Hemp seed pill may improve chronic constipation of the elderly and reduce the burden of helpers.

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Logo of jfammpc“Chronic constipation is common but serious problem of the elderly.

Hemp seed pills had been used over 1000 years as a purgative in the traditional Chinese medicine, and moreover, had the data of double-blinded randomized control trial.

Japan Geriatric Society introduced hemp seed pill as one of choice for chronic constipation of elderly in their guideline.

Hemp seed pills might improve chronic constipation of elderly and reduce the burden of nursing stuffs.

Traditional Chinese medicine Hemp seed pill (麻子仁丸) could improve chronic constipation of elderly in the difficult case.”

https://www.ncbi.nlm.nih.gov/pubmed/31334198

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618208/

Kinetics of acetylcholinesterase inhibition by hemp seed protein-derived peptides.

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Journal of Food Biochemistry banner“The aim of this work was to enhance the acetylcholinesterase (AChE)-inhibitory activity of a pepsin-produced hemp seed protein hydrolysates (HPH) through reverse-phase HPLC separation followed by identification of peptide sequences present in the most active fraction. The HPH was separated into eight fractions (F1-F8) with F7 exhibiting significantly (p < 0.05) the strongest (97.5%) in vitro inhibition of electric eel AChE (eeAChE) activity in comparison to 53.8% for HPH. The HPH consisted mostly of low molecular weight peptides of < 11 amino acid residues and most contained at least one hydrophobic amino acid. Kinetics of enzyme inhibition revealed a mixed-type inhibition of eeAChE activity by HPH whereas F7 acted through an uncompetitive mode; in contrast inhibition of human AChE by HPH and F7 was uncompetitive. The stronger inhibitory potency of the F7 peptides fraction against both enzymes was confirmed through reduced maximal velocity, catalytic efficiency, and inhibition constant values when compared to the HPH.

PRACTICAL APPLICATIONS: The use of natural products for the prevention or treatment of human diseases continues to be an area of intense research activities. Food protein-derived peptides obtained through enzymatic hydrolysis of hemp seed proteins were shown in vitro to be strong inhibitors of activities of both the eel and human forms of acetylcholinesterase (AChE). AChE is an important therapeutic target because excessive activity of this enzyme is a causative factor of neurodegenerative diseases such as dementia and Alzheimer’s. This work showed that peptides in the most active fraction are small in sizes, which may favor their absorption into blood circulation and possible permeation of the blood-brain barrier. Therefore, the hemp seed peptides are potential agents that can be used to formulate functional foods and nutraceuticals against neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/31353736

https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.12897

Effect οf Genotype and Growing Year on the Nutritional, Phytochemical, and Antioxidant Properties of Industrial Hemp (Cannabis sativa L.) Seeds.

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antioxidants-logo “Cannabis sativa L. seeds have been an important source of protein, oil, and dietary fiber for human and animals. Currently, there is a growing interest in the commercial products of these seeds, which are recognized as a legitimate source of medicaments, cosmeceuticals, and nutraceuticals.

The objective of this study was to investigate the nutritional, phytochemical composition, and antioxidant properties of seeds from seven hemp cultivars grown in Greece for three consecutive years.

All the measured parameters strongly varied under the influence of growing year and genotype. In particular, protein, oil, and carbohydrates’ content of hemp seeds as well as fatty acids’ composition were mainly affected by genotype, whereas the growing year had a major effect on phytochemical components and antioxidant activity, which was determined by the 2,2′-azino-bis (3-ethylbenzthiazoline sulfonate) (ABTS) and ferric-reducing antioxidant power (FRAP) assays. Moreover, a predominant effect of the year was observed for phenolic profiles as determined by high-performance liquid chromatography and total carotenoids’ content.

This study suggests that hemp seeds could be a promising food crop as a result of their high nutritive traits and antioxidant potential. A comparison of the studied cultivars, showed that Finola seeds had the highest oil and protein contents and, thus, appeared to be the most promising cultivar for cultivation in Greece.”

https://www.ncbi.nlm.nih.gov/pubmed/31627349

https://www.mdpi.com/2076-3921/8/10/491

Hemp seed/evening primrose oil affects expression of STAT3, IL-17, and FOXP3+ in experimental autoimmune encephalomyelitis.

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Research in Pharmaceutical Sciences“T helper (Th)-17 mediate inflammation in both peripheral tissues and the central nervous system. Signal transducer and activator of transcription factor3 (STAT3) is required for Th-cell pathogenicity and its activation in the brain has been demonstrated during the acute phase of experimental autoimmune encephalomyelitis (EAE) through the mammalian target of rapamycin (mTOR) signaling. Rapamycin (RAPA), an inhibitor of mTOR, can drive Forkhead box P3 (FOXP3+) induction as a regulatory factor.

The aim of this study was to determine the effects of hemp seed/evening primrose oils (HSO/EPO) supplement on the expression of FOXP3+, STAT3, and interleukin (IL)-17 genes in EAE lymph nodes.

