{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:33:10Z","timestamp":1792099990273,"version":"4.4.0"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["3 Biotech"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s13205-025-04641-7","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T09:10:06Z","timestamp":1766221806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Apigenin as a multifunctional flavone against liver fibrosis: mechanistic insights into its modulation of key fibrogenic signalling pathways"],"prefix":"10.1007","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2903-4293","authenticated-orcid":false,"given":"Lovedeep","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riya","family":"Kalia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakshi","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anish","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diksha","family":"Dalal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"issue":"2","key":"4641_CR1","doi-asserted-by":"publisher","first-page":"202","DOI":"10.34172\/jhp.2023.27","volume":"12","author":"RF Abdel-Rahman","year":"2023","unstructured":"Abdel-Rahman RF, Fayed HM, Mohamed MAE, Hessin AF, Asaad GF, AbdelRahman S (2023) Apigenin role against thioacetamide-triggered liver fibrosis: Deciphering the PPAR\u03b3\/TGF-\u03b21\/NF-\u03baB and the HIF\/FAK\/AKT pathways. J Herbmed Pharmacol 12(2):202\u2013213. https:\/\/doi.org\/10.34172\/jhp.2023.27","journal-title":"J Herbmed Pharmacol"},{"key":"4641_CR2","doi-asserted-by":"publisher","first-page":"671640","DOI":"10.3389\/fphar.2021.671640","volume":"12","author":"P Acharya","year":"2021","unstructured":"Acharya P, Chouhan K, Weiskirchen S, Weiskirchen R (2021) Cellular mechanisms of liver fibrosis. Front Pharmacol 12:671640. https:\/\/doi.org\/10.3389\/fphar.2021.671640","journal-title":"Front Pharmacol"},{"key":"4641_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-59745-450-6_1","volume-title":"Transforming growth Factor-\u03b2 in cancer Therapy, volume I","author":"A Atfi","year":"2008","unstructured":"Atfi A, Bourgeade MF (2008) Regulators of Smad2\/3 transcription and phosphorylation. Transforming growth Factor-\u03b2 in cancer Therapy, volume I. Humana, Totowa, NJ, pp 1\u201325. https:\/\/doi.org\/10.1007\/978-1-59745-450-6_1"},{"key":"4641_CR4","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/978-3-642-30018-9_10","volume-title":"Systems biology of free radicals and antioxidants","author":"SV Avery","year":"2014","unstructured":"Avery SV (2014) Oxidative stress and cell function. In: Laher I (ed) Systems biology of free radicals and antioxidants. Springer, Berlin, Heidelberg, pp 87\u2013100. https:\/\/doi.org\/10.1007\/978-3-642-30018-9_10"},{"key":"4641_CR5","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.2147\/DDDT.S407867","volume":"17","author":"H Batudeligen","year":"2023","unstructured":"Batudeligen H, Han Z, Chen H, Narisu X, Anda G, Han G (2023) Luteolin alleviates liver fibrosis in rat hepatic stellate cell HSC-T6: A proteomic analysis. Drug Des Devel Ther 17:1819\u20131829. https:\/\/doi.org\/10.2147\/DDDT.S407867","journal-title":"Drug Des Devel Ther"},{"key":"4641_CR6","doi-asserted-by":"publisher","first-page":"879021","DOI":"10.3389\/fnagi.2022.879021","volume":"14","author":"HM Blevins","year":"2022","unstructured":"Blevins HM, Xu Y, Biby S, Zhang S (2022) The NLRP3 inflammasome pathway: A review of mechanisms and inhibitors for the treatment of inflammatory diseases. Front Aging Neurosci 14:879021. https:\/\/doi.org\/10.3389\/fnagi.2022.879021","journal-title":"Front Aging Neurosci"},{"key":"4641_CR7","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/978-3-030-55917-4_5","volume-title":"Xenobiotic metabolic enzymes: bioactivation and antioxidant defense","author":"CH Chen","year":"2020","unstructured":"Chen CH (2020) Nrf2-ARE pathway: defense against oxidative stress. Xenobiotic metabolic enzymes: bioactivation and antioxidant defense. Springer, Cham, pp 85\u2013108. https:\/\/doi.org\/10.1007\/978-3-030-55917-4_5"},{"key":"4641_CR9","doi-asserted-by":"publisher","first-page":"1270838","DOI":"10.3389\/fragi.2023.1270838","volume":"4","author":"WT Chen","year":"2023","unstructured":"Chen WT, Dodson M (2023) The untapped potential of