Huang Lian Jie Du decoction attenuated colitis via suppressing the macrophage Csf1r/Src pathway and modulating gut microbiota

Front Immunol. 2024 Sep 26:15:1375781. doi: 10.3389/fimmu.2024.1375781. eCollection 2024.

Abstract

Introduction: Ulcerative colitis, a subtype of chronic inflammatory bowel disease (IBD), is characterized by relapsing colonic inflammation and ulcers. The traditional Chinese herbal formulation Huang Lian Jie Du (HLJD) decoction is used clinically to treat diarrhea and colitis. However, the mechanisms associated with the effects of treatment remain unclear. This study aims to elucidate the molecular mechanistic effects of HLJD formulation on colitis.

Methods: Chronic colitis in mice was induced by adding 1% dextran sulfate sodium (DSS) to their drinking water continuously for 8 weeks, and HLJD decoction at the doses of 2 and 4 g/kg was administered orally to mice daily from the second week until experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon tissues were collected for biochemical analyses. In addition, the fecal microbiome of treated mice was characterized using 16S rRNA amplicon sequencing.

Results: HLJD decoction at doses of 2 and 4 g/kg relieved DSS-induced chronic colitis in mice by suppressing inflammation through compromised macrophage activity in colonic tissues associated with the colony-stimulating factor 1 receptor (Csf1r)/Src pathway. Furthermore, the HLJD formula could modify the gut microbiota profile by decreasing the abundance of Bacteroides, Odoribacter, Clostridium_sensu_stricto_1, and Parasutterella. In addition, close correlations between DAI, colon length, spleen weight, and gut microbiota were identified.

Discussion: Our findings revealed that the HLJD formula attenuated DSS-induced chronic colitis by reducing inflammation via Csf1r/Src-mediated macrophage infiltration, as well as modulating the gut microbiota profile.

Keywords: Csf1r; Src; colitis; gut microbiota; macrophage.

MeSH terms

  • Animals
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis* / microbiology
  • Colon / drug effects
  • Colon / microbiology
  • Colon / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Gastrointestinal Microbiome* / drug effects
  • Macrophages* / drug effects
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Signal Transduction* / drug effects
  • src-Family Kinases* / metabolism

Substances

  • Csf1r protein, mouse
  • Dextran Sulfate
  • Drugs, Chinese Herbal
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • src-Family Kinases

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. X-XL is supported by The Hong Kong Polytechnic University RAP start-up foundation, grant ID I2021A016. VK is supported by Project 82073134 of the Natural Science Foundation of China; State Key Laboratory of Chemical Biology and Drug Discovery (1-BBX8) is funded by the Department of Applied and Chemical Technology, The Hong Kong Polytechnic University, and The Hong Kong Polytechnic University Research Centre for Chinese Medicine Innovation (1-BBCT).