Antioxidants Help Favorably Regulate the Kinetics of Lipid Peroxidation, Polyunsaturated Fatty Acids Degradation and Acidic Cannabinoids Decarboxylation in Hempseed Oil

 Scientific Reports“The seed of the hemp plant (Cannabis sativa L.) has been revered as a nutritional resource in Old World Cultures. This has been confirmed by contemporary science wherein hempseed oil (HSO) was found to exhibit a desirable ratio of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) considered optimal for human nutrition. HSO also contains gamma-linoleic acid (GLA) and non-psychoactive cannabinoids, which further contribute to its’ potential bioactive properties. Herein, we present the kinetics of the thermal stability of these nutraceutical compounds in HSO, in the presence of various antioxidants (e.g. butylated hydroxytoluene, alpha-tocopherol, and ascorbyl palmitate). We focussed on oxidative changes in fatty acid profile and acidic cannabinoid stability when HSO was heated at different temperatures (25 °C to 85 °C) for upto 24 h. The fatty acid composition was evaluated using both GC/MS and 1H-NMR, and the cannabinoids profile of HSO was obtained using both HPLC-UV and HPLC/MS methods. The predicted half-life (DT50) for omega-6 and omega-3 PUFAs in HSO at 25 °C was about 3 and 5 days, respectively; while that at 85 °C was about 7 and 5 hours respectively, with respective activation energies (Ea) being 54.78 ± 2.36 and 45.02 ± 2.87 kJ/mol. Analysis of the conjugated diene hydroperoxides (CDH) and p-Anisidine value (p-AV) revealed that the addition of antioxidants significantly (p < 0.05) limited lipid peroxidation of HSO in samples incubated at 25-85 °C for 24 h. Antioxidants reduced the degradation constant (k) of PUFAs in HSO by upto 79%. This corresponded to a significant (p < 0.05) increase in color stability and pigment retention (chlorophyll a, chlorophyll b and carotenoids) of heated HSO. Regarding the decarboxylation kinetics of cannabidiolic acid (CBDA) in HSO, at both 70 °C and 85 °C, CBDA decarboxylation led to predominantly cannabidiol (CBD) production. The half-life of CBDA decarboxylation (originally 4 days) could be increased to about 17 days using tocopherol as an antioxidant. We propose that determining acidic cannabinoids decarboxylation kinetics is a useful marker to measure the shelf-life of HSO. The results from the study will be useful for researchers looking into the thermal treatment of hempseed oil as a functional food product, and those interested in the decarboxylation kinetics of the acidic cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/32601363/

https://www.nature.com/articles/s41598-020-67267-0

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabinoids as anti-ROS in Aged Pancreatic Islet Cells

Life Sciences“Cannabinoids are the chemical compounds with a high affinity for cannabinoid receptors affecting the central nervous system through the release of neurotransmitters. However, the current knowledge related to the role of such compounds in the regulation of cellular aging is limited. This study aimed to investigate the effect of cannabidiol and tetrahydrocannabinol on the function of aged pancreatic islets.

Main methods: The expression of p53, p38, p21, p16, and Glut2 genes and β-galactosidase activity were measured as hallmarks of cell aging applying real-time PCR, ELISA, and immunocytochemistry techniques. Pdx1 protein expression, insulin release, and oxidative stress markers were compared between young and aged rat pancreatic islet cells.

Key findings: Upon the treatment of aged pancreatic islets cells with cannabidiol and tetrahydrocannabinol, the expression of p53, p38, p21 and the activity of β-galactosidase were reduced. Cannabidiol and tetrahydrocannabinol increase insulin release, Pdx1, Glut2, and thiol molecules expression, while the oxidative stress parameters were decreased. The enhanced expression of Pdx1 and insulin release in aged pancreatic islet cells reflects the extension of cell healthy aging due to the significant reduction of ROS.

Significance: This study provides evidence for the involvement of cannabidiol and tetrahydrocannabinol in the oxidation process of cellular aging.”

https://pubmed.ncbi.nlm.nih.gov/32553926/

https://www.sciencedirect.com/science/article/abs/pii/S0024320520307190?via%3Dihub

Reactive oxygen species (ROS) are chemically reactive chemical species containing oxygen. ROS can damage lipid, DNARNA, and proteins, which, in theory, contributes to the physiology of aging.” https://en.wikipedia.org/wiki/Reactive_oxygen_species

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

ijms-logo“Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols.

Although CBD’s effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases.

Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed.

Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor.

Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.”

https://pubmed.ncbi.nlm.nih.gov/32443623/

https://www.mdpi.com/1422-0067/21/10/3575

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabidiol on 5-FU-induced oral mucositis in mice.

Oral Diseases

“The aim of this study was to evaluate the clinical, histological, hematological and oxidative stress effects of cannabidiol (CBD) in mice with induced oral mucositis.

