Diabetes mellitus aggravates ranolazine-induced ECG changes in rats

Journal of Interventional Cardiac Electrophysiology - Diabetes mellitus (DM) is known to affect the pharmacokinetics of drugs. In this study, we evaluated the effect of DM on the liver content of...     

The protective activity of nanomicelle curcumin in bisphenol A‐induced cardiotoxicity following subacute exposure in rats

Bisphenol A (BPA), an estrogenic compound, is used in manufacture of polycarbonate plastics and epoxy resins. Curcumin, the active ingredient of turmeric, is a potent protective compound against cardiac diseases. In this study the protective effect of nanomicelle curcumin on BPA‐induced subchronic cardiotoxicity in rats was evaluated. Rats were divided into 6 groups including control, nanomicelle curcumin (50 mg/kg, gavage), BPA (50 mg/kg, gavage), nanomicelle curcumin (10, 25, and 50 mg/kg) plus BPA. The treatments were continued for 4 weeks. Results revealed that BPA significantly induced histophatological injuries including focal lymphatic inflammation, nuclear degenerative changes and cytoplasmic vacuolation, increased body weight, systolic and diastolic blood pressures, malondialdehyde and Creatine phosphokinase‐MB level and decreased glutathione content in comparison with control group. In addition, in electrocardiographic graph, RR, QT, and PQ intervals were increased by BPA. Western blot analysis showed that BPA up‐regulated phosphorylated p38 (p38‐mitogen‐activated protein kinase) and JNK (c‐jun NH₂ terminal kinases), while down‐regulated phosphorylated AKT (Protein Kinase B) and ERK1/2 (extracellular signal‐regulated protein kinases 1 and 2). However, nanomicelle curcumin (50 mg/kg) significantly improved these toxic effects of BPA in rat heart tissue. The results provide evidence that nanomicelle curcumin showed preventive effects on subchronic exposure to BPA induced toxicity in the heart tissue in rats.     

Berberis Vulgaris and Berberine: An Update Review

Berberine is an isoquinoline alkaloid present in several plants, including Coptis sp. and Berberis sp. Berberine is a customary component in Chinese medicine, and is characterized by a diversity of pharmacological effects. An extensive search in electronic databases (PubMed, Scopus, Ovid, Wiley, ProQuest, ISI, and Science Direct) were used to identify the pharmacological and clinical studies on Berberis vulgaris and berberine, during 2008 to 2015, using ‘berberine’ and ‘Berberis vulgaris’ as search words. We found more than 1200 new article studying the properties and clinical uses of berberine and B. vulgaris, for treating tumor, diabetes, cardiovascular disease, hyperlipidemia, inflammation, bacterial and viral infections, cerebral ischemia trauma, mental disease, Alzheimer disease, osteoporosis, and so on. In this article, we have updated the pharmacological effects of B. vulgaris and its active constituent, berberine. Copyright © 2016 John Wiley & Sons, Ltd.     

Effect of Linalool on Morphine Tolerance and Dependence in Mice

Linalool, a terpene alcohol, has been shown to interact with the opioid system and N‐methyl‐ d ‐aspartate (NMDA) receptor. Therefore, the effect of linalool on morphine dependence and tolerance was studied. Dependence and tolerance were induced in mice using subcutaneous morphine injections, three times a day (50, 50 and 75 mg/kg /day) for 3 days. To evaluate the effect of agents on the induction of morphine dependence and tolerance, linalool (50, 75 and100 mg/kg), clonidine (positive control), alpha‐2 receptor agonist, (0.1 mg/kg), memantine, NMDA receptor antagonist (positive control), (30 mg/kg) and saline were injected intraperitoneally three times a day for 3 days. To determine the expression of morphine dependence and tolerance, all compounds were injected once intraperitoneally on the day of experiment. The effect of linalool and other agents on dependence were evaluated by counting the number of jumps (induced by naloxone 5 mg/kg). The tolerance was evaluated by the tail‐flick test. The results showed that linalool in the induction and expression phase increased the nociception threshold. Linalool (48% and 95.6% at doses 75 and 100 mg/kg, respectively), clonidine and memantine reduced the severity of withdrawal signs in the induction and expression phases. This study indicated that linalool has a significant effect on morphine tolerance and dependence. This effect may be mediated partially through the inhibition of NMDA receptors. Copyright © 2012 John Wiley & Sons, Ltd.     

Berberine and barberry (Berberis vulgaris): A clinical review

Barberry (Berberis vulgaris L.) has different medicinal applications in folk medicine of Iran. Berberine, an alkaloid constituent of this plant, is present in the roots, rhizomes, stem, and bark of B. vulgaris and many other plants. There have been many clinical trials conducted that suggested a wide range of therapeutic applications. Here, we investigated the clinical uses of berberine and B. vulgaris in the treatment of different diseases in humans. An extensive search in electronic databases (PubMed, Scopus, Embase, Web of Sciences and Science Direct) was used to identify the clinical trials on B. vulgaris and berberine. Lipid‐lowering and insulin‐resistance improving actions are the most studied properties of berberine in numerous randomized clinical trials. There are also clinical trials regarding cardiovascular, anticancer, gastrointestinal, CNS, endocrine, and so on. Berberine has very low toxicity in usual doses and reveals clinical benefits without major side effects. Only mild gastrointestinal reactions may occur in some patients. The purpose of this review is to provide a summary concerning the clinical trials conducted on berberine to improve the clinical application of this nutraceutical in different diseases. In this review article, we used 77 clinical studies on human subjects.     

Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents,safranal and crocin,in normotensive and hypertensive rats

In this study, the effects of saffron (Crocus sativus) stigma aqueous extract and two active constituents, crocin and safranal, were investigated on blood pressure of normotensive and desoxycorticosterone acetate‐induced hypertensive rats. Three doses of crocin (50, 100 and 200 mg/kg), safranal (0.25, 0.5 and 1 mg/kg) and the aqueous extract (2.5, 5 and 10 mg/kg) were administered intravenously in different groups of normotensive and hypertensive animals and their effects on mean arterial blood pressure (MABP) and heart rate (HR) were evaluated. The aqueous extract of saffron stigma, safranal and crocin reduced the MABP in normotensive and hypertensive anaesthetized rats in a dose‐dependent manner. For example, administrations of 10 mg/kg of aqueous extract, 1 mg/kg of safranal and 200 mg/kg of crocin caused 60 ± 8.7, 50 ± 5.2 and 51 ± 3.8 mmHg reductions in MABP, respectively. It can be concluded that the aqueous extract of saffron stigma has hypotensive properties which appear to be attributable, in part, to the actions of two major constitutes of this plant, crocin and safranal. It seems that safranal is more important than crocin for lowering down blood pressure of rats. Copyright © 2009 John Wiley & Sons, Ltd.     

Vitis vinifera (grape) seed extract and resveratrol alleviate bisphenol‐A‐induced metabolic syndrome: Biochemical and molecular evidences

The mechanisms of bisphenol‐A (BPA)‐induced metabolic syndrome as well as the protective role of grape seed extract (GSE) and resveratrol were investigated. Rats were treated with BPA (0 and 35 mg·kg^?1·day^?1, gavage) plus resveratrol (25, 50, and 100 mg·kg^?1·day^?1, i.p.) or GSE (3, 6, 12 mg·kg^?1·day^?1, i.p.) or vitamin E (200 IU/kg/every other day, i.p.). After 2 months, mean systolic blood pressure, serum lipid profile, glycaemia, and fat index were examined. By enzyme‐linked immunosorbent assay, the serum concentrations of insulin, leptin, adiponectin, and paraoxonase 1, and by real‐time polymerase chain reaction as well as western blotting, key liver elements in cholesterol hemostasis (LDLR, CYP7A1, ABCG5 and 8) and insulin signaling (p‐Akt/Akt and p‐PI3K/PI3K) were measured. BPA increased mean systolic blood pressure, total cholesterol, and low‐density lipoprotein cholesterol and reduced paraoxonase1 and the hepatic expression of both ABCG5 and ABCG8. It increased the body fat index, leptin, adiponectin, insulin, and glycaemia level and decreased the hepatic protein expression of p‐Akt/Akt and p‐PI3K/PI3k. GSE, resveratrol, or vitamin E coadministration along with BPA restored the detrimental effects of BPA in some levels. Herein, the predisposing effects of BPA‐induced metabolic syndrome were restored by GSE and resveratrol, linked to the regulation of insulin signaling, ABCG8 expression, and their antioxidant properties.     

Effects of granulocyte colony-stimulating factor on electrocardiogram changes after carbon monoxide poisoning in rats

Carbon monoxide (CO), which is produced by the incomplete combustion of hydrocarbons, has many toxic effects on different organs, especially the brain and heart. CO-induced cardiotoxicity leads to several deleterious effects, including electrocardiogram (ECG) abnormalities. The present study aimed to evaluate the protective effect of recombinant human granulocyte colony-stimulation factor (G-CSF) on ECG after CO poisoning in rats. Single and multiple doses of G-CSF (10, 50, and 100 μg/kg) were administered to groups, each containing 5 male Wistar rats (16 groups for ECG analysis and 16 groups for pathological analysis). Rats were already exposed to CO at either 1,500 or 3,000 ppm concentrations for 60 minutes. ECG findings (e.g., ST-segment and T-wave changes), cardiac arrhythmias (e.g., heart blocks and ventricular and supraventricular arrhythmias), and histological changes were determined after G-CSF administration. At 3,000 ppm, frequencies of ST elevation, depression, and T inversion in ECG were significantly reduced after G-CSF treatment. Also, some of the cardiac arrhythmias (e.g., atrioventricular block type 1 and 2) after CO poisoning were suppressed after G-CSF treatment. However, G-CSF did not show protective effects on cardiomyocyte pathological consequences in CO-poisoned rats. Therefore, G-CSF could protect against ECG changes after CO-induced cardiac ischemia, but did not affect pathological changes.