{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:11:45Z","timestamp":1790262705097,"version":"4.1.0"},"reference-count":121,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"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. Pharmacol."],"abstract":"<jats:p>Gentiopicroside (GPS), a secoiridoid glycoside found in traditional medicinal plants such as Gentiana scabra Bunge, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, antidiabetic, antitumor, and skin disease-modulating effects. This review consolidates current research on GPS, highlighting its mechanisms of action across various diseases. GPS modulates key signaling pathways, such as NF-\u03baB and MAPK, to suppress pro-inflammatory cytokines and oxidative stress. It activates the Keap1-Nrf2 pathway to enhance cellular antioxidant defenses and exhibits direct free radical scavenging capabilities. In neurodegenerative diseases like Alzheimer\u2019s and Parkinson\u2019s, GPS reduces amyloid-\u03b2 accumulation and dopaminergic neuron loss, respectively. Its hepatoprotective effects include mitigating chemical- and alcohol-induced liver damage by regulating lipid metabolism and reducing fibrosis. GPS also improves insulin sensitivity in diabetes and inhibits tumor cell proliferation and migration. Additionally, GPS shows promise in treating skin conditions like psoriasis and enhancing wound healing. Despite its therapeutic potential, current evidence is limited by methodological gaps, preclinical inconsistencies and weak clinical evidence (no large-scale randomized controlled trials [RCTs]). Challenges such as low bioavailability and the need for further clinical validation remain. Future research should focus on optimizing GPS formulations and conducting rigorous RCTs, standardizing botanical drug characterization, translating preclinical findings into effective therapies.<\/jats:p>","DOI":"10.3389\/fphar.2025.1634722","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:25:29Z","timestamp":1764051929000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Therapeutic efficacy and mechanisms of gentiopicroside in various diseases"],"prefix":"10.3389","volume":"16","author":[{"given":"Ling","family":"Kui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinshi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaming","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingfeng","family":"Leng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinming","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanjiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"122106","DOI":"10.1016\/j.ijpharm.2022.122106","article-title":"Co-delivery of gentiopicroside and thymoquinone using electrospun m-peg\/pvp nanofibers: in-vitro and in vivo studies for antibacterial wound dressing in diabetic rats","volume":"625","author":"Almukainzi","year":"","journal-title":"Int. J. Pharm."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.2147\/ijn.S358606","article-title":"Gentiopicroside plga nanospheres: fabrication, in vitro characterization, antimicrobial action, and in vivo effect for enhancing wound healing in diabetic rats","volume":"17","author":"Almukainzi","year":"","journal-title":"Int. J. Nanomedicine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3390\/cells13010070","article-title":"Gentiopicroside-an insight into its pharmacological significance and future perspectives","volume":"13","author":"Antoniadi","year":"2023","journal-title":"Cells"},{"key":"B4","doi-asserted-by":"publisher","first-page":"715","DOI":"10.3389\/fphar.2019.00715","article-title":"Natural plants compounds as modulators of epithelial-to-mesenchymal transition","volume":"10","author":"Avila-Carrasco","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e07869","DOI":"10.2903\/j.efsa.2023.7869","article-title":"Safety of a feed additive consisting of a tincture derived from the roots of Gentiana lutea l. (gentian tincture) for all animal species (fefana asbl)","volume":"21","author":"Bampidis","year":"2023","journal-title":"Efsa J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1111\/ics.12878","article-title":"In vitro, ex vivo and clinical approaches to evaluate the potential effect of gentiana lutea extract on skin","volume":"45","author":"Berthon","year":"2023","journal-title":"Int. J. Cosmet. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"27159","DOI":"10.1038\/s41598-025-12255-5","article-title":"Gentiopicroside improves dss-induced ulcerative colitis and secondary liver injury in mice by enhancing the intestinal barrier and regulating the gut microbiome","volume":"15","author":"Cao","year":"2025","journal-title":"Sci. Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"107213","DOI":"10.1016\/j.intimp.2020.107213","article-title":"Gentiopicroside ameliorates ethanol-induced gastritis via regulating mmp-10 and perk1\/2 signaling","volume":"90","author":"Chang","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.jep.2011.08.001","article-title":"Isolation of gentiopicroside from gentianae radix and its pharmacokinetics on liver ischemia\/reperfusion rats","volume":"141","author":"Chang-Liao","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1016\/j.bbrc.2017.12.112","article-title":"Gentiopicroside ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibiting inflammatory and fibrotic process","volume":"495","author":"Chen","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"4685","DOI":"10.1038\/s41598-024-55525-4","article-title":"Study of the mechanism by gentiopicroside protects against skin fibroblast glycation damage via the rage pathway","volume":"14","author":"Chen","year":"2024","journal-title":"Sci. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.biopha.2018.02.014","article-title":"Gentiopicroside inhibits rankl-induced osteoclastogenesis by regulating nf-\u03bab and jnk signaling pathways","volume":"100","author":"Chen","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s40001-024-01637-6","article-title":"Gentiopicroside inhibits the progression of gastric cancer through modulating egfr\/pi3k\/akt signaling pathway","volume":"29","author":"Chen","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.mrgentox.2020.503251","article-title":"New insight into the antigenotoxic activity of gentiana lutea extracts - protective effect against food borne mutagens","author":"Cvetkovi\u0107","year":"2020","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1039\/c8fo00168e","article-title":"Hepatoprotective activity of iridoids, seco-iridoids and analog glycosides from gentianaceae on hepg2 cells via cyp3a4 induction and mitochondrial pathway","volume":"9","author":"Dai","year":"2018","journal-title":"Food Funct."},{"key":"B16","doi-asserted-by":"publisher","first-page":"339","DOI":"10.2133\/dmpk.dmpk-12-rg-090","article-title":"In vitro inhibition and induction of human liver cytochrome p450 enzymes by gentiopicroside: potent effect on cyp2a6","volume":"28","author":"Deng","year":"2013","journal-title":"Drug Metab. Pharmacokinet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1097\/wnr.0000000000001082","article-title":"Gentiopicroside protects neurons from astrocyte-mediated inflammatory injuries by inhibition of nuclear factor-\u03bab and mitogen-activated protein kinase signaling pathways","volume":"29","author":"Deng","year":"2018","journal-title":"Neuroreport"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e202402306","DOI":"10.1002\/cbdv.202402306","article-title":"Gentiopicroside: an updated review of its pharmacological activities and mechanisms","volume":"22","author":"Ding","year":"2024","journal-title":"Chem. Biodivers."},{"key":"B19","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1055\/s-0042-1759687","article-title":"Outcome of preoperative asymptomatic or minimally symptomatic druj arthritis after total wrist arthrodesis: a single-institution case series","volume":"12","author":"Dittman","year":"2023","journal-title":"J. Wrist Surg."},{"key":"B20","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1080\/13880209.2019.1643378","article-title":"Biological activities, isolated compounds and hplc profile of verbascum nubicum","volume":"57","author":"El Gizawy","year":"2019","journal-title":"Pharm. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"074902","DOI":"10.1063\/1.4993958","article-title":"Generalized einstein relation for the mutual diffusion coefficient of a binary fluid mixture","volume":"147","author":"Felderhof","year":"2017","journal-title":"J. Chem. Phys."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1111\/jphp.12266","article-title":"A rapid and sensitive uflc-ms\/ms method for the simultaneous determination of gentiopicroside and swertiamarin in rat plasma and its application in pharmacokinetics","volume":"66","author":"Feng","year":"2014","journal-title":"J. Pharm. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"7575","DOI":"10.3390\/molecules28227575","article-title":"Metabolic transformation of gentiopicrin, a liver protective active ingredient, based on intestinal bacteria","volume":"28","author":"Fu","year":"2023","journal-title":"Molecules"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.05.039","article-title":"Targeting the bile acid receptor tgr5 with gentiopicroside to activate nrf2 antioxidant signaling and mitigate Parkinson'S disease in an mptp mouse model","author":"Gao","year":"2025","journal-title":"J. Adv. Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e4","DOI":"10.1590\/s1678-9946201961004","article-title":"Safety assessment of seasonal trivalent influenza vaccine produced by instituto butantan from 2013 to 2017","volume":"61","author":"Gatt\u00e1s","year":"2018","journal-title":"Rev. Inst. Med. Trop. Sao Paulo."