RESULTS:

In the clinical evaluation, the groups treated with CBD showed less severity of oral lesions compared with the positive control at both experimental times. The intensity of the inflammatory response was also lower in the groups treated with this drug, but there was no statistically significant difference when compared with the positive control. With regard to erythrocyte, leukocyte and platelet counts and antioxidant enzyme activity, the groups treated with CBD showed better results, but only some of these variables showed statistically significant differences.

CONCLUSIONS:

CBD seems to exert an anti-inflammatory and antioxidant activity favoring a faster resolution of oral mucositis in this animal model.”

https://www.ncbi.nlm.nih.gov/pubmed/32400905

https://onlinelibrary.wiley.com/doi/abs/10.1111/odi.13413

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Beneficial effects of the phytocannabinoid Δ9-THCV in L-DOPA-induced dyskinesia in Parkinson’s disease.

Neurobiology of Disease“The antioxidant and CB2 receptor agonist properties of Δ9-tetrahydrocannabivarin (Δ9-THCV) afforded neuroprotection in experimental Parkinson’s disease (PD), whereas its CB1 receptor antagonist profile at doses lower than 5 mg/kg caused anti-hypokinetic effects.

In the present study, we investigated the anti-dyskinetic potential of Δ9-THCV (administered i.p. at 2 mg/kg for two weeks), which had not been investigated before.

In summary, our data support the anti-dyskinetic potential of Δ9-THCV, both to delay the occurrence and to attenuate the magnitude of dyskinetic signs. Although further studies are clearly required to determine the clinical significance of these data in humans, the results nevertheless situate Δ9-THCV in a promising position for developing a cannabinoid-based therapy for patients with PD.”

https://www.ncbi.nlm.nih.gov/pubmed/32387338

“Δ9-THCV exhibited anti-dyskinetic properties in L-DOPA-treated Pitx3ak mutant mice. It delayed the onset of dyskinetic signs and reduced their neurochemical changes. It also reduced their intensity when given once dyskinesia was already present. This potential adds to other properties of Δ9-THCV as antiparkinsonian therapy.

In summary, our data support the anti-dyskinetic potential of Δ9-THCV to ameliorate adverse effects caused by L-DOPA, in particular delaying the occurrence and attenuating the magnitude of dyskinetic signs. This adds to its promising symptom-alleviating and neuroprotective properties described previously. Although further studies are clearly required to determine the clinical significance of these data in humans, the results nevertheless situate Δ9-THCV in a promising position for developing a cannabinoid-based therapy for PD patients.”

https://www.sciencedirect.com/science/article/pii/S0969996120301674?via%3Dihub

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabis and Canabidinoids on the Inflammatory Bowel Diseases: Going Beyond Misuse.

ijms-logo“Inflammatory bowel diseases (IBD) are characterized by a chronic and recurrent gastrointestinal condition, including mainly ulcerative colitis (UC) and Crohn’s disease (CD). Cannabis sativa (CS) is widely used for medicinal, recreational, and religious purposes. The most studied compound of CS is tetrahydrocannabinol (THC) and cannabidiol (CBD). Besides many relevant therapeutic roles such as anti-inflammatory and antioxidant properties, there is still much controversy about the consumption of this plant since the misuse can lead to serious health problems. Because of these reasons, the aim of this review is to investigate the effects of CS on the treatment of UC and CD. The literature search was performed in PubMed/Medline, PMC, EMBASE, and Cochrane databases. The use of CS leads to the improvement of UC and CD scores and quality of life. The medical use of CS is on the rise. Although the literature shows relevant antioxidant and anti-inflammatory effects that could improve UC and CD scores, it is still not possible to establish a treatment criterion since the studies have no standardization regarding the variety and part of the plant that is used, route of administration and doses. Therefore, we suggest caution in the use of CS in the therapeutic approach of IBD until clinical trials with standardization and a relevant number of patients are performed.”

https://www.ncbi.nlm.nih.gov/pubmed/32331305

https://www.mdpi.com/1422-0067/21/8/2940

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Characterization of bioactive compounds in defatted hempseed (Cannabis sativa L.) by UHPLC-HRMS/MS and anti-inflammatory activity in primary human monocytes.

 “Hempseed (Cannabis sativa L.) has beneficial impact on human health mainly because of its wide variability of bioactive compounds. However, many of them are not fully characterized yet. In this work, hempseed was defatted and through a bio-guided studied, two fractions (F03 and F05) with the highest content of phenols, flavonoids and antioxidant capacity were selected. Fractions were chemically analyzed by UHPLC HRMS/MS. The anti-inflammatory capacities of these compounds were evaluated on human monocytes using flow cytometry, RT-qPCR and Elisa procedures. A high amount of phenolic compounds were identified, with the major compound being: N-trans-caffeoyltyramine (6.36 mg g-1 in F05 and 1.28 mg g-1 in F03). Both, F03 and F05 significantly reduced the inflammatory competence of LPS-treated human primary monocytes, decreasing TNF-α and IL-6 gene expression and secretion. These findings indicate that in the defatted fraction of the hempseed there are a wide number of compounds with beneficial potential to prevent and treat inflammatory disorders, as well as other processes caused by oxidative stress.”

https://www.ncbi.nlm.nih.gov/pubmed/32329481

https://pubs.rsc.org/en/content/articlelanding/2020/FO/D0FO00066C#!divAbstract

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Promising in vitro antioxidant, anti-acetylcholinesterase and neuroactive effects of essential oil from two non-psychotropic Cannabis sativa L. biotypes.

