{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:09:05Z","timestamp":1788952145727,"version":"build-2803163510"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver disease characterized by hepatic steatosis, persistent inflammation and progressive liver damage.\n                      <jats:italic>Smilax glabra<\/jats:italic>\n                      flavonoids (SGF), the major bioactive constituents of\n                      <jats:italic>Smilax glabra Roxb<\/jats:italic>\n                      ., exhibit potent antioxidant and anti-inflammatory activities. Nevertheless, their therapeutic role and molecular basis in NASH remain elusive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study aimed to investigate the protective effects of SGF against high-fat diet (HFD)-induced NASH in mice, with emphasis on PKM2-mediated glycolysis and AIM2 inflammasome activation. C57BL\/6J mice were fed an HFD for 20 weeks to establish a NASH model and concurrently treated with SGF (30 or 90 mg\/kg\/day) or empagliflozin (EMPA). Comprehensive assessments, including biochemical detection, histological staining and molecular biological verification, were performed.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , FFA-challenged AML-12 hepatocytes and LPS-stimulated RAW264.7 macrophages were adopted. siRNA-mediated knockdown, lentiviral overexpression, and cell co-culture models were further applied to validate the underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SGF markedly attenuated HFD-induced obesity, dyslipidemia, hepatic steatosis, fibrosis and hepatocellular damage, mitigated hepatic oxidative stress and restored mitochondrial structure integrity. Mechanistically, SGF restrained glycolytic metabolism by downregulating the expression of HK2, p-PKM2, and LDHA and by reducing pyruvate and lactate production. Besides, SGF mitigated AIM2 inflammasome activation and decreased the levels of AIM2, ASC, caspase-1, and IL-1\u03b2. Mechanistic validation confirmed that PKM2 was abundantly expressed in macrophages, and PKM2 overexpression partially abrogated the inhibitory effects of SGF on glycolysis and AIM2 inflammasome signaling. Co-culture assays further demonstrated that PKM2 overexpression in RAW264.7 macrophages exacerbated lipid deposition, oxidative stress, glycolysis, and AIM2 inflammasome activation in AML-12 hepatocytes, thereby counteracting the hepatoprotective effects of SGF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SGF effectively ameliorates HFD-induced NASH by reversing metabolic disturbance, relieving oxidative stress and liver injury, and suppressing PKM2-dependent glycolysis and AIM2 inflammasome activation. Macrophage PKM2 acts as a key mediator of pathogenic macrophage-hepatocyte crosstalk, which is critical for the hepatoprotective effects of SGF against NASH. Overall, our study findings highlight SGF as a promising therapeutic option for this specific population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1906439","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:12:35Z","timestamp":1788948755000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Smilax glabra flavonoids ameliorate non-alcoholic steatohepatitis by regulating PKM2-dependent glycolysis and suppressing AIM2 inflammasome activation"],"prefix":"10.3389","volume":"17","author":[{"given":"Ziyao","family":"Pang","sequence":"first","affiliation":[{"name":"Laboratory Animal Research Center, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"School of Pharmacy, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Ding","sequence":"additional","affiliation":[{"name":"Laboratory Animal Research Center, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyi","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihao","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowei","family":"Cai","sequence":"additional","affiliation":[{"name":"Laboratory Animal Research Center, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"School of Pharmacy, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejun","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Research Center, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"School of Pharmacy, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2741\/4892","article-title":"Current treatment paradigms and emerging therapies for NAFLD\/NASH","volume":"26","author":"Raza","year":"2021","journal-title":"Front Biosci (Landmark Ed)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.jhep.2018.05.036","article-title":"Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030","volume":"69","author":"Estes","year":"2018","journal-title":"J Hepatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0145-7","article-title":"From NASH to HCC: current concepts and future challenges","volume":"16","author":"Anstee","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.04.036","article-title":"Changing epidemiology, global trends and implications for outcomes of NAFLD","volume":"79","author":"Wong","year":"2023","journal-title":"J Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fgstr.2026.1850915","article-title":"The new era of MASH pharmacotherapy: a comprehensive review of FDA-approved and emerging agents","volume":"5","author":"Qasim","year":"2026","journal-title":"Front Gastroenterol (Lausanne)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2024.103910","article-title":"NAFLD and NASH: etiology, targets and emerging therapies","volume":"29","author":"Wei","year":"2024","journal-title":"Drug Discov Today"},{"key":"B8","doi-asserted-by":"publisher","first-page":"298","DOI":"10.7570\/jomes26005","article-title":"Pharmacological therapy for metabolic dysfunction-associated steatotic liver disease in a new era for obesity and metabolic medicine: a state-of-the-art review","volume":"35","author":"Chan","year":"2026","journal-title":"J Obes Metab Syndr"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-021-01796-x","article-title":"Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis 2020","volume":"56","author":"Tokushige","year":"2021","journal-title":"J Gastroenterol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b18-00702","article-title":"Preventive effect of Citrus aurantium peel extract on high-fat diet-induced non-alcoholic fatty liver in mice","volume":"42","author":"Han","year":"2019","journal-title":"Biol Pharm Bull"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.107990","article-title":"The role of glycolysis in MASLD development: pathogenesis and therapeutic strategies","volume":"221","author":"Shang","year":"2025","journal-title":"Pharmacol Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.3c00009","article-title":"Integration of metabolomics, lipidomics, and proteomics reveals the metabolic characterization of nonalcoholic steatohepatitis","volume":"22","author":"Zhang","year":"2023","journal-title":"J Proteome Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13071636","article-title":"Identification of glycolysis-related genes in MAFLD and their immune infiltration implications: a multi-omics analysis with experimental validation","volume":"13","author":"Chen","year":"2025","journal-title":"Biomedicines"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177424","article-title":"Arctiin attenuated NASH by inhibiting glycolysis and inflammation via FGFR2\/CSF1R signaling","volume":"996","author":"Fu","year":"2025","journal-title":"Eur J Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2018.00138","article-title":"High expression of glycolytic genes in cirrhosis correlates with the risk of developing liver cancer","volume":"6","author":"Lee","year":"2018","journal-title":"Front Cell Dev Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.73890","article-title":"Covalent inhibition of pyruvate kinase M2 reprograms metabolic and inflammatory pathways in hepatic macrophages against non-alcoholic fatty liver disease","volume":"18","author":"Fan","year":"2022","journal-title":"Int J Biol Sci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/j.cmet.2021.04.018","article-title":"PKM2-dependent metabolic skewing of hepatic Th17 cells regulates pathogenesis of non-alcoholic fatty liver disease","volume":"33","author":"Moreno-Fernandez","year":"2021","journal-title":"Cell Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103488","article-title":"Exosome-equipped TNF antisense oligodeoxynucleotide or 2-deoxy-D-glucose ameliorated nonalcoholic steatohepatitis by modulating superoxide dismutase 1 in mice","volume":"80","author":"He","year":"2025","journal-title":"Redox Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.cmet.2014.12.005","article-title":"Pyruvate kinase M2 regulates Hif-1\u03b1 activity and IL-1\u03b2 induction and is a critical determinant of the warburg effect in LPS-activated macrophages","volume":"21","author":"Palsson-McDermott","year":"2015","journal-title":"Cell Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.09.019","article-title":"Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma","volume":"12","author":"Du","year":"2022","journal-title":"Acta Pharm Sin B"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3893","article-title":"Inflammasomes: mechanism of action, role in disease, and therapeutics","volume":"21","author":"Guo","year":"2015","journal-title":"Nat Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nature07710","article-title":"AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA","volume":"458","author":"Fernandes-Alnemri","year":"2009","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1038\/s41467-021-23045-8","article-title":"Distinct axial and lateral interactions within homologous filaments dictate the signaling specificity and order of the AIM2-ASC inflammasome","volume":"12","author":"Matyszewski","year":"2021","journal-title":"Nat Commun"},{"key":"B24","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/nrgastro.2015.94","article-title":"Inflammasome activation and function in liver disease","volume":"12","author":"Szabo","year":"2015","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155758","article-title":"Tryptanthrin suppresses multiple inflammasome activation to regulate NASH progression by targeting ASC protein","volume":"131","author":"Ren","year":"2024","journal-title":"Phytomedicine"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102322","article-title":"Overexpression of NAG-1\/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation","volume":"52","author":"Wang","year":"2022","journal-title":"Redox Biol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166930","article-title":"Farnesoid X receptor overexpression prevents hepatic steatosis through inhibiting AIM2 inflammasome activation in nonalcoholic fatty liver disease","volume":"1870","author":"Xu","year":"2024","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25225295","article-title":"Antioxidant and anti-inflammatory activities of six flavonoids from Smilax glabra Roxb","volume":"25","author":"Zhao","year":"2020","journal-title":"Molecules"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.556248","article-title":"Protective effects of Smilax glabra Roxb. against lead-induced renal oxidative stress, inflammation and apoptosis in weaning rats and HEK-293 cells","volume":"11","author":"Shi","year":"2020","journal-title":"Front Pharmacol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2024.141470","article-title":"Integrating larval zebrafish model and network pharmacology for screening and identification of edible herbs with therapeutic potential for MAFLD: a promising drug Smilax glabra Roxb","volume":"464","author":"Xiong","year":"2025","journal-title":"Food Chem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.918975","article-title":"Flavonoid group of Smilax glabra Roxb. regulates the anti-tumor immune response through the STAT3\/HIF-1 signaling pathway","volume":"13","author":"Guo","year":"2022","journal-title":"Front Pharmacol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.115213","article-title":"Smilax glabra Roxb. flavonoids protect against pathological cardiac hypertrophy by inhibiting the Raf\/MEK\/ERK pathway: In vivo and in vitro studies","volume":"292","author":"Fu","year":"2022","journal-title":"J Ethnopharmacol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2013.08.009","article-title":"Modulation effect of Smilax glabra flavonoids on ryanodine receptor mediated intracellular Ca2+ release in cardiomyoblast cells","volume":"150","author":"Shou","year":"2013","journal-title":"J Ethnopharmacol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26062476","article-title":"Smilax glabra flavonoids inhibit AMPK activation and induce ferroptosis in obesity-associated colorectal cancer","volume":"26","author":"Xu","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26094054","article-title":"Empagliflozin alleviates hepatic steatosis and oxidative stress via the NRF1 pathway in high-fat diet-induced mouse model of metabolic dysfunction-associated steatotic liver disease","volume":"26","author":"Heo","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2025.102977","article-title":"IL-37 improves palmitic acid-induced lipid deposition in liver cells by inhibiting ferroptosis to regulate macrophage polarization","volume":"96","author":"Zhang","year":"2025","journal-title":"Tissue Cell"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00296.2017","article-title":"Nonalcoholic fatty liver disease and gastric bypass surgery regulate serum and hepatic levels of pyruvate kinase isoenzyme M2","volume":"315","author":"Meoli","year":"2018","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155776","article-title":"Xiezhuo Tiaozhi formula inhibits macrophage pyroptosis in the non-alcoholic fatty liver disease by targeting the SIRT1 pathway","volume":"131","author":"Tian","year":"2024","journal-title":"Phytomedicine"},{"key":"B39","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.3350\/cmh.2022.0424","article-title":"Non-alcoholic fatty liver disease: definition and subtypes","volume":"29","author":"Han","year":"2023","journal-title":"Clin Mol Hepatol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1159\/000539371","article-title":"EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)","volume":"17","year":"2024","journal-title":"Obes Facts"},{"key":"B41","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1186\/s12967-024-05686-7","article-title":"Mixed active metabolites of the SNP-6 series of novel compounds mitigate metabolic dysfunction-associated steatohepatitis and fibrosis: promising results from pre-clinical and clinical trials","volume":"22","author":"Ho","year":"2024","journal-title":"J Transl Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101634","article-title":"Annexin A5 regulates hepatic macrophage polarization via directly targeting PKM2 and ameliorates NASH","volume":"36","author":"Xu","year":"2020","journal-title":"Redox Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110011","article-title":"Transcriptome profiling reveals multiple pathways responsible for the beneficial metabolic effects of Smilax glabra flavonoids in mouse 3T3-L1 adipocytes","volume":"125","author":"Tu","year":"2020","journal-title":"BioMed Pharmacother"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010498","article-title":"Non-alcoholic steatohepatitis (NASH) and organokines: what is now and what will be in the future","volume":"23","author":"Santos","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1039\/d1fo00727k","article-title":"The interaction between gut microbiota and flavonoid extract from Smilax glabra Roxb. and its potent alleviation of fatty liver","volume":"12","author":"Zhao","year":"2021","journal-title":"Food Funct"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020278","article-title":"High-density lipoprotein proteomic composition, and not efflux capacity, reflects differential modulation of reverse cholesterol transport by saturated and monounsaturated fat diets","volume":"133","author":"O'Reilly","year":"2016","journal-title":"Circulation"},{"key":"B47","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.athplu.2023.08.001","article-title":"High-density lipoproteins and non-alcoholic fatty liver disease","volume":"53","author":"Hoekstra","year":"2023","journal-title":"Atheroscler Plus"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2026.01.058","article-title":"BMAL1 downregulation exacerbates age-related nonalcoholic steatohepatitis by promoting NLRP3 inflammasome activation via HIF-1\u0251-mediated glycolysis","volume":"246","author":"Ren","year":"2026","journal-title":"Free Radic Biol Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1016\/j.jff.2023.105872","article-title":"2'-Hydroxycinnamaldehyde mitigates acetaminophen-induced acute liver injury by inhibiting the Warburg effect-mediated pyroptosis via the PKM2-NLRP3 axis","volume":"110","author":"Zhao","year":"2023","journal-title":"J Funct Foods"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2014.tb00548.x","article-title":"Energy metabolism in the liver","volume":"4","author":"Rui","year":"2014","journal-title":"Compr Physiol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1581582","article-title":"Lactate and lactylation in liver diseases: energy metabolism, inflammatory immunity and tumor microenvironment","volume":"16","author":"Cheng","year":"2025","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s12944-023-01976-z","article-title":"Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4\/AP1 signaling pathway","volume":"22","author":"Shi","year":"2023","journal-title":"Lipids Health Dis"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0009-6","article-title":"Triggering and resolution of inflammation in NASH","volume":"15","author":"Schuster","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116952","article-title":"Gentiopicroside improves NASH and liver fibrosis by suppressing TLR4 and NLRP3 signaling pathways","volume":"177","author":"Yong","year":"2024","journal-title":"BioMed Pharmacother"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118733","article-title":"Engeletin attenuates the inflammatory response via inhibiting TLR4-NF\u03baB signaling pathway in Crohn's disease-like colitis","volume":"336","author":"Wei","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155754","article-title":"Astilbin inhibited neutrophil extracellular traps in gouty arthritis through suppression of purinergic P2Y6 receptor","volume":"130","author":"Li","year":"2024","journal-title":"Phytomedicine"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.12.050","article-title":"The flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. ameliorates renal oxidative stress and inflammation in uric acid nephropathy rats through promoting uric acid excretion","volume":"111","author":"Wang","year":"2019","journal-title":"BioMed Pharmacother"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2026.158023","article-title":"Xiayuxue decoction alleviates MASH by regulating gut microbiota, bile acid metabolism, and m6A modification","volume":"154","author":"Shi","year":"2026","journal-title":"Phytomedicine"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103314","article-title":"Carbon monoxide-loaded red blood cells ameliorate metabolic dysfunction-associated steatohepatitis progression via enhancing AMP-activated protein kinase activity and inhibiting Kupffer cell activation","volume":"76","author":"Yanagisawa","year":"2024","journal-title":"Redox Biol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s40779-023-00487-3","article-title":"Caveolin-1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease","volume":"10","author":"Deng","year":"2023","journal-title":"Mil Med Res"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.3c09601","article-title":"Puerarin induces macrophage M2 polarization to exert antinonalcoholic steatohepatitis pharmacological activity via the activation of autophagy","volume":"72","author":"Fang","year":"2024","journal-title":"J Agric Food Chem"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-025-01702-8","article-title":"\u03b2-Sitosterol ameliorates metabolic dysfunction-associated steatohepatitis by targeting the RAC1\/mTOR\/TFEB axis thus activating lipophagy-lysosomal pathway","volume":"47","author":"Wang","year":"2026","journal-title":"Acta Pharmacol Sin"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13280","article-title":"PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation","volume":"7","author":"Xie","year":"2016","journal-title":"Nat Commun"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202106_26043","article-title":"The PKM2 activator TEPP-46 attenuates MCD feeding-induced nonalcoholic steatohepatitis by inhibiting the activation of Kupffer cells","volume":"25","author":"Yang","year":"2021","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B65","doi-asserted-by":"publisher","first-page":"3902","DOI":"10.1038\/s41467-023-39311-w","article-title":"Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages","volume":"14","author":"Groeger","year":"2023","journal-title":"Nat Commun"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115465","article-title":"Hexokinase 2-mediated metabolic stress and inflammation burden of liver macrophages via histone lactylation in MASLD","volume":"44","author":"Li","year":"2025","journal-title":"Cell Rep"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000005461","article-title":"PKM2 drives lactate-mediated fibrosis in liver transplantation","volume":"109","author":"Liu","year":"2025","journal-title":"Transplantation"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119376","article-title":"Total saponins from Panax japonicus reduced lipid deposition and inflammation in hepatocyte via PHD2 and hepatic macrophage-derived exosomal miR-463-5p","volume":"342","author":"Yang","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202501513RR","article-title":"Exosomes derived from bone marrow macrophages of HFD-fed mice regulating AKT\/GSK pathway in hepatocytes via miR-222-5p","volume":"40","author":"Zuo","year":"2026","journal-title":"FASEB J"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-024-00945-1","article-title":"Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation","volume":"30","author":"Nie","year":"2024","journal-title":"Mol Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1176430","article-title":"Knowledge mapping of exosomes in metabolic diseases: a bibliometric analysis (2007-2022)","volume":"14","author":"Xu","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1674028","article-title":"The emerging role of extracellular vesicles in diabetes and complications: mechanistic insights and translational prospects","volume":"16","author":"Liu","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B73","doi-asserted-by":"publisher","first-page":"23062","DOI":"10.1038\/s41598-025-07286-x","article-title":"Predictive effect and clinical diagnosis significance of exosome-related genes for nonalcoholic fatty liver disease-related hepatocellular carcinoma","volume":"15","author":"Ding","year":"2025","journal-title":"Sci Rep"},{"key":"B74","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.eng.2024.05.005","article-title":"Therapeutic targeting of PKM2 ameliorates NASH fibrosis progression in a macrophage-specific and liver-specific manner","volume":"41","author":"Qu","year":"2024","journal-title":"Engineering"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906439\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:12:36Z","timestamp":1788948756000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906439\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":74,"alternative-id":["10.3389\/fimmu.2026.1906439"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1906439","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"article-number":"1906439"}}