Exploring the multifocal role of phytoconstituents as antidepressants.

Depression is the most prevalent and devastating neuropsychiatric disorder. There are several conventional antidepressants used for the treatment of depression. But due to their undesired adverse effects, patient compliance is very poor. Thus, developing novel medications for the treatment of depression is a critical strategic priority for meeting therapeutic demands. Current research is looking for alternatives to traditional antidepressants to reduce undesired side effects and increase efficacy. Phytoconstituents provide a wide research range in antidepressant treatments. In the present article, we have conducted a comprehensive assessment of neurological evidence, which supports the usefulness of phytoconstituents in the treatment of the depressive disorder. Secondary plant metabolites including alkaloids, polyphenols, glycosides, saponins, and terpenoids were found to exhibit antidepressant action. Most of the phytoconstituents were found to mediate their antidepressant effect through the upregulation of brain-derived neurotrophic factor (BDNF), serotonin, noradrenaline, and dopamine. Some were also found to exert antidepressant effects by inhibiting the monoamine oxidase (MAO) activity and hypothalamic-pituitary-adrenal (HPA) axis overactivity.

Polyphenols inhibiting MAPK signalling pathway mediated oxidative stress and inflammation in depression.

Depression is one of the most debilitating psychiatric disorders affecting people of all ages worldwide. Despite significant heterogeneity between studies, increased inflammation and oxidative stress have been found in depression. Oxidative stress and inflammation are involved in the pathogenesis of depression. In the current review, we discussed the markers of oxidative stress and inflammation in depressive disorder and the association between these markers and the antidepressant treatment. The role of natural polyphenols in regulating various cell signaling pathways related to oxidative stress and inflammation has also been reviewed. The inhibitory effect of polyphenols on several cell signaling pathways reveals the vital role of polyphenols in the prevention and treatment of depressive disorder. Understanding the mechanism of polyphenols implicated in the regulation of cell signaling pathways is essential for the identification of lead compounds and the development of novel effective compounds for the prevention and treatment of depressive disorder.

Elucidating the Possible Role of FoxO in Depression.

Forkhead box-O (FoxO) transcriptional factors perform essential functions in several physiological and biological processes. Recent studies have shown that FoxO is implicated in the pathophysiology of depression. Changes in the upstream mediators of FoxOs including brain-derived neurotrophic factor (BDNF) and protein kinase B have been associated with depressive disorder and the antidepressant agents are known to alter the phosphorylation of FoxOs. Moreover, FoxOs might be regulated by serotonin or noradrenaline signaling and the hypothalamic-pituitary-adrenal (HPA)-axis,both of them are associated with the development of the depressive disorder. FoxO also regulates neural morphology, synaptogenesis, and neurogenesis in the hippocampus, which accounts for the pathogenesis of the depressive disorder. The current article underlined the potential functions of FoxOs in the etiology of depressive disorder and formulate few essential proposals for further investigation. The review also proposes that FoxO and its signal pathway might establish possible therapeutic mediators for the management of depressive disorder.

Exploring Sonic Hedgehog Cell Signaling in Neurogenesis: Its Potential Role in Depressive Behavior.

Depression is the most prevalent form of neuropsychiatric disorder affecting all age groups globally. As per the estimation of the World Health Organization (WHO), depression will develop into the foremost reason for disability globally by the year 2030. The primary neurobiological mechanism implicated in depression remains ambiguous; however, dysregulation of molecular and signaling transductions results in depressive disorders. Several theories have been developed to explain the pathogenesis of depression, however, none of them completely explained all aspects of depressive-pathogenesis. In the current review, we aimed to explore the role of the sonic hedgehog (Shh) signaling pathway in the development of the depressive disorder and its potential as the therapeutic target. Shh signaling has a crucial function in neurogenesis and neural tube patterning during the development of the central nervous system (CNS). Shh signaling performs a basic function in embryogenesis and hippocampal neurogenesis. Moreover, antidepressants are also known to enhance neurogenesis in the hippocampus, which further suggests the potential of Shh signaling. Furthermore, there is decreased expression of a glioma-associated oncogene (Gli1) and Smoothened (Smo) in depression. Moreover, antidepressants also regulate brain-derived neurotrophic factor (BDNF) and wingless protein (Wnt) signaling, therefore, Shh may be implicated in the pathogenesis of the depressive disorder. Deregulation of Shh signaling in CNS results in neurological disorders such as depression.