Effects of silymarin on angiogenesis and oxidative stress in streptozotocin-induced diabetes in mice

Abstract

The present study evaluated the effects of acute treatment with silymarin, an extract that is obtained from Silybum marianum, on angiogenesis, oxidative stress, and inflammation in normoglycemic and diabetic mice. Diabetes was induced by streptozotocin (80 mg/kg, intraperitoneal) in male Swiss mice, 6 weeks of age. A polyether-polyurethane sponge was surgically implanted in the back of the mice as a model of healing in both diabetic and normoglycemic animals that were treated with oral silymarin or water for 10 days. The pancreas, liver, kidneys, blood, and sponges were collected and analyzed. Diabetes led to impairments of antioxidant defenses, reflected by a reduction of pancreatic superoxide dismutase and hepatic and renal catalase and an increase in pancreatic lipoperoxidation. An inflammatory process was observed in diabetic mice, reflected by an increase in pancreatic tumor necrosis factor α (TNF-α) and the infiltration of inflammatory cells in islets. The number of vessels was lower in the implanted sponges in diabetic mice. Silymarin treatment attenuated this damage, restoring antioxidant enzymes and reducing pancreatic TNF-α and inflammatory infiltration. However, silymarin treatment did not restore angiogenesis or glycemia. In conclusion, treatment with silymarin red uced oxidative stress and inflammation that were induced in the model of streptozotocin-induced diabetes in several organs, without apparent toxicity. Silymarin may be a promising drug for controlling diabetic complications.

Herbal antioxidants and renal ischemic-reperfusion injury; an updated review

“…Silymarin is a polyphenolic compound extracted from Silybum marianum plant. Several in vivo experimental models of diabetes and drug induced nephrotoxicity have investigated the effects of silymarin (69,70). Treatment with silymarin could reduce NO level, protein carbonyl and serum and tissue MDA in RIR rats indicating its antioxidant property against RIR (11).…”

Silymarin reduces retinal microvascular damage in streptozotocin-induced diabetic rats

“…The antioxidant activity of silymarin is probably due to its polyphenol and flavonoid constituents. Stolf et al illustrated that the administration of silymarin controlled diabetic complications in the pancreas, kidneys, and liver of STZ-induced mice by alleviating the inflammatory responses and improving the antioxidant defenses 15 . In another experimental study, Goli and her co-workers elucidated that total oxidant and malondialdehyde in the diabetic rats treated with silymarin were dramatically reduced 54 .…”

“…It has been shown that silymarin could effectively improve glucose and lipid profiles, scavenge ROS, and inhibit the production of proinflammatory cytokines in diabetic rats 14 – 16 . Thus, silymarin may be useful for controlling diabetic complications 15 . Previously, the effect of silymarin has been reported on the vascular leakage of human retinal endothelial cells 17 .…”

Effect of Cucumis sativus on Dysfunctional 3T3-L1 Adipocytes

“…Once adipocyte dysfunction was established as described below, five concentrations (5, 10, 20, 40, or 80 μg/mL) of the three Aq-Cs SFs (SF1, SF2, and SF3) were added to the culture and allowed to stand for 24 h. Either silymarin (50 μg/mL) 50,51 or metformin (1 mM) 52,53 were used as positive controls; previous reports have employed these molecules as standard drug: for silymarin as control of oxidative stress and the inflammatory condition induced by the presence of IL-1β 45,46 . For Metformin it was used as control of glucose consumption and the accumulation of lipids in adipocytes, functions that were affected by the presence of dexamethasone 27–30 .…”

“…To assess the effect of Aq-Cs SFs on cell viability 4 , mature adipocytes were incubated for 24 h in the presence of different concentrations of the three Aq-Cs SFs (5, 10, 20, 40, or 80 μg/mL) diluted in DMEM plus 10% FBS and insulin (1.0 μg/mL). Additionally, silymarin (50 μg/mL) 50,51 , metformin (1 nM) 52,53 , or DMSO (60%) were used as controls. After 24 h, the cells were incubated with 5 mg/mL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) at 37 C for 4 h. After incubation, 100 μL of 10% SDS-HCl 0.01 N (1:1) were added to each well, and the plates were incubated for 2 h at 37 °C.…”