Myricitrin exhibits antidepressant-like effects and reduces IL-6 hippocampal levels in the chronic mild stress model.

The flavonoid myricitrin showed an antidepressant-like effect in the tail suspension test and increased hippocampal neurogenesis, as well as demonstrating anti-inflammatory effects. Interestingly, inflammation has been linked to depression, and anti-inflammatory drugs showed promising results as antidepressant-like drugs. Thus, the present study evaluated the effects of myricitrin in the chronic mild stress (CMS) model, a translational and valid animal model of depression, using the mini-experiment design to improve the reproducibility of the findings. The sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were the readouts of depressive-like phenotypes induced by CMS. Relative adrenal weight was employed as an index of the hypothalamus-pituitary-adrenal (HPA) axis activation. Interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels were measured in the hippocampus. Myricitrin (10 mg/kg, intraperitoneally, for 14 days) reversed depressive-like behaviors induced by CMS (increased immobility in the FST, the TST and anhedonia), as well as decreased adrenal hypertrophy and hippocampal levels of IL-6 in stressed mice. Similar results were observed by imipramine (20 mg/kg, intraperitoneally, for 14 days), a serotonin and norepinephrine reuptake inhibitor (positive control). A significant correlation was observed between immobility time in the TST, and hippocampal IL-6 levels. Hippocampal TNF-α levels were not affected by CMS or drug treatment. In conclusion, myricitrin exhibited an antidepressant-like profile in CMS, and this effect may be associated with its anti-inflammatory activity.

Atorvastatin improves cognitive, emotional and motor impairments induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats, an experimental model of Parkinson's disease.

Affective disorders and memory impairments precede the classical motor symptoms seen in Parkinson's disease (PD) and the currently approved antiparkinsonian agents do not alleviate the non-motor symptoms as well as the underlying dopaminergic neuron degeneration. On the other hand, there is increasing evidence that inflammation plays a key role in the pathophysiology of PD and that the anti-inflammatory actions of statins are related to their neuroprotective properties against different insults in the CNS. The present data indicates that the oral treatment with atorvastatin (10mg/kg/day), once a day during 7 consecutive days, was able to prevent short-term memory impairments and depressive-like behavior of rats assessed in the social recognition and forced swimming tests at 7 and 14 days, respectively, after a single intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1mg/nostril). Importantly, at this time no significant alterations on the locomotor activity of the animals were observed in the open field test. Moreover, atorvastatin was found to protect against the long-lasting motor deficits evaluated in activity chambers and the loss of dopaminergic neurons in the substantia nigra pars compacta observed at 21 days after i.n. MPTP administration. At this time, despite the absence of spatial memory deficits in the water maze and in concentrations of the cytokines TNF-α, IL-1ß and IL-10 in striatum and hippocampus following i.n. MPTP administration, atorvastatin treatment resulted in a significant increase in the striatal and hippocampal levels of nerve growth factor (NGF). These findings reinforce and extend the notion of the neuroprotective potential of atorvastatin and suggest that it may represent a new therapeutic tool for the management of motor and non-motor symptoms of PD.

Activation of muscarinic receptors by a hydroalcoholic extract of Dicksonia sellowiana Presl. HooK (Dicksoniaceae) induces vascular relaxation and hypotension in rats.

Dicksonia sellowiana (Presl.) Hook is a native plant from the Central and South Americas that contain high levels of polyphenols, antioxidant compounds involved in protection against inflammation, cancer and cardiovascular risk. A phytomedicinal preparation obtained from aerial parts of D. sellowiana is currently under clinical evaluation in Brazil against asthma, and has been associated with several other beneficial effects. This study demonstrates that a hydroalcoholic extract obtained from D. sellowiana leaves (HEDS) fully relax, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine. Moreover, administration of HEDS (10, 20 and 40 mg/kg, i.v.) in anaesthetized rats resulted in a strong but reversible hypotension. Aortic relaxation induced by HEDS was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase inhibitor ODQ. In addition, this effect was partially inhibited by indomethacin (a cyclooxygenase inhibitor) and KT 5730 (a PKA inhibitor). The potassium channels blockade by either tetraethylammonium or charybdotoxin also resulted in a potent inhibition of HEDS-induced aortic relaxation, whereas apamine only slightly reduced it. In addition HEDS-induced relaxation was unchanged by 4-amynopiridine and glibenclamide. The selective muscarinic receptor antagonist atropine counteracted both aortic relaxation and blood pressure reduction generated by HEDS. Experiments using HPLC revealed the presence of high amounts of phenolic compounds in this extract. Taken together, our results reveal that the D. sellowiana possess substances with both in vivo and in vitro activities and that the vascular effect of HEDS involves activation of muscarinic receptors, stimulation of the nitric oxide pathway and opening of calcium-activated potassium channels.