Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway

Atherosclerosis is one of the most reported diseases worldwide, and extensive research and trials are focused on the discovery and utilizing for novel therapeutics. Nitric oxide (NO) is produced mainly by endothelial nitric oxide synthase (eNOS) and it plays a key role in regulating vascular function including systemic blood pressure and vascular inflammation in vascular endothelium. In this study hypothesized that Impressic acid (IPA), a component isolated from Acanthopanax koreanum, acts as an enhancer of eNOS activity and NO production. IPA treatment induced eNOS phosphorylation and NO production, which was correlated with eNOS phosphorylation via the activation of JNK1/2, p38 MAPK, AMPK, and CaMKII. In addition, the induction of eNOS phosphorylation by IPA was attenuated by pharmacological inhibitor of MAPKs, AMPK, and CaMKII. Finally, IPA treatment prevented the adhesion of TNF-alpha-induced monocytes to endothelial cells and suppressed the TNF-alpha-stimulated ICAM-1 expression via activation of NF-kappa B, while treatment with L-NAME, the NOS inhibitor, reversed the inhibitory effect of IPA on TNF-alpha-induced ICAM-1 expression via activation of NF-kappa B. Taken together, these findings show that IPA protects against TNF-alpha-induced vascular endothelium dysfunction through attenuation of the NF-kappa B pathway by activating eNOS/NO pathway in endothelial cells.