ABSTRACT
The present study was designed to evaluate the combined effect of lithium and aripiprazole supplemented with omega-3 fatty acids in methylphenidate (MPD)-induced manic mice. Swiss albino mice were administered with MPD or saline for 14 days, and based on changes in behavioral activities animals were treated with lithium, aripiprazole, and omega-3 fatty acids from the 8th day. Behavioral patterns were analyzed by video tracking. Thyroxine, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were assayed in serum using ELISA kits. The levels of neurotransmitters in the whole brain were analyzed spectrofluorometrically. Glycogen synthase kinase 3ß (GSK3ß) mice brain mRNA expression levels and phosphorylated Akt (pAkt) protein levels were measured using RT-PCR and western blot, respectively. Results indicated that the administration of MPD alters the behavioral activity, thyroid hormones, FSH, LH, and testosterone levels. Lithium, aripiprazole, and omega-3 fatty acids alone significantly reduced MPD-induced behavior, hormonal, and neurotransmitter abnormalities. However, GSK3ß and pAkt in the brain showed no significant differences in the level of expression. These results reveal that the combination of lithium and aripiprazole supplemented with omega-3 fatty acids provide protective effects against MPD-induced neuroendocrine system and multiple neurochemical abnormalities.
Subject(s)
Antipsychotic Agents/administration & dosage , Aripiprazole/administration & dosage , Bipolar Disorder/drug therapy , Fatty Acids, Omega-3/administration & dosage , Lithium Compounds/administration & dosage , Animals , Bipolar Disorder/metabolism , Brain/drug effects , Brain/metabolism , Disease Models, Animal , Drug Therapy, Combination , Glycogen Synthase Kinase 3 beta/genetics , Hormones/blood , Male , Mice , Neurotransmitter Agents/metabolism , Proto-Oncogene Proteins c-akt/genetics , RNA, Messenger/metabolismABSTRACT
Myocardial infarction (MI) is the one of the major causes of death worldwide, however the molecular mechanisms hidden under this disease conditions remain unknown. This demands serious attention to unravel the molecular mechanisms to identify the therapeutic strategies either to prevent or to control MI. Ayurveda is becoming one of the best alternatives for the modern medicines. On the other hand, Vitex negundo is one of the medicinally important plants used for various diseases and to date, its cardioprotective role is not fully elucidated. In the present study, we made an attempt to understand the cardiac signaling cascade of Akt1 and NF-κB in isoproterenol (ISO)-induced MI, and targeting these signaling molecules by using V. negundo leaf ethanolic extract (VNE). Our findings demonstrate that VNE significantly protects the ISO-induced MI by regulating NF-κB and Akt1experssion in rats.
