Category Archives: Cardiovascular Disease

An overview on plants cannabinoids endorsed with cardiovascular effects

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Biomedicine & Pharmacotherapy“Nowadays cardiovascular diseases (CVDs) are the major causes for the reduction of the quality of life.

The endocannabinoid system is an attractive therapeutic target for the treatment of cardiovascular disorders due to its involvement in vasomotor control, cardiac contractility, blood pressure and vascular inflammation. Alteration in cannabinoid signalling can be often related to cardiotoxicity, circulatory shock, hypertension, and atherosclerosis.

Plants have been the major sources of medicines until modern eras in which researchers are experiencing a rediscovery of natural compounds as novel therapeutics.

One of the most versatile plant is Cannabis sativa L., containing phytocannabinoids that may play a role in the treatment of CVDs.

The aim of this review is to collect and investigate several less studied plants rich in cannabinoid-like active compounds able to interact with cannabinoid system; these plants may play a pivotal role in the treatment of disorders related to the cardiovascular system.”

https://pubmed.ncbi.nlm.nih.gov/34332376/

“Cannabis sativa L. is the most investigated source of phytocannabinoids. Other plants are a rich source of cannabinoid-like compounds. Cannabinoid-like compounds may interact with cannabinoid system. Most of them may exhibit a protective role on cardiovascular system.” 

https://www.sciencedirect.com/science/article/pii/S0753332221007459?via%3Dihub

 

Cannabis Seed Oil Alleviates Experimental Atherosclerosis by Ameliorating Vascular Inflammation in Apolipoprotein-E-Deficient Mice

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Go to Volume 0, Issue 0“In recent decades, epidemiological, clinical, and experimental studies have demonstrated that a diet with antioxidant or anti-inflammatory function plays a central role in the prevention of atherosclerosis (AS).

The purpose of this study was to explore the effects of Cannabis seed oil (CO) administration on in vitro antioxidant capacity as well as blood lipid profiles, lipid peroxidation, inflammatory response, and endothelial cell integrity. Female ApoE-/- mice were fed a high-cholesterol diet and administrated with CO or phosphate-buffered saline (PBS) and seal oil by gavage for 8 weeks.

The results show that CO administration reduced the levels of serum triglycerides and low-density lipoprotein cholesterol at week 6. Additionally, a decrease in serum tumor necrosis factor α and nitric oxide was also observed. Moreover, results from CD31 staining and scanning electron microscopy revealed that CO treatment alleviated the endothelial cell damage and lipid deposition induced by a high-cholesterol diet. The ratio of lesion area to the total aorta area was 19.57% for the CO group, which was lower than the PBS control group (24.67%).

Collectively, CO exerted anti-atherosclerotic effects by modulating serum lipid profiles and inflammatory responses and improving endothelial cell integrity and arterial lipid deposition. The results provide a promising preventive strategy for the early progression of AS.”

https://pubmed.ncbi.nlm.nih.gov/34037390/

https://pubs.acs.org/doi/10.1021/acs.jafc.0c07251

Association Between Marijuana Use and Cardiovascular Disease in US Adults

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Cureus | LinkedIn “This study aims to add evidence regarding the impact marijuana use has on the prevalence of cardiovascular disease.

Our study lends support to the notion that marijuana use does not have an association with cardiovascular disease.

Although previous literature has shown that marijuana use has a negative impact on cardiovascular health, our study suggests that users and non-users of marijuana did not have an association with the prevalence of cardiovascular disease.”

https://pubmed.ncbi.nlm.nih.gov/33409101/

“The primary aim of this study was to evaluate the relationship between marijuana use and cardiovascular disease. After controlling for several confounding variables, we found that there was a decrease in the prevalence of cardiovascular events with marijuana use. In conclusion, our study found that there is no link to marijuana use and an increase in cardiovascular disease. Furthermore, there may be a link between marijuana use and lowered risk of cardiovascular disease”

https://www.cureus.com/articles/45502-association-between-marijuana-use-and-cardiovascular-disease-in-us-adults

Therapeutic Applications of Cannabinoids in Cardiomyopathy and Heart Failure

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 logo“A large number of cannabinoids have been discovered that could play a role in mitigating cardiac affections. However, none of them has been as widely studied as cannabidiol (CBD), most likely because, individually, the others offer only partial effects or can activate potential harmful pathways.

