Schisandra sphenanthera extract (Wuzhi Tablet) protects against chronic-binge and acute alcohol-induced liver injury by regulating the NRF2-ARE pathway in mice

Xuezhen Zeng; Xi Li; Chenshu Xu; Fulin Jiang; Yufei Mo; Xiaomei Fan; Yaoting Li; Yiming Jiang; Dongshun Li; Min Huang; Huichang Bi

doi:10.1016/j.apsb.2017.04.002

Schisandra sphenanthera extract (Wuzhi Tablet) protects against chronic-binge and acute alcohol-induced liver injury by regulating the NRF2-ARE pathway in mice

Acta Pharm Sin B. 2017 Sep;7(5):583-592. doi: 10.1016/j.apsb.2017.04.002. Epub 2017 May 11.

Authors

Xuezhen Zeng¹, Xi Li¹, Chenshu Xu², Fulin Jiang¹, Yufei Mo¹, Xiaomei Fan³, Yaoting Li¹, Yiming Jiang¹, Dongshun Li¹, Min Huang¹, Huichang Bi¹

Affiliations

¹ School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
² Department of Pharmacy, School of Medicine, Shenzhen University, Guangdong 518060, China.
³ Shenzhen Bao׳an Maternal and Child Health Hospital, Guangdong 518133, China.

Abstract

Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.

Keywords: ALD, alcoholic liver disease; ALT, alanine aminotransferase; ARE, antioxidant response element; AST, aspartate aminotransferase; Alcoholic liver injury; CYP2E1, cytochrome P450 2E1 enzyme; EtOH, ethanol; GCLC, glutamate–cysteine ligase catalytic subunit; GCLM, glutamate–cysteine ligase modifier subunit; GSH, glutathione; H&E, hematoxylin and eosin; HO-1, heme oxygenase-1; NRF2, nuclear factor erythroid 2-related factor 2; NRF2-ARE; Oxidative stress; SOD, superoxide dismutase; Schisandra sphenanthera; WZ, Wuzhi Tablet.; Wuzhi Tablet.