Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Silymarin Inhibits Cell Cycle Progression and Mtor Activity in Activated Human T Cells: Therapeutic Implications for Autoimmune Diseases Publisher Pubmed



Gharagozloo M1 ; Javid EN1 ; Rezaei A1 ; Mousavizadeh K2
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Basic Medical Sciences, Research Institute for Islamic and Complementary Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Basic and Clinical Pharmacology and Toxicology Published:2013


Abstract

Silymarin, a complex flavonolignan from the 'milk thistle' (Silybum marianum) plant, exhibits anticarcinogenic, anti-inflammatory and cytoprotective effects. Several reports have demonstrated immunosuppressive activity of silymarin; however, the molecular mechanisms involved in immunomodulatory activities of silymarin are not fully understood yet. In this study, the effect of silymarin on cell cycle and PI3K/Akt/mTOR signalling pathway of activated T lymphocytes was investigated in vitro. Peripheral blood mononuclear cells (PBMC) were isolated from healthy volunteers and activated with anti-CD3 (5 μg/ml) and anti-CD28 (2 μg/ml) monoclonal antibodies. Cells were cultured in Complete RPMI medium with 10, 50 and 100 μM silymarin or dimethyl sulphoxide (DMSO) and incubated for 24-96 hrs. Cell cycle analysis was performed by PI staining and flow cytometry. The effect of silymarin on PI3K/AKT signalling pathway and mTOR activity was determined in activated T cells after 72-hr incubation with silymarin or DMSO. A significant G1 arrest in cell cycle of activated T lymphocytes was found after 96-hr incubation with 100 μM silymarin without causing cell death. Silymarin also significantly inhibited the level of phospho-S6 ribosomal protein and mTOR activity in cell lysates of activated T cells after 72-hr incubation in comparison with DMSO. This study shows that silymarin inhibits cell proliferation through G1 cell cycle arrest and also through the suppression of the mTOR signalling pathway in human activated T lymphocytes in vitro. Characterizing molecular mechanism of such immunomodulatory effects may have a great potential in future practical application of silymarin in transplantation and auoimmunity. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.
Related Docs
View other Related Docs
1. Assessment of Pi3k/Akt Signaling Pathway in Activated Human T Lymphocytes in Vitro, Journal of Isfahan Medical School (2012)
2. Silymarin Impacts on Immune System As an Immunomodulator: One Key for Many Locks, International Immunopharmacology (2017)
3. The Effect of Silymarin on the Proliferating of the Activated Human T Cells in Vitro, Journal of Isfahan Medical School (2014)
4. Immunosuppressive Effect of Silymarin on Mitogen-Activated Protein Kinase Signalling Pathway: The Impact on T Cell Proliferation and Cytokine Production, Basic and Clinical Pharmacology and Toxicology (2013)
5. Silymarin Suppress Cd4+ T Cell Activation and Proliferation: Effects on Nf-Κb Activity and Il-2 Production, Pharmacological Research (2010)
6. Immunoregulatory Effects of Silymarin on Proliferation and Activation of Th1 Cells Isolated From Newly Diagnosed and Ifn-ß 1B -Treated Ms Patients, Inflammation (2019)
7. Comparing In-Vitro Effects of Two Immunosuppressive Drugs on the Expression of Foxp3 From Naive Cd4+ T Cells, Journal of Isfahan Medical School (2015)
8. Immunomodulatory Effects of Silymarin in Patients With Β-Thalassemia Major, International Immunopharmacology (2013)
Experts (# of related papers)
View all Related Experts
Nafiseh Esmaeil (6)
Nahid Eskandari (5)
Other Related Docs
9. Inhibition of Apoptosis and Proliferation in T Cells by Immunosuppressive Silymarine, Iranian Journal of Allergy, Asthma and Immunology (2017)
10. The Effect of Silymarin on the Expression of Chemokine Receptors in T Helper 1 (Th1) Cells, Journal of Isfahan Medical School (2014)
11. Expression of Nkg2d Receptors in Cd3+And Cd56+Cells in Blood Samples of Pre-Eclampsia Patients and the Effect of Silymarin on Their Activity in Vitro, Journal of Isfahan Medical School (2022)
12. Evaluating the Safety and Efficacy of Silymarin in Β-Thalassemia Patients: A Review, Hemoglobin (2015)
13. The Favorable Impacts of Silibinin Polyphenols As Adjunctive Therapy in Reducing the Complications of Covid-19: A Review of Research Evidence and Underlying Mechanisms, Biomedicine and Pharmacotherapy (2022)
14. Promising Effect of Rapamycin on Multiple Sclerosis, Multiple Sclerosis and Related Disorders (2018)
15. The Effects of Silymarin and Cyclosporine a on the Proliferation and Cytokine Production of Regulatory T Cells, Immunological Investigations (2019)
16. Combined Therapy of Silymarin and Desferrioxamine in Patients With Β-Thalassemia Major: A Randomized Double-Blind Clinical Trial, Fundamental and Clinical Pharmacology (2009)
17. The Influence of Iron Loading and Iron Chelation on the Proliferation and Telomerase Activity of Human Peripheral Blood Mononuclear Cells, Iranian Journal of Immunology (2009)
18. The Effects of Herbal Medicines on Cancer Therapy-Induced Oral Mucositis: A Literature Review, Phytotherapy Research (2022)
19. Preparation and Characterisation of a New Form of Silymarin As a Potential Antidiabetic Agent in the Adult Male Rat, Archives of Physiology and Biochemistry (2023)
20. The Significant Impact of Apigenin on Different Aspects of Autoimmune Disease, Inflammopharmacology (2018)
21. Effect of Herbal Cream Containing Fumaria Officinalis and Silymarin for Treatment of Eczema: A Randomized Double-Blind Controlled Clinical Trial, Avicenna Journal of Phytomedicine (2022)
22. The Influence of Fructose, Glucose and Sucrose on Flavonolignans Formation in Silybum Marianum Callus Culture, Journal of Medicinal Plants (2008)
23. Immunomodulatory Effects of Flavonoids: Possible Induction of T Cd4+ Regulatory Cells Through Suppression of Mtor Pathway Signaling Activity, Frontiers in Immunology (2019)
24. Effects of Silybum Marianum on Patients With Chronic Hepatitis C, Journal of Research in Medical Sciences (2011)
25. Silymarin Restores Regulatory T Cells (Tregs) Function in Multiple Sclerosis (Ms) Patients in Vitro, Inflammation (2019)
26. Preventive Effect of Novel Nanomissile of Silymarin on Liver Injury Induced by Carbon Tetrachloride in Rat, Scientific Journal of Kurdistan University of Medical Sciences (2021)
27. Serum Levels of Tgfβ, Il-10, Il-17, and Il-23 Cytokines in Β-Thalassemia Major Patients: The Impact of Silymarin Therapy, Immunopharmacology and Immunotoxicology (2014)