# Licorice Flavonoid Extract Ameliorates Intestine Damage in Ulcerative Colitis via MAPK/NF-κB Signaling Modulation and Gut Microbiome Remodeling

**Authors:** Xiaoai Zhu, Binsong Han, Anqi Hu, Jiacen Bi, Wenxue Wang, Yuhui Ye, Feng Xue, Cunzheng Zhang

PMC · DOI: 10.3390/foods15040716 · 2026-02-14

## TL;DR

Licorice flavonoid extract reduces intestinal damage in ulcerative colitis by modulating inflammation and gut microbes.

## Contribution

The study identifies licorice flavonoid extract as a natural therapeutic for UC via MAPK/NF-κB signaling and microbiome remodeling.

## Key findings

- LF reduced colon damage and inflammation in a murine UC model.
- LF suppressed pro-inflammatory cytokines and inhibited MAPK/NF-κB phosphorylation.
- LF increased gut microbiome diversity and beneficial bacterial taxa.

## Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology, characterized by non-specific colonic inflammation. Licorice (Glycyrrhiza uralensis Fisch.), a food–medicine dual-use botanical, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties, suggesting therapeutic potential for UC. However, the specific bioactive components of licorice and their underlying mechanisms of action require further elucidation. In this study, we investigated the efficacy and mechanisms of licorice flavonoid extract (LF) in a dextran sulfate sodium (DSS)-induced murine model of UC. The results demonstrated that oral administration of LF significantly alleviated disease pathology indices, reduced colon shortening, and improved histopathological colon damage. LF treatment suppressed the production of pro-inflammatory cytokines, likely through inhibiting the phosphorylation of MAPK and NF-κB p65, while upregulating PPARγ expression. Additionally, LF intervention restored gut microbial diversity, increasing the abundance of beneficial taxa such as Bacteroidetes and Firmicutes. The chemical characterization of LF revealed that 15 flavonoid compounds contribute to its therapeutic basis. These findings demonstrate that LF mitigates UC via integrated anti-inflammatory, immunomodulatory, and microbiota-regulating mechanisms, highlighting its potential as a natural therapeutic agent for UC management.

## Linked entities

- **Genes:** MAPK (mitogen activated kinase-like protein) [NCBI Gene 7446652], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468]
- **Diseases:** ulcerative colitis (MONDO:0005101)

## Full-text entities

- **Genes:** Ocln (occludin) [NCBI Gene 18260] {aka Ocl}, Rap1a (Rap1a member of RAS oncogene family) [NCBI Gene 109905] {aka G-22K, Krev-1, Rap1}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Pparg (peroxisome proliferator activated receptor gamma) [NCBI Gene 19016] {aka Nr1c3, PPAR-gamma, PPAR-gamma2, PPARgamma, PPARgamma2}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, Tjp1 (tight junction protein 1) [NCBI Gene 21872] {aka ZO1}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Cldn1 (claudin 1) [NCBI Gene 12737], Esr1 (estrogen receptor 1 (alpha)) [NCBI Gene 13982] {aka ER, ER-alpha, ERa, ERalpha, ESR, Estr}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 19225] {aka COX2, Cox-2, PES-2, PGHS-2, PHS II, PHS-2}
- **Diseases:** Inflammatory (MESH:D007249), gastric ulcers (MESH:D013276), injury to (MESH:D014947), dysbiosis (MESH:D064806), edema (MESH:D004487), bleeding (MESH:D006470), organ injury (MESH:D009102), diarrhea (MESH:D003967), DAI (MESH:C566784), colitis (MESH:D003092), weight loss (MESH:D015431), cough (MESH:D003371), ulcer (MESH:D014456), enteritis (MESH:D004751), inflammatory bowel disease (MESH:D015212), mucosal damage (MESH:D052016), hepatitis (MESH:D056486), dislocation (MESH:D004204), UC (MESH:D003093), tissue damage (MESH:D017695), colon damage (MESH:D003108), sepsis (MESH:D018805)
- **Chemicals:** paraffin (MESH:D010232), sodium chloride (MESH:D012965), methanol (MESH:D000432), xylene (MESH:D014992), polysaccharides (MESH:D011134), nitrogen (MESH:D009584), ononin (MESH:C526426), water (MESH:D014867), formononetin (MESH:C007768), isoflurane (MESH:D007530), isoliquiritigenin (MESH:C040920), licochalcone D (MESH:C541529), Echinatin (MESH:C000623341), hydrochloric acid (MESH:D006851), SDS (MESH:D012967), liquiritigenin (MESH:C083152), ethanol (MESH:D000431), glycyrrhizic acid (MESH:D019695), glycyrrhetic acid (MESH:D006034), neoglycyrol (MESH:C071429), diaminobenzidine (-), H&amp;E (MESH:D006371), sulfasalazine (MESH:D012460), hematoxylin (MESH:D006416), Butyrate (MESH:D002087), isoliquiritin (MESH:C098467), carbohydrate (MESH:D002241), fatty acids (MESH:D005227), licorisoflavan A (MESH:C558581), DSS (MESH:D016264), polyphenols (MESH:D059808), licorisoflavan B (MESH:C401293), paraformaldehyde (MESH:C003043), agarose (MESH:D012685), eosin (MESH:D004801), alcohol (MESH:D000438), polyvinylidene difluoride (MESH:C024865), Flavonoid (MESH:D005419), berberine (MESH:D001599), SCFA (MESH:D005232), glycycoumarin (MESH:C515155)
- **Species:** Escherichia coli (E. coli, species) [taxon 562], Mus musculus (house mouse, species) [taxon 10090], Glycyrrhiza (licorice, genus) [taxon 46347], Bacteroides uniformis (species) [taxon 820], Clostridia (class) [taxon 186801], Homo sapiens (human, species) [taxon 9606], Clostridiales bacterium (species) [taxon 1898207], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Shigella (genus) [taxon 620], Faecalibaculum rodentium (species) [taxon 1702221], Bacilli (class) [taxon 91061], Drosophila melanogaster (fruit fly, species) [taxon 7227], Bacteroidia (class) [taxon 200643]
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939381/full.md

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Source: https://tomesphere.com/paper/PMC12939381