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

摘要

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 ofRhodiola crenulataextract (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 RCEin 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-PKCζpathway in A549 cells. Furthermore, RCE also showed a comparable preventive effect on the reduction of Na,K-ATPase endocytosis and inhibition of AMPK-PKCξpathway in the rodent model. Our study is the first to offer substantial evidence to support the efficacy ofRhodiolaproducts against hypoxia-associated Na,K-ATPase endocytosis and clarify the ethnopharmacological relevance ofRhodiola crenulataas a popular folk medicine for high-altitude illness.