{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:48:44Z","timestamp":1790617724329,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2021SF-363"],"award-info":[{"award-number":["2021SF-363"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s00210-026-05312-x","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T06:45:41Z","timestamp":1776753941000},"page":"15133-15144","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Saikosaponin B1 alleviates hepatic fibrosis by targeting the LDHA-MCT1\/4 axis to inhibit lactate-driven profibrogenic signaling"],"prefix":"10.1007","volume":"399","author":[{"given":"Guotai","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Yong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"issue":"12","key":"5312_CR1","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1002\/term.2940","volume":"13","author":"SS Abd El-Rahman","year":"2019","unstructured":"Abd El-Rahman SS, Fayed HM (2019) Targeting AngII\/AT1R signaling pathway by perindopril inhibits ongoing liver fibrosis in rat. J Tissue Eng Regen Med 13(12):2131\u20132141","journal-title":"J Tissue Eng Regen Med"},{"issue":"212","key":"5312_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2025.107192","volume":"1","author":"RS Almalki","year":"2025","unstructured":"Almalki RS, Gazzaz M, Miski SF et al (2025) Repositioning gemigliptin for the alleviation of thioacetamide-induced liver fibrosis in rats: Targeting TLR4\/MAPK, SIRT1\/AMPK\/Nrf2, PI3K\/AKT\/mTOR axis and apoptosis. Eur J Pharm Sci 1(212):107192","journal-title":"Eur J Pharm Sci"},{"issue":"16","key":"5312_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1586231","volume":"9","author":"N ALSuhaymi","year":"2025","unstructured":"ALSuhaymi N, Alsugoor MH, Shokry AA et al (2025) Protective role of remogliflozin against experimental liver fibrosis by activating AMPK\/SIRT1\/Nrf2 and suppressing NF-\u03baB pathways. Front Pharmacol 9(16):1586231","journal-title":"Front Pharmacol"},{"issue":"1","key":"5312_CR4","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1186\/s12964-024-01951-w","volume":"22","author":"D Bandyopadhyay","year":"2024","unstructured":"Bandyopadhyay D, Tran ET, Patel RA et al (2024) Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways. Cell Commun Signal 22(1):597","journal-title":"Cell Commun Signal"},{"key":"5312_CR5","doi-asserted-by":"crossref","unstructured":"Crouchet E, Dachraoui M, J\u00fchling F et al (2025) Targeting the liver clock improves fibrosis by restoring TGF-\u03b2 signaling. J Hepatol 82(1):120\u2013133","DOI":"10.1016\/j.jhep.2024.07.034"},{"issue":"11","key":"5312_CR6","doi-asserted-by":"publisher","first-page":"16131","DOI":"10.1007\/s00210-025-04098-8","volume":"398","author":"HM Fayed","year":"2025","unstructured":"Fayed HM, Asaad GF, Elbaset MA et al (2025) Therapeutic efficacy of canagliflozin against hepatocarcinogenesis induced by CDD\/DEN\/TAA in a rat model: regulation of AMPK\/HIF-1\u03b1\/YAP-1\/TAZ signaling pathways. Naunyn Schmiedebergs Arch Pharmacol 398(11):16131\u201316148","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"1","key":"5312_CR7","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/s41589-024-01704-3","volume":"21","author":"L Gan","year":"2025","unstructured":"Gan L, Jiang Q, Huang D et al (2025) A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2. Nat Chem Biol 21(1):80\u201390","journal-title":"Nat Chem Biol"},{"issue":"408","key":"5312_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2025.111393","volume":"25","author":"K Ghimire","year":"2025","unstructured":"Ghimire K, Awasthi BP, Yadav K et al (2025) Prostate cancer-selective anticancer action of an oxindole derivative via HO-1-mediated disruption of metabolic reprogramming. Chem Biol Interact 25(408):111393","journal-title":"Chem Biol Interact"},{"issue":"3","key":"5312_CR9","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1080\/08923973.2025.2496661","volume":"47","author":"NH Hassan","year":"2025","unstructured":"Hassan NH, Kamel GM, Fayed HM et al (2025) Dapagliflozin alleviates thioacetamide induced-liver fibrosis in rats via controlling the Nrf2\/HO-1 and TLR4\/TGF-\u03b21\/PI3K signaling pathways. Immunopharmacol Immunotoxicol 47(3):392\u2013405","journal-title":"Immunopharmacol Immunotoxicol"},{"issue":"33","key":"5312_CR10","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202504223","volume":"12","author":"DM Kim","year":"2025","unstructured":"Kim DM, Pan Q, Liu Z et al (2025) GHSR-Foxo1 signaling in macrophages promotes liver fibrosis via inflammatory