Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice

Abstract

Context: Silymarin is the main flavonoid extracted from milk thistle, which has been used to treat liver diseases. Objective: The in vivo effect of silymarin on HFD-induced insulin resistance and fatty liver in mice was studied. Materials and methods: Male C57BL/6 mice were fed with high-fat diet (HFD) to induce obesity and insulin resistance and treated with 30, 60 mg/kg silymarin for 18 days. Food intake, body weight and the content/histology of epididymal fat and liver tissue were examined; the content of lipids, AST, ALT and inflammatory cytokines in serum were estimated. Results: Administration of silymarin caused bodyweight loss in diet induced obesity (DIO) mice (HFD group: 47.7 g, 60 mg/kg group: 43.0 g) while the food intake remain unchanged. Silymarin (60 mg/kg) significantly reduced the epididymal fat mass (from 1.75 g to 1.12 g). Elevated plasma lipids (TC 6.1 mM, TG 1.3 mM, LDL 1.2 mM) in DIO mice were all suppressed by silymarin (TC 4.5 mM, TG 0.89 mM, LDL 0.9 mM), as well as insulin (5.1 ng/ml in HFD group to 2.0 ng/ml (60 mg/kg silymarin). Examination of cytokine levels (TNF-a, IL-1b and IL-6) in each group proved that silymarin treatment significantly decreased inflammation in DIO mice. Finally, silymarin effectively protected liver from HFD-induced injury as evidenced by decreasing histological damage and reducing ALT and AST levels, as follows: ALT; 47.4 U/L in HFD group to 28.4 U/L (60 mg/kg silymarin); AST; 150.1 U/L in HFD group to 88.1 U/L (60 mg/kg silymarin) in serum. Discussion and conclusion: Our results suggested that silymarin-induced alleviation of inflammatory response could be a mechanism responsible for its benefits against liver damage and insulin resistance. ARTICLE HISTORY

Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: A review

“…It has been found that silymarin as a safe and well‐tolerated dietary food supplement can protect against liver damages, reducing blood glucose and cholesterol in type 1 diabetic‐like diseases in rats (Cheng et al, ) and type 2 diabetes in patients (Huseini et al, ). It also has beneficial effects for obesity‐related hyperglycemia and insulin resistance by its antioxidant (Feng et al, ), anti‐inflammatory effect, reducing fat accumulation (Guo et al, ), body weight gains, and glucose tolerance (Feng et al, ) and also increasing β cells regeneration and insulin gene expression (Soto, Raya, Pérez, et al, ) and so on.…”

“…A study on male mice received high fat diet suggested that positive effect of silymarin on obesity‐induced insulin resistance could be related on both anti‐inflammatory and fat mitigation effects (Guo et al, ). Another study demonstrated that treatment by silymarin in partially pancreatectomized rats can increase serum insulin and normalized serum glucose and may improve the reduction of β pancreatic cells by increasing transcription factors such as Nkx6.1, which is involved in growth, differentiation, and function maintenance of β‐pancreatic, and also can increase insulin gene expression (Soto, Raya, Pérez, et al, ).…”

“…A study on male mice received high fat diet‐induced obesity and insulin resistance indicated that silymarin significantly reduced epididymal fat mass and total bodyweight while the food intake remains unchanged. Silymarin did not affect on lean body weight but significantly reduced fat accumulation and ameliorated insulin resistance and glucose metabolism (Guo et al, ). Another study on high fat diet‐induced obesity for 11 or 7 weeks in rats showed silymarin induced significant improvement in BMI, insulin resistance, leptin sensitivity, and hyperlipidemia.…”

Effects of silymarin on metabolic syndrome: a review

“…36 There have been flourishing studies into the efficacy of oral silymarin on insulin resistance and glucose intolerance in animal models of obesity induced by a high fat diet. [36][37][38] When doses of 30 and 60 mg kg −1 of body weight of silymarin were applied in mice, which had been put on a high fat diet, it significantly improved insulin resistance and obesity. Furthermore, silymarin had protective effect on high fat-induced hepatic injury, and markedly improved glucose tolerance.…”

Protective Effects of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Isolated from Averrhoa Carambola L. (Oxalidaceae) Roots on High-Fat Diet-Induced Obesity and Insulin Resistance in Mice

“…The criteria for the hepatic steatosis score were as follows [26]: Grade 0 -Normal lobular architecture with central veins and no obvious steatosis, inflammation or necrosis was observed.…”