resulting in a loss of muscle strength and mass, i.e. age-related sarcopenia. Therefore, novel targets for muscle growth purposes in elderly are needed.

Here, we explored the role of the cannabinoid system in muscle plasticity through the expression of muscle cannabinoid receptors (CBs) in young and old humans.

The CB1 expression was higher (+ 25%; p = 0.04) in muscle of old (≥ 65 years) vs. young adults (20-27 years), whereas CB2 was not differently expressed. Furthermore, resistance exercise tended to increase the CB1 (+ 11%; p = 0.055) and CB2 (+ 37%; p = 0.066) expression in muscle of older adults. Interestingly, increases in the expression of CB2 following resistance exercise positively correlated with changes in key mechanisms of muscle homeostasis, such as catabolism (FOXO3a) and regenerative capacity (Pax7, MyoD).

This study for the first time shows that CB1 is differentially expressed with aging and that changes in CB2 expression upon resistance exercise training correlate with changes in mediators that play a central role in muscle plasticity.

These data confirm earlier work in cells and mice showing that the cannabinoid system might orchestrate muscle growth, which is an incentive to further explore CB-based strategies that might counteract sarcopenia.”

https://pubmed.ncbi.nlm.nih.gov/34526596/

“In conclusion, cell culture and murine experiments suggested that CBs can be a promising target to treat cachexia and sarcopenia through modulation of the metabolism and muscle regenerative capacity. These data imply that CB modulation might be a promising tool to combat muscle degeneration. ”

https://www.nature.com/articles/s41598-021-97859-3

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

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ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

Cannabidiol reverses memory impairments and activates components of the Akt/GSK3β pathway in an experimental model of estrogen depletion

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Behavioural Brain Research“Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairments and increases the susceptibility to neural damage.

Here, we have sought to investigate the effects of Cannabidiol (CBD) a non-psychotomimetic compound from Cannabis sativa, on memory deficits induced by estrogen depletion in rats, and its underlying mechanisms.

Results revealed that ovariectomy impaired avoidance memory, and CBD was able to completely reverse estrogen depletion-induced memory impairment. Ovariectomy also reduced Akt/GSK3β pathway’s activation by decreasing the phosphorylation levels of Akt and GSK3β and Bcl2 levels, which were ameliorated by CBD.

The present results indicate that CBD leads to a functional recovery accompanied by the Akt/GSK3β survival pathway’s activation, supporting its potential as a treatment for estrogen decline-induced deterioration of neural functioning and maintenance.”

https://pubmed.ncbi.nlm.nih.gov/34450240/

“In the present study, we aimed to understand the possible neuroprotective effect of CBD against estrogen depletion-induced emotional memory deficits, using an animal model of ovariectomy-induced estrogen depletion. Once CBD and estradiol modulate a common pathway, we speculated whether CBD would be able to reverse the deleterious effect of estradiol decline observed in menopause. Results revealed that ovariectomy impaired avoidance memory, and CBD was able to completely reverse estrogen depletion-induced memory impairment.”

https://www.sciencedirect.com/science/article/abs/pii/S0166432821004435?via%3Dihub

Hemp ( Cannabis sativa L.) Flour-Based Wheat Bread as Fortified Bakery Product

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plants-logo“Hemp flour from Dacia Secuieni and Zenit varieties was added to bread in different proportions (5%, 10%, 15% and 20%) to improve its nutritional properties.

The purpose of this paper was to present the advanced nutritional characteristics of these bread samples.

The selected varieties of hemp, accepted for human consumption, met the requirements for the maximum accepted level of THC in seeds. The protein content of new products increased from 8.76 to 11.48%, lipids increased from 0.59 to 5.41%, mineral content from 1.33 to 1.62%, and fiber content from 1.17 to 5.84%. Elasticity and porosity decreased from 95.51 to 80% and 78.65 to 72.24%, respectively. K, Mg, Ca, P, Mn and Fe are the main mineral substances in bread with addition of hemp flour from the Dacia Secuieni and Zenit varieties.

