The Novel Pharmacological Approaches to Coumestrol: Focusing on the Psychiatric and Neurological Benefits and the Newly Identified Receptor Interactions

For years, the health benefits of coumestrol (CMT) have been investigated by researchers around the world. Anti-oxidative properties of the phytoestrogen which can be extracted from several plant tissues, have already been reported as well as the cancer chemopreventive capabilities. Recently, psychiatric and neurological effects of this natural compound have become of interest to researchers so that strong evidence would support the idea that CMT can exert significant effects on the central nervous system. Pharmacologically, this phytoestrogen would act as a selective estrogen receptor modulator with several-fold more affinity to β sub-types of the receptors (ERβ); although other mechanisms of action may be involved. The aim of this review was to gather the recent reports regarding the most important pharmacological benefits of CMT focusing on the psychiatric and neurological ones. Furthermore, the mechanisms of action underlying the pharmacological effects were tried to be clarified more. For this purpose, some keywords such as "Coumestrol", "Pharmacological Effects", "Neurological", "Psychiatric" and "Neuropsychiatric" were searched in popular scientific databases such as Google scholar, Scopus and Pubmed. Then the delegated documentations were brought together, categorized and discussed on this basis. Reviewing the gathered information showed that, apart from the effects on reproduction and the related organs which are mainly conducted through estrogen receptors, CMT has reported to improve various disorders all over the body. Particularly, regarding the neurological and psychiatric systems, the advantages in cerebral hypoxia-ischemia, the Alzheimer’s disease, anxiety, depression and cognitive impairments would be the most important ones. Here, other receptors that have shown interactions with CMT (beside estrogen receptors which are the main target), were also reviewed among which insulin receptors, farnesoid X receptors, pregnane X receptors, and constitutive androstane receptors can be mentioned while only the last two seem to be involved in forming the neurological and psychiatric effects

Effects of transcranial photobiomodulation and methylene blue on biochemical and behavioral profiles in mice stress model

Open Access via Springer Compact Agreement. Acknowledgements This article was derived from the MSc dissertation of Mr. Reza Meynaghizadeh-Zargar. Funding The present study was supported by Neurosciences Research Center of Tabriz University of Medical Sciences (grant number, 58471).Peer reviewedPublisher PD

Beta-amyloid exhibits antagonistic effects on alpha 7 nicotinic acetylcholine receptors in orchestrated manner

AbstractAlthough beta-amyloid (Aβ) has been regarded as the principal toxic factor in the pathogenesis of Alzheimer’s disease (AD), it plays important physiological roles in phenomena such as neuron survival, synaptic plasticity, and memory formation. There are numerous plausible reasons to assume that all of the mentioned pathological and physiological functions of Aβ may be partially mediated via alpha 7 nicotinic acetylcholine receptor (nAChR). Agonistic and antagonistic aspects of Aβ on nAChRs may explain this paradox in peptide–receptor function. It seems that Aβ shows antagonistic effects on α7 nAChR in a dose-dependent manner, and its pathologic function may partially correlate with antagonization of the receptor.If this hypothesis is supported, the related mechanisms of neurotoxicity, neuroprotection, memory formation, and AD pathogenesis might be identified. In addition, such knowledge helps make a more valid interpretation of neuron signaling and a better design of AD animal models. In addition, it may provide new insights into AD therapy development via reducing the amount of Aβ and inhibiting peptide aggregation

Effects of IMOD™ on angiogenesis, miR-503 and CDC25 expression levels in heart tissue of diabetic male rats

Objective: Diabetes is associated with vascular complications and impaired angiogenesis. Since angiogenesis plays a crucial role in vascular homeostasis in ischemic heart diseases, in this study, the effect of IMOD™ on miR-503 and CDC25 expression level which are altered in impaired angiogenesis were investigated in heart tissue of diabetic rats. Materials and Methods: Forty male Wistar rats (200-250 g) were randomly classified into 4 groups: control (C), IMOD™ (I), diabetes (D), and diabetes+IMOD™ (D+I). For induction of experimental diabetes in animals, a single dose of streptozotocin (STZ; 60mg/kg) was injected intraperitoneally. After 8 weeks of treatment with IMOD™ (20 mg/kg/day), heart tissue samples were removed and used for measurement of miR-503 and CDC25 expression level as well as histological studies. Results: Results of this study showed that diabetes decreased heart tissue angiogenesis which was associated with increased miR-503 and reduced CDC25 expression levels (

Association of MS4A6A, CD33, and TREM2 gene polymorphisms with the late-onset Alzheimer’s disease

Introduction: Alzheimer’s disease (AD), which is a progressive neurodegenerative disorder, causes structural and functional brain disruption. MS4A6A, TREM2, and CD33 gene polymorphisms loci have been found to be associated with the pathobiology of late-onset AD (LOAD). In the present study, we tested the hypothesis of association of LOAD with rs983392, rs75932628, and rs3865444 polymorphisms in MS4A6A, TREM2, CD33 genes, respectively. Methods: In the present study, 113 LOAD patients and 100 healthy unrelated age- and gender-matched controls were selected. DNA was extracted from blood samples by the salting-out method and the genotyping was performed by RFLP-PCR. Electrophoresis was carried out on agarose gel. Sequencing was thereafter utilized for the confirmation of the results. Results: Only CD33 rs3865444 polymorphism revealed a significant difference in the genotypic frequencies of GG (P = 0.001) and GT (P = 0.001), and allelic frequencies of G (P = 0.033) and T (P = 0.03) between LOAD patients and controls. Conclusion: The evidence from the present study suggests that T allele of CD33 rs3865444 polymorphism is associated with LOAD in the studied Iranian population

Testosterone May Hold Therapeutic Promise for the Treatment ofIschemic Stroke in Aging: A Closer Look at Laboratory Findings

Male sex is more prone to cerebrovascular disorders, yet the exact role of androgens in cerebralischemia remains unclear. Here we reviewed current understanding of testosterone (TES)neuroprotective activity against ischemic stroke and mechanisms underlying these effects inaging. TES may exert a neuroprotective effect in aging through pathways including inhibition ofoxidant molecules production, enhancing the enzymatic antioxidant capacity of the brain andmodulation of apoptotic cell death. Given this, a better understanding of the neuroprotectiveroles of TES may propose an effective therapeutic strategy to improve the quality of life anddecrease androgen-related cerebrovascular problems in the aging men

Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review

Background: The alleged procognitive effects of nicotine and its metabolites in brain are controversial.Objective: Here, we review the pharmacologically active metabolites of nicotine in brain and their effects on neuronal mechanisms involving two main cognitive domains, i.e., learning and memory.Methods: We searched Embase, Medline via PubMed, Scopus, and Web of Science databases for entries no later than May 2018, and restricted the search to articles about nicotine metabolites and cognitive behavior or cognitive mechanisms.Results: The initial search yielded 425 articles, of which 17 were eligible for inclusion after application of exclusion criteria. Of these, 13 were experimental, two were clinical, and two were conference papers.Conclusions: The results revealed three pharmacologically active biotransformations of nicotine in the brain, including cotinine, norcotinine, and nornicotine, among which cotinine and nornicotine both had a procognitive impact without adverse effects. The observed effect was significant only for cotinine