Skip to main content
SpringerLink
Log in

Aqueous extracts of Tribulus terrestris protects against oxidized low-density lipoprotein-induced endothelial dysfunction

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate the role of aqueous extracts of Tribulus terrestris (TT) against oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) dysfunction in vitro.

Methods

HUVECs were pre-incubated for 60 min with TT (30 and 3 μg/mL respectively) or 10-5 mol/L valsartan (as positive controls) and then the injured endothelium model was established by applying 100 μg/mL ox-LDL for 24 h. Cell viability of HUVECs was observed by real-time cell electronic sensing assay and apoptosis rate by Annexin V/PI staining. The cell migration assay was performed with a transwell insert system. Cytoskeleton remodeling was observed by immunofluorescence assay. The content of endothelial nitric oxide synthase (eNOS) was measured by enzyme-linked immunosorbent assay. Intracellular reactive oxygen species (ROS) generation was assessed by immunofluorescence and flow cytometer. Key genes associated with the metabolism of ox-LDL were chosen for quantitative real-time polymerase chain reaction to explore the possible mechanism of TT against oxidized LDL-induced endothelial dysfunction.

Results

TT suppressed ox-LDL-induced HUVEC proliferation and apoptosis rates significantly (41.1% and 43.5% after treatment for 3 and 38 h, respectively; P<0.05). It also prolonged the HUVEC survival time and postponed the cell's decaying stage (from the 69th h to over 100 h). According to the immunofluorescence and transwell insert system assay, TT improved the endothelial cytoskeletal network, and vinculin expression and increased cell migration. Additionally, TT regulated of the synthesis of endothelial nitric oxide synthase and generation of intracellular reactive oxygen species (P<0.05). Both 30 and 3 μg/mL TT demonstrated similar efficacy to valsartan. TT normalized the increased mRNA expression of PI3Kα and Socs3. It also decreased mRNA expression of Akt1, AMPKα1, JAK2, LepR and STAT3 induced by ox-LDL. The most notable changes were JAK2, LepR, PI3Kα, Socs3 and STAT3.

Conclusions

TT demonstrated potential lowering lipid benefits, anti-hypertension and endothelial protective effects. It also suggested that the JAK2/STAT3 and/or PI3K/AKT pathway might be a very important pathway which was involved in the pharmacological mechanism of TT as the vascular protective agent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schächinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse longterm outcome of coronary heart disease. Circulation 2000;101:1899–1906.

    Article  PubMed  Google Scholar 

  2. Bugiardini R, Manfrini O, Pizzi C, Fontana F, Morgagni G. Endothelial function predicts future development of coronary artery disease: a study of women with chest pain and normal coronary angiograms. Circulation 2004;109:2518–2523.

    Article  PubMed  Google Scholar 

  3. Liu S, Shen H, Xu M, Liu O, Zhao L, Guo Z, Du J. FRP inhibits ox-LDL-induced endothelial cell apoptosis through an Akt-NF-kappaB-Bcl-2 pathway and inhibits endothelial cell apoptosis in an apoE-knockout mouse model. Am J Physiol Endocrinol Metab 2010;299:E351–363.

    Article  CAS  PubMed  Google Scholar 

  4. Monika S, Susanne HK. Phytochemicals in fruit and vegetables: health promotion and postharvest elicitors. Crit Rev Plant Sci 2006;25:267–278.

    Article  Google Scholar 

  5. Hempel SL, Buettner GR, O'Malley YQ, Wessels DA, Flaherty DM. Dihydrofluorescein diacetate is superior for detecting intracellular oxidants: comparison with 2',7'-dic hlorodihydrofluorescein diacetate, 5(and 6)-carboxy-2',7'- dichlorodihydrofluorescein diacetate, and dihydrorhodamine 123. Free Radic Biol Med 1999;27: 146–159.

    Article  CAS  PubMed  Google Scholar 

  6. Chang L, and Karin M. Mammalian MAP kinase signalling cascades. Nature 2001;410(6824):37–40.

    Article  CAS  PubMed  Google Scholar 

  7. Yamamoto K, Hamada H, Shinkai H, Kohno Y, Koseki H, Aoe T. The KDEL receptor modulates the endoplasmic reticulum stress response through mitogen-activated protein kinase signaling cascades. J Biol Chem 2003;278:34525–34532.

    Article  CAS  PubMed  Google Scholar 

  8. Mehta D1, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev 2006;86:279–367.

    Article  CAS  PubMed  Google Scholar 

  9. Izard T, Evans G, Borgon RA, Rush CL, Bricogne G, Bois PR. Vinculin activation by talin through helical bundle conversion. Nature 2004;427:171–175.

    Article  CAS  PubMed  Google Scholar 

  10. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol: Lung Cell Molecul Physiol 2000;279:L1005–L1028.

    CAS  Google Scholar 

  11. Shaul PW. Endothelial nitric oxide synthase, caveolae and the development of atherosclerosis. J Physiol 2003;547:21–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Bolz SS, Vogel L, Sollinger D, Derwand R, de Wit C, Loirand G, et al. Nitric oxide-induced decrease in calcium sensitivity of resistance arteries is attributable to activation of the myosin light chain phosphatase and antagonized by the RhoA/Rho kinase pathway. Circulation 2003;107:3081–3087.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China

    Yue-hua Jiang  (姜月华), Chuan-hua Yang  (杨传华), Wei Li  (李 伟), Xian-qing Meng  (孟宪卿) & Dong-na Li  (李东娜)

  2. Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China

    Sai Wu  (吴 赛)

Authors
  1. Yue-hua Jiang  (姜月华)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chuan-hua Yang  (杨传华)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Li  (李 伟)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sai Wu  (吴 赛)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xian-qing Meng  (孟宪卿)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dong-na Li  (李东娜)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chuan-hua Yang  (杨传华).

Additional information

Supported by the Development Plan Project of Science and Technology of Shandong Province (No. 2014GSF119011) and Shandong Province 'Taishan Scholar' Construction Project (No. 2012-55)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, Yh., Yang, Ch., Li, W. et al. Aqueous extracts of Tribulus terrestris protects against oxidized low-density lipoprotein-induced endothelial dysfunction. Chin. J. Integr. Med. 22, 193–200 (2016). https://doi.org/10.1007/s11655-015-2321-0

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-015-2321-0

Keywords

Search

Navigation