The effects and mechanisms of the action of galangin on spatial memory in rats.

BACKGROUND: Galangin, a flavonoid compound with acetylcholinesterase inhibitory activity, may improve cognitive functions by enhancing cholinergic transmission. OBJECTIVES: We aimed to investigate the effects of galangin on spatial memory impairment in rats. METHODS: The effects of galangin (50 and 100 mg/kg) and reference anti-dementia drug donepezil (1mg/kg) administrations were examined on memory impairment induced by the muscarinic cholinergic receptor antagonist scopolamine or the nicotinic cholinergic receptor antagonist mecamylamine in the Morris water maze (MWM) test. Hippocampal acetylcholine concentrations were also determined. RESULTS: Galangin 50 and 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in scopolamine-treated rats. Galangin 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in mecamylamine-treated rats. The effects of galangin in the MWM were comparable with donepezil. Scopolamine and mecamylamine decreased acetylcholine concentrations, whereas galangin both alone and with mecamylamine or scopolamine administration increased acetylcholine concentrations. CONCLUSION: Galangin improved memory impairment comparable to donepezil and nicotinic and muscarinic receptors may be involved in this effect. Galangin may be considered as a promising flavonoid in the prevention and treatment of memory impairment in Alzheimer's disease and other dementias (Fig. 7,Ref. 37).

HYPOTHYROIDISM INCREASES EXPRESSION OF STERILE INFLAMMATION PROTEINS IN RAT HEART TISSUE.

PURPOSE: In this study, we aimed to investigate the relationship between hypothyroidism and sterile inflammation in rat heart tissue. METHODS: Groups; control group (fed with standard rat chow diet and tab water) and the hypothyroid group (fed with a standard rat chow diet and tap water containing 0.05% 6-n-propyl-2-thiouracil for 6-weeks). At the end of the experiment, histopathologic examination was performed. The T3, T4, TSH and myocardial malondialdehyde (MDA) measurements were performed with an ELISA kit. TUNEL assay was performed to demonstrate apoptosis. Sterile inflammation markers, caspase-1 and NLRP3, were investigated by immunohistochemistry and western blot. RESULTS: In histopathological examination, we observed leukocyte infiltration, myocardial atrophy, pyknotic nucleated cells and cytoplasmic vacuolization in hypothyroid group whereas the control group showed normal structure. MDA levels in myocardial tissue were significantly high in hypothyroid group when compared to the control group (P<0.05). Myocardial apoptosis increased in hypothyroid group when compared to the control group. NLRP3 and caspase-1 immunoreactivity was higher in the hypothyroid group. In ELISA results, we found significantly higher level of TSH and lower levels of T3 and T4 in hypothyroid group when compared to the control group. CONCLUSION: Hypothyroidism increased oxidative stress, and caused inflammatory alterations in cardiac tissue. In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.

The Effects of p-nonylphenol on the Myometrial Contractile Activity.

We aimed to investigate the effects and mechanisms of action of p-nonylphenol(p-NP) on uterine contractility in rats. The uterine tissues of female Sprague Dawley rats in diestrus were bathed in isolated organ bath. The effects of vehicle alone (0.1% ethanol), the positive control 17-ß-E2 (10(-5) M) and p-NP (10(-9) M, 10(-8) M, 10(-7) M, 10(-6) M) on spontaneous and KCl-induced uterine contractility of rats were studied. Also, the effects of p-NP in combination with actinomycin D (10(-5) M) (gene transcription inhibitor), cycloheximide (10(-4) M) (protein synthesis inhibitor), fulvestrant (10(-6) M) (pure estrogen receptor antagonist), 2-hydroxy-5-nonanoylbenzamide (10(-3) M) (compound 1b, anti-uterotrophic compound) on spontaneous uterine contractions, and with propranolol (20 µM) (ß-adrenoceptor antagonist) and noradrenaline (5 µM) on KCl (40 mM) induced contractions were investigated. p-NP exhibited a concentration-dependent inhibition on spontaneous uterine contractions. There was no significant difference between the highest p-NP concentration (10(-6) M) and the positive control 17-ß-E2 in terms of % inhibition (p>0.05). The inhibitory effect of p-NP (10(-6) M) on spontaneous contractions was blocked by actinomycin D (p<0.001), cycloheximide (p<0.001), fulvestrant (p<0.001) and compound 1b (p<0.001). 17-ß-E2 (10(-5) M) exerted a higher inhibition % on KCl induced contractions than p-NP (10(-6) M). The relaxant effect of p-NP on KCl-induced uterine contractions was inhibited by noradrenaline (p<0.05) but not by propranolol (p>0.05). We suggest that p-NP inhibited uterine contractions similar as 17-ß-E2 and genomic pathways are involved and ß-adrenoceptors might modulate the activity of p-NP. In addition, compound 1b showed an uterotonic activity and reversed the effect of p-NP.

The effect of Des-Arg9-bradykinin and bradykinin-potentiating peptide C on isolated rat hearts.

OBJECTIVES: Des-Arg9-bradykinin and bradykinin-potentiating peptide C (BPPC) may contribute to the regulation of cardiovascular function. Therefore, we studied effects of these peptides on coronary perfusion pressure (CPP), heart rate, left ventricular developed pressure (LVDP) and maximum rate of increase of left ventricular pressure (+dP/dtmax). METHODS: The isolated rat hearts were perfused with modified Krebs-Henseleit solution. RESULTS: Infusion of 10, 100 and 1000 nM Des-Arg9-bradykinin decreased CPP (-13.6, -14.8 and -19.0%), LVDP (-16.5, -21.0 and -30.7%) and +dP/dtmax (-11.8, -17.8 and -23.7%), respectively (p < 0.001). Ten or 100 nM Des-Arg9-bradykinin did not alter heart rate, but 1000 nM increased it (+11.3%, p < 0.01). One, 10 and 100 nM BBPC reduced CPP (-16.3, -28.5 and -47.5%), LVDP (-12.6, -19.6 and -21.3%) and +dP/dtmax (-8.7, -18.6 and -20.3%), respectively (p < 0.001). BPPC increased heart rate at 1 nM (+9.6%, p < 0.05 ) and at 10 nM (+14.2%, p < 0.01), however 100 nM decreased it (-15.3%, p < 0.001). CONCLUSIONS: This study evidences that Des-Arg9-bradykinin and BPPC possess vasodilatory effect with modest negative inotropic action. Furthermore, high-dose of Des-Arg9-bradykinin and low-dose of BPPC may produce a tachycardic action, but high dose of BBPC may cause a bradycardic action.

Synthesis of cyclopentapyridine and thienopyridine derivatives as potential calcium channel modulators.

In this study, novel condensed 1,4-dihydropyridines bearing cyclopentanone (1-21) or tetrahydrothiophene-1,1-dioxide ring (22-42) with various ester substituents were synthesized via a modified Hantzsch reaction and their calcium channel modulator activities were investigated on isolated rat ileum and rat thoracic aorta. The introduction of a cyclopentanone ring fused to the 1,4-dihydropyridine nucleus and methyl, ethyl and allyl moieties to the ester group led to more active calcium modulators.