Insulin-Releasing Properties of a Series of Cinnamic Acid Derivatives in Vitro and in Vivo

Abstract

Cinnamic acid derivatives are naturally occurring substances found in fruits, vegetables, and flowers and are consumed as dietary phenolic compounds. In the present study, cinnamic acid and its derivatives were evaluated for insulin secreting activity in perfused rat pancreas and pancreatic beta-cells (INS-1) as well as an increase in [Ca(2+)]i in vitro. The presence of m-hydroxy or p-methoxy residues on cinnamic acid was a significantly important substituent as an effective insulin releasing agent. The introduction of p-hydroxy and m-methoxy-substituted groups in cinnamic acid structure (ferulic acid) displayed the most potent insulin secreting agent among those of cinnamic acid derivatives. In particular, the stimulatory insulin secreting activities of test compounds were associated with a rise of [Ca(2+)]i in INS-1. In perfused rat pancreas, m-hydroxycinnamic acid, p-methoxycinnamic acid, and ferulic acid (100 microM) significantly stimulated insulin secretion during 10 min of administration. The onset time of insulin secretion of those compounds was less than 1 min and reached its peak at 4 min that was about 2.8-, 3.3-, and 3.4-fold of the baseline level, respectively. Intravenous administration of p-methoxycinnamic acid and ferulic acid (5 mg/kg) significantly decreased plasma glucose and increased insulin concentration in normal rats and maintained its level for 15 min until the end of experiment. Meanwhile, m-hydroxycinnamic acid induced a significant lowering of plasma glucose after 6 min, but the effects were transient with plasma glucose concentration, rapidly returning to basal levels. Our findings suggested that p-methoxycinnamic acid and ferulic acid may be beneficial for the treatment of diabetes mellitus because they regulated blood glucose level by stimulating insulin secretion from pancreatic beta-cells.

Anti-obesity and cardioprotective effects of cinnamic acid in high fat diet- induced obese rats

“…The important inhibitory action is explained by the fact that cinnamic acid derivatives are naturally occurring substances found in fruits, vegetables, and flowers. They are consumed as dietary phenolic compounds (Adisakwattana et al 2008). As well, polyphenols have some potential efficacy for preventing obesity through inhibition of key-enzymes related to fat metabolism including pancreatic lipase (Rahul et al 2007;Mnafgui et al 2012).…”

Cinnamic Acid Derivatives as α-Glucosidase Inhibitor Agents

“…The presence of p-hydroxy (45) and m-methoxy (46) in the structure of cinnamic acid turns cinnamic acid into ferulic acid which is widely reported as the best agent to secrete insulin. In this study, it shows that the p-methoxy cinnamic acid and ferulic acid can be beneficial for the treatment of diabetes mellitus because the blood glucose levels are regulated by stimulating insulin secretion from pancreatic β-cells [29].…”

Investigation of the Safety and Antihyperglycemic Effect of <i>Apios americana</i> Flower Intake as a Food Material in Normal and Diabetic Mice

“…Therefore, it is expected that the reduction in plasma glucose level by ingestion of AFE was induced by the insulin-like action of AFE or its inhibitory action on the hydrolysis and absorption of carbohydrates in the digestive tract. Since cinnamic acid derivatives have been reported to promote insulin secretion (Adisakwattana et al, 2008), the possibility that AFE affects insulin secretion is an interesting concept. There have been several studies on the hypoglycemic activity and antidiabetic effects of flowers and their constituents (Bhaskar et al, 2011;Dias et al, 2010;Nakamura et al, 2011); however, there have been no reports on these effects in a type 2 diabetes model.…”