},{"key":"B26","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1038\/s41586-024-07871-6","article-title":"Cellular communities reveal trajectories of brain ageing and Alzheimer'S disease","volume":"633","author":"Green","year":"2024","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e32239","DOI":"10.1016\/j.heliyon.2024.e32239","article-title":"Development of a high-speed and ultrasensitive uv\/vis-cm for detecting total triterpenes in traditional chinese medicine and its application","volume":"10","author":"Guo","year":"2024","journal-title":"Heliyon"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1159\/000493409","article-title":"Exploration of hepatoprotective effect of gentiopicroside on alpha-naphthylisothiocyanate-induced cholestatic liver injury in rats by comprehensive proteomic and metabolomic signatures","volume":"49","author":"Han","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s11418-015-0894-8","article-title":"The anti-inflammatory secoiridoid glycosides from gentianae scabrae radix: the root and rhizome of gentiana scabra","volume":"69","author":"He","year":"2015","journal-title":"J. Nat. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"953205","DOI":"10.3389\/fphar.2022.953205","article-title":"Best practice in the chemical characterisation of extracts used in pharmacological and toxicological research-the conphymp-guidelines","volume":"13","author":"Heinrich","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B31","article-title":"Rectal carcinoma in a 24-year-old man with hirschsprung's disease","volume":"180","author":"Henriksen","year":"2018","journal-title":"Ugeskr. Laeger"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/j.biopha.2017.08.120","article-title":"Il-1\u03b2-induced nf-\u03bab activation down-regulates mir-506 expression to promotes osteosarcoma cell growth through jag1","volume":"95","author":"Hu","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1080\/01635581.2020.1801777","article-title":"Gentiopicroside inhibits cell growth and migration on cervical cancer via the reciprocal mapk\/akt signaling pathways","volume":"73","author":"Hu","year":"2021","journal-title":"Nutr. Cancer"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1068326","DOI":"10.1155\/2024\/1068326","article-title":"Gentiopicroside ameliorates sepsis-induced acute lung injury via inhibiting inflammatory response","volume":"2024","author":"Hu","year":"2024","journal-title":"Can. Respir. J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"5109","DOI":"10.2147\/dddt.S270757","article-title":"Research on the potential mechanism of gentiopicroside against gastric cancer based on network pharmacology","volume":"14","author":"Huang","year":"2020","journal-title":"Drug Des. Devel Ther."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1335814","DOI":"10.3389\/fphar.2024.1335814","article-title":"Gentiopicroside improves non-alcoholic steatohepatitis by activating ppar\u03b1 and suppressing hif1","volume":"15","author":"Huang","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e02830","DOI":"10.1002\/advs.202502830","article-title":"Glucose-responsive and analgesic gel for diabetic subcutaneous abscess treatment by simultaneously boosting photodynamic therapy and relieving hypoxia","volume":"12","author":"Huang","year":"2025","journal-title":"Adv. Sci. (Weinh)"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e568","DOI":"10.1038\/bcj.2017.50","article-title":"Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase ii multicentre filo trial","volume":"7","author":"Hunault-Berger","year":"2017","journal-title":"Blood Cancer J."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jep.2016.05.027","article-title":"Iridoid glycosides from the flowers of gentiana macrophylla pall. Ameliorate collagen-induced arthritis in rats","volume":"189","author":"Jia","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"10825","DOI":"10.1111\/jcmm.16410","article-title":"Gentiopicroside promotes the osteogenesis of bone mesenchymal stem cells by modulation of \u03b2-catenin-bmp2 signalling pathway","volume":"25","author":"Jiang","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"B41","first-page":"1384","article-title":"Application of afp whole blood one-step rapid detection kit in screening for hcc in qidong","volume":"7","author":"Jin","year":"2017","journal-title":"Am. J. Cancer Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2940746","DOI":"10.1155\/2020\/2940746","article-title":"Gentiopicroside ameliorates oxidative stress and lipid accumulation through nuclear factor erythroid 2-related factor 2 activation","volume":"2020","author":"Jin","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"B43","doi-asserted-by":"publisher","first-page":"81","DOI":"10.11604\/pamj.2020.36.81.23776","article-title":"Implications of covid-19 infections in sickle cell disease","author":"John","year":"2020","journal-title":"Pan Afr. Med. J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.3390\/plants13111445","article-title":"Spasmolytic, antimicrobial, and antioxidant activities of spray-dried extracts of gentiana asclepiadea l. With in silico pharmacokinetic analysis","volume":"13","author":"Jovanovi\u0107","year":"2024","journal-title":"Plants (Basel)"},{"key":"B45","doi-asserted-by":"publisher","first-page":"18465","DOI":"10.1074\/jbc.M110.200022","article-title":"Resistin promotes cardiac hypertrophy via the amp-activated protein kinase\/mammalian target of rapamycin (ampk\/mtor) and c-jun n-terminal kinase\/insulin receptor substrate 1 (jnk\/irs1) pathways","volume":"286","author":"Kang","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s00117-024-01346-5","article-title":"Medical imaging in cancer cachexia","volume":"64","author":"Ko","year":"2024","journal-title":"Radiol. (Heidelb)"},{"key":"B47","doi-asserted-by":"publisher","first-page":"3025","DOI":"10.1080\/14786419.2022.2144301","article-title":"Secondary metabolites from gentiana cruciata l. And their anti-inflammatory and analgesic activities","volume":"37","author":"Konya","year":"2023","journal-title":"Nat. Prod. Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1055\/s-0031-1298021","article-title":"Determination of the plasma pharmacokinetic and tissue distributions of swertiamarin in rats by liquid chromatography with tandem mass spectrometry","volume":"62","author":"Li","year":"2012","journal-title":"Arzneimittelforschung"},{"key":"B49","first-page":"280","article-title":"Gentiopicroside exerts convincing antitumor effects in human ovarian carcinoma cells (skov3) by inducing cell cycle arrest, mitochondrial mediated apoptosis and inhibition of cell migration","volume":"24","author":"Li","year":"2019","journal-title":"J. buon"},{"key":"B50","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13020-020-0292-3","article-title":"Integrated quality evaluation strategy for multi-species resourced herb medicine of qinjiao by metabolomics analysis and genetic comparation","volume":"15","author":"Li","year":"2020","journal-title":"Chin. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e20230183","DOI":"10.1590\/1980-220X-REEUSP-2023-0183en","article-title":"Gentiopicroside injection promotes the healing of pressure injury wounds by upregulating the expression of bfgfr1","volume":"58","author":"Li","year":"2024","journal-title":"Rev. Esc. Enferm. Usp."},{"key":"B52","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1007\/s11655-024-4206-6","article-title":"Gentiopicroside alleviates atherosclerosis by suppressing reactive oxygen species-dependent nlrp3 inflammasome activation in vascular endothelial cells via sirt1\/nrf2 pathway","volume":"31","author":"Li","year":"2025","journal-title":"Chin. J. Integr. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.cbi.2010.06.004","article-title":"Anti-apoptotic activity of gentiopicroside in d-galactosamine\/lipopolysaccharide-induced murine fulminant hepatic failure","volume":"188","author":"Lian","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"B54","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1111\/j.1755-5949.2012.00338.x","article-title":"Gentiopicroside attenuates morphine rewarding effect through downregulation of glun2b receptors in nucleus accumbens","volume":"18","author":"Liu","year":"2012","journal-title":"CNS Neurosci. Ther."},{"key":"B55","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1007\/s12017-013-8280-8","article-title":"Attenuation of reserpine-induced pain\/depression dyad by gentiopicroside through downregulation of glun2b receptors in the amygdala of mice","volume":"16","author":"Liu","year":"2014","journal-title":"Neuromolecular Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"9125752","DOI":"10.1155\/2020\/9125752","article-title":"Gentiopicroside, a secoiridoid glycoside from gentiana rigescens franch, extends the lifespan of yeast via inducing mitophagy and antioxidative stress","volume":"2020","author":"Liu","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"B57","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s00210-023-02672-6","article-title":"Regulatory mechanisms of gentiopicroside on human diseases: a brief review","volume":"397","author":"Liu","year":"2024","journal-title":"Naunyn Schmiedeb. Arch. Pharmacol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"116974","DOI":"10.1016\/j.biopha.2024.116974","article-title":"The secoiridoid glycoside gentiopicroside is a usp22 inhibitor with potent antitumor immunotherapeutic activity","volume":"177","author":"Lu","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"B59","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.fct.2012.10.034","article-title":"Hepatoprotective effects of gentiana asclepiadea l. Extracts against carbon tetrachloride induced liver injury in rats","volume":"52","author":"Mihailovi\u0107","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1039\/c4fo00088a","article-title":"Hepatoprotective effects of secoiridoid-rich extracts from gentiana cruciata l. Against carbon tetrachloride induced liver damage in rats","volume":"5","author":"Mihailovi\u0107","year":"2014","journal-title":"Food Funct."