Neuropharmacology of Secondary Metabolites from Plants with Anxiolytic and Antidepressant Properties

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 (GABA A-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.

Mechanistic insights into the role of plant polyphenols and their nano-formulations in the management of depression

“…Hesperidin is another flavonoid, which may raise hippocampal BDNF levels at 0.3 and 1 mg kg −1 daily dose for 21 days. Hesperidin produced antidepressant effect at 0.3 and 1 mg kg −1 on TST was found similar to the effects produced by imipramine at 15 mg/kg and fluoxetine at 32 mg kg −1 ( García-Ríos et al, 2020 ).…”

“…In mice brains, fucosterol prevented the reduction in the levels of NA, 5-HT and 5-HTIIA caused by stress of FST, suggesting that the antidepressant effects are due to increased monoamines and decreased metabolism rate of 5-HT. Administration of β-sitosterol (30 mg kg −1 ) produced antidepressant effects in male mice on FST and TST similar to that of fluoxetine at a dose of 20 mg kg −1 ( García-Ríos et al, 2020 ). Another study reported the antidepressants potential of α- and β-amyrin (αβAMY) isolated from the stem resin of Protium heptaphyllum on FST.…”

Biological Evaluation, DFT Calculations and Molecular Docking Studies on the Antidepressant and Cytotoxicity Activities of Cycas pectinata Buch.-Ham. Compounds

“…Thus, the phytochemical study is a topic of interest for the researcher to eValuate a lead compound to treat depression. Several phytochemicals (alkaloids, flavonoids, sterol, terpenes) are reported to have antidepressant effects [9]. Additionally, a few medicinal plants such as M. angolensis [32], N. sativa [33] R. rosea [34] are reported to have bilateral anxiolytic and antidepressant effects.…”

“…Thus, it is imperative that new antidepressant drugs demonstrate improvement of these drawbacks. Several phytochemicals (alkaloids, flavonoids, sterol, terpenes) were reported to have an antidepressant effect [9]. Oximes (R 1 R 2 C = NOH) are chemicals containing nitrogen produced by organisms in all kingdoms of life [10].…”

Anxiolytic, antidepressant and antioxidant activity of the methanol extract of Canarium resiniferum leaves

“…Many plants have anxiolytic and/or antidepressant potential and contain diverse phytoconstituents which may be exploited for the development of new drugs to treat these disorders, particularly in cases where patients do not respond to current medications. 17 , 18 The present study was undertaken to investigate the anxiolytic and antidepressant activity of the methanol extract of C. resiniferum (MECR) leaves using behavioral models in mice. As reactive oxygen species play an important role in the pathophysiology of depression and anxiety, 19 , 20 we sought to further determine the levels of total phenolics and flavonoids in MECR and investigate the antioxidant/free-radical scavenging potential of this extract.…”