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Issue 55, 2017
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The protective effects of Shikonin on lipopolysaccharide/d-galactosamine-induced acute liver injury via inhibiting MAPK and NF-κB and activating Nrf2/HO-1 signaling pathways

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Abstract

Shikonin (SHK) has various biological and pharmacological activities, including anticancer, antibacterial and anti-inflammation activities. However, the protective effects and mechanism of SHK on lipopolysaccharide (LPS) and D-galactosamine (D-GalN) induced acute liver injury remain unclear. In this study, LPS/D-GalN caused acute liver injury by intraperitoneal injection. SHK was administrated for 1 h. Then, LPS/D-GalN was given to C57BL/6 mice for 3 h. Our results showed that SHK treatment distinctly decreased serum TNF-α, IL-1β, IL-6 and IFN-γ inflammatory cytokine production, reduced serum ALT, AST, hepatic MPO and ROS production levels, and tissue histology harmful effects, inhibited JNK1/2, ERK1/2, p38 and NF-κB (p65) phosphorylation, and suppressed IκBα phosphorylation and degradation. Furthermore, our research showed that SHK could dramatically increase SOD and GSH production, as well as reduce ROS production, through up-regulating the protein expression of HO-1, Nqo1, Gclc and Gclm, which was related to the induction of Nrf2 nuclear translocation. These results showed that SHK exerted anti-inflammatory activity, which was associated to the inhibition of inflammatory production via down-regulation of the MAPK and NF-κB signaling pathways, and anti-oxidative effects were connected with GSH and SOD activation through up-regulation of the Nrf2/HO-1 signaling pathways.

Graphical abstract: The protective effects of Shikonin on lipopolysaccharide/d-galactosamine-induced acute liver injury via inhibiting MAPK and NF-κB and activating Nrf2/HO-1 signaling pathways

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Article information


Submitted
21 Mar 2017
Accepted
05 Jul 2017
First published
11 Jul 2017

This article is Open Access

RSC Adv., 2017,7, 34846-34856
Article type
Paper

The protective effects of Shikonin on lipopolysaccharide/D-galactosamine-induced acute liver injury via inhibiting MAPK and NF-κB and activating Nrf2/HO-1 signaling pathways

Y. Tian, Z. Li, B. Shen, L. Wu, L. Han, Q. Zhang and H. Feng, RSC Adv., 2017, 7, 34846
DOI: 10.1039/C7RA03291A

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    [Original citation] - Published by The Royal Society of Chemistry.

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