Phytotherapy Research“The aim of this study was to compare the micro-morphological features of two different non-drug Cannabis sativa L. biotypes (Chinese accession G-309 and one fibrante variety) and to evaluate the phytochemical profile as well as some biological properties of the essential oils (EOs) obtained by hydrodistillation of dried flowering tops. After a micro-morphological evaluation by scanning electron microscopy, the phytochemical composition was analysed by GC-FID and GC-MS analyses.

Antioxidant and anti-acetylcholinesterase properties were investigated by several in vitro cell-free assays, while neuroactive effects were evaluated on mouse cortical neuronal as well as human iPS cell-derived central nervous system cells grown on MEA chips. Both EOs showed strong antioxidant properties mainly attributable to the high content of hydroxylated compounds as well as significant anti-acetylcholinesterase activities (IC50 74.64 and 57.31 μg/ml for Chinese accession and fibrante variety, respectively).

Furthermore, they showed a concentration-dependent inhibition of spontaneous electrical activity of human and mouse neuronal networks, with the fibrante variety, which showed the best activity (MFR, IC50 0.71 and 10.60 μg/ml, respectively). The observed biological activities could be due to a synergic effect between terpenes and phytocannabinoids, although in vivo studies, which clarify the molecular mechanism, are still lacking.”

https://www.ncbi.nlm.nih.gov/pubmed/32309898

https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.6678

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases.

frontiers in pharmacology – Retraction Watch“Cannabis sativa, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects.

Besides Δ9-tetrahydrocannabinol that is the principal psychoactive constituent of Cannabiscannabidiol (CBD) is the most abundant nonpsychoactive phytocannabinoid and may represent a prototype for anti-inflammatory drug development for human pathologies where both the inflammation and oxidative stress (OS) play an important role to their etiology and progression.

To this regard, Alzheimer’s disease (AD), Parkinson’s disease (PD), the most common neurodegenerative disorders, are characterized by extensive oxidative damage to different biological substrates that can cause cell death by different pathways. Most cases of neurodegenerative diseases have a complex etiology with a variety of factors contributing to the progression of the neurodegenerative processes; therefore, promising treatment strategies should simultaneously target multiple substrates in order to stop and/or slow down the neurodegeneration.

In this context, CBD, which interacts with the eCB system, but has also cannabinoid receptor-independent mechanism, might be a good candidate as a prototype for anti-oxidant drug development for the major neurodegenerative disorders, such as PD and AD. This review summarizes the multiple molecular pathways that underlie the positive effects of CBD, which may have a considerable impact on the progression of the major neurodegenerative disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/32210795

“The present review provided evidence that the nonpsychoactive phytocannabinoids CBD could be a potential pharmacological tool for the treatment of neurodegenerative disorders; its excellent safety and tolerability profile in clinical studies renders it a promising therapeutic agent.

The molecular mechanisms associated with CBD’s improvement in PD and AD are likely multifaceted, and although CBD may act on different molecular targets all the beneficial effects are in some extent linked to its antioxidant and anti-inflammatory profile, as observed in in vitro and in vivo studies. Therefore, this review describes evidence to prove the therapeutical efficacy of CBD in patients affected by neurodegenerative disorders and promotes further research in order to better elucidate the molecular pathways involved in the therapeutic potential of CBD.”

https://www.frontiersin.org/articles/10.3389/fphar.2020.00124/full

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases.

Image result for histology and histopathology“Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of “neuroinflammaging” has emerged. In this deregulated neuroinflammatory process, a variety of immune cells participate, especially glial cells, proinflammatory cytokines, receptors, and subcellular organelles including mitochondria, which are mainly responsible for maintaining redox balance at the cellular level. Senescence and autophagic processes also play a crucial role in the neuroinflammatory disease associated with aging.

Of particular interest, melatonin, cannabinoids, and the receptors of both molecules which are closely related, exert beneficial effects on the neuroinflammatory processes that precede the onset of neurodegenerative pathologies such as Parkinson’s and Alzheimer’s diseases. Some of these neuroprotective effects are fundamentally related to its anti-inflammatory and antioxidative actions at the mitochondrial level due to the strategic functions of this organelle. The aim of this review is to summarize the most recent advances in the study of neuroinflammation and neurodegeneration associated with age and to consider the use of new mitochondrial therapeutic targets related to the endocannabinoid system and the pineal gland.”

https://www.ncbi.nlm.nih.gov/pubmed/32154907

https://www.hh.um.es/Abstracts/Vol_/_/__18212.htm

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous