PMID- 37890606 OWN - NLM STAT- MEDLINE DCOM- 20231122 LR - 20231122 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 960 DP - 2023 Dec 5 TI - Catalpol ameliorates LPS-induced inflammatory response by activating AMPK/mTOR signaling pathway in rat intestinal epithelial cells. PG - 176125 LID - S0014-2999(23)00639-8 [pii] LID - 10.1016/j.ejphar.2023.176125 [doi] AB - Intestinal inflammation is a common clinical intestinal disease. Catalpol, a natural iridoid compound, has been shown to have anti-inflammatory, anti-oxidant and anti-apoptotic functions, but the mechanism of its protection against intestinal inflammation is still unclear. This study investigated the protective effect and potential mechanism of catalpol on the lipopolysaccharide (LPS)-induced inflammatory response of intestinal epithelial cell-6 (IEC-6). The results showed that catalpol could inhibit LPS-induced inflammatory response by dose-dependently reducing the release of inflammatory factors, such as tumor necrosis (TNF)-alpha, interleukin (IL)-1beta and IL-6, and inhibiting the nuclear factor kappa-B (NF-kappaB) signaling pathway. Catalpol ameliorated cellular oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) expression. Meanwhile, catalpol also inhibited cell apoptosis, decreased the expression of B-cell lymphoma 2 (Bcl-2) - associated X (Bax), caspase 3 and caspase 9, and increased the expression of Bcl-2. This study found that catalpol activates AMP-activated protein kinase (AMPK) signaling pathway and inhibit mammalian target of rapamycin (mTOR) phosphorylationthe. In a further study, after inhibiting AMPK with dorsomorphin, the anti-inflammatory effects of catalpol were significantly reduced. Therefore, catalpol ameliorates LPS-induced inflammatory response by activating AMPK/mTOR signaling pathway in IEC-6 cells. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Gao, Feng AU - Gao F AD - Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China. FAU - He, Qifu AU - He Q AD - Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China. FAU - Wu, Shenghui AU - Wu S AD - Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China. FAU - Zhang, Kang AU - Zhang K AD - Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China. FAU - Xu, Zhiming AU - Xu Z AD - Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China. FAU - Kang, Jian AU - Kang J AD - Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China. FAU - Quan, Fusheng AU - Quan F AD - Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China. Electronic address: quanfusheng@nwsuaf.edu.cn. LA - eng PT - Journal Article DEP - 20231026 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Lipopolysaccharides) RN - 2415-24-9 (catalpol) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - 0 (NF-kappa B) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Antioxidants) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Anti-Inflammatory Agents) RN - EC 2.7.1.1 (mTOR protein, rat) SB - IM MH - Rats MH - Animals MH - *Lipopolysaccharides/pharmacology MH - *AMP-Activated Protein Kinases/metabolism MH - Signal Transduction MH - NF-kappa B/metabolism MH - Epithelial Cells/metabolism MH - TOR Serine-Threonine Kinases/metabolism MH - Oxidative Stress MH - Tumor Necrosis Factor-alpha/metabolism MH - Antioxidants/pharmacology MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Inflammation/chemically induced/drug therapy/prevention & control MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Mammals OTO - NOTNLM OT - AMPK/mTOR signaling pathway OT - Apoptosis OT - Catalpol OT - Intestinal inflammation OT - Oxidative stress COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/10/28 11:42 MHDA- 2023/11/22 06:43 CRDT- 2023/10/27 19:28 PHST- 2023/02/23 00:00 [received] PHST- 2023/10/01 00:00 [revised] PHST- 2023/10/16 00:00 [accepted] PHST- 2023/11/22 06:43 [medline] PHST- 2023/10/28 11:42 [pubmed] PHST- 2023/10/27 19:28 [entrez] AID - S0014-2999(23)00639-8 [pii] AID - 10.1016/j.ejphar.2023.176125 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Dec 5;960:176125. doi: 10.1016/j.ejphar.2023.176125. Epub 2023 Oct 26.