{"title":"Palmatine alleviates inflammation and modulates ferroptosis against dextran sulfate sodium (DSS)-induced ulcerative colitis","authors":"","doi":"10.1016/j.intimp.2024.113396","DOIUrl":null,"url":null,"abstract":"<div><div>UC, also known as ulcerative colitis, is an inflammatory bowel disease that is chronic and nonspecific. Palmatine (PAL), a natural alkaloid active ingredient, has demonstrated predominant protective effects on UC. In spite of this, PAL on UC is unclear in terms of its underlying mechanisms. Thus, this study aimed to investigate its effects and mechanism. By inducing rats with 5 % dextran sulfate sodium (DSS), an <em>in vivo</em> model of UC was developed. and then oral PAL administration. <em>In vitro</em> viability of NCM460 cells was measured using Cell Counting Kit-8. An enzyme-linked immunosorbent assay was used to determine the levels of inflammatory factores. The levels of oxidative stress parameters were also assessed, and the expression level of cyclooxygenase-2 (COX-2), acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), NF-E2-related factor 2(Nrf2), phospho-Nrf2, and heme oxygenase-1 (HO-1) was detected by Western blot. An iron kit was employed to measure iron content in cells and colonic tissues. Results indicated that PAL treatment significantly improved UC in rats, as shown by reduced disease activity index scores and increased colon length, which decreased IL-18, IL-1β, IL-6, TNF-α, MDA, NO, and LDH levels, but increased GSH level in DSS-induced rats and NCM460 cells. Further, PAL treatment markedly decreased COX-2, ACSL4, Nrf2, and HO-1 expression levels while increasing that of GPX4 and phospho-Nrf2. Furthermore, PAL inhibited the iron overload in the cells and colonic tissues. PAL may protect against UC by inhibiting the inflammatory response, oxidative stress, iron load, and suppressing ferroptosis pathway.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576924019180","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
UC, also known as ulcerative colitis, is an inflammatory bowel disease that is chronic and nonspecific. Palmatine (PAL), a natural alkaloid active ingredient, has demonstrated predominant protective effects on UC. In spite of this, PAL on UC is unclear in terms of its underlying mechanisms. Thus, this study aimed to investigate its effects and mechanism. By inducing rats with 5 % dextran sulfate sodium (DSS), an in vivo model of UC was developed. and then oral PAL administration. In vitro viability of NCM460 cells was measured using Cell Counting Kit-8. An enzyme-linked immunosorbent assay was used to determine the levels of inflammatory factores. The levels of oxidative stress parameters were also assessed, and the expression level of cyclooxygenase-2 (COX-2), acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), NF-E2-related factor 2(Nrf2), phospho-Nrf2, and heme oxygenase-1 (HO-1) was detected by Western blot. An iron kit was employed to measure iron content in cells and colonic tissues. Results indicated that PAL treatment significantly improved UC in rats, as shown by reduced disease activity index scores and increased colon length, which decreased IL-18, IL-1β, IL-6, TNF-α, MDA, NO, and LDH levels, but increased GSH level in DSS-induced rats and NCM460 cells. Further, PAL treatment markedly decreased COX-2, ACSL4, Nrf2, and HO-1 expression levels while increasing that of GPX4 and phospho-Nrf2. Furthermore, PAL inhibited the iron overload in the cells and colonic tissues. PAL may protect against UC by inhibiting the inflammatory response, oxidative stress, iron load, and suppressing ferroptosis pathway.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.