Indole Alkaloids from Plants as Potential Leads for Antidepressant Drugs: A Mini Review

This review (2017) discusses bioactive compounds containing the indole moiety (half/part of a molecule) from plants that can potentially serve as antidepressive medication due to its relation to serotonin.

Abstract

“Depression is the most common illness observed in the elderly, adults, and children. Antidepressants prescribed are usually synthetic drugs and these can sometimes cause a wide range of unpleasant side effects. Current research is focussed on natural products from plants as they are a rich source of potent new drug leads. Besides Hypericum perforatum (St. John’s wort), the plants studied include Passiflora incarnata L. (passion flower), Mitragyna speciosa (kratom), Piper methysticum G. Forst (kava) and Valeriana officinalis L. Harman, harmol, harmine, harmalol and harmaline are indole alkaloids isolated from P. incarnata, while mitragynine is isolated from M. speciosa. The structure of isolated compounds from P. methysticum G. Forst and V. officinalis L. contains an indole moiety. The indole moiety is related to the neurotransmitter serotonin which is widely implicated for brain function and cognition as the endogenous receptor agonist. An imbalance in serotonin levels may influence mood in a way that leads to depression. The moiety is present in a number of antidepressants already on the market. Hence, the objective of this review is to discuss bioactive compounds containing the indole moiety from plants that can serve as potent antidepressants.”

Authors: Hazrulrizawati A. Hamid, Aizi N. M. Ramli & Mashitah M. Yusoff

Summary

INTRODUCTION

According to the World Health Organization, depression affects 350 million people worldwide and is caused by chemicals or hormones imbalance in the brain.

Depression can be treated by psychotherapy or medication, and there are many different types of antidepressant drugs available. Herbal medicines are also used to treat depression, and are gaining wider acceptance among the medical profession and by patients.

There are few reports on research involving the active principle capable of inducing activity on the central nervous system. This review discusses the potential of natural indole alkaloids for the treatment of neurological disorder, structure-activity relationship studies, and other bioactive metabolites as potential antidepressant drug leads.

ANTIDEPRESSANT PLANTS

This review article deals with plants possessing activity on the CNS. It highlights two plants that contain indole alkaloids, and two plants that do not, and the chemical structure of isolated compounds from these plants can be used as the basis for the development of new drugs.

Studies have shown that P. incarnata and M. speciosa have similar pharmacological profiles and act through gamma-aminobutyric acid (GABA) receptors. Mitragynine, the major indole alkaloid present in M. speciosa, has antidepressant-like effect on mouse models of behavioral despair.

Kava is a drink that induces a pleasant mental state toward feeling cheerful while reducing fatigue and anxiety. The lipid-soluble extract contains at least seven pyrones, known as kavalactones, which interact with the dopaminergic, serotonin, gamma aminobutyric acid (GABA), glutamatergic neurotransmissions, and prevent monoamine oxidase B (MOB).

Valeriana officinalis L. is widely used as a sedative, anticonvulsant, for hypnotic effects, and anxiolytic activity. Its active ingredients include valepotriates, which are unstable, thermolabile and decompose rapidly in water and alcoholic solutions.

Although valerian has a variety of chemical constituents, the mechanism of action is reported to be interaction of valerian with the GABA system in the brain. Various models have been utilized to investigate the effects of plants on depression.

INDOLE ALKALOIDS

Indole alkaloids are bicyclic compounds with a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. They are widely distributed in plants of several families, and have been used to treat depression since 1952.

Indole alkaloids are often associated with the function of G-protein receptors, in particular for neuronal signal transmission through receptors for serotonin (5-HT/hydroxytryptamine). Indole alkaloids have a high occupied molecular orbital energy, which allows them to interact with nucleobases, in particular protonated atoms, as well as target proteins.

A review paper on the active constituents from plant extracts responsible for the antidepressant effect is still unclear. However, several chemical structures that are similar to serotonin and indole alkaloids have been identified that might contribute to antidepressant activity.

Serotonin, a neurotransmitter, exerts its functions through seven families of receptors (5-HT1-5-HT7). A number of compounds bearing the indole moiety have been described to own affinity toward different serotonin receptors.

The indole ring is used in the development of prototype drugs that have similar chemical and physical properties as biological molecules. These bioisosteric molecules possess dimethyltryptamine-like activity and can be used to improve the pharmacological activity and optimize the pharmacokinetic profile.

Common indole alkaloids found in natural sources are tryptophan amino acids in human nutrition, plant hormones that have therapeutic effects, and the indole scaffold has binding pockets and possesses common complementary binding domain to the target receptor.

CONCLUSION

This review found that most plant-based remedies indicated for the treatment of psychiatric ailments were crude or semipurified. The results for in vivo and in vitro varies and was not reproducible because of different biogeographical regions and the bioactivity of plants might be contributed by a single compound or mixture of compounds.