Modes of Action of Herbal Medicines and Plant Secondary Metabolites

Abstract

Plants produce a wide diversity of secondary metabolites (SM) which serve them as defense compounds against herbivores, and other plants and microbes, but also as signal compounds. In general, SM exhibit a wide array of biological and pharmacological properties. Because of this, some plants or products isolated from them have been and are still used to treat infections, health disorders or diseases. This review provides evidence that many SM have a broad spectrum of bioactivities. They often interact with the main targets in cells, such as proteins, biomembranes or nucleic acids. Whereas some SM appear to have been optimized on a few molecular targets, such as alkaloids on receptors of neurotransmitters, others (such as phenolics and terpenoids) are less specific and attack a multitude of proteins by building hydrogen, hydrophobic and ionic bonds, thus modulating their 3D structures and in consequence their bioactivities. The main modes of action are described for the major groups of common plant secondary metabolites. The multitarget activities of many SM can explain the medical application of complex extracts from medicinal plants for more health disorders which involve several targets. Herbal medicine is not a placebo medicine but a rational medicine, and for several of them clinical trials have shown efficacy.

Keywords: bioactivity; evolutionary pharmacology; non-specific interaction; phytotherapy; plant secondary metabolite; specific interactions.

Figure 1

Secondary metabolites (SM) which form covalent bonds with proteins inducing a conformational change (indicated by the change of the form of the theoretical protein) and thus modulating their bioactivities (after [51,63]). (A) Interactions of SM with SH-groups of proteins and peptides; (B) Interactions of SM with amino groups of proteins or peptides.

Figure 2

SM which form hydrogen and ionic bonds with proteins and thus modulate their conformation. (A) Schematic view of possible hydrogen and ionic bond formation by phenolic compounds (here thymol); (B) Examples for widely distributed polyphenols in medicinal plants. Phenolic OH groups are circled (after [51,63]).

Figure 3

Interaction of SM with biomembranes. Saponins can complex membrane cholesterol; polyphenols influence 3D structure of membrane proteins (receptors, transporters, ion channels); small lipophilic terpenoids assemble in the inner lipophilic core of the biomembrane (after [11,12])