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Piceatannol attenuates D-GalN/LPS-induced hepatoxicity in mice: Involvement of ER stress, inflammation and oxidative stress. 2018

Jingjing Wen, and Hongfa Lin, and Mengshu Zhao, and Liang Tao, and Yunxia Yang, and Xi Xu, and Aiqun Jia, and Jianfa Zhang, and Dan Weng
Center for Molecular Metabolism, Nanjing University of Science & Technology, 200 Xiaolingwei Street, Nanjing 210094, China.

Piceatannol, a natural derivative of resveratrol, has been shown to exert similar anti-oxidant and anti-inflammatory effects as resveratrol. However, it remains unknown whether piceatannol has hepatoprotective effect against acute liver injury. In this study, we investigated the in vivo effect of piceatannol on D-GalN/LPS-induced fulminant hepatic failure (FHF), and its in vitro effect on ER stress-inducing drug thapsigargin (TG)-induced proinflammatory cytokines production and ROS release. Our results indicated that piceatannol markedly decreased the mortality rate, reduced the serum levels of alanine transaminase and aspartic aminotransferase, ameliorated the liver damage induced by D-GalN/LPS in mice. In addition, piceatannol reduced the expression of proinflammatory cytokines, including TNF-α, IL-1β and IL-6, the expression of ER stress markers CHOP and phosphorylated-IRE1α, and the generation of oxidative stress in D-GalN/LPS-treated mouse liver. In vitro results were consistent with in vivo observations, demonstrating that piceatannol suppressed the secretion of proinflammatory cytokines, inflammasome activation and the production of ROS induced by TG with or without LPS priming in J774A.1 macrophages. Our study proposes piceatannol as a promising medication for preventing acute liver failure and the mechanisms may be related to its inhibitory effects on ER stress, inflammation and oxidative stress.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005260 Female Females
D005688 Galactosamine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000893 Anti-Inflammatory Agents Substances that reduce or suppress INFLAMMATION. Anti-Inflammatory Agent,Antiinflammatory Agent,Agents, Anti-Inflammatory,Agents, Antiinflammatory,Anti-Inflammatories,Antiinflammatories,Antiinflammatory Agents,Agent, Anti-Inflammatory,Agent, Antiinflammatory,Agents, Anti Inflammatory,Anti Inflammatories,Anti Inflammatory Agent,Anti Inflammatory Agents
D013267 Stilbenes Organic compounds that contain 1,2-diphenylethylene as a functional group. Stilbene,Stilbene Derivative,Stilbene Derivatives,Stilbenoid,Stilbenoids,Derivative, Stilbene,Derivatives, Stilbene
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine

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