response and hepatic stellate cell activation. Adv Sci 12(33):e04223","journal-title":"Adv Sci"},{"issue":"12","key":"5312_CR11","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.jconrel.2024.10.044","volume":"376","author":"Q Lai","year":"2024","unstructured":"Lai Q, Li W, Hu D et al (2024) Hepatic stellate cell-targeted chemo-gene therapy for liver fibrosis using fluorinated peptide-lipid hybrid nanoparticles. J Control Release 376(12):601\u2013617","journal-title":"J Control Release"},{"issue":"498","key":"5312_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2025.139852","volume":"12","author":"G Li","year":"2025","unstructured":"Li G, Li Z, Chen L et al (2025) PDHA1-mediated H3K18 lactylation is involved in arsenic-induced nonalcoholic fatty liver disease by activating the CD36-NLRP3 inflammasome axis. J Hazard Mater 12(498):139852","journal-title":"J Hazard Mater"},{"key":"5312_CR13","doi-asserted-by":"crossref","unstructured":"Link F, Li Y, Zhao J et al (2025) ECM1 attenuates hepatic fibrosis by interfering with mediators of latent TGF-\u03b21 activation. Gut 74(3):424\u2013439","DOI":"10.1136\/gutjnl-2024-333213"},{"issue":"4","key":"5312_CR14","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.cmet.2024.12.005","volume":"37","author":"Y Liu","year":"2025","unstructured":"Liu Y, Zhou R, Guo Y et al (2025) Muscle-derived small extracellular vesicles induce liver fibrosis during overtraining. Cell Metab 37(4):824\u2013841","journal-title":"Cell Metab"},{"issue":"12","key":"5312_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114996","volume":"43","author":"H Lu","year":"2024","unstructured":"Lu H, Liu H, Yan R et al (2024) Carbonic anhydrase 2 facilitates sorafenib resistance by counteracting MCT4-mediated intracellular pH dysregulation in HCC. Cell Rep 43(12):114996","journal-title":"Cell Rep"},{"issue":"3","key":"5312_CR16","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1097\/HEP.0000000000001195","volume":"82","author":"Y Luo","year":"2025","unstructured":"Luo Y, Fraser L, Jezykowski J et al (2025) Interleukin 8-CXCR2-mediated neutrophil extracellular trap formation in biliary atresia associated with neutrophil extracellular trap-induced stellate cell activation. Hepatology 82(3):552\u2013565","journal-title":"Hepatology"},{"issue":"1","key":"5312_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-025-03327-5","volume":"44","author":"I Masi","year":"2025","unstructured":"Masi I, Ottavi F, Caprara V et al (2025) The extracellular matrix protein type I collagen and fibronectin are regulated by \u03b2-arrestin-1\/endothelin axis in human ovarian fibroblasts. J Exp Clin Cancer Res 44(1):64","journal-title":"J Exp Clin Cancer Res"},{"issue":"12","key":"5312_CR18","doi-asserted-by":"publisher","first-page":"17135","DOI":"10.1007\/s00210-025-04327-0","volume":"398","author":"RH Mohyeldin","year":"2025","unstructured":"Mohyeldin RH, Abdelnaser M, Sharata EE et al (2025) Modulating platelet-activating factor by rupatadine attenuates gentamicin-induced nephrotoxicity in rats via NF-\u03baB\/caspase-3 and Nrf2\/HO-1 signaling cascades. Naunyn Schmiedebergs Arch Pharmacol 398(12):17135\u201317146","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"1","key":"5312_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-025-01148-4","volume":"32","author":"B Ning","year":"2025","unstructured":"Ning B, Wang S-A, Young M-J et al (2025) USP24 upregulation stabilizes PKA-C\u03b1 to promote lipogenesis, inflammation, and fibrosis during MASH progression. J Biomed Sci 32(1):54","journal-title":"J Biomed Sci"},{"issue":"4","key":"5312_CR20","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1097\/HEP.0000000000001018","volume":"81","author":"U Ojha","year":"2025","unstructured":"Ojha U, Kim S, Rhee CY et al (2025) Endothelial RUNX3 controls LSEC dysfunction and angiocrine LRG1 signaling to prevent liver fibrosis. Hepatology 81(4):1228\u20131243","journal-title":"Hepatology"},{"key":"5312_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2025.115406","volume":"200","author":"RR Rofaeil","year":"2025","unstructured":"Rofaeil RR, Sharata EE, Attya ME et al (2025) Repurposing levomilnacipran to attenuate premature ovarian insufficiency induced by cyclophosphamide in female Wistar albino rats through modulation of TLR4\/p38-MAPK\/NF-\u03baB p65, caspase-3-driven apoptosis, and Klotho protein expression. Food Chem Toxicol 200:115406","journal-title":"Food Chem Toxicol"},{"key":"5312_CR22","doi-asserted-by":"crossref","unstructured":"Sharata EE, Attya