Phenolic acids from Chicory roots ameliorate dextran sulfate sodium-induced colitis in mice by targeting TRP signaling pathways and the gut microbiota

Abstract

Background: Inflammatory bowel disease (IBD) is a type of immune-mediated condition associated with intestinal homeostasis. Our preliminary studies disclosed that Cichorium intybus L., a traditional medicinal plant, also known as Chicory in Western countries, contained substantial phenolic acids displaying significant anti-inflammatory activities. We recognized the potential of harnessing Chicory for the treatment of IBD, prompting a need for in-depth investigation into the underlying mechanisms.

Methods: On the third day, mice were given 100, 200 mg/kg of total phenolic acids (PA) from Chicory and 200 mg/kg of sulfasalazine (SASP) via gavage, while dextran sodium sulfate (DSS) concentration was 2.5 % for one week. The study measured and evaluated various health markers including body weight, disease activity index (DAI), colon length, spleen index, histological score, serum concentrations of myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD), lipid oxidation (MDA), and inflammatory factors. We evaluated the TRP family and the NLRP3 inflammatory signaling pathways by Western blot, while 16S rDNA sequencing was used to track the effects of PA on gut microbes.

Results: It was shown that PA ameliorated the weight loss trend, attenuated inflammatory damage, regulated oxidative stress levels, and repaired the intestinal barrier in DSS mice. Analyses of Western blots demonstrated that PA suppressed what was expressed of transient receptor potential family TRPV4, TRPA1, and the expression of NLRP3 inflammatory signaling pathway, NLRP3 and GSDMD. In addition, PA exerted therapeutic effects on IBD by regulating gut microbiota richness and diversity. Meanwhile, the result of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis showed that gut microbiota was mainly related to Membrane Transport, Replication and Repair, Carbohydrate Metabolism and Amino Acid Metabolism.

Conclusion: PA derived from Chicory may have therapeutic effects on IBD by regulating the TRPV4/NLRP3 signaling pathway and gut microbiome. This study provides new insights into the effects of phenolic acids from Chicory on TRP ion channels and gut microbiota, revealing previously unexplored modes of action.

Keywords: Gut microbiota; Inflammatory bowel disease; Phenolic acid; TRP family.