Tag Archives: antioxidant

Beta-caryophyllene alleviates diet-induced neurobehavioral changes in rats: The role of CB2 and PPAR-γ receptors.

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Biomedicine & Pharmacotherapy

“Insulin resistance (IR) and obesity predispose diseases such as diabetes, cardiovascular and neurodegenerative disorders.

Beta-caryophyllene (BCP), a natural sesquiterpene, exerts neuroprotective, anxiolytic and antidepressant effects via its selective agonism to cannabinoid receptor 2 (CB2R). BCP was shown to have an anti-diabetic effect, however, the implication of CB2R is yet to be elucidated. A link between CB2R agonism and PPAR-γ activation has been discussed, but the exact mechanism is not well-defined.

This study was designed to examine the role of BCP in improving diet-induced metabolic (insulin resistance), neurobehavioral (anxiety, depression and memory deficit), and neurochemical (oxidative, inflammatory and neurotrophic factor) alterations in the prefrontal cortex of obese rats’ brain. The involvement of CB2R and/or PPAR-γ dependent activity was also investigated.

KEY RESULTS:

Beta-caryophyllene alleviated HFFD-induced IR, oxidative-stress, neuroinflammation and behavioral changes. The anxiolytic, anti-oxidant and anti-inflammatory effects of BCP were mediated by both PPAR-γ and CB2R. The effects of BCP on glycemic parameters seem to be CB2R-dependent with the non-significant role of PPAR-γ. Furthermore, BCP-evoked antidepressant and memory improvement are likely mediated only via CB2R, mainly by upregulation of PGC-1α and BDNF.

CONCLUSION:

This study suggests the potential effect of BCP in treating HFFD-induced metabolic and neurobehavioral alterations. BCP seems to activate PPAR-γ in a ligand-independent manner, via upregulation and activation of PGC-1α. The BCP activation of PPAR–γ seems to be CB2R-dependent.”

https://www.ncbi.nlm.nih.gov/pubmed/30469079

https://www.sciencedirect.com/science/article/pii/S0753332218370033?via%3Dihub

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”  https://www.ncbi.nlm.nih.gov/pubmed/18574142

Cannabinoid receptor agonists reduce the short-term mitochondrial dysfunction and oxidative stress linked to excitotoxicity in the rat brain.

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Neuroscience

“The endocannabinoid system (ECS) is involved in a considerable number of physiological processes in the Central Nervous System.

Recently, a modulatory role of cannabinoid receptors (CBr) and CBr agonists on the reduction of the N-methyl-d-aspartate receptor (NMDAr) activation has been demonstrated. Quinolinic acid (QUIN), an endogenous analog of glutamate and excitotoxic metabolite produced in the kynurenine pathway (KP), selectively activates NMDAr and has been shown to participate in different neurodegenerative disorders.

Since the early pattern of toxicity exerted by this metabolite is relevant to explain the extent of damage that it can produce in the brain, in this work we investigated the effects of the synthetic CBr agonist WIN 55,212-2 (WIN) and other agonists (anandamide or AEA, and CP 55,940 or CP) on early markers of QUIN-induced toxicity in rat striatal cultured cells and rat brain synaptosomes.

WIN, AEA and CP exerted protective effects on the QUIN-induced loss of cell viability. WIN also preserved the immunofluorescent signals for neurons and CBr labeling that were decreased by QUIN. The QUIN-induced early mitochondrial dysfunction, lipid peroxidation and reactive oxygen species (ROS) formation were also partially or completely prevented by WIN pretreatment, but not when this CBr agonist was added simultaneously with QUIN to brain synaptosomes.

These findings support a neuroprotective and modulatory role of cannabinoids in the early toxic events elicited by agents inducing excitotoxic processes.”

https://www.ncbi.nlm.nih.gov/pubmed/25446347

https://www.sciencedirect.com/science/article/abs/pii/S0306452214009737?via%3Dihub

The protective effects of Δ9 -tetrahydrocannabinol against inflammation and oxidative stress in rat liver with fructose-induced hyperinsulinemia.

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“A large amount of fructose is metabolized in the liver and causes hepatic functional damage. Δ9 -tetrahydrocannabinol (THC) is known as a therapeutic agent for clinical and experimental applications.

 

The study aims to investigate the effects of THC treatment on inflammation, lipid profiles and oxidative stress in rat liver with hyperinsulinemia.

 

According to the result, long-term and low-dose THC administration may reduce hyperinsulinemia and inflammation in rats to some extent.”

 

https://www.ncbi.nlm.nih.gov/pubmed/30427077

https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.13042

Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion.

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“The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) has been shown to stimulate early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation.

The aim of the present study is to probe the possibility to prevent the molecular changes induced by the BCCAO/R with dietary natural compounds known to possess anti-inflammatory activity, such as the phytocannabinoid beta-caryophyllene (BCP).

