Pterostilbene Exerts Hepatoprotective Effects through Ameliorating LPS/D-Gal-Induced Acute Liver Injury in Mice

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ORIGINAL ARTICLE

Pterostilbene Exerts Hepatoprotective Effects through Ameliorating LPS/D-Gal-Induced Acute Liver Injury in Mice Ziyi Liu,1 Jingjing Wang,1 Yong Zhang,1 Di Wu,1 Shuangqiu Li,1 Aimin Jiang,1 ChongTao Du,1,2 and Guanghong Xie 1,2

Received 10 February 2020; accepted 24 September 2020

Abstract— Acute liver injury (ALI) refers to abnormalities in liver function caused by various

causes and accompanied by poor prognosis and high mortality. Common predisposing factors for the disease are viral hepatitis, bacteria, alcohol, and certain hepatotoxic drugs. Inflammatory response and oxidative stress are critical for the pathogenesis of ALI. Pterostilbene (Pte), a natural polyphenol product extracted from blueberries and grapes, has been reported that exerted multiple biological activities, including antioxidative, anti-inflammatory, anti-carcinogenic, and anti-apoptotic properties. However, there is very little data showing the hepatoprotective effect of Pte on lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced ALI in mice. In this study, the possible protective effect and potential mechanisms of Pte on ALI are being investigated. It has been found that Pte markedly ameliorates LPS/D-Gal-induced inflammatory infiltration, hemorrhage, and dissociation of the hepatic cord, reducing the myeloperoxidase (MPO) activity in liver tissues and serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in ALI. Pte also inhibits LPS/D-Gal-induced secretion of pro-inflammatory cytokine tumor necrosis factor-a (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β) in liver tissues. Furthermore, the western blot analysis reveals that LPS/D-Gal-activated nuclear factor-kappa B (NF-κB) is significantly inhibited by Pte, and nuclear factor (erythroid-derived 2)–like 2 (Nrf2) and heme oxygenase-1 (HO-1) are upregulated by Pte. In conclusion, our results suggest that Pte exerts anti-inflammatory and antioxidative effects, which might contribute to ameliorating LPS/D-Gal-induced ALI in mice. Pte has the potential to be a preventive hepatoprotective agent. KEY WORDS: acute liver injury; pterostilbene; LPS/D-Gal; NF-κB; cytokines.

INTRODUCTION 1

College of Veterinary Medicine, Jilin University, Changchun, 130062 Jilin, People’s Republic of China 2 To whom correspondence should be addressed at College of Veterinary Medicine, Jilin University, Changchun, 130062 Jilin, People’s Republic of China. E-mails: [email protected]; [email protected]

Acute liver injury (ALI) is a clinical syndrome characterized by coagulopathy, jaundice, hepatic encephalopathy, and ascites, which is often accompanied by poor

0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature

Liu, Wang, Zhang, Wu, Li, Jiang, Du, and Xie prognosis and high mortality [1]. Viral hepatitis, bacteria, alcohol, and certain hepatotoxic drugs are common predisposing factors for ALI [2]. Experimental liver injury induced by lipopolysaccharide combined with Dgalactosamine (LPS/D-Gal) has been extensively studie