Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications

Abstract

With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients.

Keywords: cinnamic acid and its derivatives; complications; diabetes; mechanisms.

Figure 1

The chemical structure of cinnamic acid and its derivatives. (A) Cinnamic acid; (B) o-Hydroxycinnamic acid; (C) m- Hydroxycinnamic acid; (D) p- Hydroxycinnamic acid; (E) o-Methoxycinnamic acid; (F) m-Methoxycinnamic acid; (G) p-Methoxycinnamic acid; (H) Ferulic acid (I) Isoferulic acid; (J) Caffeic acid.

Figure 2

Schematic diagram represents the mechanism actions of cinnamic acid and its derivatives for prevention and management of diabetes and its complication. (↑) Increase, (↓) Decrease.

Figure 3

Mechanisms of ferulic acid, caffeic acid, p-hydroxycinnamic acid, cinnamic acid, and isoferulic acid for stimulating glucose uptake in adipocytes and muscle.

Figure 4

Inhibition of carbohydrate digestive enzymes (pancreatic α-amylase, maltase, and sucrase) and monosaccharide absorption (GLUT2) by ferulic acid, isoferulic acid, and caffeic acid.

Figure 5

Graphical presentation of possible anti-glycation mechanisms of cinnamic acid and its derivatives.

Figure 6

The mechanism of ferulic acid and isoferulic acid on prevention of methylglyoxal-induced protein and DNA damage.