Abstract:
Angiotensin Ⅱ (Ang Ⅱ) is involved in endothelium injury during the development of hypertension.
Tribulus terrestris (TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats (SHRs) and its protective effects against Ang Ⅱ-induced injury in human umbilical vein endothelial cells (HUVECs). SHRs were administered intragastrically with TT (17.2 or 8.6 g·kg
-1·d
-1) for 6 weeks, using valsartan (13.5 mg·kg
-1·d
-1) as positive control. Blood pressure, heart rate, endothelial morphology of the thoracic aorta, serum levels of Ang Ⅱ, endothelin-1 (ET-1), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured. The endothelial injury of HUVECs was induced by 2 × 10
-6 mol·L
-1 Ang Ⅱ. Cell Apoptosisapoptosis, intracellular reactive oxygen species (ROS) was assessed. Endothelial nitric oxide synthase (eNOS), ET-1, SOD, and MDA in the cell culture supernatant and cell migration were assayed. The expression of hypertension-linked genes and proteins were analyzed. TT decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate, improved endothelial integrity of thoracic aorta, and decreased serum leptin, Ang Ⅱ, ET-1, NPY, and Hcy, while increased NO in SHRs. TT suppressed Ang Ⅱ-induced HUVEC proliferation and apoptosis and prolonged the survival, and increased cell migration. TT regulated the ROS, and decreased mRNA expression of
Akt1,
JAK2,
PI3Kα,
Erk2,
FAK, and
NF-κB p65 and protein expression of
Erk2,
FAK, and
NF-κB p65. In conclusion, TT demonstrated anti-hypertensive and endothelial protective effects by regulating
Erk2,
FAK and
NF-κB p65.