Drug Design, Development and Therapy (May 2021)
Protective Effects of Silymarin Against D-Gal/LPS-Induced Organ Damage and Inflammation in Mice
Abstract
Xin Zhao,1– 3,* Haoxiang Wang,4,* Yue Yang,1,5 Yuting Gou,1,5 Zhiying Wang,6 Dingyi Yang,7 Chong Li1– 3 1Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing, 400067, People’s Republic of China; 2Chongqing Engineering Research Center of Functional Food, Chongqing University of Education, Chongqing, 400067, People’s Republic of China; 3Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, 400067, People’s Republic of China; 4Department of Neurology, Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 5College of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 400067, People’s Republic of China; 6School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, 150040, People’s Republic of China; 7Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, 400044, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chong Li; Dingyi Yang Tel +86-23-6265-3650Email [email protected]; [email protected]: 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: silymarin, organ injury, D-galactose/lipopolysaccharide, antioxidation, anti-inflammation
