(−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis

Alberti, Thaís; Barbosa, Wagner Luiz Ramos; Vieira, José Luiz Fernandes; Raposo, Nádia Rezende Barbosa; Dutra, Rafael C.

doi:10.3390/ijms18040691

Cited by 110 publications

(73 citation statements)

References 54 publications

(75 reference statements)

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“…The positive regulatory effects of copaiba essential oil peaked at 30 min with an EC 50 of approximately 80 ng/mL and were mediated in part by CB2. The positive effects of copaiba essential oil on neuronal signaling pathways were consistent with its reported functions in metabolism [32], wound healing [33][34][35][36], and anti-inflammation [37][38][39][40][41]. Interestingly, copaiba essential oil also activated the apoptosis signaling pathway in a time-dependent manner and reduced the viability of neuronal cells with an EC 50 of approximately 400 ng/mL.…”

Section: Discussionsupporting

confidence: 78%

Fast-Acting and Receptor-Mediated Regulation of Neuronal Signaling Pathways by Copaiba Essential Oil

Urasaki

Beaumont²,

Workman³

et al. 2020

IJMS

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This study examined the biological activities of copaiba essential oil via measurement of its effects on signaling pathways in the SH-SY5Y neuronal cell line. Nanofluidic proteomic technologies were deployed to measure the phosphorylation of biomarker proteins within the signaling cascades. Interestingly, copaiba essential oil upregulated the pI3K/Akt/mTOR, MAPK, and JAK/STAT signaling pathways in neuronal cells. The effects of copaiba essential oil peaked at 30 min post-treatment, with a half-maximal effective concentration (EC50) of approximately 80 ng/mL. Treatment with cannabinoid receptor 2 (CB2) agonist AM1241 or the inverse agonist BML190 abrogated the regulatory effects of copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. Surprisingly, copaiba essential oil also activated the apoptosis signaling pathway and reduced the viability of SH-SY5Y cells with an EC50 of approximately 400 ng/mL. Furthermore, β-caryophyllene, a principal constituent of copaiba essential oil, downregulated the pI3K/Akt/mTOR signaling pathway. Taken together, the findings indicated that copaiba essential oil upregulated signaling pathways associated with cell metabolism, growth, immunity, and apoptosis. The biological activities of copaiba essential oil were determined to be fast acting, CB2 mediated, and dependent on multiple chemical constituents of the oil. Nanofluidic proteomics provided a powerful means to assess the biological activities of copaiba essential oil.

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Section: Discussionsupporting

confidence: 78%

Fast-Acting and Receptor-Mediated Regulation of Neuronal Signaling Pathways by Copaiba Essential Oil

Urasaki

Beaumont²,

Workman³

et al. 2020

IJMS

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“…Moreover, it inhibits cell T migration. The oral treatment with 50 mg/kg of BCP twice a day has decreased hyperalgesia induced by the EAE and protected from brain damage, inhibiting cytokine biosynthesis and restoring the activity of catalase, superoxide dismutase and glutathione peroxidase, all enzymes involved in the detoxification of oxidant substances [38].…”

Section: β-Caryophyllene and Nervous Systemmentioning

confidence: 99%

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

et al. 2019

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β-Caryophyllene (BCP), a natural bicyclic sesquiterpene, is a selective phytocannabinoid agonist of type 2 receptors (CB2-R). It isn’t psychogenic due to the absence of an affinity to cannabinoid receptor type 1 (CB1). Among the various biological activities, BCP exerts anti-inflammatory action via inhibiting the main inflammatory mediators, such as inducible nitric oxide synthase (iNOS), Interleukin 1 beta (IL-1β), Interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-α), nuclear factor kapp a-light-chain-enhancer of activated B cells (NF-κB), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2). Peroxisome proliferator-activated receptors alpha (PPAR-α) effects are also mediated by the activation of PPAR-α and PPAR-γ receptors. In detail, many studies, in vitro and in vivo, suggest that the treatment with β-caryophyllene improves the phenotype of animals used to model various inflammatory pathologies, such as nervous system diseases (Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, stroke), atherosclerosis, and tumours (colon, breast, pancreas, lymphoma, melanoma and glioma cancer). Furthermore, pre-clinical data have highlighted that BCP is potentially useful in Streptococcus infections, osteoporosis, steatohepatitis, and exerts anticonvulsant, analgesic, myorelaxing, sedative, and antidepressive effects. BCP is non-toxic in rodents, with a Lethal dose, 50% (LD50) greater than 5000 mg/kg. Nevertheless, it inhibits various cytochrome P450 isoforms (above all, CYP3A4), which metabolise xenobiotics, leading to adverse effects, due to drug levels over therapeutic window. All the reported data have highlighted that both pharmacological and toxicological aspects need to be further investigated with clinical trials.

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“…Moreover, in C57BL/6 female mice, BCAR at 1, 10, and 100 μM (in vitro) and 25 and 50 mg/kg (p.o. ; in vivo) exerted an immunomodulatory effect by inhibiting the microglial cells, CD4+ and CD8+ T lymphocytes, and expression of pro‐inflammatory cytokines, diminishing axonal demyelination, while modulating the Th1/Treg immune balance through the activation of CB2R (Alberti, Barbosa, Vieira, Raposo, & Dutra, ). BCAR‐mediated possible immunomodulatory pathways are depicted in Figure .…”

Section: Neuropharmacological Effects Of β‐Caryophyllenementioning

confidence: 99%

A systematic review on the neuroprotective perspectives of beta‐caryophyllene

Machado

Islam

Ali

et al. 2018

Phytotherapy Research

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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.

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(−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis

Cited by 110 publications

References 54 publications

Fast-Acting and Receptor-Mediated Regulation of Neuronal Signaling Pathways by Copaiba Essential Oil

Fast-Acting and Receptor-Mediated Regulation of Neuronal Signaling Pathways by Copaiba Essential Oil

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

A systematic review on the neuroprotective perspectives of beta‐caryophyllene

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