Retinoprotective Effects Of Crocin And Crocetin via Anti-Angiogenic Mechanism in High Glucose-Induced Human Retinal Pigment Epithelium Cells

Title:Retinoprotective Effects Of Crocin And Crocetin via Anti-Angiogenic Mechanism in High Glucose-Induced Human Retinal Pigment Epithelium Cells

Volume: 14

Author(s): Samaneh Sepahi, Zahra-Soheila Soheili , Jalil Tavakkol-Afshari , Soghra Mehri, Seyedeh M. Hosseini, Seyed A. Mohajeri*Elham Khodaverdi *

Affiliation:

• Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad,Iran

• Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad,Iran

Keywords: Diabetic retinopathy, crocin, crocetin, VEGF, MMP-2, MMP-9, Anti-angiogenesis.

Abstract:

Background: Diabetic retinopathy (DR) is one of the most common side effects of diabetes. We aimed to investigate the effects of crocin and crocetin (as a deglycosylated form of crocin in blood stream) in gene expression or protein levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor-receptor1 (VEGFR-1), matrix metalloproteinases2 (MMP-2), matrix metalloproteinases9 (MMP-9) and thrombospondin-2 (TSP-2) in high glucose cell culture media.

Methods: The retinal pigment epithelium (RPE) cells were exposed to high glucose (HG, 30 mM glucose concentration) and normal glucose (NG, 24.5 mM mannitol + 5.5 mM glucose) for six days. RPE cells were treated in four treatment groups (crocin, crocetin, Bevacizumab, and crocin + Bevacizumab). Gene expressions were measured using quantitative real-time PCR, and protein levels were evaluated by western blot.

Results: Findings showed that VEGF gene expression and protein level significantly decreased in all treatment groups. In addition, reduction in VEGFR1 gene expression was significantly higher in Bevacizumab and crocin + Bevacizumab groups than other groups. Only crocin and crocetin could reduce the gene levels of MMP-2 and MMP-9. In addition, TSP-2 protein levels increased when HG cells were exposed to crocin or crocin + Bevacizumab groups.

Conclusion: Our data showed that crocin and crocetin have anti-VEGF function similar to Bevacizumab, act as an anti-angiogenic agent. Also, crocin and crocetin could decrease MMP-2 and MMP-9 gene levels being inflammatory and angiogenesis factors. As a result, crocin and crocetin have protective effects against angiogenesis and inflammation in DR.

Cite this article as:

Sepahi Samaneh , Soheili Zahra-Soheila , Tavakkol-Afshari Jalil , Mehri Soghra , Hosseini M. Seyedeh , Mohajeri A. Seyed *, Khodaverdi Elham *, Retinoprotective Effects Of Crocin And Crocetin via Anti-Angiogenic Mechanism in High Glucose-Induced Human Retinal Pigment Epithelium Cells, Current Molecular Pharmacology 2021; 14 (5) : e200421192921 . https://dx.doi.org/10.2174/1874467214666210420111232