{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:20:19Z","timestamp":1793208019809,"version":"4.5.0"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000475"],"award-info":[{"award-number":["82000475"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In recent years, sodium butyrate has gained increased attention for its numerous beneficial properties. However, whether sodium butyrate could alleviate inflammatory damage by macrophage activation and its underlying mechanism remains unclear. The present study used an advanced glycosylation products- (AGEs-) induced inflammatory damage model to study whether sodium butyrate could alleviate oxidative stress, inflammation, and metabolic dysfunction of human monocyte-macrophage originated THP-1 cells in a PI3K-dependent autophagy pathway. The results indicated that sodium butyrate alleviated the AGEs-induced oxidative stress, decreased the level of reactive oxygen species (ROS), increased malondialdehyde (MDA) and mRNA expression of pro-inflammatory cytokines of interleukin (IL)-1\u03b2 and tumor necrosis factor (TNF)-\u03b1, and increased the content of superoxide dismutase (SOD). Sodium butyrate reduced the protein expression of the NLR family, pyrin domain-containing protein 3 (NLRP3) and Caspase-1, and decreased the nucleus expression of nuclear factor-kappaB (NF-\u03baB). Sodium butyrate decreased the expression of light-chain-associated protein B (LC3B) and Beclin-1, and inhibited autophagy. Moreover, sodium butyrate inhibited the activation of the PI3K\/Akt pathway in AGEs-induced THP-1 cells. In addition, the metabolomics analysis showed that sodium butyrate could affect the production of phosphatidylcholine, L-glutamic acid, UDP-N-acetylmuraminate, biotinyl-5\u2019-AMP, and other metabolites. In summary, these results revealed that sodium butyrate inhibited autophagy and NLRP3 inflammasome activation by blocking the PI3K\/Akt\/NF-\u03baB pathway, thereby alleviating oxidative stress, inflammation, and metabolic disorder induced by AGEs.<\/jats:p>","DOI":"10.3390\/molecules27248715","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T03:23:49Z","timestamp":1670556229000},"page":"8715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Sodium Butyrate Attenuates AGEs-Induced Oxidative Stress and Inflammation by Inhibiting Autophagy and Affecting Cellular Metabolism in THP-1 Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Man","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Laboratory Department, Huai\u2019an Second People\u2019s Hospital, Huai\u2019an 223022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4411-0562","authenticated-orcid":false,"given":"Yuanyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Affiliated Huai\u2019an No. 1 People\u2019s Hospital of Nanjing Medical University, Huai\u2019an 223300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zishang","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayuan","family":"He","sequence":"additional","affiliation":[{"name":"Zhenjiang Center for Disease Control and Prevention, Zhenjiang 212002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7377-6190","authenticated-orcid":false,"given":"Dongxu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Grain Science and Technology, Jiangsu University of Science and Technology, Zhengjiang 212100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Calle, P., and Hotter, G. (2020). Macrophage Phenotype and fibrosis in diabetic nephropathy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082806"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1089\/ars.2016.6664","article-title":"Diabetes and kidney disease: Role of oxidative stress","volume":"25","author":"Jha","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.4103\/0366-6999.171350","article-title":"Epidemiological status of chronic diabetic complications in China","volume":"128","author":"Weng","year":"2015","journal-title":"Chin. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7489795","DOI":"10.1155\/2020\/7489795","article-title":"Association of glycemic indices (Hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress and diabetic complications","volume":"2020","author":"Papachristoforou","year":"2020","journal-title":"J. Diabetes Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2022). Mechanistic insight into oxidative stress-triggered signaling pathways and type 2 diabetes. Molecules, 27.","DOI":"10.3390\/molecules27030950"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3818196","DOI":"10.1155\/2020\/3818196","article-title":"Advanced glycation end products (AGEs): Biochemistry, signaling, analytical methods, and epigenetic effects","volume":"2020","author":"Perrone","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.pharmthera.2017.02.030","article-title":"Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases","volume":"177","author":"Byun","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1093\/ndt\/gfh441","article-title":"Macrophages in streptozotocin-induced diabetic nephropathy: Potential role in renal fibrosis","volume":"19","author":"Chow","year":"2004","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1681\/ASN.2019101029","article-title":"Dietary fiber protects against diabetic nephropathy through Short\u2013Chain Fatty Acid\u2013Mediated Activation of G Protein\u2013Coupled receptors