The total amount of unsaturated fatty acids in the bread samples with hemp flour ranged from 67.93 g/100 g and 69.82 g/100 g. Eight amino acids were identified, of which three were essential (lysine, phenylalanine, histidine). Lysine, the deficient amino acid in wheat bread, increased from 0.003 to 0.101 g/100 g. Sucrose and fructose decreased with the addition of hemp flour, and glucose has not been identified. The amount of yeasts and molds decreased in the first 3 days of storage. Regarding the textural profile, the best results were obtained for the samples with 5% addition.

In conclusion, bread with the addition of hemp flour has been shown to have superior nutritional properties to wheat bread.”

https://pubmed.ncbi.nlm.nih.gov/34451603/

https://www.mdpi.com/2223-7747/10/8/1558

Cannabis Extract Has a Positive-Immunostimulating Effect through Proteolytic System and Metabolic Compounds of Honey Bee ( Apis mellifera) Workers

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animals-logo“In the study, we assessed the effect of hemp extract on activities of resistance parameters and the metabolic compound concentration in adult workers’ hemolymph. Bees were divided into the following groups: (1) control group fed with mixture of sugar and water-glycerine solution, (2) experimental group with pure sugar syrup and inside with cotton strips soaked with hemp extract, (3) experimental group with a mixture of sugar syrup with hemp extract. Hemp extracts caused an increase in the protein concentrations and reduced the protease activities regardless of the administration method. The protease inhibitor activities were decreased only in the group that received hemp extract on the strips. The biomarker activities (ALP, ALT, AST) increased from the control group and workers feeding extract in syrup and decreased in workers supplemented with the extract on strips. In young, 2-day-old workers, the glucose concentration was higher in the groups feeding with the extract than in the control. Hemp extract influenced an increase in urea concentrations in workers’ hemolymph in comparison with the control. The hemp supplementation positively influences the immune system of workers, and the appropriate method of administration may be adapted to the health problems of bees.”

https://pubmed.ncbi.nlm.nih.gov/34438647/

“The aim of our study was to test the immunostimulating effect of a diet with hemp extract on the resistance of the honey bee (Apis mellifera). The experiment compared the effect of supplementation between the bees receiving the extract in the form of a mixture with sugar syrup and on the strip with the extract, compared to the bees that had no contact with substance. In order to determine this effect, the biochemical indicators were analyzed: the proteolytic system (proteases, protease inhibitors, total protein concentration) responsible for the fight against pathogens/parasites, biomarkers (ALT, AST, ALP), and the basic components of metabolism (glucose and urea concentrations). Parameters were determined in the hemolymph of 2- and 7-day-old workers. Hemp extracts caused an increase in the protein concentrations. Regardless of the method of administration, proteases decreased. Protease inhibitors increased, except supplementation on strips where the activity decreased. The biomarker activities increased in the control group and workers feeding extract in syrup and decreased in workers supplemented with the extract on strips. The results of the metabolic component were as follows: glucose and urea concentrations indicate that the extract will not adversely affect metabolic changes in the insect’s organism. Hemp extract improves the natural immunity of bees.”

https://www.mdpi.com/2076-2615/11/8/2190

Changes in Hepatic Phospholipid Metabolism in Rats under UV Irradiation and Topically Treated with Cannabidiol

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antioxidants-logo“The liver is a key metabolic organ that is particularly sensitive to environmental factors, including UV radiation. As UV radiation induces oxidative stress and inflammation, natural compounds are under investigation as one method to counteract these consequences.

The aim of this study was to assess the effect of topical application of phytocannabinoid-cannabidiol (CBD) on the skin of nude rats chronically irradiated with UVA/UVB, paying particular attention to its impact on the liver antioxidants and phospholipid metabolism.

