{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:18:36Z","timestamp":1788247116454,"version":"build-2803163510"},"reference-count":120,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-74-31017"],"award-info":[{"award-number":["25-74-31017"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biogerontology"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1007\/s10522-026-10504-2","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:56:23Z","timestamp":1788242183000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Berberine and its derivatives as candidate modulators of immunosenescence: a critical evaluation"],"prefix":"10.1007","volume":"27","author":[{"given":"Roman A.","family":"Zinovkin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin G.","family":"Lyamzaev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Churov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Maltseva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"issue":"1","key":"10504_CR1","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12979-025-00522-y","volume":"22","author":"M Ahmed","year":"2025","unstructured":"Ahmed M (2025) Targeting aging pathways with natural compounds: a review of curcumin, epigallocatechin gallate, thymoquinone, and resveratrol. Immun Ageing 22(1):28","journal-title":"Immun Ageing"},{"key":"10504_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.762654","volume":"12","author":"X Ai","year":"2021","unstructured":"Ai X, Yu P, Peng L, Luo L, Liu J, Li S, Lai X, Luan F, Meng X (2021) Berberine: a review of its pharmacokinetics properties and therapeutic potentials in diverse vascular diseases. Front Pharmacol 12:762654","journal-title":"Front Pharmacol"},{"issue":"3","key":"10504_CR3","doi-asserted-by":"publisher","first-page":"356","DOI":"10.2174\/1871520618666181116162441","volume":"19","author":"RS Almeer","year":"2019","unstructured":"Almeer RS, Aref AM, Hussein RA, Othman MS, Abdel Moneim AE (2019) Antitumor potential of berberine and cinnamic acid against solid Ehrlich carcinoma in mice. Anticancer Agents Med Chem 19(3):356\u2013364","journal-title":"Anticancer Agents Med Chem"},{"key":"10504_CR4","doi-asserted-by":"publisher","first-page":"e57950","DOI":"10.7554\/eLife.57950","volume":"9","author":"G Alsaleh","year":"2020","unstructured":"Alsaleh G, Panse I, Swadling L, Zhang H, Richter FC, Meyer A, Lord J, Barnes E, Klenerman P, Green C, Simon AK (2020) Autophagy in T cells from aged donors is maintained by spermidine and correlates with function and vaccine responses. Elife 9:e57950","journal-title":"Elife"},{"issue":"1","key":"10504_CR5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000599","volume":"18","author":"N Basisty","year":"2020","unstructured":"Basisty N, Kale A, Jeon OH, Kuehnemann C, Payne T, Rao C, Holtz A, Shah S, Sharma V, Ferrucci L, Campisi J, Schilling B (2020) A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLoS Biol 18(1):e3000599","journal-title":"PLoS Biol"},{"key":"10504_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/antiox14040450","author":"Y Bei","year":"2025","unstructured":"Bei Y, Wang T, Guan S (2025) Berberine extends lifespan in C. elegans through multi-target synergistic antioxidant effects. Antioxidants (Basel). https:\/\/doi.org\/10.3390\/antiox14040450","journal-title":"Antioxidants (Basel)"},{"key":"10504_CR7","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics18010118","author":"J Bernatoniene","year":"2026","unstructured":"Bernatoniene J, Kopustinskiene DM, Casale R, Medoro A, Davinelli S, Saso L, Petrikonis K (2026) Nrf2 modulation by natural compounds in aging, neurodegeneration, and neuropathic pain. Pharmaceutics. https:\/\/doi.org\/10.3390\/pharmaceutics18010118","journal-title":"Pharmaceutics"},{"issue":"4","key":"10504_CR8","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.coi.2013.07.007","volume":"25","author":"SD Boyd","year":"2013","unstructured":"Boyd SD, Liu Y, Wang C, Martin V, Dunn-Walters DK (2013) Human lymphocyte repertoires in ageing. Curr Opin Immunol 25(4):511\u2013515","journal-title":"Curr Opin Immunol"},{"issue":"6","key":"10504_CR9","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.4049\/jimmunol.1302064","volume":"192","author":"OV Britanova","year":"2014","unstructured":"Britanova OV, Putintseva EV, Shugay M, Merzlyak EM, Turchaninova MA, Staroverov DB, Bolotin DA, Lukyanov S, Bogdanova EA, Mamedov IZ, Lebedev YB, Chudakov DM (2014) Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling. J Immunol 192(6):2689\u20132698","journal-title":"J Immunol"},{"issue":"2","key":"10504_CR10","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13067","volume":"19","author":"LA Callender","year":"2020","unstructured":"Callender LA, Carroll EC, Bober EA, Akbar AN, Solito E, Henson SM (2020) Mitochondrial mass governs the extent of human T cell senescence. Aging Cell 19(2):e13067","journal-title":"Aging Cell"},{"key":"10504_CR11","doi-asserted-by":"publisher","DOI":"10.3390\/nu17101716","author":"M Centonze","year":"2025","unstructured":"Centonze M, Caruso EA, De Nunzio V, Cofano M, Saponara I, Pinto G, Notarnicola M (2025) The antiaging potential of dietary plant-based polyphenols: a review on their role in cellular senescence modulation. Nutrients. https:\/\/doi.org\/10.3390\/nu17101716","journal-title":"Nutrients"},{"key":"10504_CR12","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1186\/s12967-016-0982-x","volume":"14","author":"X Chang","year":"2016","unstructured":"Chang X, Wang Z, Zhang J, Yan H, Bian H, Xia M, Lin H, Jiang J, Gao X (2016) Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease. J Transl Med 14:266","journal-title":"J Transl Med"},{"issue":"1","key":"10504_CR13","doi-asserted-by":"publisher","first-page":"2423","DOI":"10.1080\/14756366.2022.2118268","volume":"37","author":"J Chen","year":"2022","unstructured":"Chen J, Duan Y, Yu X, Zhong J, Bai J, Li NG, Zhu Z, Xu J (2022a) Development of novel 9-O-substituted-13-octylberberine derivatives as potential anti-hepatocellular carcinoma agents. J Enzyme Inhib Med Chem 37(1):2423\u20132433","journal-title":"J Enzyme Inhib Med Chem"},{"key":"10504_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.851255","volume":"9","author":"J Chen","year":"2022","unstructured":"Chen J, Huang Y, Bian X, He Y (2022b) Berberine ameliorates inflammation