In this regard, CBD has proven to be of great value as a cardioprotective agent since it is a potent antioxidant and anti-inflammatory molecule. Thus, we conducted a review to condensate the currently available knowledge on CBD as a therapy for different experimental models of cardiomyopathies and heart failure to detect the molecular pathways involved in cardiac protection.

CBD therapy can greatly limit the production of oxygen/nitrogen reactive species, thereby limiting cellular damage, protecting mitochondria, avoiding caspase activation, and regulating ionic homeostasis. Hence, it can affect myocardial contraction by restricting the activation of inflammatory pathways and cytokine secretion, lowering tissular infiltration by immune cells, and reducing the area of infarct and fibrosis formation. These effects are mediated by the activation or inhibition of different receptors and target molecules of the endocannabinoid system.

In the final part of this review, we explore the current state of CBD in clinical trials as a treatment for cardiovascular diseases and provide evidence of its potential benefits in humans.”

https://pubmed.ncbi.nlm.nih.gov/33194003/

https://www.hindawi.com/journals/omcl/2020/4587024/

Protective Effects of ( E)-β-Caryophyllene (BCP) in Chronic Inflammation

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nutrients-logo“(E)-β-caryophyllene (BCP) is a bicyclic sesquiterpene widely distributed in the plant kingdom, where it contributes a unique aroma to essential oils and has a pivotal role in the survival and evolution of higher plants.

Recent studies provided evidence for protective roles of BCP in animal cells, highlighting its possible use as a novel therapeutic tool.

Experimental results show the ability of BCP to reduce pro-inflammatory mediators such as tumor necrosis factor-alfa (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), thus ameliorating chronic pathologies characterized by inflammation and oxidative stress, in particular metabolic and neurological diseases.

Through the binding to CB2 cannabinoid receptors and the interaction with members of the family of peroxisome proliferator-activated receptors (PPARs), BCP shows beneficial effects on obesity, non-alcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) liver diseases, diabetes, cardiovascular diseases, pain and other nervous system disorders.

This review describes the current knowledge on the biosynthesis and natural sources of BCP, and reviews its role and mechanisms of action in different inflammation-related metabolic and neurologic disorders.”

https://pubmed.ncbi.nlm.nih.gov/33114564/

https://www.mdpi.com/2072-6643/12/11/3273

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Cannabis sativa extracts protect LDL from Cu 2+-mediated oxidation

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See the source image“Multiple therapeutic properties have been attributed to Cannabis sativa. However, further research is required to unveil the medicinal potential of Cannabis and the relationship between biological activity and chemical profile.

Objectives: The primary objective of this study was to characterize the chemical profile and antioxidant properties of three varieties of Cannabis sativa available in Uruguay during progressive stages of maturation.

Results: The main cannabinoids in the youngest inflorescences were tetrahydrocannabinolic acid (THC-A, 242 ± 62 mg/g) and tetrahydrocannabinol (THC, 7.3 ± 6.5 mg/g). Cannabinoid levels increased more than twice in two of the mature samples. A third sample showed a lower and constant concentration of THC-A and THC (177 ± 25 and 1 ± 1, respectively). The THC-A/THC rich cannabis extracts increased the latency phase of LDL oxidation by a factor of 1.2-3.5 per μg, and slowed down the propagation phase of lipoperoxidation (IC50 1.7-4.6 μg/mL). Hemp, a cannabidiol (CBD, 198 mg/g) and cannabidiolic acid (CBD-A, 92 mg/g) rich variety, also prevented the formation of conjugated dienes during LDL oxidation. In fact, 1 μg of extract was able to stretch the latency phase 3.7 times and also to significantly reduce the steepness of the propagation phase (IC50 of 8 μg/mL). Synthetic THC lengthened the duration of the lag phase by a factor of 21 per μg, while for the propagation phase showed an IC50 ≤ 1 μg/mL. Conversely, THC-A was unable to improve any parameter. Meanwhile, the presence of 1 μg of pure CBD and CBD-A increased the initial latency phase 4.8 and 9.4 times, respectively, but did not have an effect on the propagation phase.

