Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats

Zhang, Hongtao; Shi, Kai Hu; Baskota, Attit; Zhou, Fangli; Chen, Yaxi; Tian, Haoming

doi:10.1016/j.ejphar.2014.07.033

Cited by 28 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We detected the expression levels of two inflammation markers simultaneously, including chemotactic factor ICAM-1 and cytokine TNF-α. ICAM-1 and its ligand CD18 play an important role in mediating leukocyte adhesion 27 , and inhibition of ICAM-1 results in significant mitigation of leukocyte adhesion and vasopermeability 28 . Expression of TNF-α is also upregulated in the retina under DR conditions 29 .…”

Section: Discussionmentioning

confidence: 99%

Suppression of diabetic retinopathy with GLUT1 siRNA

You

Zhang

Shi

et al. 2017

Sci Rep

View full text Add to dashboard Cite

To investigate the effect of glucose transporter-1 (GLUT1) inhibition on diabetic retinopathy, we divided forty-eight mice into scrambled siRNA, diabetic scrambled siRNA, and GLUT1 siRNA (intravitreally injected) groups. Twenty-one weeks after diabetes induction, we calculated retinal glucose concentrations, used electroretinography (ERG) and histochemical methods to assess photoreceptor degeneration, and conducted immunoblotting, leukostasis and vascular leakage assays to estimate microangiopathy. The diabetic scrambled siRNA and GLUT1 siRNA exhibited higher glucose concentrations than scrambled siRNA, but GLUT1 siRNA group concentrations were only 50.05% of diabetic scrambled siRNA due to downregulated GLUT1 expression. The diabetic scrambled siRNA and GLUT1 siRNA had lower ERG amplitudes and ONL thicknesses than scrambled siRNA. However, compared with diabetic scrambled siRNA, GLUT1 siRNA group amplitudes and thicknesses were higher. Diabetic scrambled siRNA cones were more loosely arranged and had shorter outer segments than GLUT1 siRNA cones. ICAM-1 and TNF-α expression levels, adherent leukocyte numbers, fluorescence leakage areas and extravasated Evans blue in diabetic scrambled siRNA were higher than those in scrambled siRNA. However, these parameters in the GLUT1 siRNA were lower than diabetic scrambled siRNA. Together, these results demonstrate that GLUT1 siRNA restricted glucose transport by inhibiting GLUT1 expression, which decreased retinal glucose concentrations and ameliorated diabetic retinopathy.Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM). DR often results in decreased vision and even blindness caused by macular edema, retinal detachment, and vitreous hemorrhage. The number of patients with diabetes may grow to 642 million in 2040 1 . DR has been recognized as a microangiopathy, as well as a neurodegenerative disease. Although the detailed mechanism underlying DR is unclear, two major global multicenter studies on diabetes, DCCT 2 and UKPDS 3 , have revealed that a long-term high blood glucose level is the decisive factor for DR development. Moreover, excessive generation of retinal oxidative stress products 4 , activated protein kinase C 5 , and increased synthesis of glycosylated end products 6 under the environment of high blood glucose levels initiate the impairment of retinal tissues and cells 4 . Since lesions are induced by high blood glucose levels, we hypothesize that DR progression can be relieved by restricting glucose transfer into the retina, thereby decreasing its local glucose content. Glucose transporter-1 (GLUT1) is the only currently known carrier of glucose through the blood-retinal barrier and is also responsible for the distribution of glucose in ganglion cells, photoreceptor cells, and Müller cells in the retina; GLUT1 is primarily expressed in the vascular endothelial cells of the inner blood-retinal barrier and retinal pigment epithelial cells of the outer blood-retinal barrier 7 . GLUT1 was identified as a promising target...

show abstract

Section: Discussionmentioning

confidence: 99%

Suppression of diabetic retinopathy with GLUT1 siRNA

You

Zhang

Shi

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Silybin was administered for 22 weeks (Table ). This treatment prevented the obliteration of retinal capillaries and reduced leukostasis and retinal intercellular adhesion molecule‐1 (ICAM‐1) in experimental diabetes (Zhang et al ., ). The authors concluded that silybin prevented vascular retinal damage, which at least partially occurred as a consequence of a reduction of ICAM molecules and leukostasis.…”

