Abstract

Schisandra chinensis (S. chinensis) is a traditional Chinese herbal medicine widely used for the treatment of liver disease, whose main active components are lignans. However, the action mechanisms of the lignans in S. chinensis remain unclear. This study aimed to investigate the protective effect and related molecular mechanism of Schisandra lignan extract (SLE) against carbon tetrachloride- (CCl4-) induced acute liver injury in mice. Different doses of SLE at 50, 100, and 200 mg/kg were administered daily by gavage for 5 days before CCl4 treatment. The results showed that SLE significantly decreased the activities of serum ALT/AST and reduced liver pathologic changes induced by CCl4. Pretreatment with SLE not only decreased the content of MDA but increased SOD, GSH, and GSH-Px activities in the liver, suggesting that SLE attenuated CCl4-induced oxidative stress. The expression levels of inflammatory cytokines TNF-a, IL-1β, and IL-6 were decreased after oral administration of SLE, probably because lignans inhibited the NF-κB activity. Additionally, SLE also inhibited hepatocyte apoptosis by suppressing JNK activation and regulating Bcl-2/Bax signaling pathways. In conclusion, these results suggested that SLE prevented CCl4-induced liver injury through a combination of antioxidative stress, anti-inflammation, and antihepatocyte apoptosis and alleviated inflammation and apoptosis by regulating the NF-κB, JNK, and Bcl-2/Bax signaling pathways.

Highlights

  • Liver injury has been recognized as a serious health problem worldwide, which can be caused by viral infections, hepatotoxic drugs, and toxic chemicals [1, 2]

  • The present study aimed to evaluate the effect of Schisandra lignan extract (SLE) on oxidative stress, inflammation, and hepatocyte apoptosis after CCl4 treatment and investigate inflammation and hepatocyte apoptosis related signaling pathways to explore its possible molecular mechanism

  • We investigate the protective effect and possible molecular mechanism of SLE against CCl4induced acute liver injury in mice

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Summary

Introduction

Liver injury has been recognized as a serious health problem worldwide, which can be caused by viral infections, hepatotoxic drugs, and toxic chemicals [1, 2]. There are few effective drugs available for the clinical treatment of acute and chronic liver injury at present. Carbon tetrachloride (CCl4) is a hepatotoxic chemical that has been widely used to induce experimental liver injury models [4,5,6]. Metabolic activation of CCl4 to reactive free radicals by cytochrome P450 enzymes is the initiating event of CCl4-induced liver injury. These free radicals result in lipid peroxidation of hepatocellular membrane, leading to acute liver inflammation and hepatocyte death [4, 7]

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