β-Caryophyllene as a Potential Protective Agent Against Myocardial Injury: The Role of Toll-Like Receptors

Abstract

Myocardial infarction (MI) remains one of the major causes of mortality around the world. A possible mechanism involved in myocardial infarction is the engagement of Toll-like receptors (TLRs). This study was intended to discover the prospective cardioprotective actions of β-caryophyllene, a natural sesquiterpene, to ameliorate isoproterenol (ISO)-induced myocardial infarction through HSP-60/TLR/MyD88/NFκB pathway. β-Caryophyllene (100 or 200 mg/kg/day orally) was administered for 21 days then MI was induced via ISO (85 mg/kg, subcutaneous) on 20th and 21st days. The results indicated that ISO induced a significant infarcted area associated with several alterations in the electrocardiogram (ECG) and blood pressure (BP) indices and caused an increase in numerous cardiac indicators such as creatine phosphokinase (CPK), creatine kinase-myocardial bound (CK-MB), lactate dehydrogenase (LDH), and cardiac tropinine T (cTnT). In addition, ISO significantly amplified heat shock protein 60 (HSP-60) and other inflammatory markers, such as TNF-α, IL-Iβ, and NFκB, and affected TLR2 and TLR4 expression and their adaptor proteins; Myeloid differentiation primary response 88 (MYD88), and TIR-domain-containing adapter-inducing interferon-β (TRIF). On the other hand, consumption of β-caryophyllene significantly reversed the infarcted size, ECG and BP alterations, ameliorated the ISO elevation in cardiac indicators; it also notably diminished HSP-60, and subsequently TLR2, TLR4, MYD88, and TRIF expression, with a substantial reduction in inflammatory mediator levels. This study revealed the cardioprotective effect of β-caryophyllene against MI through inhibiting HSP-60/TLR/MyD88/NFκB signaling pathways.

Experimental model of acute myocardial infarction for evaluation of prevention and rehabilitation strategies in cardiovascular diseases – a pilot study

“…Oxidative stress plays an important role not only in AMI but also in many other cardiovascular disorders (17)(18)(19). Younis et al reported that ISO in a dose of 85 mg/kg bw decreased in P wave, QRS complex, PR segment, and RR intervals and increased in the QT interval duration and ST-segment deviation, in comparison with the control rats (20). According to results of Soraya et al rats from AMI group treated with ISO in a dose of 100 mg/kg bw showed a marked decrease in R-amplitude, a significant decrease in the RR interval and therefore, a significant increase in the heart rate (21 (13).…”

Protective Effect of Geraniol on Oxidative, Inflammatory and Apoptotic Alterations in Isoproterenol-Induced Cardiotoxicity: Role of the Keap1/Nrf2/HO-1 and PI3K/Akt/mTOR Pathways

“…Group III (ISO) resembled group I, with the difference that the animals were injected (s.c.) with isoproterenol (85 mg/kg) on days 13 and 14 to induce MI. Groups IV (ISO plus geraniol 100) and V (ISO plus geraniol 200) included animals pretreated with geraniol that (either 100 or 200 mg/kg) [ 10 , 17 ] orally via gavage for two weeks and then injected with isoproterenol (85 mg/kg, s.c.) in days 13 and 14 for MI induction [ 22 ]. Geraniol (either 100 or 200 mg/kg) was always administered orally via gavage after dissolving in 1% carboxymethyl cellulose (CMC) in normal saline (1 mL).…”

“…Animals were anesthetized using urethane (1.5 g/kg) [ 22 ] at the end of the experiments and before euthanization, and then placed in a non-invasive computerized ECG apparatus (Kent Scientific, Torrington, CT, USA) to acquire ECG recordings as described previously [ 22 ].…”

“…Real-time PCR was performed as previously described [ 22 ]. Quantification analyses were performed in an Opticon-2 Real-time PCR reactor (MJ Research, Reno, NV, USA).…”

Inhibitory Effects of β-Caryophyllene on Helicobacter pylori Infection In Vitro and In Vivo

“…[18,20,21]. Recent approval of β-caryophyllene as a food additive and flavoring agent by the Food and Drug Administration in the USA (FDA) and the European Food Safety Authority (EFSA) generated interest among the scientific community to explore its additional therapeutic benefits [22]. Numerous reports showed inhibitory effects of β-caryophyllene against bacteria, virus, and fungi [23][24][25][26].…”