CONCLUSIONS:

Collectively, the pre-treatment with BCP, likely acting as agonist for CB2 and PPAR-alpha receptors, modulates in a beneficial way the ECS activation and the lipoperoxidation, taken as indicative of oxidative stress. Furthermore, our results support the evidence that BCP may be used as a dietary supplement to control the physiological response to the hypoperfusion/reperfusion-induced oxidative stress.”

 https://www.ncbi.nlm.nih.gov/pubmed/29402275
“beta-caryophyllene (BCP), a sesquiterpene found as a common constituent of the essential oils of numerous food plants and primary component in Cannabis sativa L., is a dietary phytocannabinoid acting as selective agonist for CB2 receptor and peroxisome-proliferator activating receptor alpha (PPAR-alpha)”
https://lipidworld.biomedcentral.com/articles/10.1186/s12944-018-0661-4
“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

A systematic review on the neuroprotective perspectives of beta-caryophyllene.

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“Beta (β)-caryophyllene (BCAR) is a major sesquiterpene of various plant essential oils reported for several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, antimicrobial, and immune-modulatory activity. Recent studies suggest that it also possesses neuroprotective effect.

This study reviews published reports pertaining to the neuropharmacological activities of BCAR. Databases such as PubMed, Scopus, MedLine Plus, and Google Scholar with keywords “beta (β)-caryophyllene” and other neurological keywords were searched. Data were extracted by referring to articles with information about the dose or concentration/route of administration, test system, results and discussion, and proposed mechanism of action.

A total of 545 research articles were recorded, and 41 experimental studies were included in this review, after application of exclusion criterion. Search results suggest that BCAR exhibits a protective role in a number of nervous system-related disorders including pain, anxiety, spasm, convulsion, depression, alcoholism, and Alzheimer’s disease.

Additionally, BCAR has local anesthetic-like activity, which could protect the nervous system from oxidative stress and inflammation and can act as an immunomodulatory agent. Most neurological activities of this natural product have been linked with the cannabinoid receptors (CBRs), especially the CB2R. This review suggests a possible application of BCAR as a neuroprotective agent.”

https://www.ncbi.nlm.nih.gov/pubmed/30281175

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

Cannabidiol prevents haloperidol-induced vacuos chewing movements and inflammatory changes in mice via PPARγ receptors.

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Brain, Behavior, and Immunity

“The chronic use of drugs that reduce the dopaminergic neurotransmission can cause a hyperkinetic movement disorder called tardive dyskinesia (TD). The pathophysiology of this disorder is not entirely understood but could involve oxidative and neuroinflammatory mechanisms.

Cannabidiol (CBD), the major non-psychotomimetic compound present in Cannabis sativa plant, could be a possible therapeutic alternative for TD. This phytocannabinoid shows antioxidant, anti-inflammatory and antipsychotic properties and decreases the acute motor effects of classical antipsychotics.

The present study investigated if CBD would attenuate orofacial dyskinesia, oxidative stress and inflammatory changes induced by chronic administration of haloperidol in mice. Furthermore, we verified in vivo and in vitro (in primary microglial culture) whether these effects would be mediated by PPARγ receptors.

The results showed that the male Swiss mice treated daily for 21 days with haloperidol develop orofacial dyskinesia. Daily CBD administration before each haloperidol injection prevented this effect.

Mice treated with haloperidol showed an increase in microglial activation and inflammatory mediators in the striatum. These changes were also reduced by CBD. On the other hand, the levels of the anti-inflammatory cytokine IL-10 increased in the striatum of animals that received CBD and haloperidol.

Regarding oxidative stress, haloperidol induced lipid peroxidation and reduced catalase activity. This latter effect was attenuated by CBD. The combination of CBD and haloperidol also increased PGC-1α mRNA expression, a co-activator of PPARγ receptors. Pretreatment with the PPARγ antagonist, GW9662, blocked the behavioural effect of CBD in our TD model. CBD also prevented LPS-stimulated microglial activation, an effect that was also antagonized by GW9662.

In conclusion, our results suggest that CBD could prevent haloperidol-induced orofacial dyskinesia by activating PPARγ receptors and attenuating neuroinflammatory changes in the striatum.”

https://www.ncbi.nlm.nih.gov/pubmed/30217539
https://www.sciencedirect.com/science/article/pii/S0889159118305828?via%3Dihub
“Haloperidol, marketed under the trade name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, nausea and vomiting, delirium, agitation, acute psychosis, and hallucinations in alcohol withdrawal”  https://en.wikipedia.org/wiki/Haloperidol

Cannabis in liver disorders: a friend or a foe?

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“The recent legalization of recreational marijuana use in some parts of the world, the discovery of new indications for the clinical application of cannabis, and the acceptance of the use of cannabis in practice has been paralleled by extensive research on the active components of cannabis and the endocannabinoid system within the human body.

In this review, we evaluate the available evidence on cannabis and its constituents and the application of this evidence in clinical practice, focusing particularly on the liver and liver diseases.

Constituents of cannabis, such as cannabidiol and Δ-tetrahydrocannabinol, have shown anti-inflammatory, antioxidant, and hepatoprotective effects both in in vitro and clinical studies, and appear to have potential in the symptom management and treatment of various liver diseases that were previously considered difficult to manage conservatively.