The results of this study indicate that CBD reaches the rat liver where it is then metabolized into decarbonylated cannabidiol, 7-hydroxy-cannabidiol and cannabidiol-glucuronide. CBD increased the levels of GSH and vitamin A after UVB radiation. Moreover, CBD prevents the increase of 4-hydroxynonenal and 8-iso-prostaglandin-F2α levels in UVA-irradiated rats. As a consequence of reductions in phospholipase A2 and cyclooxygenases activity following UV irradiation, CBD upregulates the level of 2-arachidonoylglycerol and downregulates prostaglandin E2 and leukotriene B4. Finally, CBD enhances decreased level of 15-deoxy-Δ-12,14-prostaglandin J2 after UVB radiation and 15-hydroxyeicosatetraenoic acid after UVA radiation.

These data show that CBD applied to the skin prevents ROS- and enzyme-dependent phospholipid metabolism in the liver of UV-irradiated rats, suggesting that it may be used as an internal organ protector.”

https://pubmed.ncbi.nlm.nih.gov/34439405/

https://www.mdpi.com/2076-3921/10/8/1157

Localisation of Cannabinoid and Cannabinoid-Related Receptors in the Horse Ileum

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Journal of Equine Veterinary Science“Colic is a common digestive disorder in horses and one of the most urgent problems in equine medicine. A growing body of literature has indicated that the activation of cannabinoid receptors could exert beneficial effects on gastrointestinal inflammation and visceral hypersensitivity.

The localisation of cannabinoid and cannabinoid-related receptors in the intestine of the horse has not yet been investigated. The purpose of this study was to immunohistochemically localise the cellular distribution of canonical and putative cannabinoid receptors in the ileum of healthy horses.

Distal ileum specimens were collected from six horses at the slaughterhouse. The tissues were fixed and processed to obtain cryosections which were used to investigate the immunoreactivity of canonical cannabinoid receptors 1 (CB1R) and 2 (CB2R), and three putative cannabinoid-related receptors: nuclear peroxisome proliferator-activated receptor-alpha (PPARα), transient receptor potential ankyrin 1 and serotonin 5-HT1a receptor (5-HT1aR).

Cannabinoid and cannabinoid-related receptors showed a wide distribution in the ileum of the horse.

The epithelial cells showed immunoreactivity for CB1R, CB2R and 5-HT1aR. Lamina propria inflammatory cells showed immunoreactivity for CB2R and 5-HT1aR. The enteric neurons showed immunoreactivity for CB1R, transient receptor potential ankyrin 1 and PPARα. The enteric glial cells showed immunoreactivity for CB1R and PPARα. The smooth muscle cells of the tunica muscularis and the blood vessels showed immunoreactivity for PPARα.

The present study represents a histological basis which could support additional studies regarding the distribution of cannabinoid receptors during gastrointestinal inflammatory diseases as well as studies assessing the effects of non-psychotic cannabis-derived molecules in horses for the management of intestinal diseases.”

https://pubmed.ncbi.nlm.nih.gov/34416995/

“Horses are often affected by gastrointestinal pathologies. Researchers are searching for new therapies for equine gastrointestinal diseases. New products with cannabinoid receptor agonists have been produced for horses. Cannabinoid receptors showed a wide distribution in the ileum of the horse. Activation of cannabinoids receptors could attenuate intestinal inflammation.”

https://www.sciencedirect.com/science/article/abs/pii/S073708062100318X?via%3Dihub

 

The Impact of CB1 Receptor on Inflammation in Skeletal Muscle Cells

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Dove Medical Press - Open Access Publisher of Medical Journals“Background: Various factors trigger the inflammatory response and cytokine activation in skeletal muscle. Inflamed muscle will exhibit significant levels of inflammation and cytokine activity. Interleukin-6 (IL-6), a pro-inflammatory cytokine, exerts pleiotropic effects on skeletal muscle. Endocannabinoid produced by all cell types binds to a class of G protein-coupled receptors, in particular cannabinoid CB1 receptors, to induce skeletal muscle actions.

