Shikonin protects against D-Galactosamine and lipopolysaccharide-induced acute hepatic injury by inhibiting TLR4 signaling pathway
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Meng-Xiang Lin1,*, Yong-Xiang Yi2,*, Pei-Pei Fang3, Shan-Shan Huang3, Chen-Wei Pan3, Ling-Xiang Jin3, Tong Zhang4 and Guang-Yao Zhou3
1Department of Anesthesiology, Critical Care and Pain Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, P.R. China
2Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, 210003, P.R. China
3Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, P.R. China
4Department of Hepatobiliary Surgery, The People’s Hospital of Xinghua, Jiangsu, 225700, P.R. China
*These authors have contributed equally to this work
Guang-Yao Zhou, email: email@example.com
Keywords: shikonin, LPS, hepatic injury, TLR4
Received: April 12, 2017 Accepted: July 12, 2017 Published: September 16, 2017
Shikonin, a naphthoquinone isolated from the root of medical herb Lithospermum erythrorhizon, has been reported to have anti-inflammatory effect. However, there is no related research for the treatment of shikonin on hepaic injury. The purpose of this study was to investigate the effects of shikonin on D-Galactosamine and Lipopolysaccharide-induced hepatic injury in mice. Male BALB/c mice were pretreated with shikonin 1 h before LPS/D-GalN treatment. The pathological changes of hepatic injury were detected by H&E staining. The levels of TNF-α and IL-1β in hepatic tissues were detected by ELISA. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured in this study. In addition, the expression of TLR4 and NF-κB were determined by western blot analysis. These results suggest that shikonin effectively prevents LPS/D-GalN-induced liver injury by inhibiting AST and ALT levels, as well as inflammatory cytokines TNF-α and IL-1β production. The expression of TLR4 and NF-κB activation induced by LPS/D-GalN were also inhibited by treatment of shikonin. In vitro, shikonin significantly inhibited LPS-induced TNF-α and IL-1β production, as well as TLR4 expression and NF-κB activation. In conclusion, the results of the present study suggest that shikonin attenuates LPS/D-GalN-induced hepatic injury by inhibiting TLR4 signaling pathway.
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