β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors

Irrera, Natasha; D’Ascola, Angela; Pallio, Giovanni; Bitto, Alessandra; Mazzon, Emanuela; Mannino, Federica; Squadrito, Violetta; Arcoraci, Vincenzo; Minutoli, Letteria; Campo, Giuseppe M.; Avenoso, Angela; Bongiorno, Elisa Benedetta; Vaccaro, Mario; Squadrito, Francesco; Altavilla, Domenica

doi:10.3390/biom9080326

Cited by 63 publications

(61 citation statements)

References 36 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this experimental approach, U373 cells highly expressed NF-κB, whereas BCP treatment significantly reduced its expression. In addition, previous studies have indicated a possible crosstalk between the CB2 receptor and PPAR-γ [12,20]. The PPAR-γ receptor activation reduces pro-inflammatory cytokine release, thus exerting an anti-inflammatory effect [21].…”

Section: Discussionmentioning

confidence: 97%

β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

Irrera

D’Ascola

Pallio

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Glioblastomas are aggressive cancers characterized by uncontrolled proliferation and inflammation. b-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that showed an important anti-inflammatory effect through the interaction of CB2 and peroxisome proliferator-activated receptor gamma (PPARg) receptors. BCP effects were investigated in an in vitro model of glioblastoma. U-373 and U87, derived from a human glioblastoma, and human glioma stem-like cells (GSCs) were treated with BCP at different doses and time-points. AM360, a specific CB2 antagonist, was added 2 h before BCP treatment. BCP showed a significant anti-proliferative effect, reducing cell viability, inhibiting cell cycle, and increasing apoptosis, as demonstrated by Tunel assay, caspase-3 and caspase -9 activation. In addition, the pro-apoptotic BAX expression was increased, whereas the anti-apoptotic Bcl-2 expression was reduced. Treatment with BCP decreased Beclin-1, LC3 and p62/SQSTM1 expression, indicating a possible switch of autophagy to apoptosis. BCP’s anti-inflammatory effect was demonstrated by NF-κB reduction, PPARg activation and TNF-a decrease; BCP significantly reduced Jun N-Terminal Kinase (JNK) expression as a consequence of TNF-α inhibition. AM360 abrogated BCP effects, thus demonstrating the BCP mechanism of action through the CB2 receptor. These findings let us hypothesize that BCP may act as a tumor suppressor in glioblastoma, acting on CB2 receptor and modulating JNK.

show abstract

Section: Discussionmentioning

confidence: 97%

β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

Irrera

D’Ascola

Pallio

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, it has been characterized by a plethora of biological activities, among which analgesic, anti-inflammatory, antioxidant, neuroprotective, and antiproliferative were the most investigated; moreover, it has been reported to affect phospholipid cooperativity and membrane permeability ( Table 3 ). These properties have provided benefits in several experimental models of disease, such as neurodegeneration, inflammation, pain, anxiety, depression, autoimmune diseases, metabolic ailments, osteoarthritis and some cancer models [ 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 ,…”

Section: Caryophyllane Sesquiterpenesmentioning

confidence: 99%

“…Such benefits have been usually ascribed to the ability of β-caryophyllene to selectively activate the cannabinoid CB2 receptors (CB2Rs) [ 123 , 124 , 128 , 139 , 149 , 153 , 213 ], and to modulate further targets in the endocannabinoidome (i.e., the endogenous lipid signaling system including several fatty acid-derived mediators and their receptors, and their metabolic enzymes), such as the peroxisome proliferator-activated receptors (PPARs) and the fatty acid amide hydrolase (FAAH), which is a degrading enzyme of the endocannabinoid neurotransmitters [ 123 , 124 , 128 , 214 ]. Interestingly, a peripheral release of endogenous opioids seems to mediate the antinociceptive effects of β-caryophyllene, although nonpsychoactive responses have been also described [ 124 ].…”

Section: Caryophyllane Sesquiterpenesmentioning

confidence: 99%

“…The antiproliferative activity of caryophyllane sesquiterpenes has been often associated with the activation of pro-apoptotic signalings. Particularly, α-humulene induced apoptosis in liver cancer cells [ 210 ], while β-caryophyllene in different in vitro cancer models, including neuroblastoma, lymphoma, glioblastoma, osteosarcoma, and oral cancer cells [ 128 , 154 , 155 , 156 , 158 ]. The apoptotic cell death induced by the sesquiterpene in oral KB cancer cells was associated with morphological changes, lowered cell growth, and reduced metastasizing abilities, which was likely due to the activation of a mitochondrial-mediated apoptotic pathway [ 155 ].…”

Section: Caryophyllane Sesquiterpenes In Cancer Chemopreventionmentioning

confidence: 99%

See 1 more Smart Citation

Chemopreventive Potential of Caryophyllane Sesquiterpenes: An Overview of Preliminary Evidence

