{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:53:46Z","timestamp":1789570426510,"version":"build-2803163510"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"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. Nutr."],"abstract":"<jats:p>Digestive diseases remain a major challenge to public health systems globally. Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon gene (STING) play important roles in innate immunity as well as inflammatory responses. Dysregulation of the cGAS-STING pathway has been demonstrated to be an important pathogenetic mechanism in diverse gastrointestinal diseases. Therefore, targeting the cGAS-STING pathway is a potential therapeutic strategy for digestive diseases. Encouragingly, increasing studies have revealed that natural plant products are promising candidates for the treatment of digestive disorders. This review discussed the research progress of cGAS-STING pathway mediating common digestive diseases, including inflammatory bowel disease, liver disease, colorectal cancer, gastric cancer, esophageal cancer, pancreatitis, and pancreatic cancer. In addition, we systematically summarized recent advances in the treatment of gastrointestinal disorders with phytochemicals that target the cGAS-STING pathway.<\/jats:p>","DOI":"10.3389\/fnut.2025.1594120","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T04:10:46Z","timestamp":1750392646000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["cGAS-STING pathway as a promising target for digestive diseases: insights from natural plant products"],"prefix":"10.3389","volume":"12","author":[{"given":"Dan","family":"Long","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/s12974-019-1580-7","article-title":"Effect of enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain-gut axis","volume":"16","author":"Takahashi","year":"2019","journal-title":"J Neuroinflammation"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1136\/gutjnl-2024-333227","article-title":"Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021","volume":"74","author":"Danpanichkul","year":"2024","journal-title":"Gut"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1126\/science.1229963","article-title":"Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA","volume":"339","author":"Wu","year":"2013","journal-title":"Science"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway","volume":"339","author":"Sun","year":"2013","journal-title":"Science"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/nature07317","article-title":"STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling","volume":"455","author":"Ishikawa","year":"2008","journal-title":"Nature"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/nature08476","article-title":"STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity","volume":"461","author":"Ishikawa","year":"2009","journal-title":"Nature"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1186\/s12964-024-01893-3","article-title":"Immunomodulatory effects of trastuzumab deruxtecan through the cGAS-STING pathway in gastric cancer cells","volume":"22","author":"Oh","year":"2024","journal-title":"Cell Commun Signal"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1002\/art.43062","article-title":"Role of STING deficiency in amelioration of mouse models of lupus and atherosclerosis","volume":"77","author":"Liu","year":"2024","journal-title":"Arthritis Rheumatol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"cvae238","DOI":"10.1093\/cvr\/cvae238","article-title":"PINK1-mediated mitophagy attenuates pathological cardiac hypertrophy by suppressing the mtDNA release-activated cGAS-STING pathway","volume":"121","author":"Zhou","year":"2024","journal-title":"Cardiovasc Res"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1136\/annrheumdis-2018-212988","article-title":"Apoptosis-derived membrane vesicles drive the cGAS-STING pathway and enhance type I IFN production in systemic lupus erythematosus","volume":"77","author":"Kato","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"105791","DOI":"10.1016\/j.intimp.2019.105791","article-title":"Accumulation of cytosolic dsDNA contributes to fibroblast-like synoviocytes-mediated rheumatoid arthritis synovial inflammation","volume":"76","author":"Wang","year":"2019","journal-title":"Int Immunopharmacol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"7930","DOI":"10.1038\/s41467-024-52170-3","article-title":"Targeting PRMT3 impairs methylation and oligomerization of HSP60 to boost anti-tumor immunity by activating cGAS\/STING signaling","volume":"15","author":"Shi","year":"2024","journal-title":"Nat