in acute lung injury via NF-kappaB\/Nlrp3 signaling pathway. Front Nutr 9:851255","journal-title":"Front Nutr"},{"issue":"9","key":"10504_CR15","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1038\/s41423-023-01064-3","volume":"20","author":"Y Chen","year":"2023","unstructured":"Chen Y, Xu Z, Sun H, Ouyang X, Han Y, Yu H, Wu N, Xie Y, Su B (2023) Regulation of CD8(+) T memory and exhaustion by the mTOR signals. Cell Mol Immunol 20(9):1023\u20131039","journal-title":"Cell Mol Immunol"},{"key":"10504_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16091116","author":"X Chen","year":"2024","unstructured":"Chen X, Yang H, Shi L, Mao Y, Niu L, Wang J, Chen H, Jia J, Wang J, Xue J, Shen Y, Zheng C, Tian Y, Zheng Y (2024) Self-microemulsifying drug delivery system to enhance oral bioavailability of berberine hydrochloride in rats. Pharmaceutics. https:\/\/doi.org\/10.3390\/pharmaceutics16091116","journal-title":"Pharmaceutics"},{"issue":"16","key":"10504_CR17","doi-asserted-by":"publisher","first-page":"5915","DOI":"10.1016\/j.bmc.2010.06.085","volume":"18","author":"Z Cheng","year":"2010","unstructured":"Cheng Z, Chen AF, Wu F, Sheng L, Zhang HK, Gu M, Li YY, Zhang LN, Hu LH, Li JY, Li J (2010) 8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models. Bioorg Med Chem 18(16):5915\u20135924","journal-title":"Bioorg Med Chem"},{"issue":"20","key":"10504_CR18","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1101\/gad.17276711","volume":"25","author":"Y Chien","year":"2011","unstructured":"Chien Y, Scuoppo C, Wang X, Fang X, Balgley B, Bolden JE, Premsrirut P, Luo W, Chicas A, Lee CS, Kogan SC, Lowe SW (2011) Control of the senescence-associated secretory phenotype by NF-kappaB promotes senescence and enhances chemosensitivity. Genes Dev 25(20):2125\u20132136","journal-title":"Genes Dev"},{"issue":"10","key":"10504_CR19","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1038\/nrd.2017.116","volume":"16","author":"BG Childs","year":"2017","unstructured":"Childs BG, Gluscevic M, Baker DJ, Laberge RM, Marquess D, Dananberg J, van Deursen JM (2017) Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov 16(10):718\u2013735","journal-title":"Nat Rev Drug Discov"},{"key":"10504_CR20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/978-3-319-41334-1_2","volume":"928","author":"AF Cicero","year":"2016","unstructured":"Cicero AF, Baggioni A (2016) Berberine and its role in chronic disease. Adv Exp Med Biol 928:27\u201345","journal-title":"Adv Exp Med Biol"},{"issue":"3","key":"10504_CR21","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/s41577-018-0095-2","volume":"19","author":"AJ Clarke","year":"2019","unstructured":"Clarke AJ, Simon AK (2019) Autophagy in the renewal, differentiation and homeostasis of immune cells. Nat Rev Immunol 19(3):170\u2013183","journal-title":"Nat Rev Immunol"},{"issue":"5","key":"10504_CR22","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1007\/s11357-022-00612-5","volume":"44","author":"J Connors","year":"2022","unstructured":"Connors J, Taramangalam B, Cusimano G, Bell MR, Matt SM, Runner K, Gaskill PJ, DeFilippis V, Nikolich-Zugich J, Kutzler MA, Haddad EK (2022) Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists. Geroscience 44(5):2555\u20132572","journal-title":"Geroscience"},{"key":"10504_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154131","volume":"101","author":"L Dai","year":"2022","unstructured":"Dai L, Zhu L, Ma S, Liu J, Zhang M, Li J, Luo Y, Zhou X, Chen Q, Wang L, Huang Y, Chen Y (2022) Berberine alleviates NLRP3 inflammasome induced endothelial junction dysfunction through Ca(2+) signalling in inflammatory vascular injury. Phytomedicine 101:154131","journal-title":"Phytomedicine"},{"issue":"1","key":"10504_CR24","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13060","volume":"19","author":"Y Dang","year":"2020","unstructured":"Dang Y, An Y, He J, Huang B, Zhu J, Gao M, Zhang S, Wang X, Yang B, Xie Z (2020) Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression. Aging Cell 19(1):e13060","journal-title":"Aging Cell"},{"key":"10504_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1281090","volume":"14","author":"T Dehau","year":"2023","unstructured":"Dehau T, Cherlet M, Croubels S, Van De Vliet M, Goossens E, Van Immerseel F (2023) Berberine-microbiota interplay: orchestrating gut health through modulation of the gut microbiota and metabolic transformation into bioactive metabolites. Front Pharmacol 14:1281090","journal-title":"Front Pharmacol"},{"issue":"6","key":"10504_CR26","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41580-018-0003-4","volume":"19","author":"I Dikic","year":"2018","unstructured":"Dikic I, Elazar Z (2018) Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol 19(6):349\u2013364","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10504_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.121525","volume":"616","author":"TT Duong","year":"2022","unstructured":"Duong TT, Yen TTH, Nguyen LT, Nguyen TD, Nguyen TQ, Nghiem TH, Pham HT, Raal A, Heinamaki J, Pham TM (2022) Berberine-loaded liposomes for oral delivery: preparation, physicochemical characterization and in-vivo evaluation in an endogenous hyperlipidemic animal model. Int J Pharm 616:121525","journal-title":"Int J Pharm"},{"issue":"23","key":"10504_CR28","doi-asserted-by":"publisher","first-page":"13573","DOI":"10.1111\/jcmm.16049","volume":"24","author":"SM Ehteshamfar","year":"2020","unstructured":"Ehteshamfar SM, Akhbari M, Afshari JT, Seyedi M, Nikfar B, Shapouri-Moghaddam A, Ghanbarzadeh E, Momtazi-Borojeni AA (2020) Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation. J Cell Mol Med 24(23):13573\u201313588","journal-title":"J Cell Mol Med"},{"key":"10504_CR29","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12967-015-0450-z","volume":"13","author":"X Fan","year":"2015","unstructured":"Fan X, Wang J, Hou J, Lin C, Bensoussan A, Chang D, Liu J, Wang B (2015) Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK\/mTOR signaling pathway. J Transl Med 13:92","journal-title":"J Transl Med"},{"key":"10504_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/srep12155","volume":"5","author":"R Feng","year":"2015","unstructured":"Feng R, Shou JW, Zhao ZX, He CY, Ma C, Huang M, Fu J, Tan XS, Li XY, Wen BY, Chen X, Yang XY, Ren G, Lin Y, Chen