Sotto

Mancinelli

Gullì

et al. 2020

Cancers

View full text Add to dashboard Cite

Chemoprevention is referred to as a strategy to inhibit, suppress, or reverse tumor development and progression in healthy people along with high-risk subjects and oncologic patients through using pharmacological or natural substances. Numerous phytochemicals have been widely described in the literature to possess chemopreventive properties, although their clinical usefulness remains to be defined. Among them, caryophyllane sesquiterpenes are natural compounds widely occurring in nature kingdoms, especially in plants, fungi, and marine environments. Several structures, characterized by a common caryophyllane skeleton with further rearrangements, have been identified, but those isolated from plant essential oils, including β-caryophyllene, β-caryophyllene oxide, α-humulene, and isocaryophyllene, have attracted the greatest pharmacological attention. Emerging evidence has outlined a complex polypharmacological profile of caryophyllane sesquiterpenes characterized by blocking, suppressing, chemosensitizing, and cytoprotective properties, which suggests a possible usefulness of these natural substances in cancer chemoprevention for both preventive and adjuvant purposes. In the present review, the scientific knowledge about the chemopreventive properties of caryophyllane sesquiterpenes and the mechanisms involved have been collected and discussed; moreover, possible structure–activity relationships have been highlighted. Although further high-quality studies are required, the promising preclinical findings and the safe pharmacological profile encourage further studies to define a clinical usefulness of caryophyllane sesquiterpenes in primary, secondary, or tertiary chemoprevention.

show abstract

“…Cannabinoids are known to interact or crosstalk with a family of peroxisome proliferated activator receptors (PPARs) including three distinct subtypes namely PPAR-α, PPAR-β/δ, and PPAR-γ that are encoded by distinct genes and are regulated by steroids and lipid metabolites and control lipid and glucose homeostasis and inflammatory responses [ 40 , 65 , 67 , 68 ]. The activation of CB2R on the surface of the cells triggers the intracellular signaling cascade that leads to the activation of PPARs [ 69 ]. The PPARs belongs to the members of nuclear receptor superfamily that functions as ligand-activated transcription factors and plays significantly in cellular proliferation, differentiation, organogenesis, inflammation, as well as the expression of hepatic enzymes regulating glucose homeostasis, insulin sensitivity, and lipid metabolism [ 70 ].…”

Section: Effects and Possible Mechanisms Of Bcp On Diabetesmentioning

confidence: 99%

Therapeutic Potential of β-Caryophyllene: A Dietary Cannabinoid in Diabetes and Associated Complications

et al. 2020

View full text Add to dashboard Cite

Diabetes mellitus (DM), a metabolic disorder is one of the most prevalent chronic diseases worldwide across developed as well as developing nations. Hyperglycemia is the core feature of the type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), following insulin deficiency and impaired insulin secretion or sensitivity leads insulin resistance (IR), respectively. Genetic and environmental factors attributed to the pathogenesis of DM and various therapeutic strategies are available for the prevention and treatment of T2DM. Among the numerous therapeutic approaches, the health effects of dietary/nutraceutical approach due to the presence of bioactive constituents, popularly termed phytochemicals are receiving special interest for pharmacological effects and therapeutic benefits. The phytochemicals classes, in particular sesquiterpenes received attention because of potent antioxidant, anti-inflammatory, and antihyperglycemic effects and health benefits mediating modulation of enzymes, receptors, and signaling pathways deranged in DM and its complications. One of the terpene compounds, β-caryophyllene (BCP), received enormous attention because of its abundant occurrence, non-psychoactive nature, and dietary availability through consumption of edible plants including spices. BCP exhibit selective full agonism on cannabinoid receptor type 2 (CB2R), an important component of endocannabinoid system, and plays a role in glucose and lipid metabolism and represents the newest drug target for chronic inflammatory diseases. BCP also showed agonist action on peroxisome proliferated activated receptor subtypes, PPAR-α and PPAR-γ, the main target of currently used fibrates and imidazolidinones for dyslipidemia and IR, respectively. Many studies demonstrated its antioxidant, anti-inflammatory, organoprotective, and antihyperglycemic properties. In the present review, the plausible therapeutic potential of BCP in diabetes and associated complications has been comprehensively elaborated based on experimental and a few clinical studies available. Further, the pharmacological and molecular mechanisms of BCP in diabetes and its complications have been represented using synoptic tables and schemes. Given the safe status, abundant natural occurrence, oral bioavailability, dietary use and pleiotropic properties modulating receptors and enzymes, BCP appears as a promising molecule for diabetes and its complications.

show abstract

β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors

Cited by 63 publications

References 36 publications

β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells

Chemopreventive Potential of Caryophyllane Sesquiterpenes: An Overview of Preliminary Evidence

Therapeutic Potential of β-Caryophyllene: A Dietary Cannabinoid in Diabetes and Associated Complications

Contact Info

Product

Resources

About