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.

Mechanism of Action of Limonene in Tumor Cells: A Systematic Review and Meta-Analysis.

BACKGROUND: Cancer is a complex, multifactorial disease, and a major public health problem, as it is a leading cause of morbidity and mortality worldwide. Although treatments have significantly improved, still more effective drugs are searched. One source for these drugs is natural products (NPs). One NP that has shown anticancer activity is Limonene. However, the mechanisms of limonene's antiproliferative, anticancer and antineoplastic activity are not fully understood. OBJECTIVE: The objective of this study is to undertake a systematic review and meta-analysis of the literature on this subject. METHODS: A comprehensive literature search was performed using the Scopus, MEDLINE-PubMed, Web of Science, and Science Direct databases using the keywords: "limonene", "cancer", "neoplasm", and "tumor". The inclusion criteria were: in vivo and in vitro studies on the use of limonene in cancer published in English, Portuguese and Spanish until December 2019. Review articles, meta-analyses, abstracts, conference papers, editorials/ letters and case reports were excluded. RESULTS: The search identified 3568 articles, of which, 126 were selected for full reading, with 11 papers meeting the review criteria. Six more papers were added from the references of the initial 11 texts, giving a total of 17 papers. There was a high level of agreement in inclusion/exclusion (Kappa index > 80%). The risk of bias in the texts was shown to be high. CONCLUSION: The meta-analysis suggests that limonene acts mainly on tumor regression induced apoptosis and is a promising natural product for use in the treatment of several types of cancer.

Eplingiella fruticosa leaf essential oil complexed with ß-cyclodextrin produces a superior neuroprotective and behavioral profile in a mice model of Parkinson's disease.

Evidence indicates that oxidative stress has an important role in the onset and progression of Parkinson's disease (PD). Antioxidant agents from natural products have shown neuroprotective effects in animal models of PD. Eplingiella fruticosa is an aromatic and medicinal plant of the Lamiaceae family that include culinary herbs. The essential oil (EPL) has anti-inflammatory and antioxidant activities. Cyclodextrins are used to enhances pharmacological profile of essential oil. We obtained the EPL from leaves and complexed with ß-cyclodextrin (EPL-ßCD). Phytochemical analysis showed as main constituents: ß-caryophyllene, bicyclogermacrene and 1,8-cineole. We evaluated the effects of EPL and EPL-ßCD (5 mg/kg, p.o. for 40 days) on male mice submitted to the progressive reserpine PD model. Behavioral evaluations, lipid peroxidation quantification and immunohistochemistry for tyrosine hydroxylase were conducted. EPL delayed the onset of catalepsy and decreased membrane lipid peroxides levels in the striatum. EPL-ßCD also delayed the onset of catalepsy, reduced the frequency of oral diskynesia, restored memory deficit, produced anxiolytic activity and protected against dopaminergic depletion in the striatum and SNpc. These findings showed that EPL has a potential neuroprotective effect in a progressive PD animal model. Further, EPL-ßCD enhanced this protective effects, suggesting a novel therapeutic approach to ameliorate the symptoms of PD.