Y, You XF, Wang Y, Jiang JD (2015) Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep 5:12155","journal-title":"Sci Rep"},{"key":"10504_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2021.116143","volume":"38","author":"S Gaba","year":"2021","unstructured":"Gaba S, Saini A, Singh G, Monga V (2021) An insight into the medicinal attributes of berberine derivatives: a review. Bioorg Med Chem 38:116143","journal-title":"Bioorg Med Chem"},{"key":"10504_CR32","doi-asserted-by":"publisher","DOI":"10.3390\/genes12121856","author":"A Gamez-Garcia","year":"2021","unstructured":"Gamez-Garcia A, Vazquez BN (2021) Nuclear sirtuins and the aging of the immune system. Genes. https:\/\/doi.org\/10.3390\/genes12121856","journal-title":"Genes"},{"issue":"8","key":"10504_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cells10081906","volume":"10","author":"VA Garcia-Garcia","year":"2021","unstructured":"Garcia-Garcia VA, Alameda JP, Page A, Casanova ML (2021) Role of NF-kappaB in ageing and age-related diseases: lessons from genetically modified mouse models. Cells 10(8):1","journal-title":"Cells"},{"issue":"9","key":"10504_CR34","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1038\/ncb3586","volume":"19","author":"S Gluck","year":"2017","unstructured":"Gluck S, Guey B, Gulen MF, Wolter K, Kang TW, Schmacke NA, Bridgeman A, Rehwinkel J, Zender L, Ablasser A (2017) Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence. Nat Cell Biol 19(9):1061\u20131070","journal-title":"Nat Cell Biol"},{"key":"10504_CR35","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cytogfr.2020.08.003","volume":"55","author":"A Gritsenko","year":"2020","unstructured":"Gritsenko A, Green JP, Brough D, Lopez-Castejon G (2020) Mechanisms of NLRP3 priming in inflammaging and age related diseases. Cytokine Growth Factor Rev 55:15\u201325","journal-title":"Cytokine Growth Factor Rev"},{"issue":"7973","key":"10504_CR36","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41586-023-06373-1","volume":"620","author":"MF Gulen","year":"2023","unstructured":"Gulen MF, Samson N, Keller A, Schwabenland M, Liu C, Gluck S, Thacker VV, Favre L, Mangeat B, Kroese LJ, Krimpenfort P, Prinz M, Ablasser A (2023) cGAS-STING drives ageing-related inflammation and neurodegeneration. Nature 620(7973):374\u2013380","journal-title":"Nature"},{"issue":"2","key":"10504_CR37","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s00228-011-1108-2","volume":"68","author":"Y Guo","year":"2012","unstructured":"Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH (2012) Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 68(2):213\u2013217","journal-title":"Eur J Clin Pharmacol"},{"issue":"3","key":"10504_CR38","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1111\/acel.12446","volume":"15","author":"X Han","year":"2016","unstructured":"Han X, Tai H, Wang X, Wang Z, Zhou J, Wei X, Ding Y, Gong H, Mo C, Zhang J, Qin J, Ma Y, Huang N, Xiang R, Xiao H (2016) AMPK activation protects cells from oxidative stress-induced senescence via autophagic flux restoration and intracellular NAD(+) elevation. Aging Cell 15(3):416\u2013427","journal-title":"Aging Cell"},{"key":"10504_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01121","volume":"9","author":"W Hang","year":"2018","unstructured":"Hang W, He B, Chen J, Xia L, Wen B, Liang T, Wang X, Zhang Q, Wu Y, Chen Q, Chen J (2018) Berberine ameliorates high glucose-induced cardiomyocyte injury via AMPK signaling activation to stimulate mitochondrial biogenesis and restore autophagic flux. Front Pharmacol 9:1121","journal-title":"Front Pharmacol"},{"issue":"1","key":"10504_CR40","doi-asserted-by":"publisher","first-page":"5503","DOI":"10.1038\/s41467-021-25701-5","volume":"12","author":"SA Harrison","year":"2021","unstructured":"Harrison SA, Gunn N, Neff GW, Kohli A, Liu L, Flyer A, Goldkind L, Di Bisceglie AM (2021) A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes. Nat Commun 12(1):5503","journal-title":"Nat Commun"},{"issue":"2","key":"10504_CR41","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrm.2017.95","volume":"19","author":"S Herzig","year":"2018","unstructured":"Herzig S, Shaw RJ (2018) AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol 19(2):121\u2013135","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"9","key":"10504_CR42","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.mad.2004.07.001","volume":"125","author":"MS Hong","year":"2004","unstructured":"Hong MS, Dan JM, Choi JY, Kang I (2004) Age-associated changes in the frequency of naive, memory and effector CD8+ T cells. Mech Ageing Dev 125(9):615\u2013618","journal-title":"Mech Ageing Dev"},{"issue":"7","key":"10504_CR43","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202413122","volume":"12","author":"H Hu","year":"2025","unstructured":"Hu H, Wang Q, Yu D, Tao X, Guo M, Tian S, Zhang Q, Xu M, Geng X, Zhang H, Xu H, Li L, Xie S, Chen K, Zhu W, Li XW, Xu H, Li B, Zhang W, Liu S (2025) Berberine derivative B68 promotes tumor immune clearance by dual-targeting BMI1 for senescence induction and CSN5 for PD-L1 degradation. Adv Sci 12(7):e2413122","journal-title":"Adv Sci"},{"key":"10504_CR44","doi-asserted-by":"publisher","DOI":"10.3390\/cells14241963","author":"H Huan","year":"2025","unstructured":"Huan H, Panteleeva AA, Simonyan RA, Avetisyan AV, Sumbatyan NV, Lyamzaev KG, Chernyak BV (2025) 13-Decyl berberine derivative is a novel mitochondria-targeted antioxidant and a potent inhibitor of ferroptosis. Cells. https:\/\/doi.org\/10.3390\/cells14241963","journal-title":"Cells"},{"issue":"4","key":"10504_CR120","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1371\/journal.pone.0232630","volume":"21","author":"N Ivanovska","year":"1999","unstructured":"Ivanovska N, Philipov S, Hristova M (1999) Influence of berberine on T-cell mediated immunity. Immunopharmacol Immunotoxicol 21(4):771\u2013786. https:\/\/doi.org\/10.1371\/journal.pone.0232630","journal-title":"Immunopharmacol Immunotoxicol"},{"issue":"7","key":"10504_CR45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134142","volume":"10","author":"W Jiang","year":"2015","unstructured":"Jiang W, Wei W, Gaertig MA, Li S, Li XJ (2015) Therapeutic effect of berberine on Huntington\u2019s disease transgenic mouse model. PLoS ONE 10(7):e0134142","journal-title":"PLoS