Acanthoside B attenuates NLRP3-mediated pyroptosis and ulcerative colitis through inhibition of tAGE/RAGE pathway
Main Article Content
Keywords
Acanthoside B, NOD-like receptor protein 3, pyroptosis, receptor for advanced glycation end-products, ulcerative colitis
Abstract
Acanthoside B (Aca.B), a principal bioactive compound extracted from Pogostemon cablin, exhibits superior anti-inflammatory capacity. Ulcerative colitis is a nonspecific inflammatory bowel disease with unknown etiology. The potential of Aca.B as a therapeutic agent for ulcerative colitis is also unknown and remains an area for future investigation. In this study, we established both in vitro and in vivo models to investigate ulcerative colitis, utilizing Llipopolysaccharide (LPS)-stimulated MODE-K cells and dextran sulfate sodium (DSS)-induced colitis in mice, respectively. The progression of ulcerative colitis was evaluated through histologic analysis, body weight monitoring, and assessment of disease activity index assessment. Furthermore, the effects on pyroptosis were detected through immunoblot analysis. We found that Aca.B treatment significantly ameliorated LPS-induced injury in MODE-K cells, as evidenced by increased cell viability and inhibition of inflammatory response. Moreover, the Aca.B treatment attenuated pyroptosis-specific protein expression, caspase-1 activation, and inflammatory cytokine secretion. In the animal study, Aca.B administration improved bowel symptoms in DSS-induced colitis mice model. This was accompanied by reductionsreduced inweight, colon shortening, inflammatory cell infiltration, and cell pyroptosis in vivo. Furthermore, Aca.B diminished the accumulation of advanced glycation end-products (AGE), resulting in a decrease in the expression of the receptor of AGE (RAGE) and downstream phosphorylated P65 expression. e.The inhibition of the inflammatory response and pyroptosis by Aca.B depends on suppressing the AGE/RAGE pathway. This study confirms the effects of Aca.B on pyroptosis and ulcerative colitis, providing a fundamental evidence for translating Aca.B into clinical applications as an anti-inflammatory medicine.
References
2 Kucharzik T, Koletzko S, Kannengiesser K, Dignass A. Ulcerative colitis-diagnostic and therapeutic algorithms. Dtsch Arztebl Int. 2020;117(33–34):564–74. 10.3238/arztebl.2020.0564
3 Feuerstein JD, Isaacs KL, Schneider Y, Siddique SM, Falck-Ytter Y, Singh S. AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020;158(5):1450–61. 10.1053/j.gastro.2020.01.006; 10.1053/j.gastro.2020.03.012
4 Wu X, Pan S, Luo W, Shen Z, Meng X, Xiao M, et al. Roseburia intestinalis-derived flagellin ameliorates colitis by targeting miR-223-3p-mediated activation of NLRP3 inflammasome and pyroptosis. Mol Med Rep. 2020;22(4):2695–704. 10.3892/mmr.2020.11351
5 Chen M, Ding Y, Tong Z. Efficacy and safety of Sophora flavescens (Kushen)-based traditional Chinese medicine in the treatment of ulcerative colitis: Clinical evidence and potential mechanisms. Front Pharmacol. 2020;11:603476. 10.3389/fphar.2020.603476
6 Xu M, Duan XY, Chen QY, Fan H, Hong ZC, Deng SJ, et al. Effect of compound sophorae decoction on dextran sodium sulfate (DSS)-induced colitis in mice by regulating Th17/Treg cell balance. Biomed Pharmacother. 2019;109:2396–408. 10.1016/j.biopha.2018.11.087
7 Li Y, Han Y, Wang X, Yang X, Ren D. Kiwifruit polysaccharides alleviate ulcerative colitis via regulating gut microbiota-dependent tryptophan metabolism and promoting colon fucosylation. J Agric Food Chem. 2024;72(43):23859-23874. 10.1021/acs.jafc.4c06435.
8 Karthivashan G, Kweon MH, Park SY, Kim JS, Kim DH, Ganesan P, et al. Cognitive-enhancing and ameliorative effects of acanthoside B in a scopolamine-induced amnesic mouse model through regulation of oxidative/inflammatory/cholinergic systems and activation of the TrkB/CREB/BDNF pathway. Food Chem Toxicol. 2019;129:444–57. 10.1016/j.fct.2019.04.062
9 Lee JH, Sun YN, Kim YH, Lee SK, Kim HP. Inhibition of lung inflammation by Acanthopanax divaricatus var. albeofructus and its constituents. Biomol Ther (Seoul). 2016;24(1):67–74. 10.4062/biomolther.2015.070
10 Mollace A, Coluccio ML, Donato G, Mollace V, Malara N. Cross-talks in colon cancer between RAGE/AGEs axis and inflammation/immunotherapy. Oncotarget. 2021;12(13):1281–95. 10.18632/oncotarget.27990
11 Jia C, Zhang J, Chen H, Zhuge Y, Chen H, Qian F, et al. Endothelial cell pyroptosis plays an important role in Kawasaki disease via HMGB1/RAGE/cathespin B signaling pathway and NLRP3 inflammasome activation. Cell Death Dis. 2019;10(10):778. 10.1038/s41419-019-2021-3
12 Wu X, Jilin Y, Bao X, Wang Y. Toll-like receptor 4 damages the intestinal epithelial cells by activating endoplasmic reticulum stress in septic rats. PeerJ. 2024;1212(0):e18185. 10.7717/peerj.18185
13 National Research Council Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals, 8th ed. Washington, DC: National Academies of Sciences Press (US); 2011. Reports funded by National Institutes of Health. PMid: 21595115.
