Silymarin Reduces Retinal Microvascular Damage in Streptozotocin-induced Diabetic Rats

Overview

Journal Sci Rep

Specialty Science

Date 2022 Sep 23

PMID 36151457

Authors

Rahman Karimi

Ali Bakhshi

Parisa Dayati

Omid Abazari

Maryamsadat Shahidi

Mohamadreza Savaee

Ehsan Kafi

Mehdi Rahmanian

Seyed Morteza Naghib

Affiliations

Soon will be listed here.

Abstract

Diabetic retinopathy is a severe microvascular problem in diabetes mellitus. Silymarin is a flavonoid compound, and according to previous studies, it is a bioactive compound with potent antioxidant and anti-inflammatory properties. This investigation aims to peruse the impact of silymarin against diabetic retinopathy in streptozotocin (STZ)-provoked rats. Thirty-two adult male Wistar rats were randomly allocated into the control group, STZ group, STZ + silymarin (50 mg/kg), and STZ + silymarin (100 mg/kg). STZ rats received silymarin every day until 2 months after diabetes induction. The serum and retinal tissues were collected 2 months after silymarin treatment to determine biochemical and molecular analyses. Silymarin markedly lowered the serum glucose concentration in diabetic rats. Silymarin reduced the increased levels of advanced glycosylated end products (AGEs), the receptors for AGEs (RAGE), and reactive oxygen species (ROS) in diabetic rats. Silymarin also attenuated the phosphorylation of p38 MAP kinase and nuclear factor (NF)-κB p65 and diminished diabetes-induced overexpression of inflammatory cytokines, vascular endothelial growth factor (VEGF), adhesion molecules, and extracellular matrix proteins in STZ rats. Our data suggested that silymarin has protective effects against diabetic retinopathy, which might be related to the inhibition of the AGEs/RAGE axis and its antioxidant and anti-inflammatory activities.

Citing Articles

Investigating therapeutic efficacy of silymarin on intestinal and muscular phases of trichinellosis: an experimental study.

Waly W, Ismail M, Ghieth M, Abdel Gawad S, El-Wakil E, Abd El Wahab W J Parasit Dis. 2025; 49(1):111-120.

PMID: 39975605 PMC: 11833028. DOI: 10.1007/s12639-024-01735-6.

Impacts of Supplementation with Silymarin on Cardiovascular Risk Factors: A Systematic Review and Dose-Response Meta-Analysis.

Mohammadi S, Asbaghi O, Afrisham R, Farrokhi V, Jadidi Y, Mofidi F Antioxidants (Basel). 2024; 13(4).

PMID: 38671838 PMC: 11047742. DOI: 10.3390/antiox13040390.

Silymarin and Inflammation: Food for Thoughts.

Surai P, Surai A, Earle-Payne K Antioxidants (Basel). 2024; 13(1).

PMID: 38247522 PMC: 10812610. DOI: 10.3390/antiox13010098.

Neuroprotective effects of silymarin in 3-nitropropionic acid-induced neurotoxicity in male mice: improving behavioral deficits by attenuating oxidative stress and neuroinflammation.

Haddadi R, Eyvari-Brooshghalan S, Makhdoomi S, Fadaiie A, Komaki A, Daneshvar A Naunyn Schmiedebergs Arch Pharmacol. 2023; 397(4):2447-2463.

PMID: 37847410 DOI: 10.1007/s00210-023-02776-z.

Effect of silymarin on the relative gene expressions of some inflammatory cytokines in the liver of CCl-intoxicated male rats.

El-Kot S, Wanas W, Hafez A, Mahmoud N, Tolba A, Younis A Sci Rep. 2023; 13(1):15245.

PMID: 37710007 PMC: 10502111. DOI: 10.1038/s41598-023-42250-7.

References

Garcia-Ramirez M, Turch M, Simo-Servat O, Hernandez C, Simo R . Silymarin prevents diabetes-induced hyperpermeability in human retinal endothelial cells. Endocrinol Diabetes Nutr (Engl Ed). 2018; 65(4):200-205. DOI: 10.1016/j.endinu.2017.12.004. View

Wong T, Sabanayagam C . The War on Diabetic Retinopathy: Where Are We Now?. Asia Pac J Ophthalmol (Phila). 2019; 8(6):448-456. PMC: 6903323. DOI: 10.1097/APO.0000000000000267. View

Sahajpal N, Goel R, Chaubey A, Aurora R, Jain S . Pathological Perturbations in Diabetic Retinopathy: Hyperglycemia, AGEs, Oxidative Stress and Inflammatory Pathways. Curr Protein Pept Sci. 2018; 20(1):92-110. DOI: 10.2174/1389203719666180928123449. View

