Rhodiola crenulata Attenuates High Glucose Induced Endothelial Dysfunction in Human Umbilical Vein Endothelial Cells

Abstract

Rhodiola crenulata root extract (RCE), a traditional Chinese medicine, has been shown to regulate glucose and lipid metabolism via the AMPK pathway in high glucose (HG) conditions. However, the effect of RCE on HG-induced endothelial dysfunction remains unclear. The present study was designed to examine the effects and mechanisms of RCE against hyperglycemic insult in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without RCE and then exposed to 33[Formula: see text]mM HG medium. The cell viability, nitrite production, oxidative stress markers, and vasoactive factors, as well as the mechanisms underlying RCE action, were then investigated. We found that RCE significantly improved cell death, nitric oxide (NO) defects, and oxidative stress in HG conditions. In addition, RCE significantly decreased the HG-induced vasoactive markers, including endothelin-1 (ET-1), fibronectin, and vascular endothelial growth factor (VEGF). However, the RCE-restored AMPK-Akt-eNOS-NO axis and cell viability were abolished by the presence of an AMPK inhibitor. These findings suggested that the protective effects of RCE were associated with the AMPK-Akt-eNOS-NO signaling pathway. In conclusion, we showed that RCE protected endothelial cells from hyperglycemic insult and demonstrated its potential for use as a treatment for endothelial dysfunction in diabetes mellitus.

Protective Effects of Rhodiola Crenulata Extract on Hypoxia-Induced Endothelial Damage via Regulation of AMPK and ERK Pathways

“…In this study, we observed that RCE rescued endothelial NO production and signaling via AMPK-AKT-eNOS axis under hypoxia. This is consistent with our previous studies demonstrating that RCE counteracts the effect of hypobaric hypoxia in rat heart through rebalancing NO and arginase 1 signaling pathways [14], and protects HUVECs from high glucose challenge via AMPK-AKT-eNOS-NO signaling pathway [15]. In addition, NO has been reported to maintain cytoskeletal structure and suppress apoptosis in endothelial cells [32,33].…”

“…Therefore, R. crenulata might be beneficial for many vascular diseases related to hypoxic damage and NO dysfunction in the endothelium. In the case of OSA, RCE may offer additional benefits because OSA is associated with poor glycemic control [34], and RCE has shown protective effects in this context [15,35]. Based on this finding, RCE might be considered a potential agent for vascular disorders in diabetic patients with OSA syndrome.…”

“…HUVECs are widely used to study endothelial injury in vitro [15]. HUVECs (Lifeline Cell Technology, Walkersville, MD, USA) were cultured in VascuLife complete medium (Lifeline Cell Technology) at 37 °C in a humidified 5% CO 2 incubator.…”

“…MDA levels were quantified by using a commercial kit (Cayman Chemical Co., Ann Arbor, MI) as described previously [15]. Briefly, the cells were lysed in RIPA lysis buffer and centrifuged at 1600× g .…”

“…RCE also restores the eNOS-NO-cyclic guanosine monophosphate (cGMP) relaxation pathway in hypobaric hypoxic rat heart [14]. In our recent study, RCE significantly improved cell death, NO defects, and oxidative stress in human umbilical vein endothelial cells (HUVECs) grown in high glucose conditions via the AMPK-AKT-eNOS-NO signaling pathways [15]. Thus, RCE might be beneficial for hypoxia-induced vascular endothelial dysfunction.…”