Polyphenols from Lonicera caerulea L. Berry Inhibit LPS-Induced Inflammation through Dual Modulation of Inflammatory and Antioxidant Mediators

J Agric Food Chem. 2017 Jun 28;65(25):5133-5141. doi: 10.1021/acs.jafc.7b01599. Epub 2017 Jun 14.

Abstract

Lonicera caerulea L. berry polyphenols (LCBP) are considered as major components for bioactivity. This study aimed to clarify the molecular mechanisms by monitoring inflammatory and antioxidant mediator actions in lipopolysaccharide (LPS)-induced mouse paw edema and macrophage cell model. LCBP significantly attenuated LPS-induced paw edema (3.0 ± 0.1 to 2.8 ± 0.1 mm, P < 0.05) and reduced (P < 0.05) serum levels of monocyte chemotactic protein-1 (MCP-1, 100.9 ± 2.3 to 58.3 ± 14.5 ng/mL), interleukin (IL)-10 (1596.1 ± 424.3 to 709.7 ± 65.7 pg/mL), macrophage inflammatory protein (MIP)-1α (1761.9 ± 208.3 to 1369.1 ± 56.4 pg/mL), IL-6 (1262.8 ± 71.7 to 499.0 ± 67.1 pg/mL), IL-4 (93.3 ± 25.7 to 50.7 ± 12.5 pg/mL), IL-12(p-70) (580.4 ± 132.0 to 315.2 ± 35.1 pg/mL), and tumor necrosis factor-α (TNF-α, 2045.5 ± 264.9 to 1270.7 ± 158.6 pg/mL). Cell signaling analysis revealed that LCBP inhibited transforming growth factor β activated kinase-1 (TAK1)-mediated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways, and enhanced the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and manganese-dependent superoxide dismutase (MnSOD) in earlier response. Moreover, cyanidin 3-glucoside (C3G) and (-)-epicatechin (EC), two major components of LCBP, directly bound to TAK1. These data demonstrated that LCBP might inhibit LPS-induced inflammation by modulating both inflammatory and antioxidant mediators.

Keywords: Lonicera caerulea L.; anti-inflammatory; antioxidant; cytokines; polyphenol.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / chemistry
  • Antioxidants / isolation & purification
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / immunology
  • Edema / drug therapy*
  • Edema / genetics
  • Edema / immunology
  • Fruit / chemistry
  • Humans
  • Inflammation Mediators / administration & dosage*
  • Inflammation Mediators / isolation & purification
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Lipopolysaccharides / adverse effects
  • Lipopolysaccharides / immunology
  • Lonicera / chemistry*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / immunology
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Plant Extracts / administration & dosage*
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Polyphenols / administration & dosage*
  • Polyphenols / chemistry
  • Polyphenols / isolation & purification

Substances

  • Antioxidants
  • Chemokine CCL2
  • Inflammation Mediators
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Polyphenols
  • Interleukin-12
  • Interleukin-4
  • Mitogen-Activated Protein Kinases