Commun"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1128\/JVI.02760-14","article-title":"Hepatitis B virus polymerase disrupts K63-linked ubiquitination of STING to block innate cytosolic DNA-sensing pathways","volume":"89","author":"Liu","year":"2015","journal-title":"J Virol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"4932","DOI":"10.7150\/jca.32806","article-title":"STING signaling is a potential immunotherapeutic target in colorectal cancer","volume":"10","author":"Chon","year":"2019","journal-title":"J Cancer"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1020670","DOI":"10.3389\/fphar.2022.1020670","article-title":"Low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage STING activation in mice","volume":"13","author":"Gong","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2736","DOI":"10.1016\/j.immuni.2023.11.001","article-title":"Nuclear localization of STING1 competes with canonical signaling to activate AHR for commensal and intestinal homeostasis","volume":"56","author":"Zhang","year":"2023","journal-title":"Immunity"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"153495","DOI":"10.1016\/j.phymed.2021.153495","article-title":"Si-Ni-San ameliorates chronic colitis by modulating type I interferons-mediated inflammation","volume":"84","author":"Cai","year":"2021","journal-title":"Phytomedicine"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13020-021-00559-3","article-title":"Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages","volume":"17","author":"Cao","year":"2022","journal-title":"Chin Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1142\/S0192415X23500064","article-title":"Ginsenoside Rd inhibited ferroptosis to alleviate CCl4-induced acute liver injury in mice via cGAS\/STING pathway","volume":"51","author":"Li","year":"2023","journal-title":"Am J Chin Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/nature23449","article-title":"cGAS surveillance of micronuclei links genome instability to innate immunity","volume":"548","author":"Mackenzie","year":"2017","journal-title":"Nature"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1126\/science.1244040","article-title":"Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects","volume":"341","author":"Li","year":"2013","journal-title":"Science"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1002\/art.40002","article-title":"Expression of cyclic GMP-AMP synthase in patients with systemic lupus erythematosus","volume":"69","author":"An","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.celrep.2014.01.003","article-title":"The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop","volume":"6","author":"Zhang","year":"2014","journal-title":"Cell Rep"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.cell.2019.05.036","article-title":"STING polymer structure reveals mechanisms for activation, hyperactivation, and inhibition","volume":"178","author":"Ergun","year":"2019","journal-title":"Cell"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"ra20","DOI":"10.1126\/scisignal.2002521","article-title":"STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway","volume":"5","author":"Tanaka","year":"2012","journal-title":"Sci Signal"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct Target Ther"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","article-title":"Shared principles in NF-kappaB signaling","volume":"132","author":"Hayden","year":"2008","journal-title":"Cell"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/j.1600-065X.2011.01088.x","article-title":"The noncanonical NF-\u03baB pathway","volume":"246","author":"Sun","year":"2012","journal-title":"Immunol Rev"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"pe18","DOI":"10.1126\/scisignal.3123pe18","article-title":"Controlling the fate of NIK: a central stage in noncanonical NF-kappaB signaling","volume":"3","author":"Sun","year":"2010","journal-title":"Sci Signal"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"5328","DOI":"10.1128\/JVI.00037-14","article-title":"Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-\u03baB activation through TBK1","volume":"88","author":"Abe","year":"2014","journal-title":"J Virol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"107492","DOI":"10.1016\/j.celrep.2020.03.056","article-title":"TBK1 and IKK\u03b5 act redundantly to mediate STING-induced NF-\u03baB responses in myeloid cells","volume":"31","author":"Balka","year":"2020","journal-title":"Cell Rep"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e2100225118","DOI":"10.1073\/pnas.2100225118","article-title":"TBK1 recruitment to STING activates both