Glycyrrhiza uralensis Fisch. alleviates dextran sulfate sodium-induced colitis in mice through inhibiting of NF-κB signaling pathways and modulating intestinal microbiota

J Ethnopharmacol. 2022 Nov 15:298:115640. doi: 10.1016/j.jep.2022.115640. Epub 2022 Aug 24.

Abstract

Ethnopharmacological relevance: Licorice is widely used in traditional Chinese Medicine (TCM) for compound compatibility, which could reduce toxicity and increase efficacy of certain herbal medicine, and its active components prominently effects of inhibit of inflammation and regulate of immunity.

Aim of the study: The study probed into the mechanism of the anti-inflammatory and immunomodulatory effects of licorice based on the domination of the T helper type 17/regulatory T cells (Th17/Treg) differentiation balance and the composition and structure of the intestinal flora through the nuclear factor kappa B (NF-κB) signaling pathway.

Materials and methods: BALB/c mice were inoculated with dextran sulfate sodium (DSS) to establish animal models of ulcerative colitis (UC). For the pharmacodynamic study, UC mice were observed for the anti-inflammatory effect of licorice water extraction (LWE) in vivo, including clinical observation and measurement of colon length. Hematoxylin-eosin (HE) staining was used to evaluate pathological conditions. Immunohistochemistry (IHC) and transmission electron microscopy (TEM) were performed to observe the intestinal barrier of the colons. Inflammatory cytokine levels were measured using with enzyme-linked immunosorbent assay (ELISA) kits. The proportions of T helper (Th) cells in the colons was assessed using flow cytometry. Gut microbiota diversity was detected using 16S ribosomal (r)DNA sequencing. In addition, Western blot (WB) assays were used to verify ROR-γt, Foxp3, TLR4, MyD88 and NF-κB expression according to a standard protocol.

Results: LWE exerted a pharmacological anti-inflammatory effect by attenuating inflammation in the colonic tissues through affecting the protein expression of TLR4/MyD88/NF-κB, and increasing the expression of tight junction (TJ) protein in the colons, improving the integrity of the intestinal mucosal barrier in vivo. Moreover, LWE reversed the imbalance in Th17/Treg cells differentiation and influenced the protein expression of ROR-γt and Foxp3 in UC mouse colons. In particular, LWE significantly affected the diversity of the gut microbiota in UC mice, ameliorated the composition of dominant species, and significantly increased the type and quantity of probiotics.

Conclusion: Licorice tends to reduce inflammation and enhance the protective action of the intestinal mucosal barrier via the TLR4/MyD88/NF-κB signal transduction pathway and alter the imbalance of Th-cell differentiation. Notably, licorice may affect the diversity of intestinal microbiota and the content of beneficial bacteria in the colon, which is a potential mechanism for understanding anti-inflammatory and immunomodulatory effects in UC mice in vivo.

Keywords: Inflammation; Intestinal flora; Licorice; TLR4/MyD88/NF-κB; Th17/Treg; Traditional Chinese medicine; Ulcerative colitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis* / metabolism
  • Colitis, Ulcerative* / drug therapy
  • Colon
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Forkhead Transcription Factors / metabolism
  • Gastrointestinal Microbiome*
  • Glycyrrhiza uralensis*
  • Inflammation / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Forkhead Transcription Factors
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Toll-Like Receptor 4
  • Dextran Sulfate