ME, Khalaf MM et al (2025) Levomilnacipran alleviates cyclophosphamide-induced hepatic dysfunction in male Wistar albino rats; emerging role of \u03b1-Klotho\/TLR4\/p38-MAPK\/NF-\u03baB p65 and caspase-3-driven apoptosis trajectories. Int Immunopharmacol 16:152:114384","DOI":"10.1016\/j.intimp.2025.114384"},{"issue":"8059","key":"5312_CR23","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1038\/s41586-025-08677-w","volume":"640","author":"A Sugimoto","year":"2025","unstructured":"Sugimoto A, Saito Y, Wang G et al (2025) Hepatic stellate cells control liver zonation, size and functions via R-spondin 3. Nature 640(8059):752\u2013761","journal-title":"Nature"},{"issue":"1","key":"5312_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05289-2","volume":"22","author":"Z Sun","year":"2024","unstructured":"Sun Z, Ji Z, Meng H et al (2024) Lactate facilitated mitochondrial fission-derived ROS to promote pulmonary fibrosis via ERK\/DRP-1 signaling. J Transl Med 22(1):479","journal-title":"J Transl Med"},{"key":"5312_CR25","doi-asserted-by":"crossref","unstructured":"Sun Z, He W, Meng H et al (2024) Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis. Respir Res 25(1):401","DOI":"10.1186\/s12931-024-03016-5"},{"issue":"5","key":"5312_CR26","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.jhep.2024.06.016","volume":"81","author":"V Taru","year":"2024","unstructured":"Taru V, Szabo G, Mehal W et al (2024) Inflammasomes in chronic liver disease: hepatic injury, fibrosis progression and systemic inflammation. J Hepatol 81(5):895\u2013910","journal-title":"J Hepatol"},{"issue":"11","key":"5312_CR27","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/s41388-024-03243-6","volume":"44","author":"S Tsukihara","year":"2025","unstructured":"Tsukihara S, Akiyama Y, Shimada S et al (2025) Delactylase effects of SIRT1 on a positive feedback loop involving the H19-glycolysis-histone lactylation in gastric cancer. Oncogene 44(11):724\u2013738","journal-title":"Oncogene"},{"issue":"6","key":"5312_CR28","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1093\/humupd\/dmae023","volume":"30","author":"G Vissers","year":"2024","unstructured":"Vissers G, Giacomozzi M, Verdurmen W et al (2024) The role of fibrosis in endometriosis: a systematic review. Hum Reprod Update 30(6):706\u2013750","journal-title":"Hum Reprod Update"},{"issue":"1","key":"5312_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.119005","volume":"338","author":"W Wang","year":"2025","unstructured":"Wang W, Qin J, Bai S et al (2025a) Integrative transcriptomics and lipidomics unravels the amelioration effects of Radix Bupleuri on non-alcoholic fatty liver disease. J Ethnopharmacol 338(1):119005","journal-title":"J Ethnopharmacol"},{"key":"5312_CR30","doi-asserted-by":"crossref","unstructured":"Wang W, Bai X, Li J, Wang S et al (2025b) Low polarity fraction of Radix Bupleuri alleviates chronic unpredictable mild stress-induced depression in rats through FXR modulating bile acid homeostasis in liver, gut, and brain. J Pharm Biomed Anal 15(253):116523","DOI":"10.1016\/j.jpba.2024.116523"},{"key":"5312_CR31","doi-asserted-by":"crossref","unstructured":"Zhu Y, Lv X, Li R et al (2024) Saikosaponin-b2 regulates the proliferation and apoptosis of liver cancer cells by targeting the MACC1\/c-Met\/Akt signalling pathway. Adv Pharmacol Pharm Sci 6(24):2653426","DOI":"10.1155\/2024\/2653426"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05312-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-026-05312-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05312-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T03:02:15Z","timestamp":1784775735000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-026-05312-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":31,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["5312"],"URL":"https:\/\/doi.org\/10.1007\/s00210-026-05312-x","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]},"assertion":[{"value":"3 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors utilized [AI Tool Name, DeepSeek-R1] solely for language refinement purposes in this manuscript, including grammar correction, syntax optimization, and vocabulary enhancement. The AI system did not participate in research design, data interpretation, or scientific conclusions. All authors take full responsibility for the academic integrity, factual accuracy, and intellectual content of this work.","order":1,"name":"Ethics","label":"AI use declaration","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}