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", "Neurologic", "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.