Oral administration of Lentinus edodes β-glucans ameliorates DSS-induced ulcerative colitis in mice via MAPK-Elk-1 and MAPK-PPARγ pathways

Food Funct. 2016 Nov 9;7(11):4614-4627. doi: 10.1039/c6fo01043a.

Abstract

To evaluate the anti-inflammatory effect of β-glucans from Lentinus edodes, and its molecular mechanism, the dextran sulfate sodium salt (DSS) induced colitis model of mice and the LPS-stimulated RAW264.7 cell inflammation model were used in this study. 40 ICR male mice were randomly divided into 4 groups: Control, DSS (DSS treated only), DSS + low-βGs (500 mg kg-1 d-1) and DSS + high-βGs (1000 mg kg-1 d-1). The body weight of the mice with Lentinus edodes β-glucan supplementation increased significantly compared to the DSS group and the disease activity index (DAI) was improved in both βG-treated groups. Compared with the DSS group, histopathological analysis showed that the infiltration of inflammatory cells of both βG-treated groups decreased significantly in colonic tissues. Furthermore, oral administration of β-glucans decreases the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO) and inhibits the expression of iNOS and several inflammatory factors: TNF-α, IL-1β and IL-6 as well as nitric oxide (NO) of the colonic tissues. The mitogen-activated protein kinase (MAPK) pathway is closely related to the expression of pro-inflammatory factors. In the DSS-induced colitis model and the LPS-stimulated RAW264.7 cell model, βGs inhibited the expression of pro-inflammatory factors and blocked the phosphorylation of JNK/ERK1/2 and p38; βGs also suppress the phosphorylation of Elk-1 at Ser84 and the phosphorylation of PPARγ at Ser112. Altogether, these results suggest that Lentinus edodes βGs could inhibit the DSS-induced ulcerative colitis and decrease inflammatory factor expressions. The molecular mechanism may be involved in suppressing MAPK signaling and inactivation of Elk-1 and activation of PPARγ.

MeSH terms

  • Administration, Oral
  • Animals
  • Colitis, Ulcerative / chemically induced*
  • Colitis, Ulcerative / drug therapy*
  • Dextran Sulfate / toxicity*
  • Gene Expression Regulation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Inbred ICR
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Nitric Oxide / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Peroxidase / metabolism
  • Random Allocation
  • Shiitake Mushrooms / chemistry*
  • beta-Glucans / administration & dosage
  • beta-Glucans / chemistry
  • beta-Glucans / pharmacology*
  • ets-Domain Protein Elk-1 / metabolism

Substances

  • Elk1 protein, mouse
  • PPAR gamma
  • beta-Glucans
  • ets-Domain Protein Elk-1
  • Nitric Oxide
  • Malondialdehyde
  • Dextran Sulfate
  • Peroxidase
  • Mitogen-Activated Protein Kinase Kinases