Lima T, Costa M, Figueiredo I, Inacio M, Rodrigues M, Assis R . Curcumin, Alone or in Combination with Aminoguanidine, Increases Antioxidant Defenses and Glycation Product Detoxification in Streptozotocin-Diabetic Rats: A Therapeutic Strategy to Mitigate Glycoxidative Stress. Oxid Med Cell Longev. 2020; 2020:1036360. PMC: 7260652. DOI: 10.1155/2020/1036360. View

Eleazu C, Iroaganachi M, Okafor P, Ijeh I, Eleazu K . Ameliorative Potentials of Ginger (Z. officinale Roscoe) on Relative Organ Weights in Streptozotocin induced Diabetic Rats. Int J Biomed Sci. 2013; 9(2):82-90. PMC: 3708272. View

Shabab S, Gholamnezhad Z, Mahmoudabady M . Protective effects of medicinal plant against diabetes induced cardiac disorder: A review. J Ethnopharmacol. 2020; 265:113328. DOI: 10.1016/j.jep.2020.113328. View

Xu L, Li Y, Dai Y, Peng J . Natural products for the treatment of type 2 diabetes mellitus: Pharmacology and mechanisms. Pharmacol Res. 2018; 130:451-465. DOI: 10.1016/j.phrs.2018.01.015. View

Xu J, Chen L, Yu J, Wang H, Zhang F, Liu Q . Involvement of Advanced Glycation End Products in the Pathogenesis of Diabetic Retinopathy. Cell Physiol Biochem. 2018; 48(2):705-717. DOI: 10.1159/000491897. View

Dongare S, Gupta S, Mathur R, Saxena R, Mathur S, Agarwal R . Zingiber officinale attenuates retinal microvascular changes in diabetic rats via anti-inflammatory and antiangiogenic mechanisms. Mol Vis. 2016; 22:599-609. PMC: 4898299. View

10.

Rahimi R, Karimi J, Khodadadi I, Tayebinia H, Kheiripour N, Hashemnia M . Silymarin ameliorates expression of urotensin II (U-II) and its receptor (UTR) and attenuates toxic oxidative stress in the heart of rats with type 2 diabetes. Biomed Pharmacother. 2018; 101:244-250. DOI: 10.1016/j.biopha.2018.02.075. View

11.

Wang X, Yu T, Yan Q, Wang W, Meng N, Li X . AGEs Promote Oxidative Stress and Induce Apoptosis in Retinal Pigmented Epithelium Cells RAGE-dependently. J Mol Neurosci. 2015; 56(2):449-60. DOI: 10.1007/s12031-015-0496-7. View

12.

Potilinski M, Ortiz G, Salica J, Lopez E, Acquier M, Chuluyan E . Elucidating the mechanism of action of alpha-1-antitrypsin using retinal pigment epithelium cells exposed to high glucose. Potential use in diabetic retinopathy. PLoS One. 2020; 15(2):e0228895. PMC: 7006930. DOI: 10.1371/journal.pone.0228895. View

13.

Zhang H, Shi K, Baskota A, Zhou F, Chen Y, Tian H . Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats. Eur J Pharmacol. 2014; 740:233-9. DOI: 10.1016/j.ejphar.2014.07.033. View

14.

Kheiripour N, Karimi J, Khodadadi I, Tavilani H, Goodarzi M, Hashemnia M . Silymarin prevents lipid accumulation in the liver of rats with type 2 diabetes via sirtuin1 and SREBP-1c. J Basic Clin Physiol Pharmacol. 2018; 29(3):301-308. DOI: 10.1515/jbcpp-2017-0122. View

15.

Kowluru R, Kowluru A, Veluthakal R, Mohammad G, Syed I, Santos J . TIAM1-RAC1 signalling axis-mediated activation of NADPH oxidase-2 initiates mitochondrial damage in the development of diabetic retinopathy. Diabetologia. 2014; 57(5):1047-56. PMC: 10317023. DOI: 10.1007/s00125-014-3194-z. View

16.

Shahidi M, Moradi A, Dayati P . Zingerone attenuates zearalenone-induced steroidogenesis impairment and apoptosis in TM3 Leydig cell line. Toxicon. 2022; 211:50-60. DOI: 10.1016/j.toxicon.2022.03.011. View

17.

Gillessen A, Schmidt H . Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review. Adv Ther. 2020; 37(4):1279-1301. PMC: 7140758. DOI: 10.1007/s12325-020-01251-y. View

18.

Stitt A, Curtis T, Chen M, Medina R, Mckay G, Jenkins A . The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res. 2015; 51:156-86. DOI: 10.1016/j.preteyeres.2015.08.001. View

19.

Yamamoto T, Kase S, Murata M, Ishida S . Serum advanced glycation end-products and αB-crystallin in diabetic retinopathy patients. Biomed Rep. 2022; 16(4):28. PMC: 8889544. DOI: 10.3892/br.2022.1511. View

20.

Zor T, SELINGER Z . Linearization of the Bradford protein assay increases its sensitivity: theoretical and experimental studies. Anal Biochem. 1996; 236(2):302-8. DOI: 10.1006/abio.1996.0171. View