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      Vascular protective effects of aqueous extracts of Tribulus terrestris on hypertensive endothelial injury

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          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.

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          Most cited references 10

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          The KDEL receptor modulates the endoplasmic reticulum stress response through mitogen-activated protein kinase signaling cascades.

          The accumulation of misfolded proteins in the endoplasmic reticulum (ER) evokes the ER stress response. The resultant outcomes are cytoprotective but also proapoptotic. ER chaperones and misfolded proteins exit to the secretory pathway and are retrieved to the ER, during which process the KDEL receptor plays a significant role. Using an expression of a mutant KDEL receptor that lacks the ability for ligand recognition, we show that the impairment of retrieval by the KDEL receptor led to a mis-sorting of the immunoglobulin-binding protein BiP, an ER chaperone that has a retrieval signal from the early secretory pathway, which induced intense ER stress response and an increase in susceptibility to ER stress in HeLa cells. Furthermore, we show that the ER stress response accompanied the activation of p38 mitogen-activated protein (MAP) kinases and c-Jun amino-terminal kinases (JNKs) and that the expression of the mutant KDEL receptor suppressed the activation of p38 and JNK1 but not JNK2. The effect of the expression of the mutant KDEL receptor was consistent with the effect of a specific inhibitor for p38 MAP kinases, because the inhibitor sensitized HeLa cells to ER stress. We also found that activation of the KDEL receptor by the ligand induced the phosphorylation of p38 MAP kinases. These results indicate that the KDEL receptor participates in the ER stress response not only by its retrieval ability but also by modulating MAP kinase signaling, which may affect the outcomes of the mammalian ER stress response.
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            Phytopharmacological overview of Tribulus terrestris

            Tribulus terrestris (family Zygophyllaceae), commonly known as Gokshur or Gokharu or puncture vine, has been used for a long time in both the Indian and Chinese systems of medicine for treatment of various kinds of diseases. Its various parts contain a variety of chemical constituents which are medicinally important, such as flavonoids, flavonol glycosides, steroidal saponins, and alkaloids. It has diuretic, aphrodisiac, antiurolithic, immunomodulatory, antidiabetic, absorption enhancing, hypolipidemic, cardiotonic, central nervous system, hepatoprotective, anti-inflammatory, analgesic, antispasmodic, anticancer, antibacterial, anthelmintic, larvicidal, and anticariogenic activities. For the last few decades or so, extensive research work has been done to prove its biological activities and the pharmacology of its extracts. The aim of this review is to create a database for further investigations of the discovered phytochemical and pharmacological properties of this plant to promote research. This will help in confirmation of its traditional use along with its value-added utility, eventually leading to higher revenues from the plant.
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              Elevated blood pressure in adolescent boys predicts endothelial dysfunction: the cardiovascular risk in young Finns study.

              Hypertension is a major risk factor for atherosclerosis. It may cause or be a consequence of endothelial dysfunction. We studied whether systolic blood pressure measured in childhood and adolescence predicts endothelial-dependent brachial flow-mediated dilation (FMD) in adulthood. Brachial FMD was measured in 2109 white adults, aged 24 to 39 years, in the 21-year follow-up of the Cardiovascular Risk in Young Finns Study. These subjects have risk factor data available dating back to their childhood (baseline in 1980, ages 3 to 18 years). In male subjects, the level of systolic blood pressure measured in adolescence (at ages 12 to 18 years at baseline) was inversely related to adulthood FMD (P=0.004). This association was independent of brachial diameter and other childhood (P=0.003) and adulthood risk factors, including blood pressure (P=0.03). Childhood (age 3 to 9 years at baseline) systolic blood pressure did not correlate with adult FMD in men or in women (P always >0.2). In male subjects, elevated systolic blood pressure in adolescence predicts impaired brachial endothelial function 21 years later in adulthood. This association is independent of other childhood and adulthood cardiovascular risk factors suggesting that blood pressure elevation in adolescence may have an influence on biological processes that regulate endothelium-dependent flow-mediated vasodilatation capacity.
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                Author and article information

                Journal
                CJNM
                Chinese Journal of Natural Medicines
                Elsevier
                1875-5364
                20 August 2017
                : 15
                : 8
                : 606-614
                Affiliations
                1Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China
                2Shandong University of Traditional Chinese Medicine, Jinan 250355, China
                3Qingdao Hiser medical group, Qingdao 266034, China
                Author notes
                *Corresponding author: YANG Chuan-Hua, E-mail: yang_chuanhua@ 123456hotmail.com

                These authors have no conflict of interest to declare.

                Article
                S1875-5364(17)30088-2
                10.1016/S1875-5364(17)30088-2
                28939023
                Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
                Funding
                Funded by: Shandong Province ‘Taishan Scholar’ Construction Project Funds
                Award ID: 2012-55
                Funded by: National Natural Science Foundation of China
                Award ID: 81573916
                This work was supported by Shandong Province ‘Taishan Scholar’ Construction Project Funds (No. 2012-55) and the National Natural Science Foundation of China (No. 81573916).

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