β-Caryophyllene, a Dietary Phytocannabinoid, Alleviates Diabetic Cardiomyopathy in Mice by Inhibiting Oxidative Stress and Inflammation Activating Cannabinoid Type-2 Receptors.

Autor:	Mamdouh Hashiesh H; Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt., Sheikh A; Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates., Meeran MFN; Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates., Saraswathiamma D; Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates., Jha NK; Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, Uttar Pradesh, India., Sadek B; Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates., Adeghate E; Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates., Tariq S; Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates., Al Marzooqi S; Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates., Ojha S; Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates.; Zayed Bin Sultan Center for Health Sciences, College of Medicine and Health Sciences, United Arab Emirates University, PO Box: 15551, Al Ain, United Arab Emirates.
Jazyk:	angličtina
Zdroj:	ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2023 Jul 26; Vol. 6 (8), pp. 1129-1142. Date of Electronic Publication: 2023 Jul 26 (Print Publication: 2023).
DOI:	10.1021/acsptsci.3c00027
Abstrakt:	Diabetes mellitus (DM) and its associated complications are considered one of the major health risks globally. Among numerous complications, diabetic cardiomyopathy (DCM) is characterized by increased accumulation of lipids and reduced glucose utilization following abnormal lipid metabolism in the myocardium along with oxidative stress, myocardial fibrosis, and inflammation that eventually result in cardiac dysfunction. The abnormal metabolism of lipids plays a fundamental role in cardiac lipotoxicity following the occurrence and development of DCM. Recently, it has been revealed that cannabinoid type-2 (CB2) receptors, an essential component of the endocannabinoid system, play a crucial role in the pathogenesis of obesity, hyperlipidemia, and DM. Provided the role of CB2R in regulating the glucolipid metabolic dysfunction and its antioxidant as well as anti-inflammatory activities, we carried out the current study to investigate the protective effects of a selective CB2R agonist, β-caryophyllene (BCP), a natural dietary cannabinoid in the murine model of DCM and elucidated the underlying pharmacological and molecular mechanisms. Mice were fed a high-fat diet for 4 weeks followed by a single intraperitoneal injection of streptozotocin (100 mg/kg) to induce the model of DCM. BCP (50 mg/kg body weight) was given orally for 12 weeks. AM630, a CB2R antagonist, was given 30 min before BCP treatment to demonstrate the CB2R-dependent mechanism of BCP. DCM mice exhibited hyperglycemia, increased serum lactate dehydrogenase, impaired cardiac function, and hypertrophy. In addition, DCM mice showed alternations in serum lipids and increased oxidative stress concomitant to reduced antioxidant defenses and enhanced cardiac lipid accumulation in the diabetic heart. DCM mice also exhibited activation of TLR4/NF-κB/MAPK signaling and triggered the production of inflammatory cytokines and inflammatory enzyme mediators. However, treatment with BCP exerted remarkable protective effects by favorable modulation of the biochemical and molecular parameters, which were altered in DCM mice. Interestingly, pretreatment with AM630 abrogated the protective effects of BCP in DCM mice. Taken together, the findings of the present study demonstrate that BCP possesses the capability to mitigate the progression of DCM by inhibition of lipotoxicity-mediated cardiac oxidative stress and inflammation and favorable modulation of TLR4/NF-κB/MAPK signaling pathways mediating the CB2R-dependent mechanism. Competing Interests: The authors declare no competing financial interest. (© 2023 American Chemical Society.)
Databáze:	MEDLINE
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