targeting NRF2 in neurodegenerative disease. Front Aging 4:1270838. https:\/\/doi.org\/10.3389\/fragi.2023.1270838","journal-title":"Front Aging"},{"issue":"30","key":"4641_CR8","doi-asserted-by":"publisher","first-page":"21183","DOI":"10.1074\/jbc.M600481200","volume":"281","author":"SJ Chen","year":"2006","unstructured":"Chen SJ, Ning H, Ishida W, Flanders KC, Roberts AB, Sporn MB (2006) The early-immediate gene EGR-1 is induced by transforming growth factor-beta and mediates stimulation of collagen gene expression. J Biol Chem 281(30):21183\u201321197. https:\/\/doi.org\/10.1074\/jbc.M600481200","journal-title":"J Biol Chem"},{"issue":"7","key":"4641_CR10","first-page":"1010","volume":"38","author":"XD Chen","year":"2022","unstructured":"Chen XD, Yan PY, Kuang JN, Sun T, Huang B, Qin Y (2022) Apigenin inhibits liver fibrosis through PDK1\/AKT signaling pathway in mice. Chin Pharmacol Bull 38(7):1010\u20131016","journal-title":"Chin Pharmacol Bull"},{"key":"4641_CR11","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s11658-023-00450-w","volume":"28","author":"Y Chen","year":"2023","unstructured":"Chen Y, Ye X, Escames G, Venegas C, Zhou Z, Tan DX (2023) The NLRP3 inflammasome: contributions to inflammation-related diseases. Cell Mol Biology Lett 28:51. https:\/\/doi.org\/10.1186\/s11658-023-00450-w","journal-title":"Cell Mol Biology Lett"},{"issue":"3","key":"4641_CR12","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s11357-997-0024-2","volume":"20","author":"HY Chung","year":"1997","unstructured":"Chung HY, Baek BS, Song SH, Chung S, Yu BP (1997) Xanthine dehydrogenase\/xanthine oxidase and oxidative stress. AGE 20(3):127\u2013140. https:\/\/doi.org\/10.1007\/s11357-997-0024-2","journal-title":"AGE"},{"key":"4641_CR13","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1007\/s43440-025-00728-3","volume":"77","author":"D Dalal","year":"2025","unstructured":"Dalal D, Singh L, Singh A (2025) Calycosin and kidney health: A molecular perspective on its protective mechanisms. Pharmacol Rep 77:658\u2013669. https:\/\/doi.org\/10.1007\/s43440-025-00728-3","journal-title":"Pharmacol Rep"},{"key":"4641_CR14","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41392-024-01721-4","volume":"9","author":"Z Deng","year":"2024","unstructured":"Deng Z, Fan T, Xiao C et al (2024) TGF-\u03b2 signaling in health, disease, and therapeutics. Signal Transduct Target Therapy 9:61. https:\/\/doi.org\/10.1038\/s41392-024-01721-4","journal-title":"Signal Transduct Target Therapy"},{"key":"4641_CR15","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1007\/s12010-023-04667-6","volume":"195","author":"LCP Dharshini","year":"2023","unstructured":"Dharshini LCP, Rasmi RR, Kathirvelan C, Nithya N, Divya T (2023) Regulatory components of oxidative stress and inflammation and their complex interplay in carcinogenesis. Appl Biochem Biotechnol 195:2893\u20132916. https:\/\/doi.org\/10.1007\/s12010-023-04667-6","journal-title":"Appl Biochem Biotechnol"},{"issue":"2","key":"4641_CR16","doi-asserted-by":"publisher","first-page":"256","DOI":"10.3390\/antiox13020256","volume":"13","author":"S Duan","year":"2024","unstructured":"Duan S, Liu Y, Zhang Y, Zhao J, Wang W, Wu H (2024) Transcriptotype-driven discovery of apigenin as a therapy against cholestatic liver fibrosis: through Inhibition of PANoptosis and following type-I interferon responses. Antioxidants 13(2):256. https:\/\/doi.org\/10.3390\/antiox13020256","journal-title":"Antioxidants"},{"issue":"5","key":"4641_CR17","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1002\/hep.29085","volume":"65","author":"PS Dulai","year":"2017","unstructured":"Dulai PS, Singh S, Patel J, Soni M, Prokop LJ, Younossi Z, Sebastiani G, Loomba R (2017) Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology 65(5):1557\u20131565. https:\/\/doi.org\/10.1002\/hep.29085","journal-title":"Hepatology"},{"key":"4641_CR18","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1186\/s12967-024-04522-3","volume":"22","author":"AO Giarratana","year":"2024","unstructured":"Giarratana AO, Prendergast CM, Salvatore MM, Capaccione KM (2024) TGF-\u03b2 signaling: critical nexus of fibrogenesis and cancer. J Translational Med 22:594. https:\/\/doi.org\/10.1186\/s12967-024-04522-3","journal-title":"J Translational