IRF3 and NF-\u03baB that mediate immune defense against tumors and viral infections","volume":"118","author":"Yum","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.immuni.2025.03.005","article-title":"Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway","volume":"58","author":"Lai","year":"2025","journal-title":"Immunity"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.immuni.2018.07.008","article-title":"Non-canonical NF-\u03baB antagonizes STING sensor-mediated DNA sensing in radiotherapy","volume":"49","author":"Hou","year":"2018","journal-title":"Immunity"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"101215","DOI":"10.1016\/j.redox.2019.101215","article-title":"STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3","volume":"24","author":"Li","year":"2019","journal-title":"Redox Biol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e22282","DOI":"10.1096\/fj.202200138R","article-title":"Cyclic GMP-AMP synthase contributes to epithelial homeostasis in intestinal inflammation via Beclin-1-mediated autophagy","volume":"36","author":"Khan","year":"2022","journal-title":"FASEB J"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"4713","DOI":"10.7150\/ijbs.99456","article-title":"Neutrophil extracellular traps trigger alveolar epithelial cell necroptosis through the cGAS-STING pathway during acute lung injury in mice","volume":"20","author":"Sha","year":"2024","journal-title":"Int J Biol Sci"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"112990","DOI":"10.1016\/j.intimp.2024.112990","article-title":"PROTAC based STING degrader attenuates acute colitis by inhibiting macrophage M1 polarization and intestinal epithelial cells pyroptosis mediated by STING-NLRP3 axis","volume":"141","author":"Xu","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e2400305","DOI":"10.1002\/advs.202400305","article-title":"SNORD3A regulates STING transcription to promote ferroptosis in acute kidney injury","volume":"11","author":"Zhu","year":"2024","journal-title":"Adv Sci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1038\/s41419-021-04101-z","article-title":"Extracellular vesicles package dsDNA to aggravate Crohn\u2019s disease by activating the STING pathway","volume":"12","author":"Zhao","year":"2021","journal-title":"Cell Death Dis"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"G439","DOI":"10.1152\/ajpgi.00104.2022","article-title":"DNA sensor-associated type I interferon signaling is increased in ulcerative colitis and induces JAK-dependent inflammatory cell death in colonic organoids","volume":"323","author":"Flood","year":"2022","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1093\/ibd\/izy095","article-title":"Mitochondrial DNA is a pro-inflammatory damage-associated molecular pattern released during active IBD","volume":"24","author":"Boyapati","year":"2018","journal-title":"Inflamm Bowel Dis"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"593316","DOI":"10.3389\/fmed.2020.593316","article-title":"Nuclear and mitochondrial circulating cell-free DNA is increased in patients with inflammatory bowel disease in clinical remission","volume":"7","author":"Vrablicova","year":"2020","journal-title":"Front Med"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3390\/cells10010081","article-title":"Extracellular DNA correlates with intestinal inflammation in chemically induced colitis in mice","volume":"10","author":"Maronek","year":"2021","journal-title":"Cells"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"7491","DOI":"10.7150\/thno.59196","article-title":"Microbial and genetic-based framework identifies drug targets in inflammatory bowel disease","volume":"11","author":"Wang","year":"2021","journal-title":"Theranostics"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"eaaz6717","DOI":"10.1126\/sciadv.aaz6717","article-title":"Gasdermin D in macrophages restrains colitis by controlling cGAS-mediated inflammation","volume":"6","author":"Ma","year":"2020","journal-title":"Sci Adv"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"14281","DOI":"10.1038\/s41598-019-50656-5","article-title":"Stimulator of interferon genes (STING) activation exacerbates experimental colitis in mice","volume":"9","author":"Martin","year":"2019","journal-title":"Sci Rep"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"2868","DOI":"10.1084\/jem.20171029","article-title":"ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING","volume":"215","author":"Aden","year":"2018","journal-title":"J Exp Med"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/j.immuni.2021.05.008","article-title":"Dysbiosis exacerbates colitis by promoting