Phytocannabinoids—A Green Approach toward Non-Alcoholic Fatty Liver Disease Treatment

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease in adults in developed countries, with a global prevalence as high as one billion. The pathogenesis of NAFLD is a multifactorial and multi-step process. Nowadays, a growing body of research suggests the considerable role of the endocannabinoid system (ECS) as a complex cell-signaling system in NAFLD development. Although increased endocannabinoid tone in the liver highly contributes to NAFLD development, the complex effects and impacts of plant-derived cannabinoids in the aspect of NAFLD pathophysiology are yet not fully understood, and effective medications are still in demand. In our review, we present the latest reports describing the role of ECS in NAFLD, focusing primarily on two types of cannabinoid receptors. Moreover, we sum up the recent literature on the clinical use of natural cannabinoids in NAFLD treatment. This review is useful for understanding the importance of ECS in NAFLD development, and it also provides the basis for more extensive clinical phytocannabinoids testing in patients suffering from NAFLD.

Pharmacokinetic Investigation of Commercially Available Edible Marijuana Products in Humans: Potential Influence of Body Composition and Influence on Glucose Control

“…There were no differences in circulating insulin between products, nor were there any differences in glucose/insulin derived indices of glucose regulation, including the Matsuda Index. Based on our data, and in light of the epidemiological studies [ 19 , 20 , 21 , 22 , 23 ], we suggest that, in adults free from diabetes, edible marijuana does not affect acute glucose regulation, but potentially may exert a favorable chronic influence via long-term physiological responses such as decreased adiposity [ 43 ], and improved gut [ 44 ] and/or liver health [ 45 ]. Noteworthy, recent data from a Mendelian randomization study suggest that chronic use of products derived from Cannabis sativa L. does not influence the prevalence of type 2 diabetes [ 46 ].…”

Pharmacokinetic Investigation of Commercially Available Edible Marijuana Products in Humans: Potential Influence of Body Composition and Influence on Glucose Control

“…There were no differences in circulating insulin between products, nor were there any differences in glucose/insulin derived indices of glucose regulation, including the Matsuda Index. Based on our data and in light of the epidemiological studies [19][20][21][22][23], we suggest that edible marijuana does not affect acute glucose regulation, but potentially may exert a favorable chronic influence via long-term physiological responses such as decreased adiposity [43], and improved gut [44] and/or liver health [45].…”

The Endocannabinoid System and Physical Activity—A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders

“…As a result, cAMP intensifies the activity of p42/p44 mitogen-activated protein kinase (MAPK) and Jun N-terminal kinase (JNK) which activate divergent nuclear transcription factors and alter the cellular metabolism. Additionally, cannabinoid receptors activate potassium and inhibit calcium channels in the presynaptic end of neurons that results in the overall inhibition of neurotransmitter release [ 17 , 18 , 19 ]. The distribution of CB1R is mainly clustered within brain structures, especially the neocortex, hippocampus, basal ganglia, and brain stem; likewise, its presence was confirmed in the skeletal muscles, lungs, testes, gastrointestinal tract, liver, pancreas, and adipose tissue.…”

“…In turn, CB2R is mainly expressed on the immune cells (macrophages, T lymphocytes, B lymphocytes), hematopoietic stem, and progenitor cells present in bone marrow, as well as in the thymus and lymph nodes; thereby its activation triggers wide-range of immunomodulatory effects ( Figure 1 ) [ 19 , 20 , 21 , 22 ]. Endocannabinoids are synthesized on demand in response to the elevated intracellular Ca 2+ concentration [ 18 ]. 2-AG, which is synthesized from diacylglycerol (DAG), acts as a full agonist with a moderate affinity of cannabinoid receptors, whereas is hydrolyzed by monoacylglycerol lipase (MAGL) [ 23 , 24 ].…”

“…2-AG, which is synthesized from diacylglycerol (DAG), acts as a full agonist with a moderate affinity of cannabinoid receptors, whereas is hydrolyzed by monoacylglycerol lipase (MAGL) [ 23 , 24 ]. In turn, AEA constitutes a partial agonist of cannabinoid receptors synthesized from N-arachidonoyl phosphatidylethanolamine (NAPE) coordinated by N-acyl-phosphatidylethanolamine phospholipase D-like esterase (NAPE-PLD) and is degraded to arachidonic acid (AA) by the activity of fatty acid amid hydrolase (FAAH) [ 15 , 18 ]. Next to the well-known eCBs, analogous “endocannabinoid-like” lipid ligands were described namely oleoylethanolamine (OEA) and palmitoylethanolamide (PEA).…”