Dietary oleuropein and its new acyl-derivate attenuate murine lupus nephritis through HO-1/Nrf2 activation and suppressing JAK/STAT, NF-κB, MAPK and NLRP3 inflammasome signaling pathways

J Nutr Biochem. 2019 Dec:74:108229. doi: 10.1016/j.jnutbio.2019.108229. Epub 2019 Sep 13.

Abstract

Systemic lupus erythemathosus (SLE) is a chronic inflammatory and autoimmune disease which can affect multiple organ systems, without an effective and safe treatment. Olive leaf extracts are of special interest for their therapeutic effects. Oleuropein (OL) is the most abundant constituents of olive leaf extract and possesses many beneficial properties. In this study, we evaluated the effects of dietary OL and its new derivate, peracetylated oleuropein (Per-OL), in a pristane-induced SLE model. Mice received an injection of pristane or saline solution and were fed with experimental diets: enriched with OL and Per-OL. The levels of proinflammatory cytokines and markers were evaluated by enzyme-linked immunosorbent assay. The protein expressions of inducible nitric oxide synthase, microsomal prostaglandin E synthase 1, heme oxygenase (HO-1), nuclear factor E2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear transcription factor-kappa B (NF-κB) and inflammasome nucleotide-binding domain, leucine-rich repeats-containing family, pyrin domain-containing-3 (NLRP3) pathways activation were determined in kidneys by Western blot. OL and Per-OL significantly reduced renal damage and decreased serum matrix metalloproteinase 3 and prostaglandine E2 kidneys levels. Our findings indicate that Nrf2 and HO-1 antioxidant protein expressions were up-regulated in mice fed with OL and Per-OL diets, whereas the activation of JAK/STAT, MAPK, NF-κB and NLRP3 inflammasome pathways was significantly ameliorated. These results suggest that OL and Per-OL supplementation might provide a new alternative approach as a preventive/palliative treatment of nephritis in SLE management.

Keywords: HO-1/Nrf2; Inflammasome; Lupus nephritis; MAPK; NF-κB; Oleuropein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Supplements
  • Disease Models, Animal
  • Heme Oxygenase-1 / metabolism
  • Inflammasomes / drug effects*
  • Inflammasomes / metabolism
  • Iridoid Glucosides
  • Iridoids / pharmacology*
  • Janus Kinases / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Lupus Nephritis / chemically induced
  • Lupus Nephritis / diet therapy*
  • Lupus Nephritis / metabolism
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 3 / metabolism
  • Membrane Proteins / metabolism
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • STAT Transcription Factors / metabolism
  • Terpenes / toxicity

Substances

  • Inflammasomes
  • Iridoid Glucosides
  • Iridoids
  • Membrane Proteins
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • STAT Transcription Factors
  • Terpenes
  • pristane
  • oleuropein
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Janus Kinases
  • Matrix Metalloproteinase 3
  • Mmp3 protein, mouse