AIM OF THE STUDY: The present investigation aimed to investigate the anxiolytic, antidepressant and aphrodisiac potentials of methanol leaves extract of A. hookerianum (MEAH) in Swiss albino mice.
MATERIALS & METHODS: Swiss albino mice (20-30 g) were orally administrated with MEAH at the doses ranging from 100 to 400 mg/kg, b.w. The elevated plus maze (EPM) and hole board test (HBT) were performed to determine the anxiolytic activity and the forced swimming test (FST) and tail suspension test (TST) were performed to determine the antidepressant activity of MEAH. Besides, the aphrodisiac activity of MEAH was conducted through the mounting behaviour and orientation behaviour analysis. Diazepam (1 mg/kg, b.w., i.p.) for EPM and HBT; fluoxetine HCl (20 mg/kg, b.w., p.o.) for FST and TST, and sildenafil (5 mg/kg, b.w., p.o.) for the mounting behaviour analysis and orientation behaviour analysis were used as reference drugs.
RESULTS: The administration of the MEAH produced a strong (p drug candidate for the management of neurological and sexual disorders.
OBJECTIVES: The present study investigates the effect of a novel 5-HT3 receptor antagonist 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) on several pathogenic markers of depression associated with obesity such as plasma insulin resistance, hippocampal cyclic adenosine monophosphate (cAMP), brain-derived neurotrophic factor (BDNF), serotonin (5-HT) concentrations, hippocampal neuronal damage, and p53 protein expression in high-fat-diet (HFD)-fed mice.
METHODS: Obesity was experimentally induced in mice by feeding with HFD for 14 weeks followed by administration of QCM-4 (1 and 2 mg/kg, p.o.)/standard escitalopram (ESC) (10 mg/kg, p.o.)/vehicle (10 ml/kg, p.o.) for 28 days. Behavioral assays such as sucrose preference test (SPT); forced swim test (FST); elevated plus maze (EPM); biochemical assays including oral glucose tolerance tests (OGTT), insulin, cAMP, BDNF, and 5-HT concentrations; and molecular assays mainly histology and immunohistochemistry (IHC) of p53 protein in the dentate gyrus (DG), CA1, and CA3 regions of hippocampus in HFD fed mice were performed.
RESULTS: Chronic treatment with QCM-4 in HFD-fed mice reversed the behavioral alterations in SPT, FST, and EPM. QCM-4 showed poor sensitivity for plasma glucose, improved insulin sensitivity, increased hippocampal cAMP, BDNF, and 5-HT concentrations. In the hippocampal DG, CA1, and CA3 regions, QCM-4 treatment improved the neuronal morphology in the histopathology and inhibited p53 protein expression in IHC assay in HFD-fed mice.
CONCLUSION: QCM-4 attenuated the depressive-like phenotype in HFD-fed mice by improving behavioral, biochemical, and molecular alterations through serotonergic neuromodulation.
OBJECTIVES: The present study examines the cellular mechanisms by which scopolamine produces antidepressant-like effects through its action in the ventrolateral midbrain periaqueductal gray (vlPAG).
METHODS: We used a well-established mouse model of depression induced by chronic restraint stress (CRS) exposure for 14 days. Behaviors were tested using the forced swim test (FST), tail suspension test (TST), female urine sniffing test (FUST), novelty-suppressed feeding test (NSFT), and locomotor activity (LMA). Synaptic transmission in the vlPAG was measured by whole-cell patch-clamp recordings. IntravlPAG microinjection was used to pharmacologically verify the signaling cascades of scopolamine in the vlPAG.
RESULTS: The results demonstrated that intraperitoneal injection of scopolamine produced antidepressant-like effects in a dose-dependent manner without affecting locomotor activity. CRS elicited depression-like behaviors, whereas intraperitoneal injection of scopolamine alleviated CRS-induced depression-like behaviors. CRS diminished glutamatergic transmission in the vlPAG, while scopolamine reversed the above effects. Moreover, intravlPAG microinjection of the L-type voltage-dependent calcium channel (VDCC) blocker verapamil, tropomyosin-related kinase B (TrkB) receptor antagonist ANA-12, mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) antagonist CNQX prevented scopolamine-induced antidepressant-like effects.