GPR43 and GPR109A","volume":"31","author":"Li","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4074832","DOI":"10.1155\/2020\/4074832","article-title":"Short-chain fatty acids ameliorate diabetic nephropathy via GPR43-mediated inhibition of oxidative stress and NF-\u03baB signaling","volume":"2020","author":"Huang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1080\/19490976.2017.1290756","article-title":"Dietary fiber and prebiotics and the gastrointestinal microbiota","volume":"8","author":"Holscher","year":"2017","journal-title":"Gut. Microbes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.2174\/1381612824666181001153605","article-title":"Protective mechanisms of butyrate on inflammatory bowel disease","volume":"24","author":"Silva","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"628453","DOI":"10.3389\/fimmu.2021.628453","article-title":"Butyrate shapes immune cell fate and function in allergic asthma","volume":"12","author":"Yip","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.intimp.2019.01.018","article-title":"Butyrate inhibit collagen-induced arthritis via Treg\/IL-10\/Th17 axis","volume":"68","author":"Hui","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"892377","DOI":"10.3389\/fvets.2022.892377","article-title":"Platelet priming and activation in naturally occurring thermal burn injuries and wildfire smoke exposure is associated with intracardiac thrombosis and spontaneous echocardiographic contrast in feline survivors","volume":"9","author":"Tan","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1007\/s11255-020-02545-4","article-title":"Autophagy in diabetic nephropathy: A review","volume":"52","author":"Koch","year":"2020","journal-title":"Int. Urol. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1159\/000444841","article-title":"Autophagy in chronic kidney diseases","volume":"2","author":"Liu","year":"2016","journal-title":"Kidney Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116696","DOI":"10.1016\/j.lfs.2019.116696","article-title":"Knockdown of LSD1 meliorates Ox-LDL-stimulated NLRP3 activation and inflammation by promoting autophagy via SESN2-mesiated PI3K\/Akt\/mTOR signaling pathway","volume":"233","author":"Zhuo","year":"2019","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5541232","DOI":"10.1155\/2022\/5541232","article-title":"3beta,23-dihydroxy-12-ene-28-ursolic acid isolated from cyclocarya paliurus alleviates NLRP3 inflammasome-mediated gout via PI3K-AKT-mTOR- dependent autophagy","volume":"2022","author":"Lou","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1111\/jcmm.14834","article-title":"Metformin upregulates mitophagy in patients with T2DM: A randomized placebo-controlled study","volume":"24","author":"Bhansali","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/ni.2215","article-title":"Activation of autophagy by inflammatory signals limits IL-1beta production by targeting ubiquitinated inflammasomes for destruction","volume":"13","author":"Shi","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1093\/ndt\/gfv024","article-title":"Hyperuricemia-induced inflammasome and kidney diseases","volume":"31","author":"Isaka","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1093\/rheumatology\/ket474","article-title":"Enhanced p62 expression through impaired proteasomal degradation is involved in caspase-1 activation in monosodium urate crystal-induced interleukin-1\u03b2 expression","volume":"53","author":"Choe","year":"2014","journal-title":"Rheumatology"},{"key":"ref_24","first-page":"694","article-title":"Sodium butyrate improves liver glycogen metabolism in type 2 diabetes mellitus","volume":"677","author":"Zhang","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"571731","DOI":"10.3389\/fimmu.2020.571731","article-title":"Gut microbiota as a trigger for metabolic inflammation in obesity and type 2 diabetes","volume":"11","author":"Scheithauer","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41577-019-0198-4","article-title":"The intestinal microbiota fuelling metabolic inflammation","volume":"20","author":"Tilg","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109138","DOI":"10.1016\/j.biopha.2019.109138","article-title":"Research progress in the relationship between type 2 diabetes mellitus and intestinal flora","volume":"117","author":"Ma","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1097\/CM9.0000000000000228","article-title":"Roles of short-chain fatty acids in kidney diseases","volume":"132","author":"Li","year":"2019","journal-title":"Chin. Med. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1055\/s-0042-121493","article-title":"Short-Chain Fatty Acids Inhibit oxidative stress and inflammation in mesangial cells induced by high glucose and lipopolysaccharide","volume":"125","author":"Huang","year":"2017","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Giralt-L\u00f3pez, A., Molina-Van den, B.M., Vergara, A., Garc\u00eda-Carro, C., Seron, D., Jacobs-Cach\u00e1, C., and Soler, M.J. (2020). Revisiting experimental models of diabetic nephropathy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103587"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1161\/ATVBAHA.119.310961","article-title":"Diabetes mellitus and cardiovascular disease","volume":"39","author":"Schmidt","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101097","DOI":"10.1016\/j.arr.2020.101097","article-title":"Stochastic non-enzymatic modification of long-lived macromolecules\u2014A missing hallmark of aging","volume":"62","author":"Fedintsev","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1038\/s41467-022-30626-8","article-title":"Histone functions as a cell-surface receptor for AGEs","volume":"13","author":"Itakura","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13020-021-00485-4","article-title":"Flavonoids on diabetic nephropathy: Advances and therapeutic opportunities","volume":"16","author":"Hu","year":"2021","journal-title":"Chin. Med."