ABSTRACT
Demographic aging gives rise to a growing population with age-associated behavioral and cognitive deficits that may be associated at least partially to the increasing prevalence of neurodegenerative disorders, such as Alzheimer's disease (AD). In this disease, it has been observed a decrease in the cholinergic system, which is crucial to memory formation. Scopolamine-induced amnesic effect, through the disruption of the cholinergic neurotransmission, is one of the approaches used to investigate the mechanisms involved in cognitive impairment observed in AD. The aim of our study was to investigate the potential protective role of quercetin and rutin against scopolamine-induced inhibitory avoidance memory deficits in zebrafish. Scopolamine (200 µM dissolved in the tank water for 1h) given pre-training hindered memory formation while both quercetin and rutin pretreatments (50mg/kg, single injection, i.p.) prevented the scopolamine-induced amnesia. None of the compounds affected zebrafish general locomotor activity. Together, these results contribute to the increase of the knowledge about plant compounds applicability as medicines to prevent and treat neurodegenerative diseases, like Alzheimer's disease.
Subject(s)
Antioxidants/therapeutic use , Memory Disorders/prevention & control , Quercetin/therapeutic use , Rutin/therapeutic use , Scopolamine/toxicity , Animals , Avoidance Learning/drug effects , Disease Models, Animal , Drug Evaluation, Preclinical , Female , Male , Memory Disorders/chemically induced , Motor Activity/drug effects , ZebrafishABSTRACT
Carbamazepine (CBZ), phenytoin (PHT), and gabapentine (GBP) are classical antiepileptic drugs (AEDs) that act through a variety of mechanisms. We have tested the in vitro effects of CBZ, PHT, and GBP at different concentrations on ectonucleotidase and acetylcholinesterase activities in zebrafish brain. CBZ inhibited ATP hydrolysis at 1000 microM (32%) whereas acetylcholine hydrolysis decreased at 500 microM (25.2%) and 1000 microM (38.7%). PHT increased AMP hydrolysis both at 500 microM (65%) and 1000 microM (64.8%). GBP did not promote any significant changes on ectonucleotidase and acetylcholinesterase activities. These results have shown that CBZ can reduce NTPDase (nucleoside triphosphate diphosphohydrolase) and PHT enhance ecto 5'-nucleotidase activities. Therefore, it is possible to suggest that the AEDs induced-effects on ectonucleotidases are related to enzyme anchorage form. Our findings have also shown that high CBZ concentrations inhibit acetylcholinesterase activity, which can induce an increase of acetylcholine levels. Taken together, these results showed a complex interaction among AEDs, purinergic, and cholinergic systems, providing a better understanding of the AEDs pharmacodynamics.
Subject(s)
5'-Nucleotidase/metabolism , Acetylcholinesterase/metabolism , Anticonvulsants/toxicity , Brain/enzymology , Amines/toxicity , Animals , Brain/drug effects , Carbamazepine/toxicity , Cyclohexanecarboxylic Acids/toxicity , Dose-Response Relationship, Drug , Gabapentin , Phenytoin/toxicity , Zebrafish/metabolism , gamma-Aminobutyric Acid/toxicityABSTRACT
With the recognition that high levels of sustained stress are associated with the natural course of countless illnesses, effective anti-stress agents have gained importance. Improved endurance to particularly stressful periods is one of the medicinal claims for Marapuama (Ptychopetalum olacoides Bentham, PO), a popular Amazonian herbal. The purpose of this study was to evaluate if PO possesses anti-stress properties. To this end, an extract from PO (POEE) was evaluated on anxiety and glucose levels in mice submitted to the unpredictable chronic mild stress (UCMS) paradigm. POEE did not present anxiolytic effects, but was able to prevent (p<0.01) the UCMS-induced anxiety as assessed by the light/dark test (time spent in the lit area, POEE 100 and 300mg/kg 235.9+/-20.6s and 250.4+/-17.4s, respectively, compared to DMSO 104.7+/-24.4s). Likewise, although POEE did not induce noticeable effects on glycemia, it effectively (p<0.01) prevented the UCMS-induced hyperglycemia (POEE 100 and 300mg/kg 106.4+/-6.7mg/dl and 107.3+/-3.3mg/dl, respectively, compared to DMSO 134.6+/-5.9mg/dl). Additionally, POEE (50-200mg/kg i.p. and 800mg/kg p.o.) significantly (p<0.01 and p<0.05, respectively) increased the time to hypoxia-induced convulsion (by 38%, 51%, 59% and 27%, respectively for i.p. and p.o. treatments). The data indicate that POEE counteracts some of the effects brought about by chronic stress. This study combined with the identified antioxidant and neuroprotective properties, as well as the claimed benefits associated with stressful periods suggest that Ptychopetalum olacoides (Marapuama) might possess adaptogen-like properties.
