β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors
β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/9/8/326 |
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| author | Natasha Irrera Angela D’Ascola Giovanni Pallio Alessandra Bitto Emanuela Mazzon Federica Mannino Violetta Squadrito Vincenzo Arcoraci Letteria Minutoli Giuseppe Maurizio Campo Angela Avenoso Elisa Benedetta Bongiorno Mario Vaccaro Francesco Squadrito Domenica Altavilla |
| author_facet | Natasha Irrera Angela D’Ascola Giovanni Pallio Alessandra Bitto Emanuela Mazzon Federica Mannino Violetta Squadrito Vincenzo Arcoraci Letteria Minutoli Giuseppe Maurizio Campo Angela Avenoso Elisa Benedetta Bongiorno Mario Vaccaro Francesco Squadrito Domenica Altavilla |
| author_sort | Natasha Irrera |
| collection | DOAJ |
| description | β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-ĸB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ. |
| first_indexed | 2024-04-12T04:19:41Z |
| format | Article |
| id | doaj.art-299e58f5e65541cd9c138f335f494922 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-12T04:19:41Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-299e58f5e65541cd9c138f335f4949222022-12-22T03:48:15ZengMDPI AGBiomolecules2218-273X2019-07-019832610.3390/biom9080326biom9080326β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ ReceptorsNatasha Irrera0Angela D’Ascola1Giovanni Pallio2Alessandra Bitto3Emanuela Mazzon4Federica Mannino5Violetta Squadrito6Vincenzo Arcoraci7Letteria Minutoli8Giuseppe Maurizio Campo9Angela Avenoso10Elisa Benedetta Bongiorno11Mario Vaccaro12Francesco Squadrito13Domenica Altavilla14Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyIRCCS Centro Neurolesi “Bonino-Pulejo”, 98124 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyDepartment of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italyβ-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-ĸB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.https://www.mdpi.com/2218-273X/9/8/326β-caryophylleneCB2 receptorsPPAR-γCAIAarthritis |
| spellingShingle | Natasha Irrera Angela D’Ascola Giovanni Pallio Alessandra Bitto Emanuela Mazzon Federica Mannino Violetta Squadrito Vincenzo Arcoraci Letteria Minutoli Giuseppe Maurizio Campo Angela Avenoso Elisa Benedetta Bongiorno Mario Vaccaro Francesco Squadrito Domenica Altavilla β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors Biomolecules β-caryophyllene CB2 receptors PPAR-γ CAIA arthritis |
| title | β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors |
| title_full | β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors |
| title_fullStr | β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors |
| title_full_unstemmed | β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors |
| title_short | β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors |
| title_sort | β caryophyllene mitigates collagen antibody induced arthritis caia in mice through a cross talk between cb2 and ppar γ receptors |
| topic | β-caryophyllene CB2 receptors PPAR-γ CAIA arthritis |
| url | https://www.mdpi.com/2218-273X/9/8/326 |
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