Endocannabinoids as biomarkers of human reproduction.

“The search for suitable biomarkers of pregnancy outcome is a challenging issue in human reproduction, aimed at identifying molecules with predictive significance of the reproductive potential of male and female gametes.

Among the various candidates, endocannabinoids (eCBs), and in particular anandamide (AEA), represent potential biomarkers of human fertility disturbances…

Based on the available data, we suggest that the AEA tone has the potential to be exploited as a novel diagnostic biomarker of infertility,”


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Updates in Reproduction Coming from the Endocannabinoid System.

“The endocannabinoid system (ECS) is an evolutionarily conserved master system deeply involved in the central and local control of reproductive functions in both sexes. The tone of these lipid mediators-deeply modulated by the activity of biosynthetic and hydrolyzing machineries-regulates reproductive functions from gonadotropin discharge and steroid biosynthesis to the formation of high quality gametes and successful pregnancy.

This review provides an overview on ECS and reproduction and focuses on the insights in the regulation of endocannabinoid production by steroids, in the regulation of male reproductive activity, and in placentation and parturition.

Taken all together, evidences emerge that the activity of the ECS is crucial for procreation and may represent a target for the therapeutic exploitation of infertility.”


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The endocannabinoid anandamide inhibits voltage-gated sodium channels nav1.2, nav1.6, nav1.7, and nav1.8 in Xenopus oocytes.

“Anandamide is an endocannabinoid that regulates multiple physiological functions by pharmacological actions, in a manner similar to marijuana. Recently, much attention has been paid to the analgesic effect of endocannabinoids in terms of identifying new pharmacotherapies for refractory pain management, but the mechanisms of the analgesic effects of anandamide are still obscure…

Anandamide inhibited the function of α subunits in neuronal sodium channels Nav1.2, Nav1.6, Nav1.7, and Nav1.8.

These results help clarify the mechanisms of the analgesic effects of anandamide.”


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The Anti-inflammatory, Antioxidant, Antibacterial, Epstein-Barr inhibiting, Anti-allergy, Anti-osteoporosis, Anti-aging, Anti-HIV, and Anti-cancer effects of Camellia japonica.

“Anti-inflammatory activity of Camellia japonica oil. Camellia japonica oil (CJ oil) has been used traditionally in East Asia to nourish and soothe the skin as well as help restore the elasticity of skin…the anti-inflammatory effects of CJ oil and its mechanisms of action were investigated…Our results indicate that CJ oil exerts anti-inflammatory effects…” http://www.ncbi.nlm.nih.gov/pubmed/22449705

“Triterpene alcohols from camellia and sasanqua oils and their anti-inflammatory effects.” http://www.ncbi.nlm.nih.gov/pubmed/9433772

“Antioxidant Effects of the Ethanol Extract from Flower of Camellia japonica via Scavenging of Reactive Oxygen Species and Induction of Antioxidant Enzymes…  These results suggest that Camellia extract exhibits antioxidant properties by scavenging ROS and enhancing antioxidant enzymes. Camellia extract contained quercetin, quercetin-3-O-glucoside, quercitrin and kaempferol, which are antioxidant compounds.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127137/

“Camellianoside, a novel antioxidant glycoside from the leaves of Camellia japonica. A novel flavonol glycoside named camellianoside and three known flavonol glycosides were isolated from the leaves of Camellia japonica… The antioxidant activities of these glycosides evaluated by the diphenylpicrylhydrazyl (DPPH) radical scavenging reaction was higher than those of L-cysteine and L-ascorbic acid used as the reference antioxidants.” http://www.ncbi.nlm.nih.gov/pubmed/16926516

“Antibacterial activity in extracts of Camellia japonica L. petals and its application to a model food system. The potential presence of naturally occurring antimicrobials in petals of Camellia japonica L., a member of the tea family, was investigated against foodborne pathogens in microbiological media and food… An aqueous extract from the petals of C. japonica L. had an inhibitory effect on growth of all pathogens…” http://www.ncbi.nlm.nih.gov/pubmed/11510672

“Effect of Camellia japonica oil on human type I procollagen production and skin barrier function. In this study, we investigated the possibility that Camellia japonica oil (CJ oil) may be introduced as an anti-wrinkle agent…  based on these results, we suggest the possibility that CJ oil may be considered as possible wrinkle-reducing candidates for topical application.” http://www.ncbi.nlm.nih.gov/pubmed/17386986

“Inhibitory effects of natural plants of Jeju Island on elastase and MMP-1 expression. In order to search for new active cosmetic ingredients of natural origin, we screened about 60 plants collected from Jeju Island, which is located in the southernmost part of the Republic of Korea… four extracts, including… Camellia japonica (leaf), completely inhibited the expression of MMP-1 in human fibroblast cells. The results showed that four of the 60 plant extracts may hold potential for use as natural active ingredients for anti-aging cosmetics.” http://www.ncbi.nlm.nih.gov/pubmed/17342265

“Melanogenesis inhibitory and fibroblast proliferation accelerating effects of noroleanane- and oleanane-type triterpene oligoglycosides from the flower buds of Camellia japonica. Camellioside B (2), a major constituent of C. japonica grown in Japan, showed potent inhibition of melanogenesis… Interestingly, camellioside B (2) significantly accelerated fibroblast proliferation. This biological selectivity could make camellioside B useful for treating skin disorders…”  http://www.ncbi.nlm.nih.gov/pubmed/22834923

“Inhibitory effects of an ellagic acid glucoside, okicamelliaside, on antigen-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. Degranulation inhibitors in plants are widely used for prevention and treatment of immediate-type allergy. We previously isolated a new ellagic acid glucoside, okicamelliaside (OCS), from Camellia japonica leaves for use as a potent degranulation inhibitor… These results suggest the potential for OCS to alleviate symptoms of immediate-type allergy.” http://www.ncbi.nlm.nih.gov/pubmed/22330086

“Okicamelliaside, an extraordinarily potent anti-degranulation glucoside isolated from leaves of Camellia japonica… we isolated from leaves of Camellia japonica an ellagic acid glucoside named okicamelliaside… Okicamelliaside was 12,000 times more potent than the antihistaminic drug, ketotifen fumarate…”  http://www.ncbi.nlm.nih.gov/pubmed/21150097

“Camellia japonica suppresses immunoglobulin E-mediated allergic response by the inhibition of Syk kinase activation in mast cells… The leaf extract of Camelliajaponica (LECJ) exhibited the most potent effect on degranulation in antigen-stimulated rodent and human mast cells…The present results strongly suggest that the anti-allergic activity of LECJ is mediated through inhibiting degranulation and allergic cytokine secretion by inhibition of Src-family kinase in mast cells and it may be useful for the treatment of mast cell-related immediate and delayed allergic diseases.” http://www.ncbi.nlm.nih.gov/pubmed/18261158

“Hypotriglyceridemic potential of fermented mixed tea made with third-crop green tea leaves and camellia (Camelliajaponica) leaves in Sprague-Dawley rats.” http://www.ncbi.nlm.nih.gov/pubmed/23705670

“3-epicabraleahydroxylactone and other triterpenoids from camellia oil and their inhibitory effects on Epstein-Barr virus activation… triterpenoid isolated from the nonsaponifiable lipid of the seed oil of the camellia (Camellia japonica L.; Theaceae)… inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA)… three compounds showed potent inhibitory effects against EBV-EA induction…” http://www.ncbi.nlm.nih.gov/pubmed/14709887

“Inhibitory effects of Korean medicinal plants and camelliatannin H from Camellia japonica on human immunodeficiency virus type 1 protease… Camelliatannin H from the pericarp of C. japonica, showed a potent inhibitory activity on HIV-1…” http://www.ncbi.nlm.nih.gov/pubmed/12203260

“Camelliin B and nobotanin I, macrocyclic ellagitannin dimers and related dimers, and their antitumor activity. Camelliin B… isolated from Camellia japonica… Camelliin B… exhibited marked host-mediated antitumor activities.”  http://www.ncbi.nlm.nih.gov/pubmed/2632067

“Triterpenoids from Camellia japonica and their cytotoxic activity… bark of Camellia japonica, three new triterpenoids… The isolated compounds were tested in vitro for their cytotoxic activities against the A549, LLC, HL-60 and MCF-7 cancer cell lines. Among them, compound 8 showed cytotoxicity against LLC and HL-60 cancer cell lines…” http://www.ncbi.nlm.nih.gov/pubmed/20045980

“[Study on the theraputic effect of plants of Camellia genus on osteoporosis]… The results of this study indicated that effects of ethanol extracts of seed from Camellia japonica on anti-osteoporosis with retinoic acid were the strongest… Plants of Camellia genus have different degree anti-osteoporosis effect…” http://www.ncbi.nlm.nih.gov/pubmed/19230411

“Camelliatannin D, a new inhibitor of bone resorption, from Camellia japonica.” http://www.ncbi.nlm.nih.gov/pubmed/8575042

“Stereospecific positional distribution of fatty acids of Camellia (Camellia japonica L.) seed oil… The information of stereospecific positional distribution of fatty acids in the camellia oil can be used for the development of the structured lipids for food, pharmaceutical, and medical purposes.” http://www.ncbi.nlm.nih.gov/pubmed/23009642


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Potential Oil Yield, Fatty Acid Composition, and Oxidation Stability of the Hempseed Oil from Four Cannabis sativa L. Cultivars.

“The cultivation of four industrial hemp cultivars (Felina 32, Chamaeleon, Uso31, and Finola) was investigated for oil production in the north-east of Italy along two years. The oils of all cultivars resulted in rich amount of linoleic acid (ω-6) and α-linolenic acid (ω-3). Felina 32 and Chamaeleon oils exhibited the highest amount of linoleic acid (59%) and α-linolenic acid (18%). Finola and Uso31 oils resulted in the richest of γ-linolenic acid (5-6%). All hempseed oils presented high oxidation stability and an acceptable initial quality. It is suggested that these oils can be used to produce EFA dietary supplements high in ω-6 and ω-3 of vegetal origin.”


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Changes in Cerebral CB1 Receptor Availability after Acute and Chronic Alcohol Abuse and Monitored Abstinence.

“Involvement of the type 1 cannabinoid receptor (CB1R) in the effects of alcohol on the brain is supported by animal experiments…

In conclusion, whereas the acute alcohol effect is an increase in CB1R availability, chronic heavy drinking leads to reduced CB1R availability that is not reversible after 1 month of abstinence. Longer follow-up is required to differentiate whether this is a compensatory effect of repeated endocannabinoid overstimulation or an enduring trait-like feature.

An enhanced CB1R signaling may offer a new therapeutic direction for treatment of the negative affective state produced by alcohol withdrawal and abstinence, which is critical for the maintenance of alcohol addiction.”


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Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB 2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model.

“The aim of this study was to characterize the influence of WIN 55,212-2 (WIN-a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model…

These preclinical data would suggest that WIN in combination with clonazepam, phenobarbital and valproate is associated with beneficial anticonvulsant pharmacodynamic interactions in the mouse 6 Hz-induced psychomotor seizure test.”


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Protective Effects of Cannabidiol Against Hippocampal Cell Death and Cognitive Impairment Induced by Bilateral Common Carotid Artery Occlusion in Mice.

“The present study investigated whether cannabidiol (CBD), a major non-psychoactive constituent of marijuana, protects against hippocampal neurodegeneration and cognitive deficits induced by brain ischemia in adult mice…

These findings suggest a protective effect of CBD on neuronal death induced by ischemia and indicate that CBD might exert beneficial therapeutic effects in brain ischemia. The mechanisms that underlie the neuroprotective effects of CBD in BCCAO mice might involve the inhibition of reactive astrogliosis.”


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Effects of Hemp (Cannabis sativa L.) Seed Oil Press-Cake and Decaffeinated Green Tea Leaves (Camellia sinensis) on Functional Characteristics of Gluten-Free Crackers.

“A mixture, simplex centroid, 2 components experimental design was used to evaluate the addition of hemp seed oil press-cake and decaffeinated green tea leaves, as functional ingredients to assess nutritional characteristics and antioxidant properties of gluten-free crackers.

All samples with added hemp flour had much better nutritional qualities than the brown rice flour crackers in terms of higher protein, crude fibers, minerals, and essential fatty acids content. Likewise, all samples with added decaffeinated green tea leaves had much better antioxidant properties than crackers with no added green tea leaves. All crackers with added hemp flour had a significantly increased fiber content (39% to 249%) and decreased carbohydrate content (8.4% to 42.3%), compared to the brown rice flour crackers.

All samples had antioxidant properties, even without the addition of green tea leaves.

Optimization of the responses was conducted based on the maximized values for protein, fibers, omega-3 fatty acids content, as well as for the antioxidant activity and overall score. The suggested values for the addition of the hemp oil press-cake was 20% (total flour weight) with 4 g of decaffeinated green tea leaves that would provide protein content of 14.1 g/100 g; fibers content of 8.4 g/100 g; omega-3 fatty acids content of 3.2 g/100 g; antioxidant activity measured via 2,2-diphenyl-1-picrylhydrazyl value of 30.3 μmol TE/g d.w.; and an overall score of 8.9.

This formulation has demonstrated potential application in the baking industry and marketing of these gluten-free crackers as a value-added functional product.”


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Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors.

“Human OX1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes…

In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations available for cannabinoid receptors.”


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