4.7 Article

Cordycepin Attenuates Palmitic Acid-Induced Inflammation and Apoptosis of Vascular Endothelial Cells through Mediating PI3K/Akt/eNOS Signaling Pathway

Journal

AMERICAN JOURNAL OF CHINESE MEDICINE
Volume 49, Issue 7, Pages 1703-1722

Publisher

WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S0192415X21500804

Keywords

Oxidative Stress; Palmitic Acid; Cordyceps Sinensis; Cordycepin; Atherosclerosis

Funding

  1. Ministry of Science and Technology, Taiwan [MOST-1092635-B-468-001, MOST 110-2320-B-039-045-MY3]
  2. China Medical University [CMU110-MF-65]
  3. Asia University [CMU107-ASIA-10]
  4. China Medical University

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Cordycepin, the main bioactive chemical of Cordyceps sinensis, has potent anticancer, anti-oxidant and anti-inflammatory activities. In addition, its protective effects against atherosclerotic changes in vascular endothelial cells may be partially mediated by the PI3K/Akt/eNOS signaling pathway.
A well-known medicinal mushroom in the field of traditional Chinese medicine, Cordyceps sinensis, is a rare natural-occurring entomopathogenic fungus, and it typically grows at high altitudes on the plateau of the Himalayan. Previous studies indicated that cordycepin, the main bioactive chemical of Cordyceps sinensis, has very potent anticancer, anti-oxidant and anti-inflammatory activities. However, its protective effects against atherosclerotic changes in vascular endothelial cells have not been fully elucidated. In this study, we showed that pretreatment with cordycepin significantly attenuated palmitic acid (PA)-induced cytotoxicity, reactive oxygen species (ROS) generation, and inflammatory responses. We found that PA decreased phosphorylation of Akt, eNOS, and bioavailability of nitric oxide (NO), which in turn activated NF-kappa B and the downstream inflammatory responses. All these detrimental events were markedly blocked by pretreatment with cordycepin. Moreover, cordycepin ameliorated destabilization of mitochondrial permeability, cytosolic calcium rises, and apoptotic features caused by PA. In addition, all these anti-inflammatory and anti-apoptosis effects of cordycepin were found to be inhibited by the PI3K and eNOS inhibitor, suggesting that its anti-atherosclerotic effects may partially be mediated by the PI3K/Akt/eNOS signaling pathway.

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