Kakkalide is a potent lactate dehydrogenase (LDH) inhibitor, it has anti-inflammatory effects.

Human umbilical vein endothelial cells (HUVEC) were stimulated with 100 μmol/L palmitate (PA) for 30 min and the effects of 30 min pretreatment with 0.1-10 μmol/L Kakkalide on reactive oxygen species (ROS)-associated inflammation in cells were evaluated by western blot analysis and reverse transcription-polymerase chain reaction. Furthermore, we investigated the biomodulation of insulin signaling by Kakkalide along the insulin receptor substrate (IRS)-1/Akt/endothelial nitric oxide synthase (eNOS) pathway. We also determined the effects of 30 min pretreatment with 0.1-10 μmol/L Kakkalide on insulin-mediated endothelium-dependent vasodilation of rat aorta in vitro following stimulation with 100 μmol/L PA. Kakkalide inhibited ROS overproduction and effectively restored mitochondrial membrane potential, demonstrating its chemoprotection of mitochondrial function. In addition, Kakkalide inhibited ROS-associated inflammation in the endothelium by inhibiting tumor necrosis factor-α± and interleukin-6 production and gene expression, as well as suppressing the phosphorylation of c-Jun N-terminal kinase and IκB kinase β/nuclear factor-κB. Inflammation impaired insulin phosphatidylinositol 3-kinase (PI3K) signaling and reduced insulin-mediated NO production in endothelial cells. Kakkalide facilitated PI3K signaling by positively regulating serine/tyrosine phosphorylation of IRS-1.