Med"},{"key":"4641_CR19","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1475-2891-13-17","volume":"13","author":"B Grygiel-G\u00f3rniak","year":"2014","unstructured":"Grygiel-G\u00f3rniak B (2014) Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications\u2014a review. Nutr J 13:17. https:\/\/doi.org\/10.1186\/1475-2891-13-17","journal-title":"Nutr J"},{"key":"4641_CR20","doi-asserted-by":"publisher","unstructured":"Halder S, Jana S, Manna A, Jana K (2024) Apoptosis: oxidative stress and antioxidants. In: Jana, K. (Ed.), Apoptosis and Human Health: Understanding Mechanistic and Therapeutic Potential (pp. 1\u201320). Singapore: Springer. https:\/\/doi.org\/10.1007\/978-981-99-3085-0_1","DOI":"10.1007\/978-981-99-3085-0_1"},{"key":"4641_CR21","doi-asserted-by":"publisher","first-page":"6555","DOI":"10.1038\/ncomms7555","volume":"6","author":"A Ives","year":"2015","unstructured":"Ives A, Nomura J, Martinon F, Roger T, LeRoy D, Miner JN, Simon G, Gabay C (2015) Xanthine oxidoreductase regulates macrophage IL1\u03b2 secretion upon NLRP3 inflammasome activation. Nat Commun 6:6555. https:\/\/doi.org\/10.1038\/ncomms7555","journal-title":"Nat Commun"},{"key":"4641_CR22","doi-asserted-by":"publisher","unstructured":"Ji J, Yu Q, Dai W, Wu L, Feng J, Zheng Y (2021) Apigenin alleviates liver fibrosis by inhibiting hepatic stellate cell activation and autophagy via TGF-\u03b21\/Smad3 and p38\/PPAR\u03b1 pathways. PPAR Research, 2021, 6651839. https:\/\/doi.org\/10.1155\/2021\/6651839","DOI":"10.1155\/2021\/6651839"},{"key":"4641_CR23","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1007\/s00204-024-03630-1","volume":"98","author":"K Jomova","year":"2024","unstructured":"Jomova K, Alomar SY, Alwasel SH, Valko M, Costa S, Kuca K (2024) Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants. Arch Toxicol 98:1323\u20131367. https:\/\/doi.org\/10.1007\/s00204-024-03630-1","journal-title":"Arch Toxicol"},{"issue":"13","key":"4641_CR24","doi-asserted-by":"publisher","first-page":"3328","DOI":"10.3390\/ijms20133328","volume":"20","author":"N Kelley","year":"2019","unstructured":"Kelley N, Jeltema D, Duan Y, He Y (2019) The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci 20(13):3328. https:\/\/doi.org\/10.3390\/ijms20133328","journal-title":"Int J Mol Sci"},{"issue":"2","key":"4641_CR25","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/path.4104","volume":"229","author":"F Klingberg","year":"2013","unstructured":"Klingberg F, Hinz B, White ES (2013) The myofibroblast matrix: implications for tissue repair and fibrosis. J Pathol 229(2):298\u2013309. https:\/\/doi.org\/10.1002\/path.4104","journal-title":"J Pathol"},{"issue":"19","key":"4641_CR26","doi-asserted-by":"publisher","first-page":"10431","DOI":"10.3390\/ijms221910431","volume":"22","author":"G K\u00f6k\u00e9ny","year":"2021","unstructured":"K\u00f6k\u00e9ny G, Calvier L, Hansmann G (2021) PPAR\u03b3 and TGF\u03b2\u2014Major regulators of metabolism, inflammation, and fibrosis in the lungs and kidneys. Int J Mol Sci 22(19):10431. https:\/\/doi.org\/10.3390\/ijms221910431","journal-title":"Int J Mol Sci"},{"issue":"4","key":"4641_CR27","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.jaim.2018.09.001","volume":"11","author":"S Kumar","year":"2020","unstructured":"Kumar S, Modgil S, Bammidi S, Minhas G, Shri R, Kaushik S, Singh V, Anand A (2020) Allium Cepa exerts neuroprotective effect on retinal ganglion cells of pterygopalatine artery (PPA) ligated mice. J Ayurveda Integr Med 11(4):489\u2013494. https:\/\/doi.org\/10.1016\/j.jaim.2018.09.001","journal-title":"J Ayurveda Integr Med"},{"key":"4641_CR28","doi-asserted-by":"publisher","first-page":"101943","DOI":"10.1016\/j.mito.2024.101943","volume":"78","author":"S Kumari","year":"2024","unstructured":"Kumari S, Singh P, Dash D, Singh R (2024) Understanding the molecular basis of anti-fibrotic potential of intranasal Curcumin and its association with mitochondrial homeostasis in silica-exposed mice. Mitochondrion 78:101943. https:\/\/doi.org\/10.1016\/j.mito.2024.101943","journal-title":"Mitochondrion"},{"issue":"3","key":"4641_CR29","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s12264-023-01141-7","volume":"40","author":"Y Lan","year":"2024","unstructured":"Lan Y, Han X, Huang F, Wang Y, Li J, Zhang M (2024) Early growth response Gene-1 deficiency interrupts TGF\u03b21 signaling activation and aggravates neurodegeneration in experimental autoimmune encephalomyelitis mice. Neurosci Bull 40(3):283\u2013292. https:\/\/doi.org\/10.1007\/s12264-023-01141-7","journal-title":"Neurosci Bull"},{"issue":"9","key":"4641_CR30","doi-asserted-by":"publisher","first-page":"6568","DOI":"10.1080\/87559129.2022.2056048","volume":"39","author":"Z Li","year":"2023","unstructured":"Li Z, Zhou J, Ji L, Liang Y, Xie S (2023) Recent advances in the Pharmacological actions of apigenin, its complexes, and its derivatives. Food Reviews Int 39(9):6568\u20136601. https:\/\/doi.org\/10.1080\/87559129.2022.2056048","journal-title":"Food Reviews Int"},{"key":"4641_CR31","doi-asserted-by":"publisher","first-page":"104523","DOI":"10.3748\/wjg.v31.i0.104523","volume":"31","author":"MX Liang","year":"2025","unstructured":"Liang MX, Zhou Y, Li SQ, Xiang WS, Pan ZQ, Chen YH, Liu YX, Wu HZ, Tang CK (2025) Mixed lineage kinase domain-like protein in liver diseases: Cell-type-specific functions and dual roles. World J Gastroenterol 31:104523. https:\/\/doi.org\/10.3748\/wjg.v31.i0.104523","journal-title":"World J Gastroenterol"},{"key":"4641_CR32","doi-asserted-by":"publisher","first-page":"814496","DOI":"10.3389\/fmed.2021.814496","volume":"8","author":"C Liedtke","year":"2022","unstructured":"Liedtke C, Nevzorova YA, Luedde T, Zimmermann H, Kroy D, Strnad P et al (2022) Liver fibrosis\u2014from mechanisms of injury to modulation of disease. Front Med 8:814496. https:\/\/doi.org\/10.3389\/fmed.2021.814496","journal-title":"Front Med"},{"key":"4641_CR33","doi-asserted-by":"publisher","first-page":"1074911","DOI":"10.3389\/fendo.2022.1074911","volume":"13","author":"Y Lin","year":"2022","unstructured":"Lin Y, Yang L, Zhuang Y, Chen X, Chen Y, Xie L (2022) PPAR\u03b1: an emerging target of metabolic syndrome, neurodegenerative and cardiovascular diseases. Front Endocrinol 13:1074911. https:\/\/doi.org\/10.3389\/fendo.2022.1074911","journal-title":"Front Endocrinol"},{"key":"4641_CR34","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.jnutbio.2019.06.008","volume":"71","author":"Y Lv","year":"2019","unstructured":"Lv Y, Gao X, Luo Y, Fan W, Shen T, Ding C (2019) Apigenin ameliorates HFD-induced NAFLD through regulation of the XO\/NLRP3 pathways. J Nutr Biochem 71:110\u2013121. https:\/\/doi.org\/10.1016\/j.jnutbio.2019.06.008","journal-title":"J Nutr Biochem"},{"issue":"1","key":"4641_CR35","doi-asserted-by":"publisher","first-page":"17","DOI":"10.21273\/HORTSCI16953-24","volume":"60","author":"RC Maynard","year":"2025","unstructured":"Maynard RC, Ogundipe SO, Ferrarezi RS, Suh JH, Lombardini L (2025) Apigenin accumulation in Matricaria Chamomilla and Petroselinum crispum produced in a vertical hydroponic system. HortScience 60(1):17\u201322. https:\/\/doi.org\/10.21273\/HORTSCI16953-24","journal-title":"HortScience"},{"key":"4641_CR36","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.3390\/biomedicines11051342","volume":"11","author":"M Melaibari","year":"2023","unstructured":"Melaibari M, Alkreathy HM, Esmat A, Rajeh NA, Shaik RA, Alghamdi AA (2023) Anti-fibrotic efficacy of apigenin in a mice model of carbon tetrachloride-induced hepatic fibrosis by modulation of oxidative stress, inflammation, and fibrogenesis: A preclinical study. Biomedicines 11:1342. https:\/\/doi.org\/10.3390\/biomedicines11051342","journal-title":"Biomedicines"},{"key":"4641_CR37","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s12882-019-1404-2","volume":"20","author":"\u00c1 N\u00e9meth","year":"2019","unstructured":"N\u00e9meth \u00c1, M\u00f3zes MM, Calvier L, Csiky M, Peti-Peterdi J, R\u0151szer T (2019) The PPAR\u03b3 agonist Pioglitazone prevents TGF-\u03b2 induced renal fibrosis by repressing EGR-1 and STAT3. BMC Nephrol 20:245. https:\/\/doi.org\/10.1186\/s12882-019-1404-2","journal-title":"BMC Nephrol"},{"issue":"12","key":"4641_CR38","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.3390\/antiox11122345","volume":"11","author":"V Ngo","year":"2022","unstructured":"Ngo V, Duennwald ML (2022) Nrf2 and oxidative stress: A general overview of mechanisms and implications in human disease. Antioxidants 