Abstract
Depression and anxiety currently rank as the second and fifth most common causes worldwide of years lived with disability-a reality that has intensified the search for new treatments. There are many studies of herbal extracts and secondary metabolites from plants used in traditional medicine due to their antidepressant and anxiolytic properties. Clinical and preclinical studies about some of the mechanisms of action of metabolites like alkaloids, terpenes, flavonoids, and sterols, among others, have documented effects similar to those produced by clinically effective drugs. These metabolites have shown anxiolytic and antidepressant effects in various experimental models of anxiety by interacting with γ-aminobutyric acid subtype A receptors (GABAA-receptors) and by stimulating the serotonergic, noradrenergic, and dopaminergic neurotransmitter systems. These pharmacological effects can be attributed to plant metabolites that share structural similarities with monoamines, which allow them to bind to receptors. The objective of this chapter is to summarize the various mechanisms of action that have been identified in secondary metabolites with anxiolytic and antidepressant properties. Terpenes, alkaloids, flavonoids, and sterols can interact at different levels of the neurotransmission systems involved in the neurobiology of anxiety and depression, suggesting their potential for treating these mental illnesses.
Highlights
According to the Global Burden of Disease, depression and anxiety are currently the second and fifth most common causes worldwide of years lived with disability in both sexes in the age range of 15–49 years [1]
Reports of adverse reactions to medicinal plants [9] may reflect the broad variety of active metabolites they contain, highlighting the need for preclinical and clinical studies that evaluate the possible biological activity of compounds isolated from plants or standardized crude extracts, their mechanisms of action, and possible toxicity
The lower frequency of rearings, but no reduction in the steps climbed in a 3-min period, was interpreted as indications of an anxiolytic effect [45]. Those authors verified that 6-methoxyflavanone produced its effect by activating GABAA receptors with the α2-subunit, perhaps in the amygdala and brain cortex, since pretreatment with PTZ blocked this anxiolytic effect in EPM and on staircase test (ScT) [56]
Summary
According to the Global Burden of Disease, depression and anxiety are currently the second and fifth most common causes worldwide of years lived with disability in both sexes in the age range of 15–49 years [1]. These tools have allowed researchers to analyze the possible metabolites responsible for the anxiolytic or antidepressant properties of plants used by different populations, and identify how their mechanisms of action affect the functioning of the central nervous system (CNS). Their studies contribute to advancing scientific understanding of the neurobiology of depression and anxiety, and to developing new pharmacological treatments that may favorably impact public health. The studies analyzed were identified by a preliminary search in PubMed, Scopus and Ovid for articles on (i) the dose effects and possible mechanisms of action of metabolite(s) isolated from parts of plants with previously identified anxiolytic or antidepressant effects; and (ii) standard chemical tests performed with specific metabolites
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