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.

A review: Biological activity of myrtenal and some myrtenal-containing medicinal plant essential oils

“…In vitro and in vivo studies have revealed the effects of monoterpenes in diabetes, insulin resistance and obesity (8). In vitro studies on various cell lines (including pancreatic β cells, muscle, adipocyte and hepatic cells) revealed that besides carvacrol and thymol that have a phenolic skeleton, most monoterpenes do not have the properties of direct radical scavengers due to their antidiabetic effects.…”

The Sensing Liver: Localization and Ligands for Hepatic Murine Olfactory and Taste Receptors

“…Lavender essential oils largely comprised of camphor and fenchone (45.25% total composition), were also found to possess antioxidant properties in an alloxan induced rat model of diabetes ( Sebai et al, 2013 ), again raising the possibility that these compounds possess hepatoprotective properties. There have also been recent claims that monoterpenes may have anti-diabetic properties ( Habtemariam, 2017 ) and may modulate cholesterol synthesis via the inhibition of HMG-CoA reductase ( Clegg et al, 1982 ; Elson and Yu, 1994 ; Ren and Gould, 1994 ). Finally, it has been shown that several of these monoterpenes can be synthesized and released by fungi ( Elke et al, 1999 ), raising the possibility that commensal fungi could be impacting liver function via Olfr57.…”

A regulatory domain in the K2P2.1 (TREK-1) carboxyl-terminal allows for channel activation by monoterpenes

“…Using MTs, we were able to detect a novel regulatory domain in the carboxyl-terminal domain of the K2P2.1 channel. Moreover, the growing number of studies on the use of MTs for the treatment of neuropathy (Abuhamdah et al, 2015;Porres-Martinez et al, 2016), as well as for treating diabetes (Habtemariam, 2017), points to the need for better understanding of the effect of MTs on cell components, such as K2P channels, which are involved in these conditions.…”