11(12):2345. https:\/\/doi.org\/10.3390\/antiox11122345","journal-title":"Antioxidants"},{"issue":"5","key":"4641_CR39","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1007\/s10495-007-0756-2","volume":"12","author":"M Ott","year":"2007","unstructured":"Ott M, Gogvadze V, Orrenius S, Zhivotovsky B (2007) Mitochondria, oxidative stress and cell death. Apoptosis 12(5):913\u2013930. https:\/\/doi.org\/10.1007\/s10495-007-0756-2","journal-title":"Apoptosis"},{"issue":"4","key":"4641_CR40","doi-asserted-by":"publisher","first-page":"331","DOI":"10.5799\/ahinjs.01.2015.04.0555","volume":"6","author":"O \u00d6zcan","year":"2015","unstructured":"\u00d6zcan O, Erdal H, \u00c7ak\u0131rca G, Y\u00f6nden Z (2015) Oxidative stress and its impacts on intracellular lipids, proteins and DNA. J Clin Experimental Investigations 6(4):331\u2013336. https:\/\/doi.org\/10.5799\/ahinjs.01.2015.04.0555","journal-title":"J Clin Experimental Investigations"},{"issue":"5","key":"4641_CR41","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1159\/000491407","volume":"47","author":"S Paladino","year":"2018","unstructured":"Paladino S, Conte A, Caggiano R, Pierantoni GM, Faraonio R (2018) Nrf2 pathway in age-related neurological disorders: insights into MicroRNAs. Cell Physiol Biochem 47(5):1951\u20131976. https:\/\/doi.org\/10.1159\/000491407","journal-title":"Cell Physiol Biochem"},{"issue":"1","key":"4641_CR42","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1080\/13880209.2020.1782173","volume":"58","author":"X Pan","year":"2020","unstructured":"Pan X, Shao Y, Wang F, Cai Z, Liu S, Xi J (2020) Protective effect of apigenin magnesium complex on H\u2082O\u2082-induced oxidative stress and inflammatory responses in rat hepatic stellate cells. Pharm Biol 58(1):553\u2013560. https:\/\/doi.org\/10.1080\/13880209.2020.1782173","journal-title":"Pharm Biol"},{"issue":"3","key":"4641_CR43","doi-asserted-by":"publisher","first-page":"591","DOI":"10.3390\/foods13030591","volume":"13","author":"X Peng","year":"2024","unstructured":"Peng X, Liu K, Hu X, Gong D, Zhang G (2024) Hesperitin-Copper (II) complex regulates the NLRP3 pathway and attenuates hyperuricemia and renal inflammation. Foods 13(3):591. https:\/\/doi.org\/10.3390\/foods13030591","journal-title":"Foods"},{"issue":"5","key":"4641_CR44","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1007\/s11011-021-00716-3","volume":"36","author":"S Pruthi","year":"2021","unstructured":"Pruthi S, Kaur K, Singh V, Shri R (2021) Improvement of cognitive function in mice by Citrus reticulata var. Kinnow via modulation of central cholinergic system and oxidative stress. Metab Brain Dis 36(5):901\u2013910. https:\/\/doi.org\/10.1007\/s11011-021-00716-3","journal-title":"Metab Brain Dis"},{"key":"4641_CR45","unstructured":"Rai SN, Singh SK, Singh V (eds) (2025a) Advancements in modeling-based therapeutics and technology for chronic diseases. Academic"},{"key":"4641_CR46","unstructured":"Rai SN, Tiwari N, Khubber S (eds) (2025b) Phytochemicals and gut health: evidence and opportunities for Gastrointestinal management. Elsevier Science Publishing Co. Inc"},{"issue":"12","key":"4641_CR47","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.3390\/antiox9121279","volume":"9","author":"E Ramos-Tovar","year":"2020","unstructured":"Ramos-Tovar E, Muriel P (2020) Molecular mechanisms that link oxidative stress, inflammation, and fibrosis in the liver. Antioxidants 9(12):1279. https:\/\/doi.org\/10.3390\/antiox9121279","journal-title":"Antioxidants"},{"key":"4641_CR48","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1007\/978-981-15-7306-8_42","volume-title":"Handbook of oxidative stress in cancer: mechanistic aspects","author":"M Ruwali","year":"2022","unstructured":"Ruwali M, Shukla R (2022) Oxidative stress and cancer: role of the Nrf2-antioxidant response element signaling pathway. Handbook of oxidative stress in cancer: mechanistic aspects. Springer Nature, Singapore, pp 957\u2013973. https:\/\/doi.org\/10.1007\/978-981-15-7306-8_42"},{"issue":"22","key":"4641_CR49","doi-asserted-by":"publisher","first-page":"5474","DOI":"10.3390\/molecules25225474","volume":"25","author":"S Saha","year":"2020","unstructured":"Saha S, Buttari B, Panieri E, Profumo E, Saso L (2020) An overview of Nrf2 signaling pathway and its role in inflammation. Molecules 25(22):5474. https:\/\/doi.org\/10.3390\/molecules25225474","journal-title":"Molecules"},{"key":"4641_CR50","doi-asserted-by":"publisher","unstructured":"Samak M (2024) Nrf2: The guardian of cellular harmony\u2014Unveiling its role in cell biology and senescence. In: Apoptosis and Human Health. IntechOpen. https:\/\/doi.org\/10.5772\/intechopen.112456","DOI":"10.5772\/intechopen.112456"},{"key":"4641_CR51","doi-asserted-by":"publisher","first-page":"101072","DOI":"10.1016\/j.redox.2018.11.010","volume":"21","author":"HM Schmidt","year":"2019","unstructured":"Schmidt HM, Davies D, Fischer B, Franke S, Paul KN, Schr\u00f6der K (2019) The impact of Xanthine oxidase (XO) on hemolytic diseases. Redox Biol 21:101072. https:\/\/doi.org\/10.1016\/j.redox.2018.11.010","journal-title":"Redox Biol"},{"issue":"6","key":"4641_CR52","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s40495-017-0114-9","volume":"3","author":"E Shankar","year":"2017","unstructured":"Shankar E, Goel A, Gupta K, Gupta S (2017) Plant flavone apigenin: an emerging anticancer agent. Curr Pharmacol Rep 3(6):423\u2013446. https:\/\/doi.org\/10.1007\/s40495-017-0114-9","journal-title":"Curr Pharmacol Rep"},{"key":"4641_CR53","doi-asserted-by":"publisher","first-page":"502","DOI":"10.3389\/fcell.2020.00502","volume":"8","author":"Y Shi","year":"2020","unstructured":"Shi Y, Chen X, Huang C, Pollock C (2020) RIPK3: A new player in kidney fibrosis. Front Cell Dev Biology 8:502. https:\/\/doi.org\/10.3389\/fcell.2020.00502","journal-title":"Front Cell Dev Biology"},{"issue":"1","key":"4641_CR54","doi-asserted-by":"publisher","first-page":"100413","DOI":"10.1016\/j.phyplu.2023.100413","volume":"3","author":"P Singh","year":"2023","unstructured":"Singh P, Chawla R, Pandey AK, Mishra JK, Singh R (2023) Comparative evaluation of two intranasal forms of curcumin: quantitation and impact on mouse model of asthma. Phytomedicine Plus 3(1):100413. https:\/\/doi.org\/10.1016\/j.phyplu.2023.100413","journal-title":"Phytomedicine Plus"},{"key":"4641_CR56","doi-asserted-by":"publisher","first-page":"114747","DOI":"10.1016\/j.fct.2024.114747","volume":"189","author":"V Singh","year":"2024","unstructured":"Singh V, Shri R, Sood P, Singh M, Singh TG, Singh R, Kumar A, Ahmad SF (2024) 5,7-Dihydroxy-3\u2032,4\u2032,5\u2032-trimethoxyflavone mitigates lead-induced neurotoxicity in rats via its chelating, antioxidant, anti-inflammatory, and monoaminergic properties. Food Chem Toxicol 189:114747. https:\/\/doi.org\/10.1016\/j.fct.2024.114747","journal-title":"Food Chem Toxicol"},{"key":"4641_CR55","doi-asserted-by":"publisher","first-page":"107970","DOI":"10.1016\/j.bioorg.2024.107970","volume":"154","author":"P Singh","year":"2025","unstructured":"Singh P, Kumari S, Chakravortty H, Pandey A, Dash D, Singh R (2025) In vivo, in vitro, and in Silico approaches in the detailed study of di-butyl phthalate (DBP), a plasticizer-induced lung fibrosis via Nrf-2\/Keap-1\/HO-1 pathway and its regulation. Bioorg Chem 154:107970. https:\/\/doi.org\/10.1016\/j.bioorg.2024.107970","journal-title":"Bioorg Chem"},{"key":"4641_CR57","doi-asserted-by":"publisher","first-page":"150130","DOI":"10.1016\/j.bbrc.2024.150130","volume":"721","author":"T Sun","year":"2024","unstructured":"Sun T, Li S, Li X, Lei Y, Wang B, Liu X (2024) Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1\u03b1 mediated oxidative stress. Biochem Biophys Res Commun 721:150130. https:\/\/doi.org\/10.1016\/j.bbrc.2024.150130","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"4641_CR58","doi-asserted-by":"publisher","first-page":"141","DOI":"10.4103\/apjtb.apjtb_634_24","volume":"15","author":"T Sun","year":"2025","unstructured":"Sun T, Wang BY, Li XY, Zhang XZ, Lei YF, Yu SF (2025) Apigenin ameliorates CCl\u2084-induced hepatic fibrosis by inhibiting hepatic stellate cell activation via PI3K\/AKT\/GSK3\u03b2 pathway in mice. Asian Pac J Trop Biomed 15(3):141\u2013149","journal-title":"Asian Pac J Trop Biomed"},{"key":"4641_CR59","doi-asserted-by":"publisher","first-page":"865772","DOI":"10.3389\/fimmu.2022.865772","volume":"13","author":"B Tastan","year":"2022","unstructured":"Tastan B, Arioz BI, Genc S (2022) Targeting NLRP3 inflammasome with Nrf2 inducers in central nervous system disorders. Front Immunol 13:865772. https:\/\/doi.org\/10.3389\/fimmu.2022.865772","journal-title":"Front