Jujube peel polyphenols synergistically inhibit lipopolysaccharide-induced inflammation through multiple signaling pathways in RAW 264.7 cells

Food Chem Toxicol. 2022 Jun:164:113062. doi: 10.1016/j.fct.2022.113062. Epub 2022 Apr 20.

Abstract

Jujube has great potential as food and traditional drugs in several countries. To study the anti-inflammatory influence of jujube peel polyphenols in lipopolysaccharide (LPS) induced RAW 264.7 cells through mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB) and nuclear erythroid 2-related factor 2 (Nrf2) signaling pathways. In this study, the phenolic composition of polyphenols in jujube peel was analyzed using LC-MS/MS, and which was confirmed that the main polyphenols were p-coumaric acid, catechin and rutin. Meanwhile, jujube peel polyphenols attenuated the generation of TNF-α, IL-1β, IL-6, NO and PGE2 by inhibiting MAPK and NF-κB signaling pathways. Additionally, jujube peel polyphenol activate Nrf2 from the cytoplasm to the nucleus, regulate antioxidant enzymes and pro-inflammatory cytokines, and reduce oxidative stress and inflammatory responses. Results obtained from this study suggest that jujube peel polyphenols may alleviate oxidative stress and inflammation by inhibiting MAPK and NF-κB and activating Nrf2 signaling pathways. Furthermore, jujube peel polyphenols have a synergistic effect in the treatment of LPS-induced inflammatory in RAW 264.7 cells. In conclusion, this study not only reveals the mechanism by which jujube peel polyphenols inhibit LPS-induced inflammation in RAW 264.7 cells, but also provides guidance for the development of new anti-inflammatory drugs.

Keywords: Anti-inflammatory; Antioxidant; Jujube peel polyphenols; MAPK; NF-κB; Nrf2.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Chromatography, Liquid
  • Heme Oxygenase-1 / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Lipopolysaccharides* / pharmacology
  • MAP Kinase Signaling System
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Polyphenols / pharmacology
  • Polyphenols / therapeutic use
  • RAW 264.7 Cells
  • Signal Transduction
  • Tandem Mass Spectrometry
  • Ziziphus*

Substances

  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Polyphenols
  • Heme Oxygenase-1
  • Mitogen-Activated Protein Kinases