Conclusion: Cannabis whole extracts acted on both phases of lipid oxidation in copper challenged LDL. Those effects were just partially related with the content of cannabinoids and partially recapitulated by isolated pure cannabinoids. Our results support the potentially beneficial effects of cannabis sativa whole extracts on the initial phase of atherosclerosis.”

https://pubmed.ncbi.nlm.nih.gov/33123676/

“Our findings support the beneficial effects of Cannabis sativa extracts on the initial phase of atherosclerosis. Since isolated cannabinoids were less effective preventing the oxidation of LDL, a synergistic effect between the diverse arrange of phytochemicals present in complex extracts is supported, reinforcing the entourage hypothesis and the use of whole medicinal cannabis extracts for therapeutic purposes.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00042-0

Cannabinoids in Metabolic Syndrome and Cardiac Fibrosis

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 SpringerLink“This article provides a concise overview of how cannabinoids and the endocannabinoid system (ECS) have significant implications for the prevention and treatment of metabolic syndrome (MetS) and for the treatment of cardiovascular disorders, including cardiac fibrosis.

Recent findings: Over the past few years, the ECS has emerged as a pivotal component of the homeostatic mechanisms for the regulation of many bodily functions, including inflammation, digestion, and energy metabolism. Therefore, the pharmacological modulation of the ECS by cannabinoids represents a novel strategy for the management of many diseases. Specifically, increasing evidence from preclinical research studies has opened new avenues for the development of cannabinoid-based therapies for the management and potential treatment of MetS and cardiovascular diseases. Current information indicates that modulation of the ECS can help maintain overall health and well-being due to its homeostatic function. From a therapeutic perspective, cannabinoids and the ECS have also been shown to play a key role in modulating pathophysiological states such as inflammatory, neurodegenerative, gastrointestinal, metabolic, and cardiovascular diseases, as well as cancer and pain. Thus, targeting and modulating the ECS with cannabinoids or cannabinoid derivatives may represent a major disease-modifying medical advancement to achieve successful treatment for MetS and certain cardiovascular diseases.”

https://pubmed.ncbi.nlm.nih.gov/33089434/

https://link.springer.com/article/10.1007%2Fs11906-020-01112-7

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

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ijms-logo“Cannabidiol (CBD) is known for its vasorelaxant (including in the human pulmonary artery), anti-proliferative and anti-inflammatory properties. The aim of our study was to examine the potential preventive effect of chronic CBD administration (10 mg/kg/day for three weeks) on monocrotaline (MCT)-induced pulmonary hypertension (PH) rats.

PH was connected with elevation of right ventricular systolic pressure; right ventricle hypertrophy; lung edema; pulmonary artery remodeling; enhancement of the vasoconstrictor and decreasing vasodilatory responses; increases in plasma concentrations of tissue plasminogen activator, plasminogen activator inhibitor type 1 and leukocyte count; and a decrease in blood oxygen saturation.

CBD improved all abovementioned changes induced by PH except right ventricle hypertrophy and lung edema. In addition, CBD increased lung levels of some endocannabinoids (anandamide, N-arachidonoyl glycine, linolenoyl ethanolamide, palmitoleoyl ethanolamide and eicosapentaenoyl ethanolamide but not 2-arachidonoylglycerol). CBD did not affect the cardiopulmonary system of control rats or other parameters of blood morphology in PH.

