Evaluating the Role of Silymarin in Coordinating the Relationship between Inflammation and Thrombosis by Affecting Endothelial Cells

Roya  Sharifi; Minoo  Shahidi; Fatemeh  Sadeghi Shirazi; Fereshteh Parhizkary; Mahmood  Barati; Farhad  Zaker; Kazem  Mosavizadeh

doi:10.18502/ijpho.v14i4.16601

Roya Sharifi Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences Tehran, Iran
Minoo Shahidi Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
Fatemeh Sadeghi Shirazi Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
Fereshteh Parhizkary Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
Mahmood Barati Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
Farhad Zaker Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
Kazem Mosavizadeh Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijpho.v14i4.16601

Keywords: Factor VIII (FVIII), Inflammation, Silymarin, Von Willebrand factor (VWF)

Abstract

Background: A widespread crosstalk between inflammation and coagulation has been shown in numerous studies. This suggests that coagulation can trigger an inflammatory response which ultimately leads to coagulation activation. Previous research has shown that polyphenols can affect blood pressure and endothelial dysfunction, resulting in reduced risk of cardiovascular diseases. This study aimed to investigate whether Silymarin, a ﬂavonolignans, could play a role in the interaction between inflammation and coagulation by influencing endothelial cells.

Materials and Methods: In this experimental study, human umbilical vein endothelial cells (HUVECs) were seeded with and without various concentrations of silymarin. In vivo, treatment with silymarin was also carried out. Coagulative and fibrinolytic factors, including Von Willebrand factor (VWF) and Factor VIII (FVIII), tissue plasminogen activator-1 (TPA-1), and inflammatory factors, including interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-α), were evaluated by flow cytometry, Real-Time Polymerase Chain Reaction (qPCR), Enzyme-Linked Immunosorbent Assay (ELISA) and Immunocytochemistry (ICC).

Results: Silymarin increased the gene expression, release, and storage of VWF while diminishing the gene expression, release, and storage of TPA-1 (P ˂ 0.05). The activity of FVIII was dramatically increased, and IL-8 and TNF-α levels were augmented. The in vivo study also indicated an elevated plasma level of VWF and IL-8 by silymarin administration.

Conclusion: The results showed that, although silymarin reduces inflammatory factors, it can affect coagulation factors by increasing the levels of VWF and FVIII activity and inhibiting TPA-1 production, thereby making thrombosis probable. Consequently, it is advisable to prescribe this medication with caution for individuals who are susceptible to thrombotic events.