Involvement of P450s and nuclear receptors in the hepatoprotective effect of quercetin on liver injury by bacterial lipopolysaccharide

Abstract

Objective: Quercetin (Que), a flavonoid, possesses anti-inflammatory and antioxidant properties. It has been shown to protect against liver injury induced by various factors. This study was designed to investigate the underlying mechanism of its protective effect against lipopolysaccharide (LPS)- induced liver damage.

Methods: Mice were pretreated with Que for 7 consecutive days and then exposed to LPS. To study the hepatoprotective effect of Que, oxidative stress parameters, inflammatory cytokine levels in liver and serum liver function indexes were examined. Protein and mRNA expression of nuclear orphan receptors and cytochrome P450 enzymes were measured by Western Blotting and qPCR, respectively.

Results: Que significantly reduced circulating ALT, AST, ALP, and ameliorated LPS-induced histological alterations. In addition, Que obviously decreased markers of oxidative stress and pro-inflammatory cytokines. Furthermore, Que carried out the hepatoprotective effect via regulation of the expression of nuclear orphan receptors (CAR, PXR) and cytochrome P450 enzymes (CYP1A2, CYP2E1, CYP2D22, CYP3A11).

Conclusions: Our findings suggested that Que pretreatment could ameliorate LPS-induced liver injury.

Keywords:

• Quercetin
• lipopolysaccharide
• liver injury
• cytochrome P450s
• nuclear receptors
• mice

Author contributions

Xun Wang, Ling Zhao and Yuanli Zhang conceived and designed the experiments. Yuanli Zhang, Ling Yue, Hongrui Guo, Gang Ye, and Fang Chen performed the experiments. Ling Zhao and Fang Chen drafted the paper. Fei Shi, Cheng Lv, Bo Jing, Huaqiao Tang, Jvchun Lin, Hualin Fu, Zhongqiong Yin, Yinglun Li suggestion and modify. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).