In addition, the manipulation of the inherent endocannabinoid response system has found favor in many clinical fields and has generated considerable research and clinical interest. Moreover, evidence with regard to the adverse effects of marijuana use in liver diseases is weak, which has led to raise a question on the prior rules, with regard to a denial of liver transplantation to marijuana users.

All in all, the recent trends in research, clinical experiences, as well as the legislature, has opened up new avenues towards the widespread clinical application of cannabis and its derivatives as well as modifiers of the components of the endocannabinoid system. More research is required to fully exploit these new evidences.”

https://www.ncbi.nlm.nih.gov/pubmed/30169449

https://insights.ovid.com/crossref?an=00042737-900000000-97980

Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer.

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“Exosomes and microvesicles (EMV) are lipid bilayer-enclosed structures, released by cells and involved in intercellular communication through transfer of proteins and genetic material. EMV release is also associated with various pathologies, including cancer, where increased EMV release is amongst other associated with chemo-resistance and active transfer of pro-oncogenic factors.

Recent studies show that EMV-inhibiting agents can sensitize cancer cells to chemotherapeutic agents and reduce cancer growth in vivo.

Cannabidiol (CBD), a phytocannabinoid derived from Cannabis sativa, has anti-inflammatory and anti-oxidant properties, and displays anti-proliferative activity.

Here we report a novel role for CBD as a potent inhibitor of EMV release from three cancer cell lines: prostate cancer (PC3), hepatocellular carcinoma (HEPG2) and breast adenocarcinoma (MDA-MB-231).

CBD significantly reduced exosome release in all three cancer cell lines, and also significantly, albeit more variably, inhibited microvesicle release.

The EMV modulating effects of CBD were found to be dose dependent (1 and 5 μM) and cancer cell type specific. Moreover, we provide evidence that this may be associated with changes in mitochondrial function, including modulation of STAT3 and prohibitin expression, and that CBD can be used to sensitize cancer cells to chemotherapy.

We suggest that the known anti-cancer effects of CBD may partly be due to the regulatory effects on EMV biogenesis, and thus CBD poses as a novel and safe modulator of EMV-mediated pathological events.”

https://www.ncbi.nlm.nih.gov/pubmed/30150937

https://www.frontiersin.org/articles/10.3389/fphar.2018.00889/full

Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus.

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European Journal of Medicinal Chemistry

“Cannabaceae plants Cannabis sativa L. and Humulus lupulus L. are rich in terpenes – both are typically comprised of terpenes as up to 3-5% of the dry-mass of the female inflorescence.

Terpenes of cannabis and hops are typically simple mono- and sesquiterpenes derived from two and three isoprene units, respectively. Some terpenes are relatively well known for their potential in biomedicine and have been used in traditional medicine for centuries, while others are yet to be studied in detail.

The current, comprehensive review presents terpenes found in cannabis and hops. Terpenes’ medicinal properties are supported by numerous in vitro, animal and clinical trials and show anti-inflammatory, antioxidant, analgesic, anticonvulsive, antidepressant, anxiolytic, anticancer, antitumor, neuroprotective, anti-mutagenic, anti-allergic, antibiotic and anti-diabetic attributes, among others.

Because of the very low toxicity, these terpenes are already widely used as food additives and in cosmetic products. Thus, they have been proven safe and well-tolerated.”

 https://www.ncbi.nlm.nih.gov/pubmed/30096653
https://www.sciencedirect.com/science/article/pii/S0223523418306408?via%3Dihub

Neuroprotective effects of the cannabigerol quinone derivative VCE-003.2 in SOD1G93A transgenic mice, an experimental model of amyotrophic lateral sclerosis.

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“Antioxidant phytocannabinoids, synthetic compounds targeting the CB2 receptor, and inhibitors of the endocannabinoid inactivation afforded neuroprotection in SOD1G93A mutant mice, a model of ALS. These effects may involve the activation of PPAR-γ too.

Here, we have investigated the neuroprotective effects in SOD1G93A mutant mice of the cannabigerol derivative VCE-003.2, which works as by activating PPAR-γ.

As expected, SOD1G93Atransgenic mice experienced a progressive weight loss and neurological deterioration, which was associated with a marked loss of spinal cholinergic motor neurons, glial reactivity, and elevations in several biochemical markers (cytokines, glutamate transporters) that indirectly reflect the glial proliferation and activation in the spinal cord. The treatment with VCE-003.2 improved most of these neuropathological signs.

It attenuated the weight loss and the anomalies in neurological parameters, preserved spinal cholinergic motor neurons, and reduced astroglial reactivity. VCE-003.2 also reduced the elevations in IL-1β and glial glutamate transporters. Lastly, VCE-003.2 attenuated the LPS-induced generation of TNF-α and IL-1β in cultured astrocytes obtained from SOD1G93Atransgenic newborns, an effect also produced by rosiglitazone, then indicating a probable PPAR-γ activation as responsible of its neuroprotective effects.

In summary, our results showed benefits with VCE-003.2 in SOD1G93A transgenic mice supporting PPAR-γ as an additional neuroprotective target available for cannabinoids in ALS. Such benefits would need to be validated in other ALS models prior to be translated to the clinical level.”

https://www.ncbi.nlm.nih.gov/pubmed/30076846

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303198