Nerolidol attenuates isoproterenol-induced acute myocardial infarction in rats.

Cardiovascular diseases have high morbidity and mortality rates, and their treatment is not effective in reducing the damage caused by myocardial infarction (MI). This study aimed to investigate whether nerolidol (NRD), a sesquiterpene alcohol, could attenuate MI in an isoproterenol-treated rat model. MI was induced by the administration of two doses of isoproterenol (ISO, 100 mg/kg, i.p.) with an interval of 24 h between doses.The animals were divided into four groups: control (CTR) (vehicle - NaCl 0.9% + Tween 80 0.2%), MI (ISO + vehicle), MI + NRD (50 mg/kg) and MI + NRD (100 mg/kg). An electrocardiogram was performed, and contractile parameters, cardiac enzymes, infarction size, and antioxidant parameters in the heart were measured to evaluate the effects of NRD. The ISO group showed a significant rise in ST segment, QTc, and heart rate associated with a reduction in left ventricular developed pressure (LVDP), + dP/dt, and -dP/dt. In addition, there were increases in levels of creatine kinase (CK), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and thiobarbituric acid (TBARS); reductions in superoxide dismutase (SOD) and catalase (CAT) activities; and an increase in the infarction size. Interestingly, NRD significantly attenuated almost all the parameters of ISO-induced MI mentioned above. Our results suggest that nerolidol attenuates MI caused by ISO by a marked reduction in myocardial infarct size and suppression of oxidative stress. CK total, creatine kinase total; CK-MB, creatine kinase myocardial band; LDH, lactate dehydrogenase; SOD, superoxide dismutase; CAT, catalase. CTR (vehicle group), MI (100 mg/kg of isoproterenol), ISO + NRD 50 (50 mg/kg of nerolidol), and ISO + NRD 100 (100 mg/kg of nerolidol).

Cardiovascular effects of farnesol and its ß-cyclodextrin complex in normotensive and hypertensive rats.

Farnesol (FAR) is a sesquiterpene alcohol with a range of reported biological effects including cardioprotective, antioxidant and antiarrhythmic properties. However, due to its volatility, the use of drug incorporation systems, such as cyclodextrins, have been proposed to improve its pharmacological properties. Thus, the aim of this study was to evaluate and characterize the cardiovascular effects of FAR alone, and to investigate the antihypertensive effects of FAR complexed with ß-cyclodextrin (ßCD) in rats. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after intravenous administration of FAR (0,5; 2,5; 5 and 7,5 mg/kg) in normotensive rats, and after oral acute administration (200 mg/kg) of FAR and FAR/ßCD complex in NG-nitro-L-arginine-methyl-ester (L-NAME) hypertensive rats. In normotensive animals, FAR induced dose-dependent hypotension associated with bradycardia. These effects were not affected by pre-treatment with L-NAME or indomethacin (INDO), but were partially attenuated by atropine. Pre-treatment with hexamethonium (HEXA) only affected hypotension. In the hypertensive rats, FAR/ßCD potentialized the antihypertensive effect when compared to FAR alone. Molecular docking experiments demonstrated for the first time that FAR has affinity to bind to the M3 and M2 muscarinic, and nicotinic receptors through hydrogen bonds in the same residues as known ligands. In conclusion, our results demonstrated that FAR induced hypotension associated with bradycardia, possibly through the muscarinic and nicotinic receptors. The inclusion complex with ßCD improved the antihypertensive effects of FAR, which can be relevant to improve current cardiovascular therapy using volatile natural components.

Monoterpenes and their derivatives as agents for cardiovascular disease management: A systematic review and meta-analysis.

BACKGROUND: Monoterpenes are one of the most studied plant's secondary metabolites, they are found abundantly in essential oils of aromatic plants. They also have a great range of pharmacological properties, such as antihypertensive, bradycardic, antiarrhythmic and hypotensive. In the face of the burden caused by cardiovascular disease (CVDs) worldwide, studies using monoterpenes to assess their cardiovascular effects have increased over the years. PURPOSE: This systematic review aimed to summarize the use of monoterpenes in animal models of any CVDs. METHODS: PubMed, SCOPUS, LILACS and Web of Science databases were used to search for articles that used monoterpenes, in any type of administration, to treat or prevent CVDs in animal models. The PRISMA guidelines were followed. Two independent researchers extracted main characteristics of studies, methods and outcomes. Data obtained were analyzed qualitatively and quantitatively. RESULTS: At the ending of the search process, 33 articles were selected for the systematic review. Of these, 17 articles were included in the meta-analysis. A total of 16 different monoterpenes were found for the treatment of hypertension, myocardial infarction, pulmonary hypertension, cardiac hypertrophy and arrhythmia. The main actions include hypotension, bradycardia, vasodilatation, antiarrhythmic, and antioxidant and antiapoptotic properties. From our data, it can be suggested that monoterpenes may be a significant source for new drug development. However, there is still a need to apply these knowledge into clinical research and a long path to pursue before putting them in the market. CONCLUSION: The variability of cardiovascular effects demonstrated by the monoterpenes highlighted them as a promising candidates for treatment or prevention of CVDs. Nevertheless, studies that investigate their biological sites of action needs to be further encouraged.

The use of terpenes and derivatives as a new perspective for cardiovascular disease treatment: a patent review (2008-2018).

INTRODUCTION: Terpenes are a class of secondary metabolites that can be found in a variety of animal and plants species. They are considered the most structurally diversified and abundant of all natural compounds. Several studies have shown the application of terpenes, such as carvacrol, linalool, and limonene in many pharmaceutical and medicinal fields, including cardiovascular disorders, the leading cause of death worldwide. AREAS COVERED: In this review, the authors outlined patents from the last 10 years relating to the therapeutic application of terpenes for the treatment and/or prevention of cardiovascular diseases found in different databases, emphasizing the possibility of these compounds becoming new drugs that may help to decrease the burden of these disorders. EXPERT OPINION: There has been a growing awareness over recent years of the therapeutic use of terpenes and their derivatives as new pharmaceutical products. Patents involving the use of terpenes have been especially important in the technological development of new strategies for the treatment of cardiovascular diseases by bringing new scientific knowledge into the pharmaceutical industry. Therefore, the development of biotechnologies using natural products should be encouraged in order to increase the variety of drugs available for the treatment of cardiovascular diseases.