Our data suggest that CBD ameliorates MCT-induced PH in rats by improving endothelial efficiency and function, normalization of hemostatic alterations and reduction of enhanced leukocyte count determined in PH. In conclusion, CBD may be a safe, promising therapeutic or adjuvant therapy agent for the treatment of human pulmonary artery hypertension.”

https://pubmed.ncbi.nlm.nih.gov/32992900/

https://www.mdpi.com/1422-0067/21/19/7077

The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease

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ijms-logo“Cannabidiol (CBD) is a non-intoxicating and generally well-tolerated constituent of cannabis which exhibits potential beneficial properties in a wide range of diseases, including cardiovascular disorders.

Due to its complex mechanism of action, CBD may affect the cardiovascular system in different ways. Thus, we reviewed the influence of CBD on this system in health and disease to determine the potential risk of cardiovascular side effects during CBD use for medical and wellness purposes and to elucidate its therapeutic potential in cardiovascular diseases.

Administration of CBD to healthy volunteers or animals usually does not markedly affect hemodynamic parameters. Although CBD has been found to exhibit vasodilatory and antioxidant properties in hypertension, it has not affected blood pressure in hypertensive animals. Hypotensive action of CBD has been mainly revealed under stress conditions.

Many positive effects of CBD have been observed in experimental models of heart diseases (myocardial infarction, cardiomyopathy, myocarditis), stroke, neonatal hypoxic ischemic encephalopathy, sepsis-related encephalitis, cardiovascular complications of diabetes, and ischemia/reperfusion injures of liver and kidneys.

In these pathological conditions CBD decreased organ damage and dysfunction, oxidative and nitrative stress, inflammatory processes and apoptosis, among others. Nevertheless, further clinical research is needed to recommend the use of CBD in the treatment of cardiovascular diseases.”

https://pubmed.ncbi.nlm.nih.gov/32937917/

https://www.mdpi.com/1422-0067/21/18/6740

Pharmacological activation of CB2 receptor protects against ethanol-induced myocardial injury related to RIP1/RIP3/MLKL-mediated necroptosis

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 Molecular and Cellular Biochemistry | Home“Chronic ethanol abuse can lead to harmful consequences for the heart, resulting in systolic dysfunction, variability in the heart rate, arrhythmia, and cardiac remodelling. However, the precise molecular mechanism responsible for ethanol-induced cardiomyopathy is poorly understood. In this regard, the present study aimed to describe the RIP1/RIP3/MLKL-mediated necroptotic cell death that may be involved in ethanol-induced cardiomyopathy and characterize CBR-mediated effects on the signalling pathway and myocardial injury.

We performed an ethanol vapour administration experiment to analyse the effects of ethanol on cardiac structure and function in male C57BL/6J mice. Ethanol induced a significant decline in the cardiac structure and function, as evidenced by a decline in ejection fraction and fractional shortening, and an increase in serum Creatine Kinase levels, myocardial collagen content, and inflammatory reaction. Furthermore, ethanol also upregulated the expression levels of necroptosis-related markers such as p-RIP1, p-RIP3, and p-MLKL in the myocardium. Nec-1 treatment exerted significant cardioprotective effects by salvaging the heart tissue, improving the cardiac function, and mitigating inflammation and necroptosis.

In addition, ethanol abuse caused an imbalance in the endocannabinoid system and regulated two cannabinoid receptors (CB1R and CB2R) in the myocardium. Treatment with selective CB2R agonists, JWH-133 or AM1241, markedly improved the cardiac dysfunction and reduced the ethanol-induced necroptosis in the myocardium.

Altogether, our data provide evidence that ethanol abuse-induced cardiotoxicity can possibly be attributed to the RIP1/RIP3/MLKL-mediated necroptosis. Moreover, pharmacological activation of CB2R may represent a new cardioprotective strategy against ethanol-induced cardiotoxicity.”

https://pubmed.ncbi.nlm.nih.gov/32681290/

https://link.springer.com/article/10.1007%2Fs11010-020-03828-1