trans-Ferulic acid attenuates hyperglycemia-induced oxidative stress and modulates glucose metabolism by activating AMPK signaling pathway in vitro.

Adenosine monophosphate-activated
protein kinase (AMPK) is a potent metabolic regulator
and an attractive target for antidiabetic activators. Here we report for the first
that, trans-ferulic
acid (TFA) is a potent dietary bioactive molecule of hydroxycinnamic
acid derivative for the activation of AMPK with a maximum increase in phosphorylation
(2.71/2.67 ± 0.10; p < .001 vs. high glucose [HG] control) in hyperglycemia-induced
human liver cells (HepG2) and rat skeletal muscle cells (L6), where HG suppresses the
AMPK pathway. It was also observed that TFA increased activation of AMPK in a dose-and
time-dependent
manner and also increased the phosphorylation of acetyl-CoA
carboxylase (ACC), suggesting that it may promotes fatty acid oxidation; however, pretreatment
with compound C reversed the effect. In addition, TFA reduced the level of
intracellular reactive oxygen species (ROS) and nitric oxide (NO) induced by hyperglycemia
and subsequently increased the level of glutathione. Interestingly, TFA also upregulated
the glucose transporters, GLUT2 and GLUT4, and inhibited c-Jun
N-terminal
protein kinase (JNK1/2) by decreasing the phosphorylation level in tested cells under
HG condition. Our studies provide critical insights into the mechanism of action of TFA
as a potential natural activator of AMPK under hyperglycemia.
Practical applications
Hydroxycinnamic acid derivatives possess various pharmacological properties and
are found to be one of the most ubiquitous groups of plant metabolites in almost all
dietary sources. However, the tissue-specific
role and its mechanism under hyperglycemic
condition remain largely unknown. The present study showed that TFA is a
potent activator of AMPK under HG condition and it could be used as a therapeutic
agent against hyperglycemia in type 2 diabetes.