Silibinin protects human endothelial cells from high glucose‐induced injury by enhancing autophagic response

Journal of Cellular Biochemistry - Tập 119 Số 10 - Trang 8084-8094 - 2018
Aysa Rezabakhsh1,2, Farzaneh Fathi3, Hesam Saghaei Bagheri2, Hassan Malekinejad4, Azadeh Montaseri5, Reza Rahbarghazi‬6,2, Alireza Garjani1,2
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
2Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
5Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
6Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Tóm tắt

AbstractSilibin, a flavonoid from the seeds of Silybum marianum (L.) Gaertn. (Asteraceae) has been reported to produce curative properties in diabetes. Autophagy is generated by a vast array of insults for removal of damaged proteins and organelles from the cell. Inadequate autophagy promotes endothelial cells dysfunction and delays in diabetic ulcers recovery. We hypothesized that silibinin could protect endothelial cells against high glucose‐induced damage by engaging autophagic responses. HUVECs viability was evaluated by MTT assay. The Griess method and TBARS assay were used to monitor changes in the levels of nitric oxide and malondialdehyde, respectively. ROS generation was recorded in DCFDA‐stained cells analyzed by flow cytometry. To investigate the role of silibinin on migration, we used scratch test. The level of autophagy proteins LC3, Becline‐1, and P62 were measured by Western blotting. Our data showed that silibinin had potential to increase cell survival after exposure to high glucose condition. Total levels of oxidative stress markers were profoundly reduced and the activity of GSH was increased by silibinin. High glucose suppressed HUVECs migration to the scratched area. However, a significant increase in cell migration was observed after exposure to silibinin. Autophagy was blocked at the late stage by high glucose concentration and silibinin initiated an autophagic response by reducing P62 and enhancing Beclin‐1 and LC3‐II‐LC3‐I ratio. These effects were blocked by autophagy inhibitor of 3‐Methyladenine. These observations suggest that silibinin could protect HUVECs from high glucose induced‐damage possibly by activation of autophagy pathway.

Từ khóa


Tài liệu tham khảo

Tabish SA, 2010, Is diabetes becoming the biggest epidemic of the twenty‐first century, Int J Health Sci, 1, 5

10.1056/NEJMoa0908292

10.1016/j.cmet.2012.11.012

10.2522/ptj.20080008

10.1038/cddis.2016.322

Wu SC, 2007, Foot ulcers in the diabetic patient, prevention and treatment, Vasc Health Risk Manag, 3, 65

Abcouwer SF, 2013, Angiogenic factors and cytokines in diabetic retinopathy, J Clin Cell Immunol, 1, 1

10.1093/ajcn/87.1.217S

10.1016/j.yexcr.2013.01.018

10.1146/annurev-pathol-020712-163918

10.1242/jcs.064576

10.1007/s00264-013-2037-8

10.1007/978-1-59745-157-4_4

10.1038/cdd.2010.191

10.1016/S0076-6879(08)03612-4

10.1155/2015/340838

10.2337/diaclin.27.1.4

10.2337/diacare.26.5.1589

10.3748/wjg.v17.i18.2288

10.2174/092986707779941159

10.3390/ijms16048415

10.1080/10286020.2012.657180

10.1016/j.phymed.2012.02.009

Amniattalab A, 2016, Silymarin: a novel natural agent to restore defective pancreatic β cells in streptozotocin (STZ)‐induced diabetic rats, Iran J Pharm Res, 15, 493

Malekinejad H, 2013, Paraquat exposure up‐regulates cyclooxygenase‐2 in the lungs, liver and kidneys in rats, Iran J Pharm Res, 12, 887

10.1002/hep.26179

Palomino OM, 2017, Protective effect of silybum marianum and silibinin on endothelial cells submitted to high glucose concentration, Planta Med, 83, 97

10.3390/antiox4010204

10.1111/j.1742-7843.2011.00785.x

10.1016/j.tiv.2011.09.007

10.1038/srep17663

10.1002/path.2697

10.1038/nrm2882

10.1007/s10557-013-6442-4

Thông tin
Thông tin xuất bản

Journal of Cellular Biochemistry

Tập 119 Số 10

8084-8094

Thông tin tác giả