Section: Retinopathymentioning

confidence: 97%

“…In addition to label indications, many studies have reported the beneficial effects of silymarin for the treatment of several diseases (Fig. ), including sepsis (Kang et al ., ; Toklu et al ., ), burns (Toklu et al ., ), osteoporosis (Kim et al, ; Mohd Fozi et al ., ), arthritis (Gupta et al ., ), hypercholesterolemia (Krecman et al, ; Skottova and Krecman, ), cancer (Singh et al, ; Bosch‐Barrera and Menendez, ; Scavo et al, ; Yurtcu et al, ), viral infections (Lani et al, ), diabetes (Malekinejad et al , ; Soto et al , ; Zhang et al , ; Ebrahimpour Koujan et al , ), Alzheimer's disease (Duan et al, ; Kumar et al, ), and Parkinson's disease (Haddadi et al, ; Lee et al, ). Silymarin treatment likewise attenuated the severity of radiotherapy‐induced mucositis in a clinical trial (Elyasi et al , ).…”

Section: Silymarinmentioning

confidence: 99%

Effects of Silymarin on Diabetes Mellitus Complications: A Review

2017

View full text Add to dashboard Cite

Diabetes mellitus is a common metabolic disorder that is caused by a deficit in the production of (type 1) or response to (type 2) insulin. Diabetes mellitus is characterized by a state of chronic hyperglycemia and such symptoms as weight loss, thirst, polyuria, and blurred vision. These disturbances represent one of the major causes of morbidity and mortality nowadays, despite available treatments, such as insulin, insulin secretagogues, insulin sensitizers, and oral hypoglycemic agents. However, many efforts have been made to discover new drugs for diabetes treatment, including medicinal plant extracts. Silymarin is a powder extract of the seeds from Silybum marianum, a plant from the Asteraceae family. The major active ingredients include four isomers: silybin, isosilybin, silychristin, and silydianin. Silymarin is indicated for the treatment of hepatic disorders, such as cirrhosis, chronic hepatitis, and gallstones. Moreover, several studies of other pathologies, including diabetes, sepsis, osteoporosis, arthritis, hypercholesterolemia, cancer, viral infections, and Alzheimer's and Parkinson's diseases, have tested the effects of silymarin and reported promising results. This article reviews data from clinical, in vivo, and in vitro studies on the use of silymarin, with a focus on the complications of diabetes, including nephropathy, neuropathy, healing delays, oxidative stress, hepatotoxicity, and cardiomyopathy. Copyright © 2017 John Wiley & Sons, Ltd.

show abstract

“…Silibin decreases ADMA levels in db/db mice to a level that is lower than in their heterozygous lean counterparts (db/m), which served as controls [17]. In experimentally induced diabetic retinopathy, silibin seems to have a favorable effect as vascular leukostasis and levels of retinal ICAM-1 are significantly reduced [18].…”

Section: Animal In Vivo Studiesmentioning

confidence: 99%

The Therapeutic Potential of Milk Thistle in Diabetes

Kazazis¹,

Evangelopoulos²,

Kollas³

et al. 2014

Rev Diabet Stud

View full text Add to dashboard Cite

■ AbstractMilk thistle has been known for more than 2.000 years as a herbal remedy for a variety of disorders. It has mainly been used to treat liver and gallbladder diseases. Silibum marianum, the Latin term for the plant, and its seeds contain a whole family of natural compounds, called flavonolignans. Silimarin is a dry mixture of these compounds; it is extracted after processing with ethanol, methanol, and acetone. Silimarin contains mainly silibin A, silibin B, taxifolin, isosilibin A, isosilibin B, silichristin A, silidianin, and other compounds in smaller concentrations. Apart from its use in liver and gallbladder disorders, milk thistle has recently gained attention due to its hypoglycemic and hypolipidemic properties. Recently, a substance from milk thistle has been shown to possess peroxisome proliferator-activated receptor γ (PPARγ) agonist properties. PPARγ is the molecular target of thiazolidinediones, which are used clinically as insulin sensitizers to lower blood glucose levels in diabetes type 2 patients. The thiazolidinedione type of PPARγ ligands is an agonist with a very high binding affinity. However, this ligand type demonstrates a range of undesirable side effects, thus necessitating the search for new effective PPARγ agonists. Interestingly, studies indicate that partial agonism of PPARγ induces promising activity patterns by retaining the positive effects attributed to the full agonists, with reduced side effects. In this review, the therapeutic potential of milk thistle in the management of diabetes and its complications are discussed.

show abstract

Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats

Cited by 28 publications

References 32 publications

Suppression of diabetic retinopathy with GLUT1 siRNA

Suppression of diabetic retinopathy with GLUT1 siRNA

Effects of Silymarin on Diabetes Mellitus Complications: A Review

The Therapeutic Potential of Milk Thistle in Diabetes

Contact Info

Product

Resources

About