Objective: The purpose of this research was to discover whether activation of cannabinoid CB1 receptors in L6 skeletal muscle cells may promote IL-6 gene expression.

Materials and methods: L6 skeletal muscle cells were cultured in 25 cm2 flasks and quantitative reverse transcription-polymerase chain reaction (probe-based) utilised to quantify IL-6 gene expression levels among different treatment settings.

Results: Arachidonyl-2′-chloroethylamide (ACEA) 10 nM, a persistent selective CB1 receptor agonist, promotes IL-6 gene expression in a time-dependent manner. Rimonabant 100 nM, a selective cannabinoid CB1 receptor antagonist, blocks the impact of ACEA. However, insulin does not change IL-6 gene expression.

Conclusion: For the first time, a unique link between ACEA and IL-6 up-regulation has been established; IL-6 up-regulation generated by ACEA is mediated in skeletal muscle through cannabinoid CB1 receptor activation. As a result, cannabinoid CB1 receptors may be useful pharmaceutical targets in the treatment of inflammation and related disorders in skeletal muscle tissues.”

https://pubmed.ncbi.nlm.nih.gov/34421307/

“In the present study, I have demonstrated that when cannabinoid CB1 receptors are activated, the expression of IL-6 increases in a way that is influenced by time. Such findings deliver a novel mechanism characterised by cannabinoid analogue playing the role of a pro-inflammatory mediator in the skeletal muscle tissue. The findings from the present study also imply that there may be a possible therapeutic use of cannabinoid CB1 receptor antagonist at acute early states for skeletal muscle dysfunction related to inflammation. My findings point to skeletal muscle cell cannabinoid CB1 receptor as a therapeutic target, and expand its potential to include anti-inflammatory effects in diabetes, obesity, and sarcopenia.”

https://www.dovepress.com/the-impact-of-cb1-receptor-on-inflammation-in-skeletal-muscle-cells-peer-reviewed-fulltext-article-JIR

Pharmacological characterisation of the CB 1 receptor antagonist activity of cannabidiol in the rat vas deferens bioassay

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European Journal of Pharmacology“Cannabidiol is increasingly considered for treatment of a wide range of medical conditions. Binding studies suggest that cannabidiol binds to CB1 receptors. In the rat isolated vas deferens bioassay, a single electrical pulse causes a biphasic contraction from nerve-released ATP and noradrenaline. WIN 55,212-2 acts on prejunctional CB1 receptors to inhibit release of these transmitters. In this bioassay, we tested whether cannabidiol and SR141716 were acting as competitive antagonists of this receptor. Monophasic contractions mediated by ATP or noradrenaline in the presence of prazosin or NF449 (P2X1 inhibitor), respectively, were measured to a single electrical pulse delivered every 30 min. Following treatment with cannabidiol (10-100 μM) or SR141716 (0.003-10 μM), cumulative concentrations of WIN 55,212-2 (0.001-30 μM) were applied followed by a single electrical pulse. The WIN 55,212-2 concentration-contraction curve EC50 values were applied to global regression analysis to determine the pKB. The antagonist potency of cannabidiol at the CB1 receptor in the rat vas deferens bioassay matched the reported receptor binding affinity. Cannabidiol was a competitive antagonist of WIN 55,212-2 with pKB values of 5.90 when ATP was the effector transmitter and 5.29 when it was noradrenaline. Similarly, SR141716 was a competitive antagonist with pKB values of 8.39 for ATP and 7.67 for noradrenaline as the active transmitter. Cannabidiol’s low micromolar CB1 antagonist pKB values suggest that at clinical blood levels (1-3 μM) it may act as a CB1 antagonist at prejunctional neuronal sites with more potency when ATP is the effector than for noradrenaline.”

https://pubmed.ncbi.nlm.nih.gov/34416240/

https://www.sciencedirect.com/science/article/abs/pii/S0014299921005860?via%3Dihub