β-Caryophyllene Ameliorates Cyclophosphamide Induced Cardiac Injury: The Association of TLR4/NFκB and Nrf2/HO1/NQO1 Pathways

Younis, Nancy S.

doi:10.3390/jcdd9050133

Cited by 5 publications

(6 citation statements)

References 52 publications

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“…Herein, BCP amplified the antioxidant status and mitigated oxidative damage in the DCM mouse heart, evidenced by a reduced level of MDA and increased level of GSH. In agreement, BCP showed to attenuate cyclophosphamide and doxorubicin-mediated myocardial injury via repressing lipid peroxidation and amelioration of the endogenous antioxidant system. Moreover, the antioxidant potential and free radical scavenging activity of BCP might be linked to the noticed alleviation of oxidative injury in DCM mice .…”

Section: Discussionsupporting

confidence: 54%

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

Hashiesh

Azimullah

Meeran

et al. 2023

ACS Pharmacol. Transl. Sci.

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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.

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Section: Discussionsupporting

confidence: 54%

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

Hashiesh

Azimullah

Meeran

et al. 2023

ACS Pharmacol. Transl. Sci.

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“…β-Caryophyllene: β-Caryophyllene is a terpenoid found in many herbs and spices, including black pepper, oregano, and cloves. Studies have shown that β-caryophyllene can shield the cardiac tissues against cardiotoxicity by mitigating inflammation, reducing collagen deposition, and improving cardiac function in rat models [151].…”

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confidence: 99%

“…Bioactive against cardiac fibrosis (Figures were adopted and modified from ACS, MDPI, Sigma, and Pepdraw).β-CaryophylleneTerpenoids many herbs and spices, including black pepper, oregano, and cloves[151] Apple, grape, tomato, green tea, broccoli, pine, and ginkgo leaf. [138] Apigenin Flavonoids J. Cardiovasc.…”

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confidence: 99%

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Bioactive Compounds and Cardiac Fibrosis: Current Insight and Future Prospect

Majid

Hassan

Hoque

et al. 2023

JCDD

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Cardiac fibrosis is a pathological condition characterized by excessive deposition of collagen and other extracellular matrix components in the heart. It is recognized as a major contributor to the development and progression of heart failure. Despite significant research efforts in characterizing and identifying key molecular mechanisms associated with myocardial fibrosis, effective treatment for this condition is still out of sight. In this regard, bioactive compounds have emerged as potential therapeutic antifibrotic agents due to their anti-inflammatory and antioxidant properties. These compounds exhibit the ability to modulate fibrogenic processes by inhibiting the production of extracellular matrix proteins involved in fibroblast to myofibroblast differentiation, or by promoting their breakdown. Extensive investigation of these bioactive compounds offers new possibilities for preventing or reducing cardiac fibrosis and its detrimental consequences. This comprehensive review aims to provide a thorough overview of the mechanisms underlying cardiac fibrosis, address the limitations of current treatment strategies, and specifically explore the potential of bioactive compounds as therapeutic interventions for the treatment and/or prevention of cardiac fibrosis.

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“…However, these metabolic alterations were attenuated in rats receiving doxycycline. Similarly, the study by Nancy S. Younis demonstrated the cardioprotective effects of β-caryophyllene, a natural sesquiterpene found in the essential oils of several plants, on cardiac injury induced by cyclophosphamide exposure, in 30 male Wistar rats (group 1: normal, group 2: β-caryophyllene, group 3: cyclophosphamide, group 4: β-caryophyllene + cyclophosphamide (100 mg/kg), group 5: β-caryophyllene + cyclophosphamide (200 mg/kg)) [ 12 ]. β-caryophyllene administration was associated with activated Nrf2/HO1/NQO1 and inhibited TLR4/NFkB pathways with ensuing antioxidative action and diminished inflammatory and apoptosis responses.…”

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confidence: 99%