EAE was induced by myelin oligodendrocyte glycoprotein peptide in mice, and then the mice were assigned to three treatment groups compared to two control groups (EAE and naive). The histological findings of the spinal cord were evaluated. To determine the expression of FOXP3+, STAT3, and IL-17 genes in the lymphocytes, qRT-PCR was used.

Our results showed that EAE severity was reduced in HSO/EPO mice by reducing the expression of STAT3 and IL-17 genes and increasing the expression of FOXP3+ gene, which was confirmed by slight inflammation in the spinal cord. Histological findings showed a significant improvement in the HSO/EPO group.

Our findings suggest that the HSO/EPO treatment can be used to ameliorate the demyelination of spinal cord, which was confirmed by immunological and histological findings.”

https://www.ncbi.nlm.nih.gov/pubmed/31620191

http://www.rpsjournal.net/article.asp?issn=1735-5362;year=2019;volume=14;issue=2;spage=146;epage=154;aulast=Rezapour%2DFirouzi

The endocannabinoid system: Novel targets for treating cancer induced bone pain.

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Biomedicine & Pharmacotherapy“Treating Cancer-induced bone pain (CIBP) continues to be a major clinical challenge and underlying mechanisms of CIBP remain unclear.

Recently, emerging body of evidence suggested the endocannabinoid system (ECS) may play essential roles in CIBP. Here, we summarized the current understanding of the antinociceptive mechanisms of endocannabinoids in CIBP and discussed the beneficial effects of endocannabinoid for CIBP treatment.

Targeting non-selective cannabinoid 1 receptors or selective cannabinoid 2 receptors, and modulation of peripheral AEA and 2-AG, as well as the inhibition the function of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have produced analgesic effects in animal models of CIBP.

Management of ECS therefore appears to be a promising way for the treatment of CIBP in terms of efficacy and safety. Further clinical studies are encouraged to confirm the possible translation to humans of the very promising results already obtained in the preclinical studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31627091

“Thus, cannabinoids may be clinically useful for treating chronic pain and CIBP.”

https://www.sciencedirect.com/science/article/pii/S075333221933731X?via%3Dihub

Ligands of the CB2 cannabinoid receptors augment activity of the conventional antidepressant drugs in the behavioural tests in mice.

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Behavioural Brain Research“Although a lot of information can be found on the specific dual role of the endocannabinoid system in the emotional-related responses, little is known whether stimulation or inhibition of the CB receptors may affect the activity of the frequently prescribed antidepressant drugs.

Our interests have been particularly focused on the potential influence of the CB2 receptors, as the ones whose central effects are relatively poorly documented when compared to the central effects of the CB1 receptors. Therefore, we evaluated the potential interaction between the CB2 receptor ligands (i.e., JWH133 – CB2 receptor agonist and AM630 – CB2 receptor inverse agonist) and several common antidepressant drugs that influence the monoaminergic system (i.e., imipramine, escitalopram, reboxetine).

Summarizing, the results of the present study revealed that both activation and inhibition of the CB2 receptor function have a potential to strengthen the antidepressant activity of drugs targeting the monoaminergic system. Most probably, the described interaction has a pharmacodynamic background.”

https://www.ncbi.nlm.nih.gov/pubmed/31626848

“Interplay between CB2 receptor ligands and antidepressants is pharmacodynamic in nature.”

https://www.sciencedirect.com/science/article/pii/S0166432819311891?via%3Dihub

Altered cannabinoid receptor expression in pancreatic islets in experimental model of uremia.

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Folia Morphologica “Uremia leads to a number of metabolic and hormonal disorders including defective carbohydrate metabolism.

Endocannabinoids exert their effect on insulin and glucagon secretion via activation of specific receptors named CB1 and CB2. For this reason and the absence of reports on location and immunoreactivity of CB1, CB2 receptors compared to immunoreactivity of insulin- and glucagon- secreting cells in experimental uremia, the author decided to investigate this issue.

The aim of the present study was the immunohistochemical localization and evaluation of cannabinoid receptors (CB1, CB2), insulin and glucagon in the pancreatic islets of uremic rats.

RESULTS:

It was revealed the decreased immunoreactivity of the CB1 receptor and higher intensity of the immunohistochemical reaction against CB2 receptor as compared to the value in the control animals. Significantly higher immunoreactivity of glucagon-positive cells and weaker immunoreactivity of insulin-positive cells were observed in pancreatic islets of uremic rats.

CONCLUSIONS:

The obtained results indicate the involvement of cannabinoid receptors in the pathomechanism of carbohydrate metabolism disorders, associated with abnormal secretion of hormones by the α and β cells in uremia.”

https://www.ncbi.nlm.nih.gov/pubmed/31625133

https://journals.viamedica.pl/folia_morphologica/article/view/64828

“Uremia is a clinical syndrome marked by elevated concentrations of urea in the blood and associated with fluid, electrolyte, and hormone imbalances and metabolic abnormalities, which develop in parallel with deterioration of renal function.  The term uremia, which literally means urine in the blood, was first used by Piorry to describe the clinical condition associated with renal failure”  https://emedicine.medscape.com/article/245296-overview

Neuropeptide Y and cannabinoids interaction in the amygdala after exposure to shock and reminders model of PTSD.