14 Chen X, Liu G, Yuan Y, Wu G, Wang S, Yuan L. NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF-κB signaling. Cell Death Dis. 2019;10(12):906. 10.1038/s41419-019-2157-1
15 Huang MH, Han Y, Xi QH, Jin YF, Liu YL, Han YW, et al. Exploration on correlation of high DLX2 expression with poor prognosis and cellular proliferation in epithelial ovarian cancers. Eur J Gynaecol Oncol. 2021;42(3):521–9. 10.31083/j.ejgo.2021.03.2093
16 Zhang SR, Shao QM, Jia LH, Zhou F. ANXA3 regulates HIF1 alpha-induced NLRP3 inflammasome activity and promotes LPS-induced inflammatory response in bronchial epithelial cells. Signa Vitae. 2021;17(3):206–13.
17 Hou J, Hsu JM, Hung MC. Molecular mechanisms and functions of pyroptosis in inflammation and antitumor immunity. Mol Cell. 2021;81(22):4579–90. 10.1016/j.molcel.2021.09.003
18 Sun L, Ma W, Gao W, Xing Y, Chen L, Xia Z, et al. Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome. Cell Death Dis. 2019;10(8):542. 10.1038/s41419-019-1761-4
19 Du L, Ha C. Epidemiology and pathogenesis of ulcerative colitis. Gastroenterol Clin North Am. 2020;49(4):643–54. 10.1016/j.gtc.2020.07.005
20 Zeng M, Liang G, Yuan F, Yan S, Liu J, He Z. Macrophages-derived high-mobility group box-1 protein induces endothelial progenitor cells pyroptosis. iScience. 2024;27(10):110996. 10.1016/j.isci.2024.110996
21 Burri E, Maillard MH, Schoepfer AM, Seibold F, Van Assche G, Rivière P, et al. Treatment algorithm for mild and moderate-to-severe ulcerative colitis: An update. Digestion. 2020;101(Suppl 1):2–15. 10.1159/000504092
22 Zhen Y, Zhang H. NLRP3 inflammasome and inflammatory bowel disease. Front Immunol. 2019;10:276. 10.3389/fimmu.2019.00276
23 Bauer C, Duewell P, Mayer C, Lehr HA, Fitzgerald KA, Dauer M, et al. Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut. 2010;59(9):1192–9. 10.1136/gut.2009.197822
24 Mei Y, Fang C, Ding S, Liu X, Hu J, Xu J, et al. PAP-1 ameliorates DSS-induced colitis with involvement of NLRP3 inflammasome pathway. Int Immunopharmacol. 2019;75:105776. 10.1016/j.intimp.2019.105776
25 Kim MJ, Wang HS, Lee MW. Anti-inflammatory effects of fermented bark of Acanthopanax sessiliflorus and its isolated compounds on lipopolysaccharide-treated RAW 264.7 macrophage cells. Evid Based Complement Alternat Med. 2020;2020:6749425. 10.1155/2020/6749425
26 Fang Y, Tian S, Pan Y, Li W, Wang Q, Tang Y, et al. Pyroptosis: A new frontier in cancer. Biomed Pharmacother. 2020;121:109595. 10.1016/j.biopha.2019.109595
27 Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: Mechanisms and diseases. Signal Transduct Target Ther. 2021;6(1):128. 10.1038/s41392-021-00507-5
28 Kovacs SB, Miao EA. Gasdermins: Effectors of pyroptosis. Trends Cell Biol. 2017;27(9):673–84. 10.1016/j.tcb.2017.05.005
29 Chen L, Zhao Y, Lai D, Zhang P, Yang Y, Li Y, et al. Neutrophil extracellular traps promote macrophage pyroptosis in sepsis. Cell Death Dis. 2018;9(6):597. 10.1038/s41419-018-0538-5
30 Deng M, Tang Y, Li W, Wang X, Zhang R, Zhang X, et al. The endotoxin delivery protein HMGB1 mediates caspase-11-dependent lethality in sepsis. Immunity. 2018;49(4):740–53.e7. 10.1016/j.immuni.2018.08.016
