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

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

n-3 Polyunsaturated Fatty Acid Amides: New Avenues in the Prevention and Treatment of Breast Cancer.

ijms-logo “Over the last decades a renewed interest in n-3 very long polyunsaturated fatty acids (PUFAs), derived mainly from fish oils in the human diet, has been observed because of their potential effects against cancer diseases, including breast carcinoma. These n-3 PUFAs mainly consist of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that, alone or in combination with anticancer agents, induce cell cycle arrest, autophagy, apoptosis, and tumor growth inhibition. A large number of molecular targets of n-3 PUFAs have been identified and multiple mechanisms appear to underlie their antineoplastic activities. Evidence exists that EPA and DHA also elicit anticancer effects by the conversion to their corresponding ethanolamide derivatives in cancer cells, by binding and activation of different receptors and distinct signaling pathways. Other conjugates with serotonin or dopamine have been found to exert anti-inflammatory activities in breast tumor microenvironment, indicating the importance of these compounds as modulators of tumor epithelial/stroma interplay. The objective of this review is to provide a general overview and an update of the current n-3 PUFA derivative research and to highlight intriguing aspects of the potential therapeutic benefits of these low-toxicity compounds in breast cancer treatment and care.”

https://www.ncbi.nlm.nih.gov/pubmed/32224850

https://www.mdpi.com/1422-0067/21/7/2279

“Anticancer effects of n-3 EPA and DHA and their endocannabinoid derivatives on breast cancer cell growth and invasion.”  https://www.ncbi.nlm.nih.gov/pubmed/31679810

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Dietary intake of polyunsaturated fatty acids alleviates cognition deficits and depression-like behaviour via cannabinoid system in sleep deprivation rats.

Behavioural Brain Research“Sleep deprivation (SD) is a common feature in modern society. Prolonged sleep deprivation causes cognition deficits and depression-like behavior in the model of animal experiments.

Endocannabinoid system are key modulators of synaptic function, which were related to memory and mood. Although the underlying mechanism remains unknown, several studies indicated the benefits of polyunsaturated fatty acids (PUFAs, linolenic acid, 39.7%; linoleic acid, 28%; and oleic acid, 22%) on brain function through the endocannabinoid system.

The present study aimed to evaluate the influence of dietary PUFAs on cognition deficits induced by sleep deprivation in Sprague Dawley rats.

The results revealed that SD led to the disorder of cognition and mood which was improved by the supplement of PUFAs.

SD significantly increased the mEPSC frequency, and decreased the protein level of cannabinoid type-1 receptors (CB1R). These changes were restored by supplement of PUFAs, which showed a similar level to the control group. Behaviour tests showed that the positive effects on repairing cognition and anxiety disorders were almost completely abolished when the CB1R receptor antagonist rimonabant was applied to the SD rats.

These findings indicated that PUFAs are a factor regulating cognition deficits and depression induced by SD via cannabinoid type-1 receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/32035867

“PUFAs reduced cognition deficits and depression-like behaviours of sleep deprivation rats in the behaviour tests.”

https://www.sciencedirect.com/science/article/pii/S0166432819317218?via%3Dihub

“Hempseed oil is over 80% in polyunsaturated fatty acids (PUFAs), and is an exceptionally rich source of the two essential fatty acids (EFAs) linoleic acid (18:2 omega-6) and alpha-linolenic acid (18:3 omega-3). The omega-6 to omega-3 ratio (n6/n3) in #hempseed oil is normally between 2:1 and 3:1, which is considered to be optimal for human health.”

https://www.researchgate.net/publication/226272227_Hempseed_as_a_nutritional_resource_An_overview

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

The effect of high maternal linoleic acid on endocannabinoid signalling in rodent hearts.

Image result for journal of developmental origins of health and disease “The endocannabinoid system (ECS), modulated by metabolites of linoleic acid (LA), is important in regulating cardiovascular function.

In pregnancy, LA is vital for foetal development.