ONE"},{"key":"10504_CR46","doi-asserted-by":"publisher","first-page":"5431","DOI":"10.2147\/DDDT.S282206","volume":"14","author":"C Jiang","year":"2020","unstructured":"Jiang C, Xie N, Sun T, Ma W, Zhang B, Li W (2020) Xanthohumol inhibits TGF-beta1-induced cardiac fibroblasts activation via mediating PTEN\/Akt\/mTOR signaling pathway. Drug des Devel Ther 14:5431\u20135439","journal-title":"Drug des Devel Ther"},{"key":"10504_CR47","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.ejphar.2016.11.037","volume":"794","author":"Y Jin","year":"2017","unstructured":"Jin Y, Liu S, Ma Q, Xiao D, Chen L (2017) Berberine enhances the AMPK activation and autophagy and mitigates high glucose-induced apoptosis of mouse podocytes. Eur J Pharmacol 794:106\u2013114","journal-title":"Eur J Pharmacol"},{"key":"10504_CR48","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13122138","author":"MV Khvostov","year":"2021","unstructured":"Khvostov MV, Gladkova ED, Borisov SA, Zhukova NA, Marenina MK, Meshkova YV, Luzina OA, Tolstikova TG, Salakhutdinov NF (2021) Discovery of the first in class 9-N-berberine derivative as hypoglycemic agent with extra-strong action. Pharmaceutics. https:\/\/doi.org\/10.3390\/pharmaceutics13122138","journal-title":"Pharmaceutics"},{"key":"10504_CR49","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214186","author":"MV Khvostov","year":"2022","unstructured":"Khvostov MV, Gladkova ED, Borisov SA, Fedotova MS, Zhukova NA, Marenina MK, Meshkova YV, Luzina OA, Tolstikova TG, Salakhutdinov NF (2022) Study of hypoglycemic activity of novel 9-N-alkyltetrahydroberberine derivatives. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms232214186","journal-title":"Int J Mol Sci"},{"key":"10504_CR50","doi-asserted-by":"publisher","DOI":"10.3390\/polym13213833","author":"K Kohli","year":"2021","unstructured":"Kohli K, Mujtaba A, Malik R, Amin S, Alam MS, Ali A, Barkat MA, Ansari MJ (2021) Development of natural polysaccharide-based nanoparticles of berberine to enhance oral bioavailability: formulation, optimization, ex vivo, and in vivo assessment. Polymers. https:\/\/doi.org\/10.3390\/polym13213833","journal-title":"Polymers"},{"key":"10504_CR51","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.coph.2021.01.003","volume":"57","author":"KA Lee","year":"2021","unstructured":"Lee KA, Robbins PD, Camell CD (2021) Intersection of immunometabolism and immunosenescence during aging. Curr Opin Pharmacol 57:107\u2013116","journal-title":"Curr Opin Pharmacol"},{"issue":"10","key":"10504_CR52","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1002\/mc.22179","volume":"54","author":"W Li","year":"2015","unstructured":"Li W, Hua B, Saud SM, Lin H, Hou W, Matter MS, Jia L, Colburn NH, Young MR (2015) Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice. Mol Carcinog 54(10):1096\u20131109","journal-title":"Mol Carcinog"},{"issue":"4","key":"10504_CR53","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.bbrc.2019.01.023","volume":"509","author":"AN Li","year":"2019","unstructured":"Li AN, Chen JJ, Li QQ, Zeng GY, Chen QY, Chen JL, Liao ZM, Jin P, Wang KS, Yang ZC (2019) Alpha-glucosidase inhibitor 1-deoxynojirimycin promotes beige remodeling of 3T3-L1 preadipocytes via activating AMPK. Biochem Biophys Res Commun 509(4):1001\u20131007","journal-title":"Biochem Biophys Res Commun"},{"key":"10504_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102653","volume":"104","author":"S Li","year":"2025","unstructured":"Li S, Wang K, Wu J, Zhu Y (2025a) The immunosenescence clock: a new method for evaluating biological age and predicting mortality risk. Ageing Res Rev 104:102653","journal-title":"Ageing Res Rev"},{"issue":"4","key":"10504_CR55","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/s43587-025-00819-z","volume":"5","author":"W Li","year":"2025","unstructured":"Li W, Zhang Z, Kumar S, Botey-Bataller J, Zoodsma M, Ehsani A, Zhan Q, Alaswad A, Zhou L, Grondman I, Koeken V, Yang J, Wang G, Volland S, Crisan TO, Joosten LAB, Illig T, Xu CJ, Netea MG, Li Y (2025b) Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination. Nat Aging 5(4):607\u2013621","journal-title":"Nat Aging"},{"issue":"1","key":"10504_CR56","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1507\/endocrj.EJ18-0109","volume":"66","author":"Y Liang","year":"2019","unstructured":"Liang Y, Xu X, Yin M, Zhang Y, Huang L, Chen R, Ni J (2019) Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis. Endocr J 66(1):51\u201363","journal-title":"Endocr J"},{"issue":"4","key":"10504_CR57","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1111\/j.1474-9726.2009.00489.x","volume":"8","author":"Y Liu","year":"2009","unstructured":"Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Ibrahim JG, Thomas NE, Sharpless NE (2009) Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell 8(4):439\u2013448","journal-title":"Aging Cell"},{"issue":"4","key":"10504_CR58","doi-asserted-by":"publisher","first-page":"5580","DOI":"10.3892\/mmr.2015.4061","volume":"12","author":"SJ Liu","year":"2015","unstructured":"Liu SJ, Yin CX, Ding MC, Wang YZ, Wang H (2015) Berberine inhibits tumor necrosis factor-alpha-induced expression of inflammatory molecules and activation of nuclear factor-kappaB via the activation of AMPK in vascular endothelial cells. Mol Med Rep 12(4):5580\u20135586","journal-title":"Mol Med Rep"},{"issue":"1","key":"10504_CR59","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1142\/S0192415X24500101","volume":"52","author":"YL Liu","year":"2024","unstructured":"Liu YL, Guo T, Zhang YJ, Tang SC, Zhao XM, He HY, Yu CL, Deng YH (2024) Berberine alleviates ischemic brain injury by enhancing autophagic flux via facilitation of TFEB nuclear translocation. Am J Chin Med 52(1):231\u2013252","journal-title":"Am J Chin Med"},{"key":"10504_CR60","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1572197","volume":"16","author":"D Liu","year":"2025","unstructured":"Liu D, Zhao H, Zhang Y, Hu J, Xu H (2025) Efficacy and safety of berberine on the components of metabolic syndrome: a systematic review and meta-analysis of randomized placebo-controlled trials. Front Pharmacol 16:1572197","journal-title":"Front Pharmacol"},{"issue":"3","key":"10504_CR61","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1021\/acsinfecdis.5c00988","volume":"12","author":"Y