Abstract
Advanced glycation end-products (AGEs) considered as a fatal mediator in the diabetic atherosclerotic pathology. In this study, we evaluated the effects of chebulic acid (CA) on anti-oxidant activities and its glycoaldehyde-induced AGEs (glycol-AGEs)-mediates systemic vascular dysfunction in endothelium, monocytes, and smooth muscle cells (SMC) co-culture condition. CA exhibited strong at free radical scavenging activity by blocking intracellular ROS formation in endothelium. They also suppressed endothelial activation by blocking the monocytes adhesion to endothelium, and pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6 as well as enhancing anti-oxidant detoxification defensing mediators such as HO-1 and NQO1 expression, through ERK/Nrf2 signaling in HUVEC. Furthermore, CA administration provided powerful anti-inflammatory supplements to mice, and also has similar results by enhancing Nrf2, and their down-streamed mediators. These in vitro and in vivo studies indicated that CA attenuated glycol-AGEs-mediates vascular dysfunction by ameliorating AGEs-induced inflammation and oxidative stress via enhancing the detoxification defensing pathway of ERK/Nrf2.
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