},{"key":"B61","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.jtcme.2016.12.013","article-title":"Medicinal, biological and phytochemical properties of gentiana species","volume":"7","author":"Mirzaee","year":"2017","journal-title":"J. Tradit. Complement. Med."},{"key":"B62","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3390\/pharmaceutics17010071","article-title":"Dual-mechanism gastroretentive tablets with encapsulated gentian root extract","volume":"17","author":"Mudri\u0107","year":"2025","journal-title":"Pharmaceutics"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1080\/15476286.2018.1486661","article-title":"The bifurcated stem loop 4 (sl4) is crucial for efficient packaging of mouse mammary tumor virus (mmtv) genomic rna","volume":"15","author":"Mustafa","year":"2018","journal-title":"RNA Biol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1021\/np900322c","article-title":"DNA-damaging, mutagenic, and clastogenic activities of gentiopicroside isolated from cephalaria kotschyi roots","volume":"73","author":"Mustafayeva","year":"2010","journal-title":"J. Nat. Prod."},{"key":"B65","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.intimp.2016.07.003","article-title":"Protective effect of gentiopicroside against dextran sodium sulfate induced colitis in mice","volume":"39","author":"Niu","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"7","DOI":"10.2174\/1574891x13666180913154355","article-title":"Amarogentin as topical anticancer and anti-infective potential: scope of lipid based vesicular in its effective delivery","volume":"14","author":"Patel","year":"2019","journal-title":"Recent Pat. Antiinfect Drug Discov."},{"key":"B67","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1080\/13880209.2024.2354341","article-title":"Comprehensive profiling of the chemical constituents in dayuanyin decoction using uplc-qtof-ms combined with molecular networking","volume":"62","author":"Peng","year":"2024","journal-title":"Pharm. Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"13018","DOI":"10.1074\/jbc.271.22.13018","article-title":"Tumor necrosis factor (Tnf)-alpha inhibits insulin signaling through stimulation of the p55 tnf receptor and activation of sphingomyelinase","volume":"271","author":"Peraldi","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B69","doi-asserted-by":"publisher","first-page":"919","DOI":"10.2147\/dddt.S398861","article-title":"Synthesis and biological evaluation of gentiopicroside derivatives as novel cyclooxygenase-2 inhibitors with anti-inflammatory activity","volume":"17","author":"Ren","year":"2023","journal-title":"Drug Des. Devel Ther."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1038\/s41401-024-01449-8","article-title":"Gentiopicroside ameliorates psoriasis-like skin lesions in mice via regulating the keap1-nrf2 pathway and inhibiting keratinocyte activation","volume":"46","author":"Ren","year":"2025","journal-title":"Acta Pharmacol. Sin."},{"key":"B71","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.fitote.2015.04.015","article-title":"Attenuation of stress-induced gastrointestinal motility disorder by gentiopicroside, from gentiana macrophylla pall","volume":"103","author":"Ruan","year":"2015","journal-title":"Fitoterapia"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1007\/s12010-024-05114-y","article-title":"Phytochemical analysis, isolation, and characterization of gentiopicroside from gentiana kurroo and cytotoxicity of biosynthesized silver nanoparticles against hela cells","volume":"197","author":"Sharma","year":"2025","journal-title":"Appl. Biochem. Biotechnol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.14670\/hh-18-879","article-title":"Gentiopicroside alleviates neuroinflammation in Parkinson'S disease by mediating microglial pyroptosis via the nf-\u03bab\/nlrp3\/gsdmd pathway","volume":"40","author":"Shen","year":"2025","journal-title":"Histol. Histopathol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.3389\/fphar.2020.01295","article-title":"An integrated pharmacokinetic study of an acanthopanax senticosus extract preparation by combination of virtual screening, systems pharmacology, and multi-component pharmacokinetics in rats","volume":"11","author":"Shi","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.pathophys.2019.09.002","article-title":"Gastrointestinal effects of standardized brazilian phytomedicine (arthur de carvalho drops\u00ae) containing matricaria recutita, gentiana lutea and foeniculum vulgare","volume":"26","author":"Silveira","year":"2019","journal-title":"Pathophysiology"},{"key":"B76","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1248\/cpb.c17-00720","article-title":"Secoiridoid glycosides from the twigs of ligustrum obtusifolium possess anti-inflammatory and neuroprotective effects","volume":"66","author":"Suh","year":"2018","journal-title":"Chem. Pharm. Bull. (Tokyo)"},{"key":"B77","first-page":"473","article-title":"Determination and tissue distribution comparisons of gentiopicroside after oral administration of raw and wine-processed gentiana radix","volume":"35","author":"Sun","year":"2022","journal-title":"Pak J. Pharm. Sci."},{"key":"B78","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3390\/ph16010099","article-title":"Preparation, characterization, and in vivo evaluation of gentiopicroside-phospholipid complex (gtp-pc) and its self-nanoemulsion drug delivery system (gtp-pc-snedds)","volume":"16","author":"Tong","year":"2023","journal-title":"Pharm. (Basel)"},{"key":"B79","doi-asserted-by":"publisher","first-page":"23699","DOI":"10.1021\/jacs.4c08960","article-title":"Mixed-metal alloying in hybrid bronzes","volume":"146","author":"Walte","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"B80","doi-asserted-by":"publisher","first-page":"118689","DOI":"10.1016\/j.lfs.2020.118689","article-title":"Hepatoprotective effect of gentiopicroside in combination with leflunomide and\/or methotrexate in arthritic rats","volume":"265","author":"Wan","year":"2021","journal-title":"Life Sci."},{"key":"B81","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/bf03190598","article-title":"Pharmacokinetics and tissue distribution of gentiopicroside following oral and intravenous administration in mice","volume":"29","author":"Wang","year":"2004","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.jpba.2007.04.036","article-title":"Pharmacokinetics and bioavailability of gentiopicroside from decoctions of gentianae and longdan xiegan tang after oral administration in rats-comparison with gentiopicroside alone","volume":"44","author":"Wang","year":"2007","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpba.2014.12.003","article-title":"Two main metabolites of gentiopicroside detected in rat plasma by lc-tof-ms following 2,4-dinitrophenylhydrazine derivatization","volume":"107","author":"Wang","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B84","doi-asserted-by":"publisher","first-page":"731","DOI":"10.21037\/atm.2019.11.126","article-title":"Gentiopicroside (gent) protects against sepsis induced by lipopolysaccharide (lps) through the nf-\u03bab signaling pathway","volume":"7","author":"Wang","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"B85","doi-asserted-by":"publisher","first-page":"515","DOI":"10.3389\/fphar.2020.00515","article-title":"Anti-rheumatic properties of gentiopicroside are associated with suppression of ros-nf-\u03bab-nlrp3 axis in fibroblast-like synoviocytes and nf-\u03bab pathway in adjuvant-induced arthritis","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1506499","DOI":"10.3389\/fphar.2025.1506499","article-title":"Gentiopicroside targeting akt1 activates hif-1\u03b1\/vegf axis promoting diabetic ulcer wound healing","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"154730","DOI":"10.1016\/j.phymed.2023.154730","article-title":"A new gentiopicroside derivative improves cognitive deficits of ad mice via activation of wnt signaling pathway and regulation of gut microbiota homeostasis","volume":"113","author":"Wang","year":"2023","journal-title":"Phytomedicine"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1172360","DOI":"10.3389\/fphar.2023.1172360","article-title":"Gentiopicroside modulates glucose homeostasis in high-fat-diet and streptozotocin-induced type 2 diabetic mice","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"104559","DOI":"10.1016\/j.phrs.2019.104559","article-title":"Gentiopicroside activates the bile acid receptor gpbar1 (tgr5) to repress nf-kappab pathway and ameliorate diabetic nephropathy","volume":"151","author":"Xiao","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B90","doi-asserted-by":"publisher","first-page":"2887","DOI":"10.1016\/j.apsb.2021.12.023","article-title":"Gentiopicroside targets paqr3 to activate the pi3k\/akt signaling pathway and ameliorate disordered glucose and lipid metabolism","volume":"12","author":"Xiao","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"B91","doi-asserted-by":"publisher","first-page":"105840","DOI":"10.1016\/j.intimp.2019.105840","article-title":"Therapeutic effects of gentiopicroside on adjuvant-induced arthritis by inhibiting inflammation and oxidative stress in rats","volume":"76","author":"Xie","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"5565748","DOI":"10.1155\/2021\/5565748","article-title":"Gentiopicroside produces endothelium-independent vasodilation by deactivating the pi3k\/akt\/rho-kinase pathway in isolated rat thoracic aorta","volume":"2021","author":"Xing","year":"2021","journal-title":"Biomed. Res. Int."},{"key":"B93","doi-asserted-by":"publisher","first-page":"e0311152","DOI":"10.1371\/journal.pone.0311152","article-title":"Gentiopicroside-induced gastric cancer necroptosis via the hif-1 signaling pathway: a study involving molecular docking and experimental validation","volume":"19","author":"Xiong","year":"2024","journal-title":"PLoS One"},{"key":"B94","doi-asserted-by":"publisher","first-page":"848915","DOI":"10.3389\/fphar.2022.848915","article-title":"Gentiopicroside ameliorates diabetic renal tubulointerstitial fibrosis via inhibiting the at1r\/ck2\/nf-\u03bab pathway","volume":"13","author":"Xu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B95","first-page":"3141","article-title":"Determination and quality assessment of 10 ingredients gentiopicroside and sweroside and so on in tibetan medicine jia di (swertia chirayita)","volume":"37","author":"Yang","year":"2012","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B96","first-page":"569","article-title":"Hepatoprotective effects of gentianella turkestanerum extracts on acute liver injury induced by carbon tetrachloride in mice","volume":"9","author":"Yang","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"B97","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1002\/ptr.5965","article-title":"Protective effect of gentiopicroside from gentiana macrophylla pall. In ethanol-induced gastric mucosal injury in mice","volume":"32","author":"Yang","year":"2018","journal-title":"Phytother. Res."},{"key":"B98","doi-asserted-by":"publisher","first-page":"320","DOI":"10.4062\/biomolther.2020.008","article-title":"Gentiopicroside ameliorates the progression from hepatic steatosis to fibrosis induced by chronic alcohol intake","volume":"28","author":"Yang","year":"2020","journal-title":"Biomol. Ther. Seoul."},{"key":"B99","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/s1875-5364(20)30006-6","article-title":"Three new secoiridoid glycosides from the flower buds of lonicera japonica","volume":"18","author":"Yang","year":"2020","journal-title":"Chin. J. Nat. Med."},{"key":"B100","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1055\/a-1942-5504","article-title":"Metabolite profiling of swertia cincta extract in rats and pharmacokinetics study of three bioactive compounds using uhplc-ms\/ms","volume":"89","author":"Ye","year":"2023","journal-title":"Planta Med."},{"key":"B101","doi-asserted-by":"publisher","first-page":"206.e1","DOI":"10.1016\/j.jtct.2022.12.004","article-title":"Risk factors and outcomes of nocardiosis in hematopoietic stem cell transplantation recipients","volume":"29","author":"Yetmar","year":"2023","journal-title":"Transpl. Cell Ther."},{"key":"B102","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1248\/bpb.b17-00882","article-title":"Effects of oridonin on hepatic cytochrome p450 expression and activities in pxr-humanized mice","volume":"41","author":"Yi-Wen","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"B103","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1007\/s00210-023-02646-8","article-title":"Gentiopicroside inhibits retinoblastoma cell proliferation, invasion, and tumorigenesis in nude mice by suppressing the pi3k\/akt pathway","volume":"397","author":"Yin","year":"2024","journal-title":"Naunyn Schmiedeb. Arch. Pharmacol."},{"key":"B104","doi-asserted-by":"publisher","first-page":"107124","DOI":"10.1016\/j.ijid.2024.107124","article-title":"Pioneering cord blood transplantation in relapsed\/refractory hiv-related lymphoma: a case study with concurrent intramuscular antiretroviral therapy","volume":"146","author":"Yokota","year":"2024","journal-title":"Int. J. Infect. Dis."},{"key":"B105","doi-asserted-by":"publisher","first-page":"116952","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":"B106","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.1007\/s10068-024-01575-3","article-title":"Impact of different organic acids on heat-moisture treated potato starch for enhancing prebiotic potential","volume":"33","author":"Yu","year":"2024","journal-title":"Food Sci. Biotechnol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1002\/bmc.2917","article-title":"Identification of bio-active metabolites of gentiopicroside by uplc\/q-tof ms and nmr","volume":"27","author":"Zeng","year":"2013","journal-title":"Biomed. Chromatogr."},{"key":"B108","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.2147\/ijn.S45031","article-title":"Preparation, characterization, and in vivo pharmacokinetics of nanostructured lipid carriers loaded with oleanolic acid and gentiopicrin","volume":"8","author":"Zhang","year":"2013","journal-title":"Int. J. Nanomedicine"},{"key":"B109","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1002\/ptr.6981","article-title":"Gentiopicroside prevents alcoholic liver damage by improving mitochondrial dysfunction in the rat model","volume":"35","author":"Zhang","year":"2021","journal-title":"Phytother. Res."},{"key":"B110","doi-asserted-by":"publisher","first-page":"565","DOI":"10.24976\/Discov.Med.202335177.57","article-title":"Gentiopicroside ameliorates cerebrovascular angiogenesis, neuronal injury and immune disorder in rats with cerebral ischemia\/reperfusion injury via vegf and phosphorylated nrf2 elevation","volume":"35","author":"Zhang","year":"2023","journal-title":"Discov. Med."},{"key":"B111","doi-asserted-by":"publisher","first-page":"113978","DOI":"10.1016\/j.bios.2022.113978","article-title":"Sars-cov-2 detection using quantum dot fluorescence immunochromatography combined with isothermal amplification and crispr\/cas13a","volume":"202","author":"Zhang","year":"2022","journal-title":"Biosens. Bioelectron."},{"key":"B112","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/s1875-5364(22)60187-0","article-title":"Synthesis, and anti-inflammatory activities of gentiopicroside derivatives","volume":"20","author":"Zhang","year":"2022","journal-title":"Chin. J. Nat. Med."},{"key":"B113","doi-asserted-by":"publisher","first-page":"340992","DOI":"10.1016\/j.aca.2023.340992","article-title":"Determination of lead in gentiana rigescens and evaluation of the effect of lead exposure on the liver protection of the natural medicine","volume":"1251","author":"Zhang","year":"2023","journal-title":"Anal. Chim. Acta."},{"key":"B114","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.phymed.2018.04.020","article-title":"Botany, traditional use, phytochemistry, pharmacology, quality control, and authentication of radix gentianae macrophyllae-a traditional medicine: a review","volume":"46","author":"Zhang","year":"2018","journal-title":"Phytomedicine"},{"key":"B115","doi-asserted-by":"publisher","first-page":"3000605231204501","DOI":"10.1177\/03000605231204501","article-title":"Gentiopicroside ameliorates ccl(4)-induced liver injury in mice by regulating the ppar-\u03b3\/nrf2 and nf-\u03bab\/i\u03bab signaling pathways","volume":"51","author":"Zhang","year":"2023","journal-title":"J. Int. Med. Res."},{"key":"B116","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1159\/000486600","article-title":"Effect of oridonin on cytochrome p450 expression and activities in heparg cell","volume":"101","author":"Zhang Y. W.","year":"2018","journal-title":"Pharmacology"},{"key":"B117","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jep.2015.06.031","article-title":"Gentiopicroside prevents interleukin-1 beta induced inflammation response in rat articular chondrocyte","volume":"172","author":"Zhao","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"B118","doi-asserted-by":"publisher","first-page":"3781","DOI":"10.2147\/ijn.S406649","article-title":"Gentiopicroside-loaded chitosan nanoparticles inhibit tnf-\u03b1-induced proliferation and inflammatory response in hacat keratinocytes and ameliorate imiquimod-induced dermatitis lesions in mice","volume":"18","author":"Zhao","year":"2023","journal-title":"Int. J. Nanomedicine"},{"key":"B119","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.1002\/cbdv.200900420","article-title":"Concentrations of the active constituents of the tibetan folk medicine qinjiao (gentiana sect. Cruciata) within and between taxonomic species across the Qinghai-Tibetan plateau","volume":"7","author":"Zhou","year":"2010","journal-title":"Chem. Biodivers."},{"key":"B120","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1111\/all.15111","article-title":"Regulatory roles of three mirnas on allergen mrna expression in tyrophagus putrescentiae","volume":"77","author":"Zhou","year":"2022","journal-title":"Allergy"},{"key":"B121","doi-asserted-by":"publisher","first-page":"102034","DOI":"10.1016\/j.pupt.2021.102034","article-title":"Gentiopicroside ameliorates ovalbumin-induced airway inflammation in a mouse model of allergic asthma via regulating sirt1\/nf-\u03bab signaling pathway","volume":"68","author":"Zou","year":"2021","journal-title":"Pulm. Pharmacol. Ther."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1634722\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:25:31Z","timestamp":1764051931000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1634722\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":121,"alternative-id":["10.3389\/fphar.2025.1634722"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1634722","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]},"article-number":"1634722"}}