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·d) for 6 weeks, using valsartan (13.5 mg·kg·d) 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 mol·L 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.
Subject(s)
Animals , Humans , Male , Rats , Angiotensin II , Metabolism , Antihypertensive Agents , Apoptosis , Blood Pressure , Endothelium, Vascular , Metabolism , Human Umbilical Vein Endothelial Cells , Hypertension , Drug Therapy , Genetics , Metabolism , NF-kappa B , Genetics , Metabolism , Nitric Oxide Synthase Type III , Genetics , Metabolism , Oxidative Stress , Plant Extracts , Proto-Oncogene Proteins c-akt , Genetics , Metabolism , Rats, Inbred SHR , Rats, Inbred WKY , Reactive Oxygen Species , Metabolism , Tribulus , ChemistryABSTRACT
PURPOSE: To evaluate corneal endothelial protection effect of ascorbic acid (AA) at the most appropriate concentration, and determine the synergistic effect of glutathione in irrigation solution during phacoemulsification. METHODS: Phacoemulsification was performed in the anterior chamber of 30 rabbit eyes for 5 minutes without damage to other ocular structures. Thirty rabbit eyes were divided into 6 groups, of 5 eyes each, according to the following irrigation solutions in phacoemulsification.: BSS(R) in group 1, BSS(R) with 1 mM AA in group 2, BSS Plus(R) in group 3, BSS Plus(R) with 0.1 mM AA in group 4, BSS Plus(R) with 1 mM AA in group 5 and BSS Plus(R) with 10 mM AA in group 6. Corneal endothelial loss was measured with specular microscopic photographies taken before and 1 week after surgery. RESULTS: Postoperatively endothelial counts were reduced by 592.0 +/- 100.0, 275.9 +/- 51.9, 658.2 +/- 107.1, 466.3 +/- 88.6, 259.3 +/- 61.6 and 451.6 +/- 63.7 (mean cells/mm2 +/- SD) in groups 1-6, respectively. Endothelial cells in group 2 were less reduced than in group 1 (P=0.009), but there was no difference between groups 2 and 5. Though the reduction of endothelial cells in groups 4, 5, and 6 were less than in group 3 (P<0.05), group 5 showed more significant endothelial protection effect than groups 4 and 6 (P=0.009, 0.009). CONCLUSIONS: AA in irrigation solution showed endothelial protection effect against free radicals during phacoemulsification, and 1 mM was the most effective concentration. Combination of glutathione with AA did not show any synergistic endothelial protection effect.