Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight

Abstract

Monoterpenes belong to the terpenoids class of natural products and are bio-synthesized through the mevalonic acid pathway. Their small molecular weight coupled with high non-polar nature make them the most abundant components of essential oils which are often considered to have some general antioxidant and antimicrobial effects at fairly high concentrations. These compounds are however reported to have antidiabetic effects in recent years. Thanks to the ingenious biosynthetic machinery of nature, they also display a fair degree of structural complexity/diversity for further consideration in structure-activity studies. In the present communication, the merit of monoterpenes as antidiabetic agents is scrutinized by assessing recent in vitro and in vivo studies reported in the scientific literature. Both the aglycones and glycosides of these compounds of rather small structural size appear to display antidiabetic along with antiobesity and lipid lowering effects. The diversity of these effects vis-à-vis their structures and mechanisms of actions are discussed. Some key pharmacological targets include the insulin signaling pathways and/or the associated PI3K-AKT (protein kinase B), peroxisome proliferator activated receptor-γ (PPARγ), glucose transporter-4 (GLUT4) and adenosine monophosphate-activated protein kinase (AMPK) pathways; proinflammatory cytokines and the NF-κB pathway; glycogenolysis and gluconeogenesis in the liver; glucagon-like-1 receptor (GLP-1R); among others.

Keywords: diabetes; monoterpenes; multiple mechanisms; obesity.

Figure 1

An overview of biosynthesis pathway of monoterpenes; isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP); glycogen phosphorylase (GP); OPP: diphosphate leaving group.

Figure 2

Structures of monoterpenes discussed in this review as antidiabetic agents.