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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 284150, 15 pages
Research Article

Rhodiola crenulata and Its Bioactive Components, Salidroside and Tyrosol, Reverse the Hypoxia-Induced Reduction of Plasma-Membrane-Associated Na,K-ATPase Expression via Inhibition of ROS-AMPK-PKCξ Pathway

1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan
2Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei 114, Taiwan
3Department of Biotechnology, National Formosa University, Yunlin 632, Taiwan
4Department of Biochemistry, National Defense Medical Center, P.O. Box 90048-501, Nei-hu, Taipei 114, Taiwan
5Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan
6Graduate Institute of Basic Medical Science, China Medical University, Taichung 400, Taiwan

Received 9 March 2013; Revised 5 May 2013; Accepted 20 May 2013

Academic Editor: Evan Paul Cherniack

Copyright © 2013 Shih-Yu Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Exposure to hypoxia leads to impaired pulmonary sodium transport, which is associated with Na,K-ATPase dysfunction in the alveolar epithelium. The present study is designed to examine the effect and mechanism of Rhodiola crenulata extract (RCE) and its bioactive components on hypoxia-mediated Na,K-ATPase endocytosis. A549 cells were exposed to hypoxia in the presence or absence of RCE, salidroside, or tyrosol. The generation of intracellular ROS was measured by using the fluorescent probe DCFH-DA, and the endocytosis was determined by measuring the expression level of Na,K-ATPase in the PM fraction. Rats exposed to a hypobaric hypoxia chamber were used to investigate the efficacy and underlying mechanism of RCE in vivo. Our results showed that RCE and its bioactive compounds significantly prevented the hypoxia-mediated endocytosis of Na,K-ATPase via the inhibition of the ROS-AMPK-PKCζ pathway in A549 cells. Furthermore, RCE also showed a comparable preventive effect on the reduction of Na,K-ATPase endocytosis and inhibition of AMPK-PKCξ pathway in the rodent model. Our study is the first to offer substantial evidence to support the efficacy of Rhodiola products against hypoxia-associated Na,K-ATPase endocytosis and clarify the ethnopharmacological relevance of Rhodiola crenulata as a popular folk medicine for high-altitude illness.