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

Drug Des Devel Ther. 2021 May 4:15:1903-1914. doi: 10.2147/DDDT.S305033. eCollection 2021.

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Galactose / antagonists & inhibitors*
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Lipopolysaccharides / antagonists & inhibitors*
  • Liver / drug effects*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Protective Agents / administration & dosage
  • Protective Agents / pharmacology*
  • Silymarin / administration & dosage
  • Silymarin / pharmacology*

Substances

  • Lipopolysaccharides
  • Protective Agents
  • Silymarin
  • Galactose