ubiquitination and accumulation of the innate immune adaptor STING in myeloid cells","volume":"54","author":"Shmuel-Galia","year":"2021","journal-title":"Immunity"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.molcel.2013.01.039","article-title":"STING recognition of cytoplasmic DNA instigates cellular defense","volume":"50","author":"Abe","year":"2013","journal-title":"Mol Cell"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.7150\/ijbs.94548","article-title":"Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway","volume":"20","author":"Lan","year":"2024","journal-title":"Int J Biol Sci"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1038\/mi.2017.88","article-title":"The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation","volume":"11","author":"Canesso","year":"2018","journal-title":"Mucosal Immunol"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/j.jcmgh.2023.01.010","article-title":"Intrinsic STING switches off pathogenetic programs of Th1 cells to inhibit colitis","volume":"15","author":"Yang","year":"2023","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nri2515","article-title":"The gut microbiota shapes intestinal immune responses during health and disease","volume":"9","author":"Round","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/ni.1915","article-title":"Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3+ regulatory T cells","volume":"11","author":"Gandhi","year":"2010","journal-title":"Nat Immunol"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"2460538","DOI":"10.1080\/19490976.2025.2460538","article-title":"AhR activation transcriptionally induces anti-microbial peptide alpha-defensin 1 leading to reversal of gut microbiota dysbiosis and colitis","volume":"17","author":"Palrasu","year":"2025","journal-title":"Gut Microbes"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.7150\/ijbs.67356","article-title":"Atrial natriuretic peptide attenuates colitis via inhibition of the cGAS-STING pathway in colonic epithelial cells","volume":"18","author":"Chen","year":"2022","journal-title":"Int J Biol Sci"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"4547","DOI":"10.1096\/fj.201801585R","article-title":"Brefeldin A-sensitive ER-Golgi vesicle trafficking contributes to NLRP3-dependent caspase-1 activation","volume":"33","author":"Hong","year":"2019","journal-title":"FASEB J"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"4393","DOI":"10.7150\/thno.96184","article-title":"Intestinal epithelial damage-derived mtDNA activates STING-IL12 axis in dendritic cells to promote colitis","volume":"14","author":"Cai","year":"2024","journal-title":"Theranostics"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1002\/hep.30054","article-title":"Hepatitis B virus evasion from cyclic guanosine monophosphate-adenosine monophosphate synthase sensing in human hepatocytes","volume":"68","author":"Verrier","year":"2018","journal-title":"Hepatology"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41374-019-0342-6","article-title":"STING expression in monocyte-derived macrophages is associated with the progression of liver inflammation and fibrosis in patients with nonalcoholic fatty liver disease","volume":"100","author":"Wang","year":"2020","journal-title":"Lab Investig"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1038\/s41423-020-0395-x","article-title":"DNA sensing and associated type 1 interferon signaling contributes to progression of radiation-induced liver injury","volume":"18","author":"Du","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1053\/j.gastro.2018.09.010","article-title":"Expression of STING is increased in liver tissues from patients with NAFLD and promotes macrophage-mediated hepatic inflammation and fibrosis in mice","volume":"155","author":"Luo","year":"2018","journal-title":"Gastroenterology"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"16544","DOI":"10.1073\/pnas.1308331110","article-title":"STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease","volume":"110","author":"Petrasek","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"26794","DOI":"10.1074\/jbc.M116.736991","article-title":"Endoplasmic reticulum stress-induced hepatocellular death pathways mediate liver injury and fibrosis via stimulator of interferon genes","volume":"291","author":"Iracheta-Vellve","year":"2016","journal-title":"J Biol Chem"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.metabol.2017.09.010","article-title":"Activation of the STING-IRF3 pathway promotes hepatocyte inflammation, apoptosis and induces metabolic disorders in nonalcoholic fatty liver disease","volume":"81","author":"Qiao","year":"2018","journal-title":"Metabolism"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"102691","DOI":"10.1016\/j.redox.2023.102691","article-title":"STING mediates hepatocyte pyroptosis in liver fibrosis by epigenetically activating the NLRP3 inflammasome","volume":"62","author":"Xiao","year":"2023","journal-title":"Redox Biol"},{"key":"ref68","first-page":"351","article-title":"Decreased expressions of STING but not IRF3 molecules in chronic HBV infected patients","volume":"18","author":"Karimi-Googheri","year":"2015","journal-title":"Arch Iran Med"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"592","DOI":"10.3390\/v12060592","article-title":"Hepatitis B virus DNA is a substrate for the cGAS\/STING pathway but is not sensed in infected hepatocytes","volume":"12","author":"Lauterbach-Rivi\u00e8re","year":"2020","journal-title":"Viruses"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41423-021-00801-w","article-title":"STING signaling activation inhibits HBV replication and attenuates the severity of liver injury and HBV-induced fibrosis","volume":"19","author":"Li","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1053\/j.gastro.2017.10.012","article-title":"Mitochondrial dysfunction, through impaired autophagy, leads to endoplasmic reticulum stress, deregulated lipid metabolism, and pancreatitis in animal models","volume":"154","author":"Biczo","year":"2018","journal-title":"Gastroenterology"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"180","DOI":"10.4049\/jimmunol.2200484","article-title":"JMJD3 is required for acute pancreatitis and pancreatitis-associated lung injury","volume":"210","author":"Chen","year":"2023","journal-title":"J Immunol"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1053\/j.gastro.2018.01.065","article-title":"STING signaling promotes inflammation in experimental acute pancreatitis","volume":"154","author":"Zhao","year":"2018","journal-title":"Gastroenterology"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"113630","DOI":"10.1016\/j.yexcr.2023.113630","article-title":"Effect of STING signaling on intestinal barrier damage in severe acute pancreatitis","volume":"428","author":"Zhang","year":"2023","journal-title":"Exp Cell Res"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s11658-024-00575-9","article-title":"Mitochondrial (mt)DNA-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling promotes pyroptosis of macrophages via interferon regulatory factor (IRF)7\/IRF3 activation to aggravate lung injury during severe acute pancreatitis","volume":"29","author":"Peng","year":"2024","journal-title":"Cell Mol Biol Lett"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1136\/gutjnl-2018-317098","article-title":"STING signalling protects against chronic pancreatitis by modulating Th17 response","volume":"68","author":"Zhao","year":"2019","journal-title":"Gut"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13046-025-03357-z","article-title":"USP10\/XAB2\/ANXA2 axis promotes DNA damage repair to enhance chemoresistance to oxaliplatin in colorectal cancer","volume":"44","author":"Liu","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"101294","DOI":"10.1016\/j.jhepr.2024.101294","article-title":"Molecular MRI of T-cell immune response to cryoablation in immunologically hot vs. cold hepatocellular carcinoma","volume":"7","author":"Santana","year":"2025","journal-title":"JHEP Rep"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41565-018-0342-5","article-title":"Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy","volume":"14","author":"Shae","year":"2019","journal-title":"Nat Nanotechnol"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.immuni.2017.07.016","article-title":"Dendritic cells but not macrophages sense tumor mitochondrial DNA for cross-priming through signal regulatory protein \u03b1 signaling","volume":"47","author":"Xu","year":"2017","journal-title":"Immunity"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"eaay9013","DOI":"10.1126\/scitranslmed.aay9013","article-title":"cGAS-STING-mediated DNA sensing maintains CD8+ T cell stemness and promotes antitumor T cell therapy","volume":"12","author":"Li","year":"2020","journal-title":"Sci Transl Med"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1111\/cas.14266","article-title":"Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer","volume":"111","author":"Loo","year":"2020","journal-title":"Cancer Sci"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s40364-024-00606-9","article-title":"Gasdermin E benefits CD8+ T cell mediated anti-immunity through mitochondrial damage to activate cGAS-STING-interferon\u03b2 axis in colorectal cancer","volume":"12","author":"Luo","year":"2024","journal-title":"Biomark Res"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"e010889","DOI":"10.1136\/jitc-2024-010889","article-title":"Selective BCL-2 inhibitor triggers STING-dependent antitumor immunity via inducing mtDNA release","volume":"13","author":"Zhang","year":"2025","journal-title":"J Immunother Cancer"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"39858","DOI":"10.1038\/srep39858","article-title":"Decreased expression of STING predicts poor prognosis in patients with gastric cancer","volume":"7","author":"Song","year":"2017","journal-title":"Sci Rep"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"807","DOI":"10.4149\/neo_2022_211012N1441","article-title":"Anlotinib suppresses proliferation, migration, and immune escape of gastric cancer cells by activating the cGAS-STING\/IFN-\u03b2 pathway","volume":"69","author":"Yuan","year":"2022","journal-title":"Neoplasma"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"498","DOI":"10.7150\/thno.37745","article-title":"Targeting the STING pathway in tumor-associated macrophages regulates innate immune sensing of gastric cancer cells","volume":"10","author":"Miao","year":"2020","journal-title":"Theranostics"},{"key":"ref88","first-page":"10066","article-title":"Expression of STING and MIF in tumor infiltration lymphocytes as prognostic factors in patients with ESCC","volume":"10","author":"Wang","year":"2017","journal-title":"Int J Clin Exp Pathol"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"292","DOI":"10.18632\/oncotarget.27886","article-title":"Intratumoral immunotherapy with STING agonist, ADU-S100, induces CD8+ T-cell mediated anti-tumor immunity in an esophageal adenocarcinoma model","volume":"12","author":"Zaidi","year":"2021","journal-title":"Oncotarget"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"e2203264","DOI":"10.1002\/adhm.202203264","article-title":"In situ formed ROS-responsive hydrogel with STING agonist and gemcitabine to intensify immunotherapy against pancreatic ductal adenocarcinoma","volume":"12","author":"Wang","year":"2023","journal-title":"Adv Healthc Mater"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s40425-019-0573-5","article-title":"STING agonist inflames the pancreatic cancer immune microenvironment and reduces tumor burden in mouse models","volume":"7","author":"Jing","year":"2019","journal-title":"J Immunother Cancer"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"e003246","DOI":"10.1136\/jitc-2021-003246","article-title":"High potency STING agonists engage unique myeloid pathways to reverse pancreatic cancer immune privilege","volume":"9","author":"Ager","year":"2021","journal-title":"J Immunother Cancer"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/s41419-024-07102-w","article-title":"Dronedarone hydrochloride (DH) induces pancreatic cancer cell death by triggering mtDNA-mediated pyroptosis","volume":"15","author":"Li","year":"2024","journal-title":"Cell Death Dis"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"3019","DOI":"10.1002\/ptr.6734","article-title":"Ginsenoside Rd therapy improves histological and functional recovery in a rat model of inflammatory bowel disease","volume":"34","author":"Yang","year":"2020","journal-title":"Phytother Res"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"5606","DOI":"10.1039\/d3fo01315d","article-title":"Ginsenoside Rd, a natural production for attenuating fibrogenesis and inflammation in hepatic fibrosis by regulating the ERR\u03b1-mediated P2X7r pathway","volume":"14","author":"Cui","year":"2023","journal-title":"Food Funct"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"136687","DOI":"10.1016\/j.ijbiomac.2024.136687","article-title":"Curcumin-loaded polysaccharide microparticles alleviated DSS-induced ulcerative colitis by improving intestinal microecology and regulating MAPK\/NF-\u03baB\/Nrf2\/NLRP3 pathways","volume":"281","author":"Wang","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.apsb.2021.03.043","article-title":"DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS-STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis","volume":"12","author":"Wang","year":"2022","journal-title":"Acta Pharm Sin B"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"176644","DOI":"10.1016\/j.ejphar.2024.176644","article-title":"Licochalcone D ameliorates lipid metabolism in hepatocytes by modulating lipogenesis and autophagy","volume":"975","author":"Liou","year":"2024","journal-title":"Eur J Pharmacol"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"344","DOI":"10.4062\/biomolther.2024.123","article-title":"Licochalcone D exerts antitumor activity in human colorectal cancer cells by inducing ROS generation and phosphorylating JNK and p38 MAPK","volume":"33","author":"Lee","year":"2025","journal-title":"Biomol Ther"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"7324","DOI":"10.3390\/ijms22147324","article-title":"Licochalcone D ameliorates oxidative stress-induced senescence via AMPK activation","volume":"22","author":"Maharajan","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"2664","DOI":"10.1007\/s11427-024-2703-6","article-title":"Targeting STING oligomerization with licochalcone D ameliorates STING-driven inflammatory diseases","volume":"67","author":"Zhang","year":"2024","journal-title":"Sci China Life Sci"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"9939","DOI":"10.3390\/ijms25189939","article-title":"Decursin induces G1 cell cycle arrest and apoptosis through reactive oxygen species-mediated endoplasmic reticulum stress in human colorectal cancer cells in in vitro and xenograft models","volume":"25","author":"Kim","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1139\/bcb-2022-0027","article-title":"Decursin ameliorates carbon-tetrachloride-induced liver fibrosis by facilitating ferroptosis of hepatic stellate cells","volume":"100","author":"Que","year":"2022","journal-title":"Biochem Cell Biol"},{"key":"ref104","first-page":"1304","article-title":"Decursin inhibits cell growth and autophagic flux in gastric cancer via suppression of cathepsin C","volume":"11","author":"Kim","year":"2021","journal-title":"Am J Cancer Res"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"5119","DOI":"10.1007\/s00210-024-03589-4","article-title":"Decursin protects against DSS-induced experimental colitis in mice by inhibiting the cGAS-STING signaling pathway","volume":"398","author":"Wang","year":"2024","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"1351538","DOI":"10.3389\/fphar.2024.1351538","article-title":"Quercetin ameliorates ulcerative colitis by restoring the balance of M2\/M1 and repairing the intestinal barrier via downregulating cGAS-STING pathway","volume":"15","author":"Gao","year":"2024","journal-title":"Front Pharmacol"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"114653","DOI":"10.1016\/j.biopha.2023.114653","article-title":"Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway","volume":"162","author":"Sun","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"106590","DOI":"10.1016\/j.phrs.2022.106590","article-title":"Oroxylin A regulates cGAS DNA hypermethylation induced by methionine metabolism to promote HSC senescence","volume":"187","author":"Zhao","year":"2023","journal-title":"Pharmacol Res"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1089\/jmf.2019.0265","article-title":"Naringenin ameliorate carbon tetrachloride-induced hepatic damage through inhibition of endoplasmic reticulum stress and autophagy in rats","volume":"23","author":"Ustuner","year":"2020","journal-title":"J Med Food"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"26","DOI":"10.14218\/JCTH.2022.00120","article-title":"Naringenin is a potential immunomodulator for inhibiting liver fibrosis by inhibiting the cGAS-STING pathway","volume":"11","author":"Chen","year":"2023","journal-title":"J Clin Transl Hepatol"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"176044","DOI":"10.1016\/j.ejphar.2023.176044","article-title":"Ginsenoside Rd attenuates myocardial ischemia injury through improving mitochondrial biogenesis via WNT5A\/Ca2+ pathways","volume":"957","author":"Cui","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"120036","DOI":"10.1016\/j.lfs.2021.120036","article-title":"Vanillin augments liver regeneration effectively in thioacetamide induced liver fibrosis rat model","volume":"286","author":"Ghanim","year":"2021","journal-title":"Life Sci"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1177\/0960327119831067","article-title":"Beneficial role of vanillin, a polyphenolic flavoring agent, on maneb-induced oxidative stress, DNA damage, and liver histological changes in Swiss albino mice","volume":"38","author":"Sefi","year":"2019","journal-title":"Hum Exp Toxicol"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3390\/nu11020333","article-title":"Potential of Schisandra chinensis (Turcz.) Baill. in human health and nutrition: a review of current knowledge and therapeutic perspectives","volume":"11","author":"Nowak","year":"2019","journal-title":"Nutrients"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"116427","DOI":"10.1016\/j.jep.2023.116427","article-title":"Schisandrin