Liu","year":"2026","unstructured":"Liu Y, Wu C, Guan M, Shang F, Kan W, Luo X, Liu D, Zou Y, Zhou L, Zhang Y (2026) Recent advances in pleuromutilin derivatives as antimicrobial agents (2015\u20132025). ACS Infect Dis 12(3):946\u2013966","journal-title":"ACS Infect Dis"},{"issue":"2","key":"10504_CR62","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s43440-021-00348-7","volume":"74","author":"Q Lu","year":"2022","unstructured":"Lu Q, Fu Y, Li H (2022) Berberine and its derivatives represent as the promising therapeutic agents for inflammatory disorders. Pharmacol Rep 74(2):297\u2013309","journal-title":"Pharmacol Rep"},{"key":"10504_CR63","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.958563","volume":"9","author":"C Luis","year":"2022","unstructured":"Luis C, Maduro AT, Pereira P, Mendes JJ, Soares R, Ramalho R (2022) Nutritional senolytics and senomorphics: implications to immune cells metabolism and aging\u2014from theory to practice. Front Nutr 9:958563","journal-title":"Front Nutr"},{"issue":"7","key":"10504_CR64","doi-asserted-by":"publisher","first-page":"3726","DOI":"10.1128\/AAC.04794-14","volume":"59","author":"Z Lv","year":"2015","unstructured":"Lv Z, Peng G, Liu W, Xu H, Su J (2015) Berberine blocks the relapse of Clostridium difficile infection in C57BL\/6 mice after standard vancomycin treatment. Antimicrob Agents Chemother 59(7):3726\u20133735","journal-title":"Antimicrob Agents Chemother"},{"issue":"268","key":"10504_CR65","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009892","volume":"6","author":"JB Mannick","year":"2014","unstructured":"Mannick JB, Del Giudice G, Lattanzi M, Valiante NM, Praestgaard J, Huang B, Lonetto MA, Maecker HT, Kovarik J, Carson S, Glass DJ, Klickstein LB (2014) mTOR inhibition improves immune function in the elderly. Sci Transl Med 6(268):268ra179","journal-title":"Sci Transl Med"},{"issue":"5","key":"10504_CR66","first-page":"2436","volume":"39","author":"L Mao","year":"2018","unstructured":"Mao L, Chen Q, Gong K, Xu X, Xie Y, Zhang W, Cao H, Hu T, Hong X, Zhan YY (2018) Berberine decelerates glucose metabolism via suppression of mTOR-dependent HIF-1alpha protein synthesis in colon cancer cells. Oncol Rep 39(5):2436\u20132442","journal-title":"Oncol Rep"},{"issue":"5","key":"10504_CR67","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13344","volume":"20","author":"RI Martinez-Zamudio","year":"2021","unstructured":"Martinez-Zamudio RI, Dewald HK, Vasilopoulos T, Gittens-Williams L, Fitzgerald-Bocarsly P, Herbig U (2021) Senescence-associated beta-galactosidase reveals the abundance of senescent CD8+ T cells in aging humans. Aging Cell 20(5):e13344","journal-title":"Aging Cell"},{"issue":"13","key":"10504_CR68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/JCI158447","volume":"132","author":"S Miwa","year":"2022","unstructured":"Miwa S, Kashyap S, Chini E, von Zglinicki T (2022) Mitochondrial dysfunction in cell senescence and aging. J Clin Invest 132(13):1","journal-title":"J Clin Invest"},{"key":"10504_CR69","doi-asserted-by":"publisher","DOI":"10.3390\/nu14010124","author":"JM Moon","year":"2021","unstructured":"Moon JM, Ratliff KM, Hagele AM, Stecker RA, Mumford PW, Kerksick CM (2021) Absorption kinetics of berberine and dihydroberberine and their impact on glycemia: a randomized, controlled, crossover pilot trial. Nutrients. https:\/\/doi.org\/10.3390\/nu14010124","journal-title":"Nutrients"},{"issue":"7A","key":"10504_CR70","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.4236\/ajps.2012.327123","volume":"3","author":"VV Navrotskaya","year":"2012","unstructured":"Navrotskaya VV, Oxenkrug G, Vorobyova LI, Summergrad P (2012) Berberine prolongs life span and stimulates locomotor activity of Drosophila melanogaster. Am J Plant Sci 3(7A):1037\u20131040","journal-title":"Am J Plant Sci"},{"issue":"3","key":"10504_CR71","doi-asserted-by":"publisher","first-page":"275","DOI":"10.4236\/ajps.2014.53037","volume":"5","author":"V Navrotskaya","year":"2014","unstructured":"Navrotskaya V, Oxenkrug G, Vorobyova L, Summergrad P (2014) Berberine attenuated aging-accelerating effect of high temperature in Drosophila model. Am J Plant Sci 5(3):275\u2013278","journal-title":"Am J Plant Sci"},{"key":"10504_CR72","doi-asserted-by":"publisher","first-page":"557","DOI":"10.3389\/fphar.2018.00557","volume":"9","author":"MA Neag","year":"2018","unstructured":"Neag MA, Mocan A, Echeverria J, Pop RM, Bocsan CI, Crisan G, Buzoianu AD (2018) Berberine: botanical occurrence, traditional uses, extraction methods, and relevance in cardiovascular, metabolic, hepatic, and renal disorders. Front Pharmacol 9:557","journal-title":"Front Pharmacol"},{"issue":"6","key":"10504_CR73","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s00210-007-0219-x","volume":"376","author":"AT Nies","year":"2008","unstructured":"Nies AT, Herrmann E, Brom M, Keppler D (2008) Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). Naunyn Schmiedebergs Arch Pharmacol 376(6):449\u2013461","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"1","key":"10504_CR74","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s12902-023-01442-y","volume":"23","author":"A Panigrahi","year":"2023","unstructured":"Panigrahi A, Mohanty S (2023) Efficacy and safety of HIMABERB(R) berberine on glycemic control in patients with prediabetes: double-blind, placebo-controlled, and randomized pilot trial. BMC Endocr Disord 23(1):190","journal-title":"BMC Endocr Disord"},{"issue":"2","key":"10504_CR75","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1093\/toxsci\/kfn131","volume":"105","author":"CV Pereira","year":"2008","unstructured":"Pereira CV, Machado NG, Oliveira PJ (2008) Mechanisms of berberine (natural yellow 18)-induced mitochondrial dysfunction: interaction with the adenine nucleotide translocator. Toxicol Sci 105(2):408\u2013417","journal-title":"Toxicol Sci"},{"issue":"1","key":"10504_CR76","first-page":"7563889","volume":"2021","author":"G Petrangolini","year":"2021","unstructured":"Petrangolini G, Corti F, Ronchi M, Arnoldi L, Allegrini P, Riva A (2021) Development of an innovative berberine food-grade formulation with an ameliorated absorption: in vitro evidence confirmed by healthy human volunteers pharmacokinetic study. Evid Based Complement Alternat Med 2021(1):7563889","journal-title":"Evid Based Complement Alternat Med"},{"issue":"1","key":"10504_CR77","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13020-023-00746-4","volume":"18","author":"Z Pu","year":"2023","unstructured":"Pu Z, Wen H, Jiang H, Hou Q, Yan H (2023) Berberine improves negative symptoms and cognitive function in patients with chronic schizophrenia via anti-inflammatory effect: a randomized clinical trial. Chin Med 18(1):41","journal-title":"Chin Med"},{"issue":"16","key":"10504_CR78","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/molecules26164733","volume":"26","author":"KK Reddi","year":"2021","unstructured":"Reddi KK, Li H, Li W, Tetali SD (2021) Berberine, a phytoalkaloid, inhibits inflammatory response induced by LPS through NF-kappabeta pathway: possible involvement of the IKKalpha. Molecules 26(16):1","journal-title":"Molecules"},{"key":"10504_CR79","doi-asserted-by":"publisher","DOI":"10.3390\/nu16172835","author":"NA Rivero-Segura","year":"2024","unstructured":"Rivero-Segura NA, Zepeda-Arzate EA, Castillo-Vazquez SK, Fleischmann-delaParra P, Hernandez-Pineda J, Flores-Soto E, Garcia-delaTorre P, Estrella-Parra EA, Gomez-Verjan JC (2024) Exploring the geroprotective potential of nutraceuticals. Nutrients. https:\/\/doi.org\/10.3390\/nu16172835","journal-title":"Nutrients"},{"key":"10504_CR80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.604591","volume":"11","author":"IJ Rodriguez","year":"2020","unstructured":"Rodriguez IJ, Lalinde Ruiz N, Llano Leon M, Martinez Enriquez L, Montilla Velasquez MDP, Ortiz Aguirre JP, Rodriguez Bohorquez OM, Velandia Vargas EA, Hernandez ED, Parra Lopez CA (2020) Immunosenescence study of T cells: a systematic review. Front Immunol 11:604591","journal-title":"Front Immunol"},{"issue":"14","key":"10504_CR81","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1177\/09564624231196600","volume":"34","author":"VV Ruiz-Herrera","year":"2023","unstructured":"Ruiz-Herrera VV, Navarro-Lara SA, Andrade-Villanueva JF, Alvarez-Zavala M, Sanchez-Reyes K, Toscano-Pina M, Mendez-Clemente AS, Martinez-Ayala P, Valle-Rodriguez A, Gonzalez-Hernandez LA (2023) Pilot study on the efficacy and safety of berberine in people with metabolic syndrome and human immunodeficiency virus infection. Int J STD AIDS 34(14):1042\u20131052","journal-title":"Int J STD AIDS"},{"issue":"2","key":"10504_CR82","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.arr.2011.12.005","volume":"11","author":"A Salminen","year":"2012","unstructured":"Salminen A, Kaarniranta K (2012) AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev 11(2):230\u2013241","journal-title":"Ageing Res Rev"},{"key":"10504_CR83","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26206238","author":"P Sarbadhikary","year":"2021","unstructured":"Sarbadhikary P, George BP, Abrahamse H (2021) Inhibitory role of berberine, an isoquinoline alkaloid, on NLRP3 inflammasome activation for the treatment of inflammatory diseases. Molecules. https:\/\/doi.org\/10.3390\/molecules26206238","journal-title":"Molecules"},{"issue":"1","key":"10504_CR84","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41514-026-00366-w","volume":"12","author":"M Sato","year":"2026","unstructured":"Sato M, Tanabu D, Torigoe D, Kadomatsu T, Taniwaka K, Ogata Y, Shiiba I, Suzuki Y, Ito N, Inatome R, Tokuyama T, Takeiwa T, Inoue S, Kanai E, Hamano T, Hirata H, Kanamitsu K, Kusuhara H, Yokosuka A, Mimaki Y, Abe H, Oike Y, Yanagi S (2026) Mitorubin, berberrubine-based compounds that improve mitochondrial function, exhibit cardioprotective effects against age-related cardiac dysfunction. NPJ Aging 12(1):56","journal-title":"NPJ Aging"},{"key":"10504_CR85","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s43587-021-00082-y","volume":"1","author":"N Sayed","year":"2021","unstructured":"Sayed N, Huang Y, Nguyen K, Krejciova-Rajaniemi Z, Grawe AP, Gao T, Tibshirani R, Hastie T, Alpert A, Cui L, Kuznetsova T, Rosenberg-Hasson Y, Ostan R, Monti D, Lehallier B, Shen-Orr SS, Maecker HT, Dekker CL, Wyss-Coray T, Franceschi C, Jojic V, Haddad F, Montoya JG, Wu JC, Davis MM, Furman D (2021) An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nat Aging 1:598\u2013615","journal-title":"Nat Aging"},{"issue":"4","key":"10504_CR86","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1002\/ptr.8077","volume":"38","author":"F Shakeri","year":"2024","unstructured":"Shakeri F, Kiani S, Rahimi G, Boskabady MH (2024) Anti-inflammatory, antioxidant, and immunomodulatory effects of Berberis vulgaris and its constituent berberine, experimental and clinical, a review. Phytother Res 38(4):1882\u20131902","journal-title":"Phytother Res"},{"key":"10504_CR87","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.591227","volume":"11","author":"Y Shan","year":"2020","unstructured":"Shan Y, Zhang S, Gao B, Liang S, Zhang H, Yu X, Zhao J, Ye L, Yang Q, Shang W (2020) Adipose tissue SIRT1 regulates insulin sensitizing and anti-inflammatory effects of berberine. Front Pharmacol 11:591227","journal-title":"Front Pharmacol"},{"issue":"4","key":"10504_CR88","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.coi.2010.05.003","volume":"22","author":"AC Shaw","year":"2010","unstructured":"Shaw AC, Joshi S, Greenwood H, Panda A, Lord JM (2010) Aging of the innate immune system. Curr Opin Immunol 22(4):507\u2013513","journal-title":"Curr Opin Immunol"},{"key":"10504_CR89","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15112567","author":"J Solnier","year":"2023","unstructured":"Solnier J, Zhang Y, Kuo YC, Du M, Roh K, Gahler R, Wood S, Chang C (2023) Characterization and pharmacokinetic assessment of a new berberine formulation with enhanced absorption in vitro and in human volunteers. Pharmaceutics. https:\/\/doi.org\/10.3390\/pharmaceutics15112567","journal-title":"Pharmaceutics"},{"issue":"1","key":"10504_CR90","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12979-022-00277-w","volume":"19","author":"P Songkiatisak","year":"2022","unstructured":"Songkiatisak P, Rahman SMT, Aqdas M, Sung MH (2022) NF-kappaB, a culprit of both inflamm-ageing and declining immunity? Immun Ageing 19(1):20","journal-title":"Immun Ageing"},{"key":"10504_CR91","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1368950","volume":"15","author":"A Sun","year":"2024","unstructured":"Sun A, Yang H, Li T, Luo J, Zhou L, Chen R, Han L, Lin Y (2024a) Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies. Front Pharmacol 15:1368950","journal-title":"Front Pharmacol"},{"issue":"4","key":"10504_CR92","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2024.e00347","volume":"21","author":"J Sun","year":"2024","unstructured":"Sun J, Zeng Q, Wu Z, Huang L, Sun T, Ling C, Zhang B, Chen C, Wang H (2024b) Berberine inhibits NLRP3 inflammasome activation and proinflammatory macrophage M1 polarization to accelerate peripheral nerve regeneration. Neurotherapeutics 21(4):e00347","journal-title":"Neurotherapeutics"},{"issue":"5","key":"10504_CR93","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.2337\/db07-1552","volume":"57","author":"N Turner","year":"2008","unstructured":"Turner N, Li JY, Gosby A, To SW, Cheng Z, Miyoshi H, Taketo MM, Cooney GJ, Kraegen EW, James DE, Hu LH, Li J, Ye JM (2008) Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes 57(5):1414\u20131418","journal-title":"Diabetes"},{"issue":"41","key":"10504_CR94","doi-asserted-by":"publisher","first-page":"66944","DOI":"10.18632\/oncotarget.11396","volume":"7","author":"J Wang","year":"2016","unstructured":"Wang J, Qi Q, Feng Z, Zhang X, Huang B, Chen A, Prestegarden L, Li X, Wang J (2016) Berberine induces autophagy in glioblastoma by targeting the AMPK\/mTOR\/ULK1-pathway. Oncotarget 7(41):66944\u201366958","journal-title":"Oncotarget"},{"issue":"2","key":"10504_CR95","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41401-022-00956-w","volume":"44","author":"L Wang","year":"2023","unstructured":"Wang L, Tang XQ, Shi Y, Li HM, Meng ZY, Chen H, Li XH, Chen YC, Liu H, Hong Y, Xu HH, Liu L, Zhao L, Han WN, Liu X, Zhang Y (2023) Tetrahydroberberrubine retards heart aging in mice by promoting PHB2-mediated mitophagy. Acta Pharmacol Sin 44(2):332\u2013344","journal-title":"Acta Pharmacol Sin"},{"key":"10504_CR96","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155258","volume":"128","author":"K Wang","year":"2024","unstructured":"Wang K, Yin J, Chen J, Ma J, Si H, Xia D (2024) Inhibition of inflammation by berberine: molecular mechanism and network pharmacology analysis. Phytomedicine 128:155258","journal-title":"Phytomedicine"},{"key":"10504_CR97","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157425","volume":"148","author":"Y Wang","year":"2025","unstructured":"Wang Y, Wang P, Yuan S, Du X, Yan R, Wang X, Hu Y, Pu S, Shen Y, Fang Y, Zhou X, Gao X, Zhang Y, Cheng L, Guo D, Duan Y, Lu H, Zhu J, Li F (2025) Reversal of BCAA-driven inflammatory senescence by traditional herbal oil prevents atopic dermatitis relapse. Phytomedicine 148:157425","journal-title":"Phytomedicine"},{"issue":"5","key":"10504_CR119","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0232630","volume":"15","author":"Y Wang","year":"2020","unstructured":"Wang Y, Zhou X, Zhao D, Wang X, Gurley EC, Liu R, Li X, Hylemon PB, Chen W, Zhou H (2020) Berberine inhibits free fatty acid and LPS-induced inflammation via modulating ER stress response in macrophages and hepatocytes. PLoS ONE 15(5):e0232630. https:\/\/doi.org\/10.1371\/journal.pone.0232630","journal-title":"PLoS ONE"},{"key":"10504_CR98","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2025.109862","volume":"139","author":"BA Watkins","year":"2025","unstructured":"Watkins BA, Mitchell AE, Shin AC, Dehghani F, Shen CL (2025) Dietary flavonoid actions on senescence, aging, and applications for health. J Nutr Biochem 139:109862","journal-title":"J Nutr Biochem"},{"issue":"8","key":"10504_CR99","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s00228-005-0952-3","volume":"61","author":"X Wu","year":"2005","unstructured":"Wu X, Li Q, Xin H, Yu A, Zhong M (2005) Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 61(8):567\u2013572","journal-title":"Eur J Clin Pharmacol"},{"key":"10504_CR100","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1536143","volume":"16","author":"Y Xiao","year":"2025","unstructured":"Xiao Y, Cui Y, Zhang Y, Fu W, Liu Y, Liu F (2025a) Berberine hydrochloride enhances innate immunity to protect against pathogen infection via p38 MAPK pathway. Front Immunol 16:1536143","journal-title":"Front Immunol"},{"key":"10504_CR101","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2024.105644","volume":"128","author":"Y Xiao","year":"2025","unstructured":"Xiao Y, Zhang L, Zhou H, Cui Y, Chen K, Zhang H, Wu Q, Liu F (2025b) Berberine extends healthspan and delays neurodegenerative diseases in Caenorhabditis elegans through ROS-dependent PMK-1\/SKN-1 activation. Arch Gerontol Geriatr 128:105644","journal-title":"Arch Gerontol Geriatr"},{"issue":"11","key":"10504_CR102","doi-asserted-by":"publisher","first-page":"5841","DOI":"10.1021\/acs.jmedchem.0c00088","volume":"63","author":"B Xu","year":"2020","unstructured":"Xu B, Jiang X, Xiong J, Lan J, Tian Y, Zhong L, Wang X, Xu N, Cao H, Zhang W, Zhang H, Hong X, Zhan YY, Zhang Y, Hu T (2020a) Structure-activity relationship study enables the discovery of a novel berberine analogue as the RXRalpha activator to inhibit colon cancer. J Med Chem 63(11):5841\u20135855","journal-title":"J Med Chem"},{"issue":"10","key":"10504_CR103","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1038\/s41556-020-00579-5","volume":"22","author":"C Xu","year":"2020","unstructured":"Xu C, Wang L, Fozouni P, Evjen G, Chandra V, Jiang J, Lu C, Nicastri M, Bretz C, Winkler JD, Amaravadi R, Garcia BA, Adams PD, Ott M, Tong W, Johansen T, Dou Z, Berger SL (2020b) SIRT1 is downregulated by autophagy in senescence and ageing. Nat Cell Biol 22(10):1170\u20131179","journal-title":"Nat Cell Biol"},{"issue":"1","key":"10504_CR104","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1158\/1940-6207.CAPR-19-0258","volume":"13","author":"L Xu","year":"2020","unstructured":"Xu L, Zhang Y, Xue X, Liu J, Li ZS, Yang GY, Song Y, Pan Y, Ma Y, Hu S, Wen A, Jia Y, Rodriguez LM, Tull MB, Benante K, Khan SA, Cao Y, Jovanovic B, Richmond E, Umar A, Bergan R, Wu K (2020c) A phase I trial of berberine in Chinese with ulcerative colitis. Cancer Prev Res 13(1):117\u2013126","journal-title":"Cancer Prev Res"},{"issue":"12","key":"10504_CR105","doi-asserted-by":"publisher","first-page":"3173","DOI":"10.7150\/ijbs.62556","volume":"17","author":"Y Xu","year":"2021","unstructured":"Xu Y, Yu T, Ma G, Zheng L, Jiang X, Yang F, Wang Z, Li N, He Z, Song X, Wen D, Kong J, Yu Y, Cao L (2021) Berberine modulates deacetylation of PPARgamma to promote adipose tissue remodeling and thermogenesis via AMPK\/SIRT1 pathway. Int J Biol Sci 17(12):3173\u20133187","journal-title":"Int J Biol Sci"},{"issue":"12","key":"10504_CR106","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1002\/ptr.6196","volume":"32","author":"YQ Yan","year":"2018","unstructured":"Yan YQ, Fu YJ, Wu S, Qin HQ, Zhen X, Song BM, Weng YS, Wang PC, Chen XY, Jiang ZY (2018) Anti-influenza activity of berberine improves prognosis by reducing viral replication in mice. Phytother Res 32(12):2560\u20132567","journal-title":"Phytother Res"},{"key":"10504_CR107","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-14-49","volume":"14","author":"R Yu","year":"2014","unstructured":"Yu R, Zhang ZQ, Wang B, Jiang HX, Cheng L, Shen LM (2014) Berberine-induced apoptotic and autophagic death of HepG2 cells requires AMPK activation. Cancer Cell Int 14:49","journal-title":"Cancer Cell Int"},{"key":"10504_CR108","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110245","volume":"128","author":"Q Zhang","year":"2020","unstructured":"Zhang Q, Wang X, Cao S, Sun Y, He X, Jiang B, Yu Y, Duan J, Qiu F, Kang N (2020) Berberine represses human gastric cancer cell growth in vitro and in vivo by inducing cytostatic autophagy via inhibition of MAPK\/mTOR\/p70S6K and Akt signaling pathways. Biomed Pharmacother 128:110245","journal-title":"Biomed Pharmacother"},{"key":"10504_CR109","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107628","volume":"151","author":"X Zhang","year":"2024","unstructured":"Zhang X, Wang G, Kuang W, Xu L, He Y, Zhou L, Zhang Y, Chen R, Li H, Fan T, Song Y, Wang J (2024) Discovery and evolution of berberine analogues as anti-Helicobacter pylori agents with multi-target mechanisms. Bioorg Chem 151:107628","journal-title":"Bioorg Chem"},{"issue":"8","key":"10504_CR110","doi-asserted-by":"publisher","first-page":"623","DOI":"10.18632\/aging.100593","volume":"5","author":"H Zhao","year":"2013","unstructured":"Zhao H, Halicka HD, Li J, Darzynkiewicz Z (2013) Berberine suppresses gero-conversion from cell cycle arrest to senescence. Aging 5(8):623\u2013636","journal-title":"Aging"},{"issue":"1","key":"10504_CR111","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1142\/S0192415X25500107","volume":"53","author":"Y Zheng","year":"2025","unstructured":"Zheng Y, Kou J, Gao X, Guo J, Liu Q, Ren H, Gao T, Wang Q, Zhao Y, Wang Y, Li H, Yang L (2025) Berberine inhibited SASP-related inflammation through RXRalpha\/PPARgamma\/NEDD4 pathway in atherosclerosis. Am J Chin Med 53(1):251\u2013283","journal-title":"Am J Chin Med"},{"key":"10504_CR112","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.176253","volume":"964","author":"C Zhong","year":"2024","unstructured":"Zhong C, Xie Y, Wang H, Chen W, Yang Z, Zhang L, Deng Q, Cheng T, Li M, Ju J, Liu Y, Liang H (2024) Berberine inhibits NLRP3 inflammasome activation by regulating mTOR\/mtROS axis to alleviate diabetic cardiomyopathy. Eur J Pharmacol 964:176253","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"10504_CR113","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.fitote.2010.08.019","volume":"82","author":"JY Zhou","year":"2011","unstructured":"Zhou JY, Zhou SW (2011) Protective effect of berberine on antioxidant enzymes and positive transcription elongation factor b expression in diabetic rat liver. Fitoterapia 82(2):184\u2013189","journal-title":"Fitoterapia"},{"key":"10504_CR114","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.biopha.2017.03.003","volume":"89","author":"H Zhou","year":"2017","unstructured":"Zhou H, Feng L, Xu F, Sun Y, Ma Y, Zhang X, Liu H, Xu G, Wu X, Shen Y, Sun Y, Wu X, Xu Q (2017) Berberine inhibits palmitate-induced NLRP3 inflammasome activation by triggering autophagy in macrophages: a new mechanism linking berberine to insulin resistance improvement. Biomed Pharmacother 89:864\u2013874","journal-title":"Biomed Pharmacother"},{"key":"10504_CR115","doi-asserted-by":"publisher","first-page":"2391820","DOI":"10.1155\/2017\/2391820","volume":"2017","author":"X Zhu","year":"2017","unstructured":"Zhu X, Yue H, Guo X, Yang J, Liu J, Liu J, Wang R, Zhu W (2017) The preconditioning of berberine suppresses hydrogen peroxide-induced premature senescence via regulation of sirtuin 1. Oxid Med Cell Longev 2017:2391820","journal-title":"Oxid Med Cell Longev"},{"issue":"3","key":"10504_CR116","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s12192-020-01081-5","volume":"25","author":"N Zhu","year":"2020","unstructured":"Zhu N, Cao X, Hao P, Zhang Y, Chen Y, Zhang J, Li J, Gao C, Li L (2020) Berberine attenuates mitochondrial dysfunction by inducing autophagic flux in myocardial hypoxia\/reoxygenation injury. Cell Stress Chaperones 25(3):417\u2013426","journal-title":"Cell Stress Chaperones"},{"issue":"1","key":"10504_CR117","doi-asserted-by":"publisher","first-page":"dmm049345","DOI":"10.1242\/dmm.049345","volume":"15","author":"H Zinecker","year":"2022","unstructured":"Zinecker H, Simon AK (2022) Autophagy takes it all\u2014autophagy inducers target immune aging. Dis Model Mech 15(1):dmm049345","journal-title":"Dis Model Mech"},{"issue":"3","key":"10504_CR118","doi-asserted-by":"publisher","first-page":"202","DOI":"10.2174\/1874467212666181127151059","volume":"12","author":"RA Zinovkin","year":"2019","unstructured":"Zinovkin RA, Zamyatnin AA (2019) Mitochondria-targeted drugs. Curr Mol Pharmacol 12(3):202\u2013214","journal-title":"Curr Mol Pharmacol"}],"container-title":["Biogerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-026-10504-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10522-026-10504-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-026-10504-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:04:07Z","timestamp":1788246247000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10522-026-10504-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":120,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10504"],"URL":"https:\/\/doi.org\/10.1007\/s10522-026-10504-2","relation":{},"ISSN":["1389-5729","1573-6768"],"issn-type":[{"value":"1389-5729","type":"print"},{"value":"1573-6768","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"13 July 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"153"}}