The cannabinoid 2 receptor agonist β-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration

Andrade-Silva, Magaiver; Corrêa, Luana Barbosa; Candéa, André Luis Peixoto; Cavalher-Machado, Simone C.; Barbosa, Helene Santos; Rosas, Elaine Cruz; Henriques, Maria das Graças

doi:10.1007/s00011-016-0969-3

Cited by 36 publications

(28 citation statements)

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“…Agonism of CB1 and CB2 receptors by exogenous ligands or endocannabinoids in animal models of MS have demonstrated suppression of pro-inflammatory mediators [38], as well as induction of neuroprotection and immunomodulation [39,40,41,42]. BCP (Figure 1), a dietary functional non-psychoactive CB2 receptor ligand [12,13,14] showed analgesic, anti-inflammatory, anticonvulsant, and neuroprotective effects [15,27,29,43,44,45,46]. Nonetheless, the effects of BCP on immune inflammatory diseases of the CNS, such as MS, have not yet been reported.…”

Section: Resultsmentioning

confidence: 99%

“…(−)-β-caryophyllene (BCP), a functional non-psychoactive CB2 receptor agonist [12,13,14], is found in, for example, plant-derived oleoresins, essential oils, solutes, distillates, extracts, fermentations, infusions, and leachates, from several plants [15,16,17,18,19,20,21,22,23,24,25]. Furthermore, BCP showed analgesic, anti-inflammatory, neuroprotective, anti-depressive, anxiolytic, and anti-nephrotoxicity effects [12,13,26,27,28,29,30,31].…”

Section: Introductionmentioning

confidence: 99%

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

Alberti

Barbosa

Vieira

et al. 2017

IJMS

114

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(−)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain. Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Furthermore, we sought to demonstrate some of the mechanisms that underlie the modulation BCP exerts on autoimmune activated T cells, the pro-inflammatory scenery of the central nervous system (CNS), and demyelination. Our findings demonstrate that BCP significantly ameliorates both the clinical and pathological parameters of EAE. In addition, data hereby presented indicates that mechanisms underlying BCP immunomodulatory effect seems to be linked to its ability to inhibit microglial cells, CD4+ and CD8+ T lymphocytes, as well as protein expression of pro-inflammatory cytokines. Furthermore, it diminished axonal demyelination and modulated Th1/Treg immune balance through the activation of CB2 receptor. Altogether, our study represents significant implications for clinical research and strongly supports the effectiveness of BCP as a novel molecule to target in the development of effective therapeutic agents for MS.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Alberti

Barbosa

Vieira

et al. 2017

IJMS

114

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“…A number of animal model studies have demonstrated the anti‐inflammatory properties of BPEO and its major active components caryophyllene and d‐limonene (Andrade‐Silva et al, ; Jeena et al, ; Varga et al, ; Yu, Yan, & Sun, ). In a human colon cell line, caryophyllene was found to inhibit chemokine and cytokine production including tumor necrosis factor‐α and interleukin‐1β (Cho et al, ).…”

Section: Resultsmentioning

confidence: 99%

Black pepper (Piper nigrum) essential oil demonstrates tissue remodeling and metabolism modulating potential in human cells

Han¹,

Beaumont²,

Rodriguez³

et al. 2018

Phytotherapy Research

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Very few studies have investigated the biological activities of black pepper essential oil (BPEO) in human cells. Therefore, in the current study, we examined the biological activities of BPEO in cytokine-stimulated human dermal fibroblasts by analyzing the levels of 17 important protein biomarkers pertinent to inflammation and tissue remodeling. BPEO exhibited significant antiproliferative activity in these skin cells and significantly inhibited the production of Collagen I, Collagen III, and plasminogen activator inhibitor 1. In addition, we studied the effect of BPEO on the regulation of genome-wide expression and found that BPEO diversely modulated global gene expression. Further analysis showed that BPEO affected many important genes and signaling pathways closely related to metabolism, inflammation, tissue remodeling, and cancer signaling. This study is the first to provide evidence of the biological activities of BPEO in human dermal fibroblasts. The data suggest that BPEO possesses promising potential to modulate the biological processes of tissue remodeling, wound healing, and metabolism. Although further research is required, BPEO appears to be a good therapeutic candidate for a variety of health conditions including wound care and metabolic diseases. Research into the biological and pharmacological mechanisms of action of BPEO and its major active constituents is recommended.

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“…However, there are no reports of studies that combine BCP and DHA and evaluate histological sections with respect to inflammation. Activation of CB2 receptors by agonists, such as BCP, reduces the migration of neutrophils into the lungs, to the infarcted myocardium, and to the brain in cerebral ischemia . Therefore, CB2 receptors are possible critical regulators of the immune response to sepsis .…”

Section: Discussionmentioning

confidence: 99%

“…Activation of CB2 receptors by agonists, such as BCP, reduces the migration of neutrophils into the lungs, to the infarcted myocardium, and to the brain in cerebral ischemia. 52 Therefore, CB2 receptors are possible critical regulators of the immune response to sepsis. 53 Decreased damage to the blood-brain barrier in cases of cerebral ischemia and neuroprotection in cases of stroke, also showed positive histological results in animal models with DHA-based therapy.…”

Section: Discussionmentioning

confidence: 99%

Anti‐inflammatory activity of β‐caryophyllene combined with docosahexaenoic acid in a model of sepsis induced by Staphylococcus aureus in mice

et al. 2019

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BACKGROUND Sepsis is a set of serious organic manifestations caused by an infection, whose progression culminates in exacerbated inflammation and oxidative stress, poor prognosis, and high hospital costs. Antioxidants used against sepsis have been evaluated, including essential oils such as β‐caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The aim of this study was to evaluate the anti‐inflammatory activity of the association of these two compounds. RESULTS Treatment with BCP‐DHA, at a dose of 200 μL/animal, significantly inhibited the migration of neutrophils in a Cg‐induced peritonitis model. After Staphylococcus aureus infection, in the groups treated with BCP‐DHA there was a significant decrease in the total and differential count of leukocytes, increased expression of cytokines TNF‐α and IFN‐γ in treated groups, an increase of IL‐4 and IL‐5 in B/D and B/D + SA groups, and an augmentation of IL‐6 and IL‐12 groups in B/D + SA groups. Histological and bacterial analysis revealed lower neutrophil migration and lower bacterial load in the infected and treated groups. CONCLUSION In general, the BCP‐DHA association presented anti‐inflammatory activity against two different models of acute inflammation and infection, showing promising potential as a therapeutic adjuvant in sepsis. © 2019 Society of Chemical Industry

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The cannabinoid 2 receptor agonist β-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration

Abstract: These results suggest that the CB receptor may represent a new target for modulating the inflammatory reaction induced by mycobacteria.

Cited by 36 publications

References 50 publications

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

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

Black pepper (Piper nigrum) essential oil demonstrates tissue remodeling and metabolism modulating potential in human cells

Anti‐inflammatory activity of β‐caryophyllene combined with docosahexaenoic acid in a model of sepsis induced by Staphylococcus aureus in mice

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