Immunol"},{"issue":"19","key":"4641_CR60","doi-asserted-by":"publisher","first-page":"3535","DOI":"10.1091\/mbc.E15-05-0275","volume":"26","author":"K Tazat","year":"2015","unstructured":"Tazat K, Hector-Greene M, Blobe GC, Henis YI (2015) T\u03b2RIII independently bonds type I and type II TGF-\u03b2 receptors to inhibit TGF-\u03b2 signaling. Mol Biol Cell 26(19):3535\u20133545. https:\/\/doi.org\/10.1091\/mbc.E15-05-0275","journal-title":"Mol Biol Cell"},{"key":"4641_CR61","doi-asserted-by":"publisher","first-page":"1508060","DOI":"10.3389\/fphar.2024.1508060","volume":"15","author":"C Wang","year":"2024","unstructured":"Wang C, Feng X, Li W, Chen L, Wang X, Lan Y, Liu Y, Zhou Z, Zhang J, Huang X (2024) Apigenin as an emerging hepatoprotective agent: current status and future perspectives. Front Pharmacol 15:1508060. https:\/\/doi.org\/10.3389\/fphar.2024.1508060","journal-title":"Front Pharmacol"},{"issue":"21","key":"4641_CR62","doi-asserted-by":"publisher","first-page":"8103","DOI":"10.1128\/MCB.20.21.8103-8111.2000","volume":"20","author":"SJ Wicks","year":"2000","unstructured":"Wicks SJ, Grocott T, Walmsley SR, Monaghan P, James P, Hesketh R (2000) Inactivation of Smad-transforming growth factor beta signaling by Ca(2+)-calmodulin-dependent protein kinase II. Mol Cell Biol 20(21):8103\u20138111. https:\/\/doi.org\/10.1128\/MCB.20.21.8103-8111.2000","journal-title":"Mol Cell Biol"},{"issue":"3","key":"4641_CR63","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1369\/0022155415622481","volume":"64","author":"F Xu","year":"2016","unstructured":"Xu F, Liu C, Zhou D, Zhang L (2016) TGF-\u03b2\/SMAD pathway and its regulation in hepatic fibrosis. J Histochem Cytochemistry 64(3):157\u2013167. https:\/\/doi.org\/10.1369\/0022155415622481","journal-title":"J Histochem Cytochemistry"},{"issue":"2","key":"4641_CR64","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.3390\/ijms24021131","volume":"24","author":"M Yan","year":"2023","unstructured":"Yan M, Li H, Xu S, Wu J, Li J, Xiao C, Zhang Y, Wang J, Li X, Wang Y (2023) Targeting endothelial necroptosis disrupts profibrotic endothelial\u2013hepatic stellate cells crosstalk to alleviate liver fibrosis in nonalcoholic steatohepatitis. Int J Mol Sci 24(2):1131. https:\/\/doi.org\/10.3390\/ijms24021131","journal-title":"Int J Mol Sci"},{"key":"4641_CR65","doi-asserted-by":"publisher","first-page":"e626","DOI":"10.14800\/rci.626","volume":"2","author":"K Yang","year":"2015","unstructured":"Yang K, Zheng W, Shi Y, Chen S, Zhang C, Zhao W (2015) Mutual inhibitory mechanisms between PPAR\u03b3 and Hif-1\u03b1: implication in pulmonary hypertension. Receptor Clin Invest 2:e626. https:\/\/doi.org\/10.14800\/rci.626","journal-title":"Receptor Clin Invest"},{"key":"4641_CR66","doi-asserted-by":"publisher","first-page":"118557","DOI":"10.1016\/j.jep.2023.118557","volume":"334","author":"Y Yang","year":"2024","unstructured":"Yang Y, Chen Y, Feng D, Wu H, Long C, Zhang J (2024) Ficus Hirta Vahl ameliorates liver fibrosis by triggering hepatic stellate cell ferroptosis through GSH\/GPX4 pathway. J Ethnopharmacol 334:118557. https:\/\/doi.org\/10.1016\/j.jep.2023.118557","journal-title":"J Ethnopharmacol"},{"issue":"4","key":"4641_CR67","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.3892\/ijo.2014.2559","volume":"45","author":"K Yoshida","year":"2014","unstructured":"Yoshida K, Murata M, Yamaguchi T, Matsuzaki K (2014) TGF-\u03b2\/Smad signaling during hepatic fibro-carcinogenesis. Int J Oncol 45(4):1363\u20131371. https:\/\/doi.org\/10.3892\/ijo.2014.2559","journal-title":"Int J Oncol"},{"issue":"1","key":"4641_CR68","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","volume":"64","author":"ZM Younossi","year":"2016","unstructured":"Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M (2016) Global epidemiology of nonalcoholic fatty liver disease\u2014meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64(1):73\u201384","journal-title":"Hepatology"},{"key":"4641_CR69","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.3389\/fphar.2019.01272","volume":"10","author":"W Yuan","year":"2019","unstructured":"Yuan W, Zhang L, Li J, Ma D, Zhang M (2019) Yes-associated protein (YAP) signaling in fibrosis: mechanisms and therapeutic targets. Front Pharmacol 10:1272. https:\/\/doi.org\/10.3389\/fphar.2019.01272","journal-title":"Front Pharmacol"},{"issue":"3","key":"4641_CR70","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/S1534-5807(02)00129-3","volume":"2","author":"Z Yun","year":"2002","unstructured":"Yun Z, Maecker HL, Johnson RS, Giaccia AJ (2002) Inhibition of PPAR\u03b32 gene expression by the HIF-1\u2013regulated gene DEC1\/Stra13: A mechanism for regulation of adipogenesis by hypoxia. Dev Cell 2(3):331\u2013341. https:\/\/doi.org\/10.1016\/S1534-5807(02)00129-3","journal-title":"Dev Cell"},{"issue":"7","key":"4641_CR71","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/j.cgh.2024.08.020","volume":"23","author":"M Zamani","year":"2025","unstructured":"Zamani M, Tabari A, Ajmera S, Singh V, Montori S, Murad VM, M. H., Loomba R (2025) Global prevalence of advanced liver fibrosis and cirrhosis in the general population: A systematic review and meta-analysis. Clin Gastroenterol Hepatol 23(7):1123\u20131134. https:\/\/doi.org\/10.1016\/j.cgh.2024.08.020","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"4","key":"4641_CR73","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1002\/hep.23112","volume":"50","author":"L Zhang","year":"2009","unstructured":"Zhang L (2009a) Transforming growth factor \u03b2 signaling in liver diseases: from pathogenesis to therapy. Hepatology 50(4):1307\u20131313. https:\/\/doi.org\/10.1002\/hep.23112","journal-title":"Hepatology"},{"issue":"5938","key":"4641_CR72","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1126\/science.1172308","volume":"325","author":"DW Zhang","year":"2009","unstructured":"Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J (2009b) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325(5938):332\u2013336. https:\/\/doi.org\/10.1126\/science.1172308","journal-title":"Science"},{"key":"4641_CR74","doi-asserted-by":"publisher","first-page":"108864","DOI":"10.1016\/j.intimp.2022.108864","volume":"108","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Liu H, Li X, Wang J, Chen Q (2022) PPAR\u03b3 mediates the anti-inflammatory effects of apigenin in activated macrophages. Int Immunopharmacol 108:108864. https:\/\/doi.org\/10.1016\/j.intimp.2022.108864","journal-title":"Int Immunopharmacol"},{"issue":"8","key":"4641_CR75","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.4049\/jimmunol.2000649","volume":"205","author":"W Zhao","year":"2020","unstructured":"Zhao W, Wang L, Zhang M, Wang P, Yuan C, Gao J (2020) AKT regulates NLRP3 inflammasome activation by phosphorylating NLRP3 Serine 5. J Immunol 205(8):2255\u20132264. https:\/\/doi.org\/10.4049\/jimmunol.2000649","journal-title":"J Immunol"},{"issue":"5","key":"4641_CR76","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.1039\/d0fo02910f","volume":"12","author":"S Zheng","year":"2021","unstructured":"Zheng S, Cao P, Yin Z et al (2021) Apigenin protects mice against 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestasis. Food Funct 12(5):2323\u20132334. https:\/\/doi.org\/10.1039\/d0fo02910f","journal-title":"Food Funct"},{"key":"4641_CR77","doi-asserted-by":"publisher","first-page":"826204","DOI":"10.3389\/fcell.2022.826204","volume":"10","author":"J Zhou","year":"2022","unstructured":"Zhou J, Zheng Q, Chen Z (2022) The Nrf2 pathway in liver diseases. Front Cell Dev Biology 10:826204. https:\/\/doi.org\/10.3389\/fcell.2022.826204","journal-title":"Front Cell Dev Biology"}],"container-title":["3 Biotech"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13205-025-04641-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13205-025-04641-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13205-025-04641-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:28:15Z","timestamp":1768390095000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13205-025-04641-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,20]]},"references-count":77,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["4641"],"URL":"https:\/\/doi.org\/10.1007\/s13205-025-04641-7","relation":{},"ISSN":["2190-572X","2190-5738"],"issn-type":[{"value":"2190-572X","type":"print"},{"value":"2190-5738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,20]]},"assertion":[{"value":"7 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}],"article-number":"32"}}