2'O-galloylhyperin attenuates LPS-induced acute lung injury via up-regulation antioxidation and inhibition of inflammatory responses in vivo

  • Chem Biol Interact. 2019 May 1:304:20-27. doi: 10.1016/j.cbi.2019.02.029.
Sun-Dong Zhang  1 ,  Peng Wang  1 ,  Jing Zhang  1 ,  Wei Wang  1 ,  Li-Ping Yao  1 ,  Cheng-Bo Gu  1 ,  Thomas Efferth  2 ,  Yu-Jie Fu  3
Affiliations
  • 1. Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, 150040, China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, 150040, China.
  • 2. Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, 55128, Mainz, Germany.
  • 3. Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, 150040, China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin, 150040, China; College of Forestry, Beijing Forestry University, Beijing, 100083, China. Electronic address: [email protected].
PMID: 30849337 DOI: 10.1016/j.cbi.2019.02.029
Abstract

2'O-galloylhyperin, an active flavonol glycoside compound with remarkable anti-immune activity, was isolated from Pyrola [P. incarnata Fisch.]. However, the evidence of anti-inflammatory activity in pulmonary diseases was still not convincing. The aim of the present study was (1) to investigate the effect of 2'O-galloylhyperin on LPS-induced acute lung injury in mice, and (2) to identify the mechanisms of attenuation of inflammatory responses. The results demonstrated that 2'O-galloylhyperin significantly reduced LPS-induced inflammation damage in a dose-dependent manner. After LPS challenge, treatment with 2'O-galloylhyperin reduced the production of pro-inflammatory cytokines and chemokines, and also improved LPS-induced lung histopathology changes. 2'O-galloylhyperin also increased the activities of antioxidant Enzymes, including SOD and GSH-Px to maintain cellular redox homeostasis. Furthermore, 2'O-galloylhyperin inhibited translocation of nuclear factor (NF-κB) activation and suppressed phosphorylation of MAPK signaling pathway consisting of p38, ERK, JNK. In addition, 2'O-galloylhyperin enhanced heme oxygenase-1 (HO-1) expression to block LPS-induced inflammation via activating nuclear factor-crythroid 2-related factor (Nrf2). Moreover, 2'O-galloylhyperin induced adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation. 2'O-galloylhyperin attenuated LPS-induced acute lung injury by inhibiting the MAPK and NF-κB signaling pathways, presumably related to up-regulation of the AMPK and Nrf2 signaling pathways. Furthermore, 2'O-galloylhyperin is a potential protective antioxidant to protect lung tissues from the acute injury.

Keywords
2′O-galloylhyperin; Acute lung injury; Antioxidation; Inflammation response; Lipopolysaccharide.
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