Schisanhenol Attenuates OxLDL-Induced Endothelial Dysfunction via an AMPK-Dependent Mechanism

Tsan Hung Chiu, Chang Wen Ku, Tsung Jung Ho, Kun Ling Tsai, Wei Ching Hsu, Yu An Chen, Hsiu Chung Ou, Hsiu I. Chen

研究成果: Article同行評審

摘要

Atherosclerotic cardiovascular diseases, commonly known as the formation of fibrofatty lesions in the artery wall, are the leading causes of death globally. Oxidized low-density lipoprotein (oxLDL) is one of the major components of atherosclerotic plaques. It is evident that dietary supplementation containing sources of antioxidants can prevent atherogenic diseases. Schisanhenol (SAL), a dibenzocyclooctene lignin, has been shown to attenuate oxLDL-induced apoptosis and the generation of reactive oxygen species (ROS) in endothelial cells. However, the underlying molecular mechanisms are still largely unknown. In this study, human umbilical vein endothelial cells (HUVECs) were pre-treated with SAL and oxLDL. Our results showed that adenosine monophosphate-activated protein kinase (AMPK) phosphorylation was enhanced in cells pre-treated with SAL in time-dependent and dose-dependent manners. Subsequently, oxLDL-induced AMPK dephosphorylation and protein kinase C (PKC) phosphorylation were significantly reversed in the presence of SAL. In addition, SAL treatment led to an inhibiting effect on the oxLDL-induced membrane assembly of NADPH oxidase subunits, and a similar effect was observed in ROS generation. This effect was further confirmed using knockdown AMPK with small interfering RNA (siRNA) and pharmaceutical reagents, such as the AMPK activator (AICAR), PKC inhibitor (Gö 6983), and ROS inhibitor (DPI). Furthermore, the oxLDL-induced intracellular calcium rise and the potential collapse of the mitochondrial membrane reduced the Bcl-2/Bax ratio, and released cytochrome c from the mitochondria, leading to the subsequent activation of caspase-3 in HUVECs, which were also markedly suppressed by SAL pretreatment. The results mentioned above may provide additional insights into the possible molecular mechanisms underlying the cardiovascular protective effects of SAL.

原文English
頁(從 - 到)1459-1475
頁數17
期刊American Journal of Chinese Medicine
51
發行號6
DOIs
出版狀態Published - 2023

All Science Journal Classification (ASJC) codes

  • 補充和替代醫學

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