CONCLUSIONS: Scopolamine ameliorated CRS-elicited depression-like behavior required activation of VDCC, resulting in activity-dependent release of brain-derived neurotrophic factor (BDNF), engaging the TrkB receptor and downstream mTORC1 signaling in the vlPAG.
METHODS: This study was a systematic review and meta-analysis including articles published in the SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed and Web of Science databases were searched systematically to find articles published from 2006 to March 2019. Heterogeneity index was determined using the Cochran's test (Qc) and I2. Considering heterogeneity of studies, the random effects model was used to estimate the standardized difference of mean score for depression. Subsequently, the level of depression reduction in Iran and worldwide in the intervention group before and after the testwas measured.
RESULTS: A total of 19 articles met the inclusion criteria, and were therefore selected for this systematic review and meta-analysis. The sample size of the intervention group in the selected studies was 1948. According to the meta-analysis results, the mean depression score in the intervention group was 26.4 ± 5.6 and 18.4 ± 2.6 before and after intervention respectively, indicating the reducing effect of methadone on depression, and this difference was statistically significant (P drug treatment plan.
METHOD: Electronic literature search on PubMed was conducted using the following keywords: methylphenidate, cancer, carcinoma, oncology, oncological and tumour. We identified forty two relevant studies and publications on the use of methylphenidate in cancer patients to be included in this review.
RESULTS: Methylphenidate was found to have some evidence in reducing opioid-induced sedation, improving cognitive symptoms and reduction of fatigue in cancer patients. Nevertheless, the results were inconsistent due to variations in the study populations, study design and outcome measures, among others. There was minimal evidence on its use in treating depression. Otherwise, methylphenidate was generally well-tolerated by patients.
CONCLUSION: This review potentially supports the use of methylphenidate for opioid-induced sedation, cognitive decline and fatigue in cancer patients. Further placebo-controlled trials would help in strengthening the evidence for this treatment.
PURPOSE: The purpose of this comprehensive review is to compile and analyze the information related to the pharmacokinetic, pharmacological, and toxicological studies reported on α- and β-asarone using preclinical in vitro and in vivo models. Besides, the molecular targets and mechanism(s) involved in the biological activities of α- and β-asarone were discussed.
METHODS: Databases including PubMed, ScienceDirect and Google scholar were searched and the literature from the year 1960 to January 2017 was retrieved using keywords such as α-asarone, β-asarone, pharmacokinetics, toxicology, pharmacological activities (e.g. depression, anxiety).
RESULTS: Based on the data obtained from the literature search, the pharmacokinetic studies of α- and β-asarone revealed that their oral bioavailability in rodents is poor with a short plasma half-life. Moreover, the metabolism of α- and β-asarone occurs mainly through cytochrome-P450 pathways. Besides, both α- and/or β-asarone possess a wide range of pharmacological activities such as antidepressant, antianxiety, anti-Alzheimer's, anti-Parkinson's, antiepileptic, anticancer, antihyperlipidemic, antithrombotic, anticholestatic and radioprotective activities through its interaction with multiple molecular targets. Importantly, the toxicological studies revealed that both α- and β-asarone can cause hepatomas and might possess mutagenicity, genotoxicity, and teratogenicity.
CONCLUSIONS: Taken together, further preclinical studies are required to confirm the pharmacological properties of α-asarone against depression, anxiety, Parkinson's disease, psychosis, drug dependence, pain, inflammation, cholestasis and thrombosis. Besides, the anticancer effect of β-asarone should be further studied in different types of cancers using in vivo models. Moreover, further dose-dependent in vivo studies are required to confirm the toxicity of α- and β-asarone. Overall, this extensive review provides a detailed information on the preclinical pharmacological and toxicological activities of α-and β-asarone and this could be very useful for researchers who wish to conduct further preclinical studies using α- and β-asarone.