},{"key":"ref_36","first-page":"323","article-title":"Dexmedetomidine attenuates high glucose-induced HK-2 epithelial-mesenchymal transition by inhibiting AKT and ERK","volume":"33","author":"Pan","year":"2020","journal-title":"Biomed. Environ. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.3389\/fphar.2020.01036","article-title":"Kuijieyuan decoction improved intestinal barrier injury of ulcerative colitis by affecting TLR4-dependent PI3K\/AKT\/NF-\u03baB oxidative and inflammatory signaling and gut microbiota","volume":"11","author":"Liu","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1056\/NEJMra2022774","article-title":"Autophagy in human diseases","volume":"383","author":"Mizushima","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"74","DOI":"10.7150\/ijbs.33787","article-title":"Metformin induces cell cycle arrest, apoptosis and autophagy through ROS\/JNK signaling pathway in human osteosarcoma","volume":"16","author":"Li","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105628","DOI":"10.1016\/j.phrs.2021.105628","article-title":"Crosstalk between extracellular vesicles and autophagy in cardiovascular pathophysiology","volume":"172","author":"Yang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.trecan.2021.05.003","article-title":"Autophagy regulates stress responses, metabolism, and anticancer immunity","volume":"7","author":"White","year":"2021","journal-title":"Trends Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.immuni.2021.01.018","article-title":"Autophagy in inflammation, infection, and immunometabolism","volume":"54","author":"Deretic","year":"2021","journal-title":"Immunity"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e2121987119","DOI":"10.1073\/pnas.2121987119","article-title":"A ferroptosis defense mechanism mediated by glycerol-3-phosphate dehydrogenase 2 in mitochondria","volume":"119","author":"Wu","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"jcs213876","DOI":"10.1242\/jcs.213876","article-title":"Lipid droplet consumption is functionally coupled to vacuole homeostasis independent of lipophagy","volume":"131","author":"Ouahoud","year":"2018","journal-title":"J. Cell. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1186\/s12967-019-2096-8","article-title":"Metabolic signature of obesity-associated insulin resistance and type 2 diabetes","volume":"17","author":"Diboun","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"151488","DOI":"10.1016\/j.ijmm.2021.151488","article-title":"The effect of gut microbiota on the intestinal lipidome of mice","volume":"311","author":"Liebisch","year":"2021","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1080\/15257770.2020.1825733","article-title":"Comparison of plasma nucleotide metabolites and amino acids pattern in patients with binge eating disorder and obesity","volume":"40","author":"Wichowicz","year":"2021","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41573-021-00339-6","article-title":"Targeting cancer metabolism in the era of precision oncology","volume":"21","author":"Stine","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e2105885","DOI":"10.1002\/advs.202105885","article-title":"Targeting glutamine metabolism to enhance immunoprevention of EGFR-Driven lung cancer","volume":"9","author":"Huang","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"356","DOI":"10.5005\/jp-journals-10071-23218","article-title":"Effects of early enteral glutamine supplementation on intestinal permeability in critically ill patients","volume":"23","author":"Shariatpanahi","year":"2019","journal-title":"Indian J. Crit. Care Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/advances\/nmy084","article-title":"Glutamine metabolism in macrophages: A novel target for obesity\/type 2 diabetes","volume":"10","author":"Ren","year":"2019","journal-title":"Adv. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bolanle, I.O., and Palmer, T.M. (2022). Targeting protein O-GlcNAcylation, a link between type 2 diabetes mellitus and inflammatory disease. Cells, 11.","DOI":"10.3390\/cells11040705"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cmet.2019.11.019","article-title":"Glutamine links obesity to inflammation in human white adipose tissue","volume":"31","author":"Petrus","year":"2020","journal-title":"Cell. Metab."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/24\/8715\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:00Z","timestamp":1760146620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/24\/8715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":53,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["molecules27248715"],"URL":"https:\/\/doi.org\/10.3390\/molecules27248715","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,9]]}}}