Natural Products for the Treatment of Post-stroke Depression

Abstract

Post-stroke depression (PSD) is the most frequent and important neuropsychiatric consequence of stroke. It is strongly associated with exacerbated deterioration of functional recovery, physical and cognitive recoveries, and quality of life. However, its mechanism is remarkably complicated, including the neurotransmitters hypothesis (which consists of a monoaminergic hypothesis and glutamate-mediated excitotoxicity hypothesis), inflammation hypothesis, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophic hypothesis and neuroplasticity. So far, the underlying pathogenesis of PSD has not been clearly defined yet. At present, selective serotonin reuptake inhibitors (SSRIs) have been used as the first-line drugs to treat patients with PSD. Additionally, more than SSRIs, a majority of the current antidepressants complied with multiple side effects, which limits their clinical application. Currently, a wide variety of studies revealed the therapeutic potential of natural products in the management of several diseases, especially PSD, with minor side effects. Accordingly, in our present review, we aim to summarize the therapeutic targets of these compounds and their potential role in-clinic therapy for patients with PSD.

Post-Stroke Neuropsychiatric Complications: Types, Pathogenesis, and Therapeutic Intervention

“…Antidepressants used to treat PSD mainly include TCAs, SSRIs, dual serotonin and noradrenergic reuptake inhibitors, and these are the basis of current PSD intervention. Compelling clinical and preclinical evidence suggests that various phytochemical compounds extracted from natural products and compound prescriptions of TMC have strong antidepressant activities and few side effects, and these may represent promising new interventions for PSD [144][145][146]. Unlike clinically available agents, the mechanism of drugs being evaluated in basic research of PSD mainly focused on the regulation of the HPA axis and inflammation [147].…”

Antidepressant-like Effect of 1-(2-(4-(4-Ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one in Mice: Evidence of the Contribution of the Serotonergic System

“…For this reason, the pathophysiology of depression is not yet fully understood, with various theories and evidence related to its etiology. − For decades, the monoamine hypothesis was the most widely accepted theory for explaining this disorder. This theory suggests that depression is the result of a deficit in the biological monoamine system in the brain, such as serotonin, norepinephrine, and dopamine, as these neurotransmitters are involved in mood control. ,, …”

“…Most of the existing antidepressant drugs act on the regulation of the monoamine system, with the main function of increasing the availability of these neurotransmitters, allowing them to act for longer in the central nervous system (CNS). ,, Despite acting on the regulation of the same system, they have distinct mechanisms for this purpose and are classified according to this distinction. , Among the classes of antidepressants are the selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SSNRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs). − However, approximately 30% of depressed individuals do not respond to pharmacological treatments, and patients who do respond may not show improvement in symptoms up to 4 weeks after the start of the treatment. ,,, These data, combined with the lack of a fully elucidated pathophysiology, demonstrate the many problems encountered in the research of psychiatric disorders …”

“…6,8,9 Most of the existing antidepressant drugs act on the regulation of the monoamine system, with the main function of increasing the availability of these neurotransmitters, allowing them to act for longer in the central nervous system (CNS). 3,8,10 Despite acting on the regulation of the same system, they have distinct mechanisms for this purpose and are classified according to this distinction. 3,11 Among the classes of antidepressants are the selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SSNRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs).…”

“…This theory suggests that depression is the result of a deficit in the biological monoamine system in the brain, such as serotonin, norepinephrine, and dopamine, as these neurotransmitters are involved in mood control. 6,8,9 Most of the existing antidepressant drugs act on the regulation of the monoamine system, with the main function of increasing the availability of these neurotransmitters, allowing them to act for longer in the central nervous system (CNS). 3,8,10 Despite acting on the regulation of the same system, they have distinct mechanisms for this purpose and are classified according to this distinction.…”