PMID- 38193197 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20240214 IS - 1522-1547 (Electronic) IS - 0193-1857 (Linking) VI - 326 IP - 3 DP - 2024 Mar 1 TI - An inulin-type fructan CP-A from Codonopsis pilosula alleviates TNBS-induced ulcerative colitis based on serum-untargeted metabolomics. PG - G216-G227 LID - 10.1152/ajpgi.00214.2023 [doi] AB - Ulcerative colitis (UC) is an inflammatory disease with abdominal pain, diarrhea, and bloody stool as the main symptoms. Several studies have confirmed that polysaccharides are effective against UC. It is commonly accepted that the traditional benefits of Radix Codonopsis can be attributed to its polysaccharide contents, and inulin-type fructan CP-A is the main active monomer in the polysaccharide components. Herein, we established a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC rat model and lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) to investigate the effect of CP-A on UC. Untargeted metabolomics studies were conducted to identify differential metabolites using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) and enrich metabolic pathways in rat serum. The in vivo assays demonstrated that CP-A reduces colonic macroscopic injury, disease activity index (DAI), histopathological score, interleukin (IL)-8, and tumor necrosis factor-alpha (TNF-alpha) levels, as well as the expression of intercellular adhesion molecules. On the other hand, CP-A increases IL-10 and transforming growth factor-beta (TGF-beta) levels. The in vitro experiments indicated that CP-A treatment could reduce nitric oxide (NO) and IL-1beta after LPS stimulation. The metabolomics results suggested that CP-A therapy for UC may be related to the mammalian target of rapamycin (mTOR) signaling pathway. The in vitro and in vivo validation of the pathway showed similar results, indicating that CP-A alleviates UC by preventing the activation of mTOR/p70S6K signaling pathway. These findings offer a fresh approach to treating UC and a theoretical foundation for the future advancement of CP-A.NEW & NOTEWORTHY We report that an inulin-type fructan from Codonopsis pilosula CP-A exhibits a therapeutic effect on experimental colitis. Its mechanism may be to alleviate intestinal inflammation by preventing the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling pathway. These findings offer a fresh approach to treating ulcerative colitis (UC) and a theoretical foundation for the future advancement of CP-A. FAU - Zhou, Jiangtao AU - Zhou J AD - School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China. ROR: https://ror.org/0265d1010 AD - Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, People's Republic of China. ROR: https://ror.org/0265d1010 AD - Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, People's Republic of China. FAU - Wang, Jiajing AU - Wang J AD - School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China. ROR: https://ror.org/0265d1010 FAU - Li, Deyun AU - Li D AD - School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China. ROR: https://ror.org/0265d1010 FAU - Zhang, Zhijia AU - Zhang Z AD - Urology Surgery, Shanxi Provincial People's Hospital, Taiyuan, People's Republic of China. FAU - Wang, Changjian AU - Wang C AD - School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China. ROR: https://ror.org/0265d1010 FAU - Zhang, Xuepeng AU - Zhang X AD - School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China. ROR: https://ror.org/0265d1010 FAU - Xu, Xiexin AU - Xu X AD - School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China. ROR: https://ror.org/0265d1010 FAU - Gao, Jianping AU - Gao J AUID- ORCID: 0000-0002-8115-6298 AD - School of Pharmacy, Shanxi Medical University, Taiyuan, People's Republic of China. ROR: https://ror.org/0265d1010 AD - Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, People's Republic of China. ROR: https://ror.org/0265d1010 AD - Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, People's Republic of China. LA - eng GR - 81904031/MOST | National Natural Science Foundation of China (NSFC)/ GR - 2019YFC1710800/MOST | National Key Research and Development Program of China (NKPs)/ GR - 201901D211325/| Natural Science Foundation of Shanxi Province (Shanxi Natural Science Foundation)/ PT - Journal Article DEP - 20240109 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 9005-80-5 (Inulin) RN - 0 (Fructans) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - 0 (Sulfonic Acids) RN - 0 (Lipopolysaccharides) RN - 0 (Polysaccharides) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Rats MH - Animals MH - *Colitis, Ulcerative/chemically induced/drug therapy/metabolism MH - Inulin/pharmacology MH - Fructans/adverse effects/chemistry MH - *Codonopsis/chemistry MH - Ribosomal Protein S6 Kinases, 70-kDa/therapeutic use MH - Sulfonic Acids/adverse effects MH - Lipopolysaccharides MH - Polysaccharides MH - TOR Serine-Threonine Kinases MH - *Colitis/chemically induced/drug therapy MH - Disease Models, Animal MH - Mammals OTO - NOTNLM OT - Codonopsis pilosula OT - inulin-type fructan CP-A OT - metabolomics OT - ulcerative colitis EDAT- 2024/01/09 06:42 MHDA- 2024/02/13 00:42 CRDT- 2024/01/09 04:05 PHST- 2024/02/13 00:42 [medline] PHST- 2024/01/09 06:42 [pubmed] PHST- 2024/01/09 04:05 [entrez] AID - 10.1152/ajpgi.00214.2023 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2024 Mar 1;326(3):G216-G227. doi: 10.1152/ajpgi.00214.2023. Epub 2024 Jan 9.