Daphnetin alleviates lipopolysaccharide/d-galactosamine-induced acute liver failure via the inhibition of NLRP3, MAPK and NF-κB, and the induction of autophagy

International Journal of Biological Macromolecules
Hongming LvXinxin Ci

Abstract

Acute liver failure (ALF), an inflammation-mediated hepatocellular injury process, is a life-threatening and fatal clinical syndrome. Daphnetin (Daph) has been reported to exhibit various pharmacological activities, particularly its antiinflammatory property. The present study was designed to evaluate the protective effects and underlying mechanisms of Daph against lipopolysaccharide and d-galactosamine (LPS/GalN)-induced ALF in mice. Our findings suggested that Daph treatment efficiently protected against LPS/GalN-induced ALF by lessening the lethality, decreasing the alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 secretion, malondialdehyde (MDA) formation and myeloperoxidase (MPO) level, inhibiting nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein expression, and increasing the glutathione (GSH) and superoxide dismutase (SOD) contents. Moreover, Daph treatment effectively inhibited LPS/GalN-induced nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway activation, and significantly induced autophagy activation by enhancing the ...Continue Reading

Citations

Oct 10, 2018·The Journal of Pharmacy and Pharmacology·Yulei CuiYanduo Tao
Jun 4, 2020·Journal of Cellular and Molecular Medicine·Shuqin ZhangQun Zhang
Dec 5, 2020·Immunopharmacology and Immunotoxicology·Liyan NiuXiaolei Shi
Dec 29, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jian ZouJian-Bo Wan
Jan 25, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xiaoye FanSongling Zhang

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