Protective effects of hesperetin on lipopolysaccharide-induced acute lung injury by targeting MD2

  • Eur J Pharmacol. 2019 Jun 5;852:151-158. doi: 10.1016/j.ejphar.2019.02.042.
Jinyan Ye  1 ,  Minqiang Guan  2 ,  Yao Lu  3 ,  Dan Zhang  3 ,  Chengye Li  3 ,  Yuping Li  3 ,  Caicun Zhou  4
Affiliations
  • 1. Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; The Third Affiliated Hospital of Soochow University, Changzhou 213000, China. Electronic address: [email protected].
  • 2. Laboratory Animal Center, Wenzhou Medical University, Wenzhou 325000, China.
  • 3. Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 4. Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: [email protected].
PMID: 30807747 DOI: 10.1016/j.ejphar.2019.02.042
Abstract

Inflammation plays an important role in acute lung injury (ALI). Hesperetin (HES), a natural flavanone and an aglycone of hesperidin, has established potent anti-inflammatory activity. The aim of this study was to evaluate the potential protective effect of HES on lipopolysaccharide (LPS)-induced ALI in mice and to illuminate its possible directly target. Results indicated that HES pretreatment significantly attenuated LPS-induced pulmonary pathological injury, total protein concentration, markedly decreased the number of neutrophils and the levels of inflammatory cytokines, TNF-α and IL-6, in ALI model in vivo and in vitro. Meanwhile, pretreatment with HES dramatically reduced myeloperoxidase (MPO) activity in LPS-induced ALI mice. Additionally, using molecular docking and co-immunoprecipitation assay, HES showed a directly bind with myeloid differentiation 2 (MD2), in which HES could inhibit MAPK activation, regulate IκB degradation, block the interaction MD2 and its co-receptor Toll-like Receptor 4 (TLR4). Taken together, HES showed a significantly protective effect against LPS-induced ALI, which might be associated with MD2 protein. These results attested HES worthy of further progress into an adjunctive potential drug for the treatment for ALI.

Keywords
Acute lung injury; Hesperetin; Inflammation; Myeloid differentiation 2.
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