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Neuropharmacology“Modulation of cannabinoid and neuropeptide Y (NPY) receptors may offer therapeutic benefits for post-traumatic stress disorder (PTSD).

In this study, we aimed to investigate the functional interaction between these systems in the basolateral amygdala (BLA) in a rat model of PTSD.

The findings suggest that the functional interaction between the eCB and NPY1 systems is complex and provide a rationale for exploring novel therapeutic strategies that target the cannabinoid and NPY systems for stress-related diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/31622603

https://www.sciencedirect.com/science/article/pii/S0028390819303661?via%3Dihub

Systematic Affinity Purification Coupled to Mass Spectrometry Identified p62 as Part of the Cannabinoid Receptor CB2 Interactome.

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Image result for frontiers in molecular neuroscience“The endocannabinoid system (ECS) consists particularly of cannabinoid receptors 1 and 2 (CB1 and CB2), their endogenous ligands, and enzymes that synthesize and degrade their ligands. It acts in a variety of organs and disease states ranging from cancer progression over neuropathic pain to neurodegeneration. Protein components engaged in the signaling, trafficking, and homeostasis machinery of the G-protein coupled CB2, are however largely unknown. It is therefore important to identify further interaction partners to better understand CB2 receptor functions in physiology and pathophysiology. For this purpose, we used an affinity purification and mass spectrometry-based proteomics approach of Strep-HA-CB2 receptor in HEK293 cells. After subtraction of background interactions and protein frequency library assessment we could identify 83 proteins that were classified by the identification of minimally 2 unique peptides as highly probable interactors. A functional protein association network analysis obtained an interaction network with a significant enrichment of proteins functionally involved in protein metabolic process, in endoplasmic reticulum, response to stress but also in lipid metabolism and membrane organization. The network especially contains proteins involved in biosynthesis and trafficking like calnexin, Sec61A, tubulin chains TUBA1C and TUBB2B, TMED2, and TMED10. Six proteins that were only expressed in stable CB2 expressing cells were DHC24, DHRS7, GGT7, HECD3, KIAA2013, and PLS1. To exemplify the validity of our approach, we chose a candidate having a relatively low number of edges in the network to increase the likelihood of a direct protein interaction with CB2 and focused on the scaffold/phagosomal protein p62/SQSTM1. Indeed, we independently confirmed the interaction by co-immunoprecipitation and immunocytochemical colocalization studies. 3D reconstruction of confocal images furthermore showed CB2 localization in close proximity to p62 positive vesicles at the cell membrane. In summary, we provide a comprehensive repository of the CB2 interactome in HEK293 cells identified by a systematic unbiased approach, which can be used in future experiments to decipher the signaling and trafficking complex of this cannabinoid receptor. Future studies will have to analyze the exact mechanism of the p62-CB2 interaction as well as its putative role in disease pathophysiology.”

https://www.ncbi.nlm.nih.gov/pubmed/31616248

https://www.frontiersin.org/articles/10.3389/fnmol.2019.00224/full

Cannabinoid Receptor Interacting Protein 1a (CRIP1a): Function and Structure.

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molecules-logo“Cannabinoid receptor interacting protein 1a (CRIP1a) is an important CB1 cannabinoid receptor-associated protein, first identified from a yeast two-hybrid screen to modulate CB1-mediated N-type Ca2+ currents. In this paper we review studies of CRIP1a function and structure based upon in vitro experiments and computational chemistry, which elucidate the specific mechanisms for the interaction of CRIP1a with CB1 receptors. N18TG2 neuronal cells overexpressing or silencing CRIP1a highlighted the ability of CRIP1 to regulate cyclic adenosine 3′,5’monophosphate (cAMP) production and extracellular signal-regulated kinase (ERK1/2) phosphorylation. These studies indicated that CRIP1a attenuates the G protein signaling cascade through modulating which Gi/o subtypes interact with the CB1 receptor. CRIP1a also attenuates CB1 receptor internalization via β-arrestin, suggesting that CRIP1a competes for β-arrestin binding to the CB1 receptor. Predictions of CRIP1a secondary structure suggest that residues 34-110 are minimally necessary for association with key amino acids within the distal C-terminus of the CB1 receptor, as well as the mGlu8a metabotropic glutamate receptor. These interactions are disrupted through phosphorylation of serines and threonines in these regions. Through investigations of the function and structure of CRIP1a, new pharmacotherapies based upon the CRIP-CB1 receptor interaction can be designed to treat diseases such as epilepsy, motor dysfunctions and schizophrenia.”

https://www.ncbi.nlm.nih.gov/pubmed/31614728

https://www.mdpi.com/1420-3049/24/20/3672