C enhances cGAS-STING pathway activation and inhibits HBV replication","volume":"311","author":"Zhao","year":"2023","journal-title":"J Ethnopharmacol"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13020-024-00888-z","article-title":"The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages","volume":"19","author":"Wu","year":"2024","journal-title":"Chin Med"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"845959","DOI":"10.3389\/fphar.2022.845959","article-title":"Saikosaponin D inhibited IL-1\u03b2 induced ATDC 5 chondrocytes apoptosis in vitro and delayed articular cartilage degeneration in OA model mice in vivo","volume":"13","author":"Wu","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"735079","DOI":"10.3389\/fphar.2021.735079","article-title":"Saikosaponin D attenuates pancreatic injury through suppressing the apoptosis of acinar cell via modulation of the MAPK signaling pathway","volume":"12","author":"Li","year":"2021","journal-title":"Front Pharmacol"},{"key":"ref119","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1002\/jat.4594","article-title":"Saikosaponin d protects pancreatic acinar cells against cerulein-induced pyroptosis through alleviating mitochondrial damage and inhibiting cGAS-STING pathway","volume":"44","author":"Chen","year":"2024","journal-title":"J Appl Toxicol"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"113387","DOI":"10.1016\/j.biopha.2022.113387","article-title":"Icariside I\u2014a novel inhibitor of the kynurenine-AhR pathway with potential for cancer therapy by blocking tumor immune escape","volume":"153","author":"Chen","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"117134","DOI":"10.1016\/j.biopha.2024.117134","article-title":"Icariside I enhances the effects of immunotherapy in gastrointestinal cancer via targeting TRPV4 and upregulating the cGAS-STING-IFN-I pathway","volume":"177","author":"Li","year":"2024","journal-title":"Biomed Pharmacother"},{"key":"ref122","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.freeradbiomed.2018.11.004","article-title":"Andrographolide enhances redox status of liver cells by regulating microRNA expression","volume":"130","author":"Khole","year":"2019","journal-title":"Free Radic Biol Med"},{"key":"ref123","doi-asserted-by":"publisher","first-page":"113954","DOI":"10.1016\/j.jep.2021.113954","article-title":"Andrographis paniculata (Burm.f.) Nees and its major constituent andrographolide as potential antiviral agents","volume":"272","author":"Jiang","year":"2021","journal-title":"J Ethnopharmacol"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.intimp.2014.03.015","article-title":"Andrographolide sulfonate ameliorates experimental colitis in mice by inhibiting Th1\/Th17 response","volume":"20","author":"Liu","year":"2014","journal-title":"Int Immunopharmacol"},{"key":"ref125","doi-asserted-by":"publisher","first-page":"1424219","DOI":"10.3389\/fphar.2024.1424219","article-title":"Protective effect of andrographolide against ulcerative colitis by activating Nrf2\/HO-1 mediated antioxidant response","volume":"15","author":"Shu","year":"2024","journal-title":"Front Pharmacol"},{"key":"ref126","doi-asserted-by":"publisher","first-page":"112266","DOI":"10.1016\/j.fct.2021.112266","article-title":"Naringin prevents cyclophosphamide-induced hepatotoxicity in rats by attenuating oxidative stress, fibrosis, and inflammation","volume":"153","author":"Akamo","year":"2021","journal-title":"Food Chem Toxicol"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"112801","DOI":"10.1016\/j.intimp.2024.112801","article-title":"Naringin safeguards vertebral endplate chondrocytes from apoptosis and NLRP3 inflammasome activation through SIRT3-mediated mitophagy","volume":"140","author":"Wang","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"ref128","doi-asserted-by":"publisher","first-page":"3495","DOI":"10.1002\/ptr.7824","article-title":"Naringin protects against inflammation and apoptosis induced by intestinal ischemia-reperfusion injury through deactivation of cGAS-STING signaling pathway","volume":"37","author":"Gu","year":"2023","journal-title":"Phytother Res"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1594120\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T04:10:47Z","timestamp":1750392647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1594120\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,20]]},"references-count":128,"alternative-id":["10.3389\/fnut.2025.1594120"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1594120","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,20]]},"article-number":"1594120"}}