Protective Effects of Silymarin Against D-Gal/LPS-Induced Organ Damage and Inflammation in Mice

Abstract

Aim: Silymarin contains various flavonoids and exhibits antioxidative, anti-inflammatory, and anticancer effects, in addition to other pharmacological properties. This study explored the alleviating effect of silymarin on multiple-organ damage induced by D-galactose/lipopolysaccharide in Kunming mice.

Methods: Kunming mice were injected intraperitoneally with D-galactose (30 mg/kg·BW)/LPS (3 μg/kg·BW) and then treated using silymarin with different doses (75 mg/kg·bw and 150 mg/kg·bw) via intragastric administration. Changes in organ indexes, pathological changes, liver-function index, biochemical indexes, molecular biological indexes, and genes related to the oxidation and inflammation of main organs were evaluated.

Results: After the mice were treated with silymarin, their body weight showed no significant change, and the liver, kidney, and lung indexes of the treated mice were higher than those of the model group; meanwhile, the corresponding histopathological formation was reduced. Compared with the model group, the silymarin-treated group showed reductions in ALT, AST, and liver function indexes in the mouse serum. Silymarin treatment also increased the SOD, CAT, GSH, GSH-Px, T-AOC, IL-10, and IL-12 levels, as well as reduced the MDA, NO, IL-6, IL-1β, TNF-α, IFN-γ levels in the mouse serum and liver tissues. In addition, quantitative polymerase chain reaction analysis indicated that the mRNA expression levels of SOD1, SOD2, CAT, GSH-Px, IL-10, Nrf2, HO-1, NQO1, Trx, and IκB-α were higher in the liver tissue of the silymarin-treated mice than in those of the model group; meanwhile, the mRNA expression levels of IL-6, IL-1β, TNF-α, IFN-γ, NF-κB, NLRP3, COX2, and p38 were lower than those in the model group.

Conclusion: Silymarin, which exhibits antioxidative and anti-inflammatory effects, can alleviate the liver, lung, and kidney damage induced by D-galactose/lipopolysaccharide. High-dose (150 mg/kg·bw) silymarin can more effectively inhibit organ damage, compared with low-dose silymarin (75 mg/kg·bw) in Kunming mice.

Keywords: D-galactose/lipopolysaccharide; anti-inflammation; antioxidation; organ injury; silymarin.

Figure 1

Chemical structures of key components of silymarin in this study A: silybin; B: isosilybin; C: silydianin; D: silychristin.

Figure 2

H&E pathological staining structure of liver tissues. Model: treated with D-Gal/LPS (30 mg/kg·bw/3 μg/kg·bw) intraperitoneal injection; silymarin-L: treated with silymarin (75 mg/kg·bw) intragastric administration; silymarin-H: treated with silymarin (150 mg/kg·bw) intragastric administration.

Figure 3

H&E pathological staining structure of lung tissues. Model: treated with D-Gal/LPS (30 mg/kg·bw/3 μg/kg·bw) intraperitoneal injection; silymarin-L: treated with silymarin (75 mg/kg·bw) intragastric administration; silymarin-H: treated with silymarin (150 mg/kg·bw) intragastric administration.

Figure 4

H&E pathological staining structure of kidney tissues. Model: treated with D-Gal/LPS (30 mg/kg·bw/3 μg/kg·bw) intraperitoneal injection; silymarin-L: treated with silymarin (75 mg/kg·bw) intragastric administration; silymarin-H: treated with silymarin (150 mg/kg·bw) intragastric administration.

Figure 5

mRNA expression in mice liver tissue with D-Gal/LPS-induced organ injury. (A) SOD1, SOD2, CAT and GSH-Px; (B) IL-6, IL-10, IL-1β, TNF-α and IFN-γ; (C) Nrf2, HO-1, NQO1 and Trx; (D) NF-κB, IκBα, NLRP3, COX2 and p38. Model: treated with D-Gal/LPS (30 mg/kg·bw/3 μg/kg·bw) intraperitoneal injection; silymarin-L: treated with silymarin (75 mg/kg·bw) intragastric administration; silymarin-H: treated with silymarin (150 mg/kg·bw) intragastric administration. ^a–dMean values with different letters in the same column are significantly different (p < 0.05) according to Tukey’s test.