Data indicate that a high LA diet alters cell viability and CB2 expression, potentially influencing cardiac function during pregnancy and development of the offspring’s heart.”

https://www.ncbi.nlm.nih.gov/pubmed/31814560

https://www.cambridge.org/core/journals/journal-of-developmental-origins-of-health-and-disease/article/effect-of-high-maternal-linoleic-acid-on-endocannabinoid-signalling-in-rodent-hearts/C92E2C1126249B7CF9D8A929F0E52FA2

“A number of previous studies have shown that polyunsaturated fatty acids (PUFAs) and phytosterols are critically important for human health. Hempseed is a rich source of plant oil, which contains more than 80% PUFAs. The fatty acids in hempseed oil include a variety of essential fatty acids, including linoleic acid ”

https://link.springer.com/article/10.1007%2Fs10059-011-0042-6

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

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

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

Figure thumbnail fx1

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabinoid receptor type 1 modulates the effects of polyunsaturated fatty acids on memory of stressed rats.

 Publication Cover“Memory and GABAergic activity in the hippocampus of stressed rats improve after n-3 polyunsaturated fatty acid (PUFA) supplementation.

On the other hand, cannabinoid receptor type 1 (CB1) strongly regulates inhibitory neurotransmission in the hippocampus. Speculation about a possible relation between stress, endocannabinoids, and PUFAs.

Here, we examined whether the effects of PUFAs on memory of chronically stressed rats depends on pharmacological manipulation of CB1 receptors.

Memory improved in the stressed rats that were treated with AM251 and/or n-3 PUFAs. Supplementation with n-6 PUFAs did not affect memory of stressed rats, but co-treatment with AM251 improved it, while co-treatment with WIN55,212-2 did not affect memory.

Our results demonstrate that activity of the CB1 receptors may modulate the effects of PUFAs on memory of stressed rats. This study suggests that endocannabinoids and PUFAs can both become a singular system by being self-regulated in limbic areas, so they control the effects of stress on the brain.”

https://www.ncbi.nlm.nih.gov/pubmed/31637966

https://www.tandfonline.com/doi/abs/10.1080/1028415X.2019.1659561?journalCode=ynns20

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

N-Eicosapentaenoyl Dopamine, A Conjugate of Dopamine and Eicosapentaenoic Acid (EPA), Exerts Anti-inflammatory Properties in Mouse and Human Macrophages.

nutrients-logo“A large body of evidence suggests that dietary n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), contribute to a reduced inflammatory tone thereby lowering the risk for several chronic and degenerative diseases. Different mechanisms have been proposed to explain these anti-inflammatory effects, including those involving endocannabinoids and endocannabinoid-like molecules.

In this context, fatty acid amides (FAAs), conjugates of fatty acids with amines or amino acids, are an emerging class of compounds. Dopamine conjugates of DHA (N-docosahexaenoyl dopamine, DHDA) and EPA (N-eicosapentaenoyl dopamine, EPDA) have previously been shown to induce autophagy, apoptosis, and cell death in different tumor lines. Additionally, DHDA has displayed anti-inflammatory properties in vitro.

Here, we tested the immune-modulatory properties of EPDA in mouse RAW 264.7 and human THP-1 macrophages stimulated with lipopolysaccharide (LPS). EPDA suppressed the production of monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in both cell lines, and nitric oxide (NO), and macrophage-inflammatory protein-3α (MIP3A) in RAW 264.7 macrophages. At a transcriptional level, EPDA attenuated cyclooxygenase-2 (COX-2) expression in both cell lines and that of MCP-1, IL-6, and interleukin-1β (IL-1β) in THP-1 macrophages.

Although further research is needed to reveal whether EPDA is an endogenous metabolite, our data suggest that this EPA-derived conjugate possesses interesting immune-modulating properties.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Stress and Western diets increase vulnerability to neuropsychiatric disorders: A common mechanism.

Publication Cover“In modern lifestyle, stress and Western diets are two major environmental risk factors involved in the etiology of neuropsychiatric disorders. Lifelong interactions between stress, Western diets, and how they can affect brain physiology, remain unknown.

A possible relation between dietary long chain polyunsaturated fatty acids (PUFA), endocannabinoids, and stress is proposed.

This review suggests that both Western diets and negative stress or distress increase n-6/n-3 PUFA ratio in the phospholipids of the plasma membrane in neurons, allowing an over-activation of the endocannabinoid system in the limbic areas that control emotions. As a consequence, an excitatory/inhibitory imbalance is induced, which may affect the ability to synchronize brain areas involved in the control of stress responses. These alterations increase vulnerability to neuropsychiatric disorders.

Accordingly, dietary intake of n-3 PUFA would counter the effects of stress on the brain of stressed subjects. In conclusion, this article proposes that PUFA, endocannabinoids, and stress form a unique system which is self-regulated in limbic areas which in turn controls the effects of stress on the brain throughout a lifetime.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Novel Anti-inflammatory and Vasodilatory ω-3 Endocannabinoid Epoxide Regioisomers.

 “Accumulating evidence suggests that diets rich in ω-3 polyunsaturated fatty acids (PUFAs) offer protection against vascular inflammation, neuroinflammation, hypertension, and thrombosis.

Recently, biochemical studies have demonstrated that these benefits are partially mediated by their conversion to ω-3 endocannabinoid epoxide metabolites. These lipid metabolites originate from the epoxidation of ω-3 endocannabinoids, docosahexanoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA) by cytochrome P450 (CYP) epoxygenases to form epoxydocosapentaenoic acid-ethanolamides (EDP-EAs) and epoxyeicosatetraenoic acid-ethanolamides (EEQ-EAs), respectively.

The EDP-EAs and EEQ-EAs are endogenously produced in rat brain and peripheral organs. Additionally, EDP-EAs and EEQ-EAs dose-dependently decrease pro-inflammatory IL-6 cytokine and increased anti-inflammatory IL-10 cytokine. Furthermore, the EEQ-EAs and EDP-EAs attenuate angiogenesis and cell migration in cancer cells, induce vasodilation in bovine coronary arteries, and reciprocally regulate platelet aggregation in washed human platelets.

Taken together, the ω-3 endocannabinoid epoxides represent a new class of dual acting molecules that display unique pharmacological properties.”

https://www.ncbi.nlm.nih.gov/pubmed/31562632

https://link.springer.com/chapter/10.1007%2F978-3-030-21735-8_17

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Novel CB1-ligands maintain homeostasis of the endocannabinoid-system in ω3- and ω6-long chain-PUFA deficiency.

The Journal of Lipid Research“Mammalian ω3- and ω6-PUFAs are synthesized from essential fatty acids (EFAs) or supplied by the diet. PUFAs are constitutive elements of membrane-architecture and precursors of lipid signaling molecules. EFAs and long chain PUFAs are precursors in the synthesis of endocannabinoid-ligands of the Gi/o-protein coupled cannabinoid receptors 1 and 2 in the endocannabinoid-system, which critically regulates energy homeostasis, as metabolic signaling system in hypothalamic neuronal circuits, and behavioral parameters. We utilized the auxotrophic fatty acid desaturase 2 deficient (fads2-/-) mouse, deficient in long chain PUFA-synthesis, to follow the age dependent dynamics of the PUFA pattern in the CNS-phospholipidome in unbiased dietary studies of three cohorts on sustained long chain PUFA-free, ω6-arachidonic and ω3-docosahexaenoic acid supplemented diets and their impact on the precursor pool of CB1 ligands. We discovered the transformation of eicosa-all cis-5,11,14-trienoic acid, uncommon in mammalian lipidomes, into two novel endocannabinoids, 20:35,11,14-ethanolamide and 2-20:35,11,14-glycerol, acting as ligands of CB1 in HEK293-cells. Labeling experiments excluded a Δ8-desaturase activity and proved the position-specificity of FADS2. The fads2 -/- mutant might serve as an unbiased model in vivo in the development of novel CB1-agonists and antagonists.”

https://www.ncbi.nlm.nih.gov/pubmed/31167809

http://www.jlr.org/content/early/2019/06/05/jlr.M094664

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous