{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:28:16Z","timestamp":1786969696531,"version":"build-2736575974"},"reference-count":290,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women of reproductive age and is characterized by ovarian hyperandrogenism and irregular ovulation. This often leads to infertility. Beyond reproduction, PCOS causes widespread metabolic issues such as insulin resistance (IR), increasing long-term risks for diabetes, obesity, and heart disease. In a vicious cycle, IR acts as a core driver of both clinical symptoms and associated obesity, whereas compensatory hyperinsulinemia stimulates ovarian androgen production, causing ovulatory dysfunction and worsening weight gain, with immune imbalances exacerbating systemic chronic low-grade inflammation (CLGI). Berberine is a natural plant alkaloid that, owing to its multifaceted metabolic effects\u2014including activation of 5\u2032 adenosine monophosphate (AMP)-activated protein kinase (AMPK) and improvement of insulin sensitivity\u2014effectively supports the restoration of homeostasis in women with PCOS. The aim of this narrative review is to comprehensively analyze the metabolic and anti-inflammatory actions of berberine, which, in combination with the known pathomechanisms of PCOS, may constitute a rationale for its therapeutic application. Attention was given to the necessity of actions aimed at increasing the bioavailability of berberine and to the consequences of the fact that berberine, unlike metformin, which is commonly used and has similar properties, is a dietary supplement and not a Food and Drug Administration (FDA)-approved prescription drug.<\/jats:p>","DOI":"10.3390\/ijms27167287","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic and Anti-Inflammatory Effects of Berberine\u2014Rationale for Its Therapeutic Potential in Polycystic Ovary Syndrome"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0124-060X","authenticated-orcid":false,"given":"Dariusz","family":"Szukiewicz","sequence":"first","affiliation":[{"name":"Department of Biophysics, Physiology & Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155999","DOI":"10.1016\/j.metabol.2024.155999","article-title":"Global burden of metabolic diseases, 1990\u20132021","volume":"160","author":"Zhang","year":"2024","journal-title":"Metabolism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.1111\/dom.15748","article-title":"The global burden of disease attributable to high body mass index in 204 countries and territories: Findings from 1990 to 2019 and predictions to 2035","volume":"26","author":"Chen","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00424-025-03066-8","article-title":"The obesity pandemic and its impact on non-communicable disease burden","volume":"477","author":"Hildebrand","year":"2025","journal-title":"Pflug. Arch."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Prosperi, S., and Chiarelli, F. (2025). Insulin resistance, metabolic syndrome and polycystic ovaries: An intriguing conundrum. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1669716"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.lfs.2019.04.046","article-title":"Multi-system reproductive metabolic disorder: Significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS)","volume":"228","author":"Li","year":"2019","journal-title":"Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chosdon, S., Prasad, N., Agarwal, N., and Jain, D. (2026). More than Cysts: Decoding Polycystic Ovarian Syndrome from Cells to Solutions. Curr. Drug Res. Rev.","DOI":"10.2174\/0125899775407761251202140105"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000194971","article-title":"Obesity and polycystic ovary syndrome","volume":"2","author":"Vrbikova","year":"2009","journal-title":"Obes. Facts."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bila, J., Dotlic, J., Andjic, M., Ivanovic, K., Micic, J., Tulic, L., Pupovac, M., Stojnic, J., Vukovic, I., and Ivanovic, S. (2025). Obesity as a Part of Polycysric Ovary Syndrome (PCOS)-A Review of Pathophysiology and Comprehensive Therapeutic Strategies. J. Clin. Med., 14.","DOI":"10.3390\/jcm14165642"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/cen.14421","article-title":"Obesity and polycystic ovary syndrome","volume":"95","author":"Barber","year":"2021","journal-title":"Clin. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4239\/wjd.v13.i1.5","article-title":"Polycystic ovary syndrome and type 2 diabetes mellitus: A state-of-the-art review","volume":"13","author":"Livadas","year":"2022","journal-title":"World J. Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/ejendo\/lvaf026","article-title":"Diabetic complications in women with type 2 diabetes and polycystic ovary syndrome","volume":"192","author":"Ollila","year":"2025","journal-title":"Eur. J. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"42649","DOI":"10.1038\/s41598-025-26718-2","article-title":"Insulin resistance in polycystic ovary syndrome phenotypes and the vicious cycle model in its etiology","volume":"15","author":"Szkodziak","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ding, H., Zhang, J., Zhang, F., Zhang, S., Chen, X., Liang, W., and Xie, Q. (2021). Resistance to the Insulin and Elevated Level of Androgen: A Major Cause of Polycystic Ovary Syndrome. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.741764"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rudnicka, E., Suchta, K., Grymowicz, M., Calik-Ksepka, A., Smolarczyk, K., Duszewska, A.M., Smolarczyk, R., and Meczekalski, B. (2021). Chronic Low Grade Inflammation in Pathogenesis of PCOS. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073789"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Szukiewicz, D., Trojanowski, S., Kociszewska, A., and Szewczyk, G. (2022). Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)-Searching for Epigenetic Factors. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314663"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Deng, H., Chen, Y., Xing, J., Zhang, N., and Xu, L. (2024). Systematic low-grade chronic inflammation and intrinsic mechanisms in polycystic ovary syndrome. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1470283"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/S0140-6736(26)00717-8","article-title":"Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: A multistep global consensus process","volume":"407","author":"Teede","year":"2026","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yuan, J., Li, Z., Yu, Y., Wang, X., and Zhao, Y. (2025). Natural compounds in the management of polycystic ovary syndrome: A comprehensive review of hormonal regulation and therapeutic potential. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1520695"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Liu, S., Wang, R., Yu, W., Shi, C., Wang, X., Liu, A., and Zhang, L. (2026). Natural Products in the Metabolic and Endocrine Modulation of Polycystic Ovary Syndrome: Current Perspectives. Nutrients, 18.","DOI":"10.3390\/nu18060964"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Habtemariam, S. (2020). The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches. Biomedicines, 8.","DOI":"10.3390\/biomedicines8040090"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Neag, M.A., Mocan, A., Echeverr\u00eda, J., Pop, R.M., Bocsan, C.I., Cri\u015fan, G., and Buzoianu, A.D. (2018). Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00557"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105085","DOI":"10.1016\/j.phrs.2020.105085","article-title":"Goldenseal (Hydrastis canadensis L.) and its active constituents: A critical review of their efficacy and toxicological issues","volume":"160","author":"Mandal","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.12659\/MSM.911849","article-title":"Berberine, a Traditional Chinese Medicine, Reduces Inflammation in Adipose Tissue, Polarizes M2 Macrophages, and Increases Energy Expenditure in Mice Fed a High-Fat Diet","volume":"25","author":"Lin","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s11684-019-0724-6","article-title":"Biological properties and clinical applications of berberine","volume":"14","author":"Song","year":"2020","journal-title":"Front. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-3-319-41334-1_2","article-title":"Berberine and Its Role in Chronic Disease","volume":"928","author":"Cicero","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1142\/S0192415X14500669","article-title":"Effects of berberine in the gastrointestinal tract\u2014A review of actions and therapeutic implications","volume":"42","author":"Chen","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1002\/ptr.5693","article-title":"Berberis Vulgaris and Berberine: An Update Review","volume":"30","author":"Imenshahidi","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Almatroodi, S.A., Alsahli, M.A., and Rahmani, A.H. (2022). Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways. Molecules, 27.","DOI":"10.3390\/molecules27185889"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rauf, A., Abu-Izneid, T., Khalil, A.A., Imran, M., Shah, Z.A., Emran, T.B., Mitra, S., Khan, Z., Alhumaydhi, F.A., and Aljohani, A.S.M. (2021). Berberine as a Potential Anticancer Agent: A Comprehensive Review. Molecules, 26.","DOI":"10.3390\/molecules26237368"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liu, T., Tang, J., Lu, X., Jiang, L., Zhang, R., Zhang, M., Zhang, J., Song, D., Zhang, D., and Xu, M. (2025). Ocular Toxicity and Mechanistic Investigation for Berberine and Its Metabolite Berberrubine on Zebrafish. Molecules, 30.","DOI":"10.3390\/molecules30234602"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cai, Y., Yang, Q., Yu, Y., Yang, F., Bai, R., and Fan, X. (2023). Efficacy and underlying mechanisms of berberine against lipid metabolic diseases: A review. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1283784"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zieniuk, B., and Pawe\u0142kowicz, M. (2025). Berberine as a Bioactive Alkaloid: Multi-Omics Perspectives on Its Role in Obesity Management. Metabolites, 15.","DOI":"10.3390\/metabo15070467"},{"key":"ref_33","first-page":"3322","article-title":"Berberine is a potential therapeutic agent for metabolic syndrome via brown adipose tissue activation and metabolism regulation","volume":"10","author":"Hu","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chen, W., and Pang, Y. (2021). Metabolic Syndrome and PCOS: Pathogenesis and the Role of Metabolites. Metabolites, 11.","DOI":"10.3390\/metabo11120869"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.cmet.2025.08.002","article-title":"Polycystic ovary syndrome: A metabolic disorder with therapeutic opportunities","volume":"37","author":"Zhang","year":"2025","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5142","DOI":"10.1002\/jsfa.70394","article-title":"A comprehensive compendium of berberine: Sources, chemistry, and pharmacological activities","volume":"106","author":"Mohapatra","year":"2025","journal-title":"J. Sci. Food Agric."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"24596","DOI":"10.1039\/D5RA02170G","article-title":"A comprehensive review of recent advances in the extraction and therapeutic potential of berberine","volume":"15","author":"Huang","year":"2025","journal-title":"RSC Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9970338","DOI":"10.1155\/2021\/9970338","article-title":"Effective Extraction of Palmatine and Berberine from Coptis chinensis by Deep Eutectic Solvents-Based Ultrasound-Assisted Extraction","volume":"2021","author":"Li","year":"2021","journal-title":"J. Anal. Methods Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e70008","DOI":"10.1002\/bmc.70008","article-title":"Taguchi L9 Optimization of Microwave-Assisted Solid-Liquid Duo Heating for Berberine Extraction With HPTLC Analysis","volume":"39","author":"Satija","year":"2025","journal-title":"Biomed. Chromatogr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.jpba.2006.01.034","article-title":"Extraction of berberine from rhizome of Coptis chinensis Franch using supercritical fluid extraction","volume":"41","author":"Liu","year":"2006","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1208\/s12249-010-9520-y","article-title":"Physicochemical characterization of berberine chloride: A perspective in the development of a solution dosage form for oral delivery","volume":"11","author":"Battu","year":"2010","journal-title":"AAPS PharmSciTech."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sikora, B., Bahadori, B., Magg, A.D., Moghadasian, N., and Moghadasian, M.H. (2025). Berberine: A Bitter Phytochemical With Diversely Sweet Therapeutic Properties. Nutr. Rev., nuaf172.","DOI":"10.1093\/nutrit\/nuaf172"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17431","DOI":"10.1038\/s41598-022-21568-8","article-title":"Preparation, physicochemical characterization, and bioactivity evaluation of berberine-entrapped albumin nanoparticles","volume":"12","author":"Younis","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_44","unstructured":"(2026, April 30). PubChem. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 2353, Berberine, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Berberine."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhang, C., Zhao, R., Yan, W., Wang, H., Jia, M., Zhu, N., Zhu, Y., Zhang, Y., Wang, P., and Lei, H. (2016). Compositions, Formation Mechanism, and Neuroprotective Effect of Compound Precipitation from the Traditional Chinese Prescription Huang-Lian-Jie-Du-Tang. Molecules, 21.","DOI":"10.3390\/molecules21081094"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s007060050325","article-title":"Media Influence on the Enhancement of the Fluorescence of Berberine Hydrochloride","volume":"131","author":"Iwunze","year":"2000","journal-title":"Monatshefte F\u00fcr Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ai, X., Yu, P., Peng, L., Luo, L., Liu, J., Li, S., Lai, X., Luan, F., and Meng, X. (2021). Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.762654"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.2174\/1871520619666190503121820","article-title":"Berberine as Source of Antiproliferative Hybrid Compounds: In Vitro Antiproliferative Activity and Quantitative Structure-activity Relationship","volume":"19","author":"Berber","year":"2019","journal-title":"Anticancer. Agents Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"113839","DOI":"10.1016\/j.ejmech.2021.113839","article-title":"Plant isoquinoline alkaloids: Advances in the chemistry and biology of berberine","volume":"226","author":"Singh","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"116143","DOI":"10.1016\/j.bmc.2021.116143","article-title":"An insight into the medicinal attributes of berberine derivatives: A review","volume":"38","author":"Gaba","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.2174\/1389557517666170321103139","article-title":"Berberine Derivatives with Different Pharmacological Activities via Structural Modifications","volume":"18","author":"Xiao","year":"2018","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5915","DOI":"10.1016\/j.bmc.2010.06.085","article-title":"8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models","volume":"18","author":"Cheng","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.metabol.2012.09.009","article-title":"Berberine analogue IMB-Y53 improves glucose-lowering efficacy by averting cellular efflux especially P-glycoprotein efflux","volume":"62","author":"Shan","year":"2013","journal-title":"Metabolism"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.1016\/j.bmcl.2016.08.027","article-title":"Synthesis and hypoglycemic activity of 9-O-(lipophilic group substituted) berberine derivatives","volume":"26","author":"Zhang","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.2147\/IDR.S431256","article-title":"Potentiation and Mechanism of Berberine as an Antibiotic Adjuvant Against Multidrug-Resistant Bacteria","volume":"16","author":"Zhou","year":"2023","journal-title":"Infect. Drug Resist."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13573","DOI":"10.1111\/jcmm.16049","article-title":"Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation","volume":"24","author":"Ehteshamfar","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.2337\/db06-0006","article-title":"Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states","volume":"55","author":"Lee","year":"2006","journal-title":"Diabetes"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Koperska, A., Weso\u0142ek, A., Moszak, M., and Szuli\u0144ska, M. (2022). Berberine in Non-Alcoholic Fatty Liver Disease-A Review. Nutrients, 14.","DOI":"10.3390\/nu14173459"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Liu, S., Shen, J., Xu, F., Niu, L., Wang, F., and Zhao, G. (2026). Beneficial effects of berberine in the treatment of diabetes and its complications. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1701513"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Och, A., Och, M., Nowak, R., Podg\u00f3rska, D., and Podg\u00f3rski, R. (2022). Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease. Molecules, 27.","DOI":"10.3390\/molecules27041351"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Guo, P., Cai, C., Wu, X., Fan, X., Huang, W., Zhou, J., Wu, Q., Huang, Y., Zhao, W., and Zhang, F. (2019). An Insight Into the Molecular Mechanism of Berberine Towards Multiple Cancer Types Through Systems Pharmacology. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00857"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"695","DOI":"10.2147\/CMAR.S242329","article-title":"The Anti-Cancer Mechanisms of Berberine: A Review","volume":"12","author":"Wang","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1111\/j.1745-7254.2008.00786.x","article-title":"Berberine inhibits cyclin D1 expression via suppressed binding of AP-1 transcription factors to CCND1 AP-1 motif","volume":"29","author":"Luo","year":"2008","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ni, L., Sun, P., Fan, X., Li, Z., Ren, H., and Li, J. (2022). Berberine Inhibits FOXM1 Dependent Transcriptional Regulation of POLE2 and Interferes With the Survival of Lung Adenocarcinoma. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.775514"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"12234","DOI":"10.1111\/jcmm.15803","article-title":"Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management","volume":"24","author":"Shen","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Majdalawieh, A.F., Yousef, S.M., Abu-Yousef, I.A., and Nasrallah, G.K. (2022). Immunomodulatory and Anti-Inflammatory Effects of Berberine in Lung Tissue and its Potential Application in Prophylaxis and Treatment of COVID-19. Front. Biosci., 27.","DOI":"10.31083\/j.fbl2705166"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"154343","DOI":"10.1016\/j.phymed.2022.154343","article-title":"Exploring the mechanism of berberine-mediated Tfh cell immunosuppression","volume":"105","author":"Vita","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1167\/iovs.12-11217","article-title":"Berberine suppresses Th17 and dendritic cell responses","volume":"54","author":"Yang","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"152390","DOI":"10.1016\/j.bbrc.2025.152390","article-title":"Berberine alleviates T cell-driven lung inflammation by inhibiting cytokine secretion and regulating pulmonary microbiota","volume":"778","author":"Ma","year":"2025","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Fan, K.Q., Zhang, L., Song, F., Zhang, Y.H., Chen, T., Cheng, X., Su, N., Zou, Y., Yu, T., and Tan, F. (2025). Pharmacological properties and therapeutic potential of berberine: A comprehensive review. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1604071"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gong, M., Duan, H., Wu, F., Ren, Y., Gong, J., Xu, L., Lu, F., and Wang, D. (2021). Berberine Alleviates Insulin Resistance and Inflammation via Inhibiting the LTB4-BLT1 Axis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.722360"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"155258","DOI":"10.1016\/j.phymed.2023.155258","article-title":"Inhibition of inflammation by berberine: Molecular mechanism and network pharmacology analysis","volume":"128","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3617514","DOI":"10.1155\/2020\/3617514","article-title":"Berberine Inhibits MDA-MB-231 Cells by Attenuating Their Inflammatory Responses","volume":"2020","author":"Zhao","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1002\/mc.22179","article-title":"Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice","volume":"54","author":"Li","year":"2015","journal-title":"Mol. Carcinog."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.1158\/0008-5472.CAN-08-0511","article-title":"Berberine modifies cysteine 179 of IkappaBalpha kinase, suppresses nuclear factor-kappaB-regulated antiapoptotic gene products, and potentiates apoptosis","volume":"68","author":"Pandey","year":"2008","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1002\/ptr.7407","article-title":"Berberine as a natural modulator of inflammatory signaling pathways in the immune system: Focus on NF-\u03baB, JAK\/STAT, and MAPK signaling pathways","volume":"36","author":"Haftcheshmeh","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"902","DOI":"10.5152\/tjg.2020.19568","article-title":"Berberine inhibits liver damage in rats with non-alcoholic fatty liver disease by regulating TLR4\/MyD88\/NF-\u03baB pathway","volume":"31","author":"Wang","year":"2020","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Tsang, C.M., Cheung, Y.C., Lui, V.W., Yip, Y.L., Zhang, G., Lin, V.W., Cheung, K.C., Feng, Y., and Tsao, S.W. (2013). Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-619"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1600-065X.2008.00707.x","article-title":"Regulation of interferon and Toll-like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms","volume":"226","author":"Hu","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.intimp.2017.08.032","article-title":"Berberine suppresses LPS-induced inflammation through modulating Sirt1\/NF-\u03baB signaling pathway in RAW264.7 cells","volume":"52","author":"Zhang","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5068","DOI":"10.1128\/AAC.02427-14","article-title":"Downregulation of cellular c-Jun N-terminal protein kinase and NF-\u03baB activation by berberine may result in inhibition of herpes simplex virus replication","volume":"58","author":"Song","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6795481","DOI":"10.1155\/np\/6795481","article-title":"Berberine Alleviates Lipopolysaccharide-Induced Impairments in Neuroplasticity and Spatial Memory by Modulating Microglial Polarization via MAPK Signaling Inhibition","volume":"2026","author":"Jiang","year":"2026","journal-title":"Neural Plast."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e00347","DOI":"10.1016\/j.neurot.2024.e00347","article-title":"Berberine inhibits NLRP3 inflammasome activation and proinflammatory macrophage M1 polarization to accelerate peripheral nerve regeneration","volume":"21","author":"Sun","year":"2024","journal-title":"Neurotherapeutics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s11418-025-01935-1","article-title":"Berberine attenuates the expression of NLRP3 and downstream inflammasome effectors in diabetic retinopathy","volume":"79","author":"Li","year":"2025","journal-title":"J. Nat. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Roy, T., Boateng, S.T., Uddin, M.B., Banang-Mbeumi, S., Yadav, R.K., Bock, C.R., Folahan, J.T., Siwe-Noundou, X., Walker, A.L., and King, J.A. (2023). The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds. Cells, 12.","DOI":"10.3390\/cells12121671"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.joca.2020.02.027","article-title":"The PI3K\/AKT\/mTOR signaling pathway in osteoarthritis: A narrative review","volume":"28","author":"Sun","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Acosta-Martinez, M., and Cabail, M.Z. (2022). The PI3K\/Akt Pathway in Meta-Inflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315330"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Peng, Y., Wang, Y., Zhou, C., Mei, W., and Zeng, C. (2022). PI3K\/Akt\/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.819128"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"8135","DOI":"10.1080\/21655979.2021.1987130","article-title":"Berberine inhibited carotid atherosclerosis through PI3K\/AKTmTOR signaling pathway","volume":"12","author":"Song","year":"2021","journal-title":"Bioengineered"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Amen, O.M., Sarker, S.D., Ghildyal, R., and Arya, A. (2019). Endoplasmic Reticulum Stress Activates Unfolded Protein Response Signaling and Mediates Inflammation, Obesity, and Cardiac Dysfunction: Therapeutic and Molecular Approach. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00977"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Martinotti, S., and Ranzato, E. (2025). Targeting the Unfolded Protein Response with Natural Products: Therapeutic Potential in ER Stress-Related Diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26188814"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhou, X., Zhao, D., Wang, X., Gurley, E.C., Liu, R., Li, X., Hylemon, P.B., Chen, W., and Zhou, H. (2020). Berberine inhibits free fatty acid and LPS-induced inflammation via modulating ER stress response in macrophages and hepatocytes. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232630"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"855","DOI":"10.2174\/0118715303319434241113161606","article-title":"Berberine Improves Glucose and Lipid Metabolism in Obese Mice Through the Reduction of IRE1\/GSK-3\u03b2 Axis-Mediated Inflammation","volume":"25","author":"Ding","year":"2025","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1021\/acschemneuro.0c00808","article-title":"Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer\u2019s Disease via Regulation of \u03b2-Amyloid Production and Endoplasmic Reticulum Stress","volume":"12","author":"Liang","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"20848","DOI":"10.1038\/srep20848","article-title":"Berberine prevents progression from hepatic steatosis to steatohepatitis and fibrosis by reducing endoplasmic reticulum stress","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Reddi, K.K., Li, H., Li, W., and Tetali, S.D. (2021). Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappa\u03b2 Pathway: Possible Involvement of the IKK\u03b1. Molecules, 26.","DOI":"10.3390\/molecules26164733"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11298","DOI":"10.1038\/s41598-021-90752-z","article-title":"Berberine modulates hyper-inflammation in mouse macrophages stimulated with polyinosinic-polycytidylic acid via calcium-CHOP\/STAT pathway","volume":"11","author":"Kim","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Cai, Y., Xin, Q., Lu, J., Miao, Y., Lin, Q., Cong, W., and Chen, K. (2021). A New Therapeutic Candidate for Cardiovascular Diseases: Berberine. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.631100"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1142\/S0192415X19500393","article-title":"Efficacy and Safety of Berberine Alone or Combined with Statins for the Treatment of Hyperlipidemia: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials","volume":"47","author":"Zhang","year":"2019","journal-title":"Am. J. Chin. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/0127724328346501250404175826","article-title":"Mechanistic Effects and Complications of Berberine on Cardiac Arrhythmias: A Systematic Review","volume":"20","author":"Masoumi","year":"2025","journal-title":"Curr. Rev. Clin. Exp. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1530\/JME-17-0014","article-title":"Berberine reduced blood pressure and improved vasodilation in diabetic rats","volume":"59","author":"Ma","year":"2017","journal-title":"J. Mol. Endocrinol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s44325-026-00113-w","article-title":"Berberine signature and cardiometabolic diseases using randomized controlled trial, cohort study and Mendelian randomization","volume":"3","author":"Zhao","year":"2026","journal-title":"npj Cardiovasc. Health"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Zhang, P., Jin, M., Zhang, L., Cui, Y., Dong, X., Yang, J., Zhang, J., and Wu, H. (2025). Berberine alleviates atherosclerosis by modulating autophagy and inflammation through the RAGE-NF-\u03baB pathway. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1540835"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.2147\/DDDT.S250524","article-title":"Berberine Attenuates Arterial Plaque Formation in Atherosclerotic Rats with Damp-Heat Syndrome via Regulating Autophagy","volume":"14","author":"Ke","year":"2020","journal-title":"Drug Des. Devel Ther."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Xing, L., Zhou, X., Li, A.H., Li, H.J., He, C.X., Qin, W., Zhao, D., Li, P.Q., Zhu, L., and Cao, H.L. (2021). Atheroprotective Effects and Molecular Mechanism of Berberine. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.762673"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Cao, R.Y., Zhang, Y., Feng, Z., Liu, S., Liu, Y., Zheng, H., and Yang, J. (2021). The Effective Role of Natural Product Berberine in Modulating Oxidative Stress and Inflammation Related Atherosclerosis: Novel Insights Into the Gut-Heart Axis Evidenced by Genetic Sequencing Analysis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.764994"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Duda-Madej, A., Viscardi, S., \u0141abaz, J.P., Topola, E., Szewczyk, W., and Gagat, P. (2025). Berberine in Bowel Health: Anti-Inflammatory and Gut Microbiota Modulatory Effects. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262412021"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Zhang, H., Ye, P., Yang, W., Dou, Y., Tian, Z., Zhang, N., Cui, N., Sun, L., Liu, Z., and Chen, Y. (2026). Berberine protects against hypoxia-induced intestinal injury through modulation of gut microbiota and bile acid metabolism. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1784245"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"117865","DOI":"10.1016\/j.envpol.2021.117865","article-title":"Berberine improves intestinal barrier function and reduces inflammation, immunosuppression, and oxidative stress by regulating the NF-\u03baB\/MAPK signaling pathway in deoxynivalenol-challenged piglets","volume":"289","author":"Tang","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e005784","DOI":"10.1161\/JAHA.117.005784","article-title":"Gut-Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet","volume":"6","author":"Pastori","year":"2017","journal-title":"J. Am. Heart. Assoc."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.atherosclerosis.2017.11.023","article-title":"Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe-\/- mice","volume":"268","author":"Zhu","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1002\/jsfa.12242","article-title":"Berberine alleviates intestinal barrier dysfunction in glucolipid metabolism disorder hamsters by modulating gut microbiota and gut-microbiota-related tryptophan metabolites","volume":"103","author":"Chen","year":"2023","journal-title":"J. Sci. Food Agric."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Gong, J., Hu, M., Huang, Z., Fang, K., Wang, D., Chen, Q., Li, J., Yang, D., Zou, X., and Xu, L. (2017). Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00042"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3892\/etm.2022.11357","article-title":"Myocardial ischemia\/reperfusion injury: Mechanisms of injury and implications for management (Review)","volume":"23","author":"He","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Han, D.Y., Ahn, H.S., and Park, H.J. (2026). Myocardial Ischemia-Reperfusion Injury-Mechanistic Insights and Novel Therapeutics. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27052106"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zhang, J., Zhang, D., Yu, P., Zhang, J., and Yu, S. (2022). Research Progress on the Role of Pyroptosis in Myocardial Ischemia-Reperfusion Injury. Cells, 11.","DOI":"10.3390\/cells11203271"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e14952","DOI":"10.7717\/peerj.14952","article-title":"Relationship between ferroptosis and mitophagy in cardiac ischemia reperfusion injury: A mini-review","volume":"11","author":"Liu","year":"2023","journal-title":"PeerJ"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1177\/1089253211436350","article-title":"Myocardial ischemia reperfusion injury: From basic science to clinical bedside","volume":"16","author":"Frank","year":"2012","journal-title":"Semin. Cardiothorac. Vasc. Anesth."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Chen, C., Lin, Q., Zhu, X.Y., Xia, J., Mao, T., Chi, T., Wan, J., Lu, J.J., Li, Y., and Cui, J. (2021). Pre-clinical Evidence: Berberine as a Promising Cardioprotective Candidate for Myocardial Ischemia\/Reperfusion Injury, a Systematic Review, and Meta-Analysis. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.646306"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"849783","DOI":"10.1155\/2014\/849783","article-title":"Protective Effects of Berberine on Isoproterenol-Induced Acute Myocardial Ischemia in Rats through Regulating HMGB1-TLR4 Axis","volume":"2014","author":"Zhang","year":"2014","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.7150\/thno.30787","article-title":"Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics","volume":"9","author":"Feng","year":"2019","journal-title":"Theranostics"},{"key":"ref_122","first-page":"31","article-title":"Berberine Intervention Mitigates Myocardial Ischemia-Reperfusion Injury in a Rat. Model: Mechanistic Insights via miR-184 Signaling","volume":"19","author":"Yang","year":"2025","journal-title":"Biologics"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1016\/j.ajpath.2018.08.007","article-title":"Hypertension Enhances Advanced Atherosclerosis and Induces Cardiac Death in Watanabe Heritable Hyperlipidemic Rabbits","volume":"188","author":"Ning","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Poznyak, A.V., Sadykhov, N.K., Kartuesov, A.G., Borisov, E.E., Melnichenko, A.A., Grechko, A.V., and Orekhov, A.N. (2022). Hypertension as a risk factor for atherosclerosis: Cardiovascular risk assessment. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.959285"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Gallo, G., Volpe, M., and Savoia, C. (2022). Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Front. Med., 8.","DOI":"10.3389\/fmed.2021.798958"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Liu, Y., Luo, X., Jia, H., and Yu, B. (2022). The Effect of Blood Pressure Variability on Coronary Atherosclerosis Plaques. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.803810"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Chang, G., Hu, Y., Ge, Q., Chu, S., Avolio, A., and Zuo, J. (2023). Arterial Stiffness as a Predictor of the Index of Atherosclerotic Cardiovascular Disease in Hypertensive Patients. Int. J. Environ. Res. Public. Health, 20.","DOI":"10.3390\/ijerph20042832"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"112212","DOI":"10.1016\/j.jbiomech.2024.112212","article-title":"Impact of hypertension and arterial wall expansion on transport properties and atherosclerosis progression","volume":"174","author":"Laita","year":"2024","journal-title":"J. Biomech."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0014-2999(00)00339-3","article-title":"Vasorelaxant and antiproliferative effects of berberine","volume":"399","author":"Ko","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"101287","DOI":"10.1016\/j.ctcp.2020.101287","article-title":"Berberine for the treatment of hypertension: A systematic review","volume":"42","author":"Suadoni","year":"2021","journal-title":"Complement. Ther. Clin. Pract."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.bbrc.2015.02.028","article-title":"Berberine improves endothelial function by inhibiting endoplasmic reticulum stress in the carotid arteries of spontaneously hypertensive rats","volume":"458","author":"Liu","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Heidary Moghaddam, R., Samimi, Z., Asgary, S., Mohammadi, P., Hozeifi, S., Hoseinzadeh-Chahkandak, F., Xu, S., and Farzaei, M.H. (2022). Natural AMPK Activators in Cardiovascular Disease Prevention. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.738420"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1007\/s11655-026-4034-y","article-title":"Berberine Ameliorates Angiotensin II-Induced Endothelial Dysfunction by Blocking AT1R, Inhibiting PDE4b and Activating AKT\/eNOS Pathway","volume":"32","author":"Zhang","year":"2026","journal-title":"Chin. J. Integr. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"158084","DOI":"10.1016\/j.phymed.2026.158084","article-title":"Healing the heart naturally: The role of bioactive phytocompounds in cardiovascular therapeutics","volume":"155","author":"Anand","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/FJC.0000000000001303","article-title":"The Ameliorative Effect of Berberine on Vascular Calcification by Inhibiting Endoplasmic Reticulum Stress","volume":"80","author":"Li","year":"2022","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1080\/00015385.2023.2168876","article-title":"Effects of berberine hydrochloride on left ventricular structure and function in rats with myocardial hypertrophy","volume":"78","author":"Kou","year":"2023","journal-title":"Acta Cardiol."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Fang, X., Wu, H., Wei, J., Miao, R., Zhang, Y., and Tian, J. (2022). Research progress on the pharmacological effects of berberine targeting mitochondria. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.982145"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1111\/bph.13833","article-title":"Activation of AMP-activated protein kinase by metformin ablates angiotensin II-induced endoplasmic reticulum stress and hypertension in mice in vivo","volume":"174","author":"Duan","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1161\/CIRCRESAHA.121.318063","article-title":"Oxidative Stress and Hypertension","volume":"128","author":"Griendling","year":"2021","journal-title":"Circ. Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S1537-1891(03)00005-3","article-title":"Effects of berberine on angiotensin-converting enzyme and NO\/cGMP system in vessels","volume":"39","author":"Kang","year":"2002","journal-title":"Vasc. Pharmacol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"9928986","DOI":"10.1155\/2021\/9928986","article-title":"Berberine Reshapes the Balance of the Local Renin-Angiotensin System by Modulating Autophagy under Metabolic Stress in Pancreatic Islets","volume":"2021","author":"Huang","year":"2021","journal-title":"J. Renin Angiotensin Aldosterone Syst."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000445618","article-title":"Berberine Improved Aldo-Induced Podocyte Injury via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress Pathways both In Vivo and In Vitro","volume":"39","author":"Wang","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"750","DOI":"10.7150\/ijbs.125140","article-title":"Microbiota-gut-kidney axis in health and renal disease","volume":"22","author":"Jin","year":"2026","journal-title":"Int. J. Biol. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Wang, S., Hu, Y., Li, X., Ou, Y., Chen, J., Chen, Y., Chen, J., Bai, K., Xu, F., and Wang, X. (2026). Gut microbiota-dependent anti-inflammatory mechanisms of berberine in ameliorating hypertension: Role of SCFAs, LPS reduction, and STAT3 signaling. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1696934"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41366-025-01943-x","article-title":"The effect of berberine on obesity indices: A systematic review and meta-analysis","volume":"50","author":"Nojumi","year":"2026","journal-title":"Int. J. Obes."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.metabol.2008.01.013","article-title":"Efficacy of berberine in patients with type 2 diabetes mellitus","volume":"57","author":"Yin","year":"2008","journal-title":"Metabolism"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"905749","DOI":"10.1155\/2015\/905749","article-title":"Application of berberine on treating type 2 diabetes mellitus","volume":"2015","author":"Pang","year":"2015","journal-title":"Int. J. Endocrinol."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Ren, G., Guo, J.H., Qian, Y.Z., Kong, W.J., and Jiang, J.D. (2020). Berberine Improves Glucose and Lipid Metabolism in HepG2 Cells Through AMPK\u03b11 Activation. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00647"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"bqaf105","DOI":"10.1210\/endocr\/bqaf105","article-title":"Berberine Protects Pancreatic \u03b2-Cells From IL-1\u03b2 Damage Through Hormetic Mechanisms Via P53-Mediated Apoptosis Pathways","volume":"166","author":"Yang","year":"2025","journal-title":"Endocrinology"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Liu, D., Zhao, L., Wang, Y., Wang, L., Wu, D., and Liu, Y. (2025). Berberine: A Rising Star in the Management of Type 2 Diabetes-Novel Insights into Its Anti-Inflammatory, Metabolic, and Epigenetic Mechanisms. Pharmaceuticals, 18.","DOI":"10.3390\/ph18121890"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"E148\u2013156","DOI":"10.1152\/ajpendo.00211.2007","article-title":"Berberine improves glucose metabolism through induction of glycolysis","volume":"294","author":"Yin","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2074610","DOI":"10.1155\/2021\/2074610","article-title":"The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"2021","author":"Guo","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e16947","DOI":"10.1097\/MD.0000000000016947","article-title":"Efficacy and safety of berberine in the treatment of type 2 diabetes with insulin resistance: Protocol for a systematic review","volume":"98","author":"Wang","year":"2019","journal-title":"Medicine"},{"key":"ref_154","first-page":"3009","article-title":"Effects of berberine on glucose-lipid metabolism, inflammatory factors and insulin resistance in patients with metabolic syndrome","volume":"17","author":"Cao","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s13020-025-01251-6","article-title":"Berberine ameliorates high-fat diet-induced metabolic disorders through promoting gut Akkermansia and modulating bile acid metabolism","volume":"20","author":"Hang","year":"2025","journal-title":"Chin. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"7173920","DOI":"10.1155\/2018\/7173920","article-title":"Update on the Benefits and Mechanisms of Action of the Bioactive Vegetal Alkaloid Berberine on Lipid Metabolism and Homeostasis","volume":"2018","author":"Wang","year":"2018","journal-title":"Cholesterol"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.metabol.2014.05.013","article-title":"Berberine decreases cholesterol levels in rats through multiple mechanisms, including inhibition of cholesterol absorption","volume":"63","author":"Wang","year":"2014","journal-title":"Metabolism"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jchromb.2017.05.004","article-title":"Comprehensive evaluation of SCFA production in the intestinal bacteria regulated by berberine using gas-chromatography combined with polymerase chain reaction","volume":"1057","author":"Wang","year":"2017","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1124\/mol.116.106617","article-title":"Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway","volume":"91","author":"Sun","year":"2017","journal-title":"Mol. Pharmacol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1053\/j.gastro.2016.08.057","article-title":"An Intestinal Microbiota-Farnesoid X Receptor Axis Modulates Metabolic Disease","volume":"151","author":"Gonzalez","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1055\/s-0032-1328321","article-title":"The effects of berberine on blood lipids: A systemic review and meta-analysis of randomized controlled trials","volume":"79","author":"Dong","year":"2013","journal-title":"Planta Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s40265-023-01841-4","article-title":"Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials","volume":"83","author":"Blais","year":"2023","journal-title":"Drugs"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Xiong, R.G., Huang, S.Y., Wu, S.X., Zhou, D.D., Yang, Z.J., Saimaiti, A., Zhao, C.N., Shang, A., Zhang, Y.J., and Gan, R.Y. (2022). Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review. Molecules, 27.","DOI":"10.3390\/molecules27144523"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Zhang, C., Sheng, J., Li, G., Zhao, L., Wang, Y., Yang, W., Yao, X., Sun, L., Zhang, Z., and Cui, R. (2020). Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01461"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Xie, N., Chai, Y., Nie, Y., Liu, K., Liu, Y., Yang, Y., Su, J., and Zhang, C. (2022). Apoptosis Induction, a Sharp Edge of Berberine to Exert Anti-Cancer Effects, Focus on Breast, Lung, and Liver Cancer. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.803717"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.5114\/aoms\/132969","article-title":"Berberine induces apoptosis and arrests the cell cycle in multiple cancer cell lines","volume":"19","author":"Li","year":"2021","journal-title":"Arch. Med. Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1038\/s41401-025-01728-y","article-title":"A novel photosensitizer berberine derivative B12 induces apoptosis and suppresses HIF-1\u03b1 expression in colorectal cancer cells via mitochondria-to-nucleus sequential-targeting","volume":"47","author":"Pei","year":"2026","journal-title":"Acta. Pharmacol. Sin."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Farooqi, A.A., Qureshi, M.Z., Khalid, S., Attar, R., Martinelli, C., Sabitaliyevich, U.Y., Nurmurzayevich, S.B., Taverna, S., Poltronieri, P., and Xu, B. (2019). Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy. Cancers, 11.","DOI":"10.3390\/cancers11040478"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"110245","DOI":"10.1016\/j.biopha.2020.110245","article-title":"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","volume":"128","author":"Zhang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/ajco.14134","article-title":"Berberine and Lung Cancer: From Pure Form to Its Nanoformulations","volume":"21","author":"Tamtaji","year":"2025","journal-title":"Asia Pac. J. Clin. Oncol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.3390\/molecules13122975","article-title":"Berberine suppresses TNF-alpha-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells","volume":"13","author":"Kim","year":"2008","journal-title":"Molecules"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"8499","DOI":"10.1007\/s11033-020-05892-8","article-title":"Berberine reverses epithelial-mesenchymal transition and modulates histone methylation in osteosarcoma cells","volume":"47","author":"Mishra","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1440-1746.2010.06389.x","article-title":"Berberine inhibits angiogenic potential of Hep G2 cell line through VEGF down-regulation in vitro","volume":"26","author":"Jie","year":"2011","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"471","DOI":"10.4103\/ijc.ijc_846_24","article-title":"Berberine\u2019s role in enhancing lung cancer treatment: Exploring mechanisms, efficacy, and adjuvant potential","volume":"62","author":"Sakthivel","year":"2025","journal-title":"Indian J. Cancer"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"\u00d6zalp, Y., Alloush, T., Serak\u0131nc\u0131, N., and Kartal, M. (2026). Berberine as a Multifunctional Adjuvant in Cancer Therapy: Mechanistic Insights, Nanotechnological Strategies, and Translational Challenges. Pharmaceuticals, 19.","DOI":"10.3390\/ph19040613"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Achi, I.T., Sarbadhikary, P., George, B.P., and Abrahamse, H. (2022). Multi-Target Potential of Berberine as an Antineoplastic and Antimetastatic Agent: A Special Focus on Lung Cancer Treatment. Cells, 11.","DOI":"10.3390\/cells11213433"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"102293","DOI":"10.1016\/j.xcrm.2025.102293","article-title":"Berberine for preventing colorectal adenoma recurrence and neoplasm occurrence: 6-Year follow-up of a randomized clinical trial","volume":"6","author":"Tan","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1208\/s12249-011-9632-z","article-title":"Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats","volume":"12","author":"Chen","year":"2011","journal-title":"AAPS PharmSciTech"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/03602532.2017.1306544","article-title":"The metabolism of berberine and its contribution to the pharmacological effects","volume":"49","author":"Wang","year":"2017","journal-title":"Drug Metab. Rev."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"104722","DOI":"10.1016\/j.phrs.2020.104722","article-title":"Berberine pharmacology and the gut microbiota: A hidden therapeutic link","volume":"155","author":"Habtemariam","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1124\/dmd.110.033936","article-title":"Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats","volume":"38","author":"Liu","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1002\/jps.10268","article-title":"P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers","volume":"91","author":"Maeng","year":"2002","journal-title":"J. Pharm. Sci."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"8485","DOI":"10.1007\/s00210-024-03199-0","article-title":"Research progress on pharmacological effects and bioavailability of berberine","volume":"397","author":"Cui","year":"2024","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Feng, X., Wang, K., Cao, S., Ding, L., and Qiu, F. (2021). Pharmacokinetics and Excretion of Berberine and Its Nine Metabolites in Rats. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.594852"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1002\/ptr.7589","article-title":"Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review","volume":"36","author":"Khoshandam","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"9987097","DOI":"10.1155\/2021\/9987097","article-title":"Pharmacokinetics and Pharmacological Activities of Berberine in Diabetes Mellitus Treatment","volume":"2021","author":"Han","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/ptr.6282","article-title":"Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials","volume":"33","author":"Fogacci","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"126177","DOI":"10.1016\/j.ijpharm.2025.126177","article-title":"Improving the oral bioavailability of berberine: A crystal engineering approach","volume":"685","author":"Prasad","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Cui, H.X., Hu, Y.N., Li, J.W., Yuan, K., and Guo, Y. (2018). Preparation and Evaluation of Antidiabetic Agents of Berberine Organic Acid Salts for Enhancing the Bioavailability. Molecules, 24.","DOI":"10.3390\/molecules24010103"},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Lin, H.J., Ho, J.H., Tsai, L.C., Yang, F.Y., Yang, L.L., Kuo, C.D., Chen, L.G., Liu, Y.W., and Wu, J.Y. (2020). Synthesis and In Vitro Photocytotoxicity of 9-\/13-Lipophilic Substituted Berberine Derivatives as Potential Anticancer Agents. Molecules, 25.","DOI":"10.20944\/preprints202001.0081.v1"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"7563889","DOI":"10.1155\/2021\/7563889","article-title":"Development of an Innovative Berberine Food-Grade Formulation with an Ameliorated Absorption: In Vitro Evidence Confirmed by Healthy Human Volunteers Pharmacokinetic Study","volume":"2021","author":"Petrangolini","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s12978-021-01207-7","article-title":"Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: A network meta-analysis","volume":"18","author":"Zhao","year":"2021","journal-title":"Reprod. Health"},{"key":"ref_193","first-page":"2","article-title":"The polycystic ovary syndrome: The first 150 years of study","volume":"4","author":"Adashi","year":"2022","journal-title":"F S Rep."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.fertnstert.2016.05.009","article-title":"Introduction: Determinants of polycystic ovary syndrome","volume":"106","author":"Azziz","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_195","first-page":"261","article-title":"Measuring the global disease burden of polycystic ovary syndrome in 194 countries: Global Burden of Disease Study 2017. The Prevalence of Polycystic Ovary Syndrome: A Brief Systematic Review","volume":"13","author":"Deswal","year":"2020","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"e250126","DOI":"10.1530\/REP-25-0126","article-title":"POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Genetics of polycystic ovary syndrome (PCOS)","volume":"170","author":"Louwers","year":"2025","journal-title":"Reproduction"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Singh, S., Pal, N., Shubham, S., Sarma, D.K., Verma, V., Marotta, F., and Kumar, M. (2023). Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics. J. Clin. Med., 12.","DOI":"10.3390\/jcm12041454"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/ejendo\/lvaf030","article-title":"The PCOS Phenotype in Unselected Populations study: Ethnic variation in population-based normative cut-offs for defining hirsutism","volume":"192","author":"Bizuneh","year":"2025","journal-title":"Eur. J. Endocrinol."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Joshi, A. (2024). PCOS stratification for precision diagnostics and treatment. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1358755"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1210\/er.2015-1104","article-title":"The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited","volume":"37","author":"Rosenfield","year":"2016","journal-title":"Endocr. Rev."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/obr.12762","article-title":"Metabolic syndrome in polycystic ovary syndrome: A systematic review, meta-analysis and meta-regression","volume":"20","author":"Lim","year":"2019","journal-title":"Obes. Rev."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Pililis, S., Lampsas, S., Kountouri, A., Pliouta, L., Korakas, E., Livadas, S., Thymis, J., Peppa, M., Kalantaridou, S., and Oikonomou, E. (2024). The Cardiometabolic Risk in Women with Polycystic Ovarian Syndrome (PCOS): From Pathophysiology to Diagnosis and Treatment. Medicina, 60.","DOI":"10.3390\/medicina60101656"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.fertnstert.2022.03.009","article-title":"Polycystic ovary syndrome: A \u201crisk-enhancing\u201d factor for cardiovascular disease","volume":"117","author":"Guan","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1007\/s43032-026-02087-7","article-title":"A Comprehensive Review on Recent Advancements in Navigating the Complexities of Polycystic Ovarian Syndrome (PCOS)","volume":"33","author":"Waqar","year":"2026","journal-title":"Reprod. Sci."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Rotterdam ESHRE\/ASRM-Sponsored PCOS consensus workshop group (2004). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum. Reprod., 19, 41\u201347.","DOI":"10.1093\/humrep\/deh098"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/cen.14757","article-title":"Challenges in diagnosis and understanding of natural history of polycystic ovary syndrome","volume":"97","author":"Joham","year":"2022","journal-title":"Clin. Endocrinol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ando.2014.07.111","article-title":"Long term complications of polycystic ovary syndrome (PCOS)","volume":"75","author":"Dewailly","year":"2014","journal-title":"Ann. Endocrinol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"2633494120911038","DOI":"10.1177\/2633494120911038","article-title":"Characteristics of polycystic ovary syndrome throughout life","volume":"14","author":"Louwers","year":"2020","journal-title":"Ther. Adv. Reprod. Health"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/GRF.0000000000000581","article-title":"Polycystic Ovarian Syndrome Genetics and Epigenetics","volume":"64","author":"Combs","year":"2021","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1111\/j.1471-0528.2009.02347.x","article-title":"Characteristics of different phenotypes of polycystic ovary syndrome based on the Rotterdam criteria in a large-scale Chinese population","volume":"116","author":"Zhang","year":"2009","journal-title":"BJOG"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"100937","DOI":"10.1016\/j.molmet.2020.01.001","article-title":"Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies","volume":"35","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.2337\/db12-0963","article-title":"miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance","volume":"62","author":"Chen","year":"2013","journal-title":"Diabetes"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1210\/jc.2003-032028","article-title":"Evidence for the presence of glucose transporter 4 in the endometrium and its regulation in polycystic ovary syndrome patients","volume":"89","author":"Mioni","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"S\u00f8rensen, A.E., Udesen, P.B., Maciag, G., Geiger, J., Saliani, N., Januszewski, A.S., Jiang, G., Ma, R.C., Hardikar, A.A., and Wissing, M.L.M. (2019). Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome. Front. Med., 6.","DOI":"10.3389\/fmed.2019.00242"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2147\/IJWH.S500692","article-title":"Impact of Polycystic Ovary Syndrome Hyperandrogenic Phenotypes A and Non-Hyperandrogenic D on Pregnancy Outcomes After in vitro Fertilization (IVF)\/Intracytoplasmic Sperm Injection (ICSI)","volume":"17","author":"Khamaiseh","year":"2025","journal-title":"Int. J. Womens Health"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"e240269","DOI":"10.1530\/JOE-24-0269","article-title":"Reappraising the relationship between hyperinsulinemia and insulin resistance in PCOS","volume":"265","author":"Houston","year":"2025","journal-title":"J. Endocrinol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/09513590.2021.2003326","article-title":"Polycystic ovarian syndrome: Signs and feedback effects of hyperandrogenism and insulin resistance","volume":"38","author":"Barrera","year":"2022","journal-title":"Gynecol. Endocrinol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.tem.2011.09.005","article-title":"Sex hormone-binding globulin and type 2 diabetes mellitus","volume":"23","author":"Le","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/19396368.2017.1410591","article-title":"Sex hormone binding globulin\u2014An important biomarker for predicting PCOS risk: A systematic review and meta-analysis","volume":"64","author":"Deswal","year":"2018","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_220","doi-asserted-by":"crossref","unstructured":"Orisaka, M., Mizutani, T., Miyazaki, Y., Shirafuji, A., Tamamura, C., Fujita, M., Tsuyoshi, H., and Yoshida, Y. (2023). Chronic low-grade inflammation and ovarian dysfunction in women with polycystic ovarian syndrome, endometriosis, and aging. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1324429"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ando.2010.02.007","article-title":"Aberrant follicle development and anovulation in polycystic ovary syndrome","volume":"71","author":"Franks","year":"2010","journal-title":"Ann. Endocrinol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.jsps.2023.03.021","article-title":"Association between insulin resistance and abnormal menstrual cycle in Saudi females with polycystic ovary syndrome","volume":"31","author":"Hussein","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/humupd\/dmae030","article-title":"Functional hypothalamic amenorrhoea and polycystic ovarian morphology: A narrative review about an intriguing association","volume":"31","author":"Ott","year":"2025","journal-title":"Hum. Reprod. Update"},{"key":"ref_224","first-page":"e82350","article-title":"A Systematic Review of Inflammatory Markers in Polycystic Ovary Syndrome (PCOS) and Meta-Analysis of Interleukin-6 (IL-6) in Case-Control Studies","volume":"17","author":"Bansal","year":"2025","journal-title":"Cureus"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"4092470","DOI":"10.1155\/2020\/4092470","article-title":"Inflammatory Markers in Women with Polycystic Ovary Syndrome","volume":"2020","author":"Rudnicka","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"3506","DOI":"10.1097\/MS9.0000000000000879","article-title":"Vitamin D and polycystic ovary syndrome (PCOS): A review","volume":"85","author":"Mohan","year":"2023","journal-title":"Ann. Med. Surg."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1186\/s12967-025-06315-7","article-title":"Gut microbiota: A hidden player in polycystic ovary syndrome","volume":"23","author":"Senthilkumar","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"e42228","DOI":"10.1097\/MD.0000000000042228","article-title":"The role of macrophages in polycystic ovary syndrome: A review","volume":"104","author":"Li","year":"2025","journal-title":"Medicine"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"616","DOI":"10.4239\/wjd.v12.i5.616","article-title":"Role of insulin and insulin resistance in androgen excess disorders","volume":"12","author":"Unluhizarci","year":"2021","journal-title":"World J. Diabetes"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"289","DOI":"10.5455\/medarh.2020.74.289-293","article-title":"Follicle Stimulating Hormone (LH: FSH) Ratio in Polycystic Ovary Syndrome (PCOS)\u2014Obese vs. Non- Obese Women","volume":"74","author":"Saadia","year":"2020","journal-title":"Med. Arch."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"e230342","DOI":"10.1530\/JOE-23-0342","article-title":"Hormonal changes in PCOS","volume":"261","author":"Yang","year":"2024","journal-title":"J. Endocrinol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"108789","DOI":"10.4239\/wjd.v16.i7.108789","article-title":"Decoding androgen excess in polycystic ovary syndrome: Roles of insulin resistance and other key intraovarian and systemic factors","volume":"16","author":"Rambaran","year":"2025","journal-title":"World J. Diabetes"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"8229","DOI":"10.1038\/s41598-024-58064-0","article-title":"Mechanism of elevated LH\/FSH ratio in lean PCOS revisited: A path analysis","volume":"14","author":"Pratama","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"e4275","DOI":"10.1210\/clinem\/dgab422","article-title":"Targeting Elevated GnRH Pulsatility to Treat Polycystic Ovary Syndrome","volume":"106","author":"Abbara","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/cen.14711","article-title":"Impaired steroid hormone feedback in polycystic ovary syndrome: Evidence from preclinical models for abnormalities within central circuits controlling fertility","volume":"97","author":"Moore","year":"2022","journal-title":"Clin. Endocrinol."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"102086","DOI":"10.1016\/j.arr.2023.102086","article-title":"Impose of KNDy\/GnRH neural circuit in PCOS, ageing, cancer and Alzheimer\u2019s disease: StAR actions in prevention of neuroendocrine dysfunction","volume":"92","author":"Panda","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.coemr.2020.04.005","article-title":"Abnormal GnRH Pulsatility in Polycystic Ovary Syndrome: Recent Insights","volume":"12","author":"McCartney","year":"2020","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1210\/en.2019-00137","article-title":"Prenatal Testosterone Exposure Alters GABAergic Synaptic Inputs to GnRH and KNDy Neurons in a Sheep Model of Polycystic Ovarian Syndrome","volume":"160","author":"Porter","year":"2019","journal-title":"Endocrinology"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"276","DOI":"10.5603\/gpl.95138","article-title":"The role of berberine in polycystic ovary syndrome\u2014A summary of knowledge","volume":"95","author":"Jurgiel","year":"2024","journal-title":"Ginekol. Pol."},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"Ionescu, O.M., Frincu, F., Mehedintu, A., Plotogea, M., Cirstoiu, M., Petca, A., Varlas, V., and Mehedintu, C. (2023). Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile\/Pregnant Women. Life, 13.","DOI":"10.3390\/life13010125"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.2337\/db07-1552","article-title":"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","volume":"57","author":"Turner","year":"2008","journal-title":"Diabetes"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"e23768","DOI":"10.1002\/mrd.23768","article-title":"Effect of berberine combined with metformin on autophagy in polycystic ovary syndrome by regulating AMPK\/AKT\/mTOR pathway","volume":"91","author":"Jin","year":"2024","journal-title":"Mol. Reprod. Dev."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"104937","DOI":"10.1016\/j.jpet.2026.104937","article-title":"Therapeutic potential of crystal-engineered berberine cocrystals ameliorates PCOS phenotypes via AMPK-IRS1\/PI3K\/Akt axis: An integrative computational and preclinical study","volume":"393","author":"Kamalakannan","year":"2026","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"111468","DOI":"10.1016\/j.biopha.2021.111468","article-title":"Effect and mechanism of berberine against polycystic ovary syndrome","volume":"138","author":"Zhang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_245","doi-asserted-by":"crossref","unstructured":"Di Pierro, F., Sultana, R., Eusaph, A.Z., Abrar, S., Bugti, M., Afridi, F., Farooq, U., Iqtadar, S., Ghauri, F., and Makhduma, S. (2023). Effect of Berberine Phytosome on reproductive, dermatologic, and metabolic characteristics in women with polycystic ovary syndrome: A controlled, randomized, multi-centric, open-label clinical trial. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1269605"},{"key":"ref_246","doi-asserted-by":"crossref","unstructured":"Wu, S., Oceguera Nava, E.I., Ashong, D., Chen, G., and Chen, Q.H. (2025). Natural Products Targeting the Androgen Receptor Signaling Pathway: Therapeutic Potential and Mechanisms. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47090780"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"7918631","DOI":"10.1155\/2019\/7918631","article-title":"The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials","volume":"2019","author":"Xie","year":"2019","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"153654","DOI":"10.1016\/j.phymed.2021.153654","article-title":"Berberine improves ovulation and endometrial receptivity in polycystic ovary syndrome","volume":"91","author":"Wang","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Gao, L., Ju, Y., Zhu, Y., Xu, J., and Lu, D. (2026). Adjunctive berberine improves hormonal, metabolic, and inflammatory profiles in women with polycystic ovary syndrome: A retrospective case-control study. Front. Endocrinol., 17.","DOI":"10.3389\/fendo.2026.1700331"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.joim.2024.05.003","article-title":"Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress","volume":"22","author":"Liu","year":"2024","journal-title":"J. Integr. Med."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s10787-022-00976-2","article-title":"The effects of berberine on inflammatory markers in Chinese patients with metabolic syndrome and related disorders: A meta-analysis of randomized controlled trials","volume":"30","author":"Lu","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1124\/jpet.115.231043","article-title":"Berberine Decreased Inducible Nitric Oxide Synthase mRNA Stability through Negative Regulation of Human Antigen R in Lipopolysaccharide-Induced Macrophages","volume":"358","author":"Shin","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/s41419-018-0890-5","article-title":"Berberine ameliorates blockade of autophagic flux in the liver by regulating cholesterol metabolism and inhibiting COX2-prostaglandin synthesis","volume":"9","author":"Sun","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"102337","DOI":"10.1016\/j.ctim.2020.102337","article-title":"Effects of berberine and barberry on anthropometric measures: A systematic review and meta-analysis of randomized controlled trials","volume":"49","author":"Amini","year":"2020","journal-title":"Complement. Ther. Med."},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Rondanelli, M., Riva, A., Petrangolini, G., Allegrini, P., Giacosa, A., Fazia, T., Bernardinelli, L., Gasparri, C., Peroni, G., and Perna, S. (2021). Berberine Phospholipid Is an Effective Insulin Sensitizer and Improves Metabolic and Hormonal Disorders in Women with Polycystic Ovary Syndrome: A One-Group Pretest-Post-Test Explanatory Study. Nutrients, 13.","DOI":"10.3390\/nu13103665"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"113776","DOI":"10.1016\/j.bcp.2019.113776","article-title":"Berberine suppresses colon cancer cell proliferation by inhibiting the SCAP\/SREBP-1 signaling pathway-mediated lipogenesis","volume":"174","author":"Liu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.clnesp.2020.04.010","article-title":"The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials","volume":"38","author":"Asbaghi","year":"2020","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_258","doi-asserted-by":"crossref","unstructured":"Rong, Q., Han, B., Li, Y., Yin, H., Li, J., and Hou, Y. (2022). Berberine Reduces Lipid Accumulation by Promoting Fatty Acid Oxidation in Renal Tubular Epithelial Cells of the Diabetic Kidney. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.729384"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"11340","DOI":"10.1038\/s41598-017-11860-3","article-title":"Berberine ameliorates fatty acid-induced oxidative stress in human hepatoma cells","volume":"7","author":"Sun","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.atherosclerosis.2015.09.032","article-title":"Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies","volume":"243","author":"Pirillo","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"29400","DOI":"10.1038\/s41598-025-15495-7","article-title":"Metformin and berberine synergistically improve NAFLD via the AMPK-SREBP1-FASN signaling pathway","volume":"15","author":"Li","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"e2554152","DOI":"10.1001\/jamanetworkopen.2025.54152","article-title":"Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial","volume":"9","author":"Lei","year":"2026","journal-title":"JAMA Netw. Open"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"8683404","DOI":"10.1155\/2020\/8683404","article-title":"Improvement of Endothelial Dysfunction of Berberine in Atherosclerotic Mice and Mechanism Exploring through TMT-Based Proteomics","volume":"2020","author":"Tan","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_264","doi-asserted-by":"crossref","unstructured":"Zhao, J.V., Yeung, W.F., Chan, Y.H., Vackova, D., Leung, J.Y.Y., Ip, D.K.M., Zhao, J., Ho, W.K., Tse, H.F., and Schooling, C.M. (2021). Effect of Berberine on Cardiovascular Disease Risk Factors: A Mechanistic Randomized Controlled Trial. Nutrients, 13.","DOI":"10.3390\/nu13082550"},{"key":"ref_265","doi-asserted-by":"crossref","unstructured":"Zamani, M., Zarei, M., Nikbaf-Shandiz, M., Hosseini, S., Shiraseb, F., and Asbaghi, O. (2022). The effects of berberine supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.1013055"},{"key":"ref_266","doi-asserted-by":"crossref","unstructured":"He, Q., Dong, H., Guo, Y., Gong, M., Xia, Q., Lu, F., and Wang, D. (2022). Multi-target regulation of intestinal microbiota by berberine to improve type 2 diabetes mellitus. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1074348"},{"key":"ref_267","doi-asserted-by":"crossref","unstructured":"Wang, H., Zhang, H., Gao, Z., Zhang, Q., and Gu, C. (2022). The mechanism of berberine alleviating metabolic disorder based on gut microbiome. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.854885"},{"key":"ref_268","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wu, X., Yang, R., Chen, F., Liao, Y., Zhu, Z., Wu, Z., Sun, X., and Wang, L. (2021). Effects of Berberine on the Gastrointestinal Microbiota. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.588517"},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jpha.2021.10.003","article-title":"Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine","volume":"12","author":"Cheng","year":"2022","journal-title":"J. Pharm. Anal."},{"key":"ref_270","first-page":"516","article-title":"Toxicology effects of Berberis vulgaris (barberry) and its active constituent, berberine: A review","volume":"20","author":"Rad","year":"2017","journal-title":"Iran. J. Basic. Med. Sci."},{"key":"ref_271","first-page":"201","article-title":"Displacement of bilirubin from albumin by berberine","volume":"63","author":"Chan","year":"1993","journal-title":"Biol. Neonate"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"103040","DOI":"10.1016\/j.explore.2024.103040","article-title":"Berberine as adjuvant therapy for treating reduced fertility potential in women with polycystic ovary syndrome: A meta-analysis of randomized controlled trials","volume":"20","author":"Ha","year":"2024","journal-title":"Explore"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"2532935","DOI":"10.1155\/2018\/2532935","article-title":"The Effect of Berberine on Polycystic Ovary Syndrome Patients with Insulin Resistance (PCOS-IR): A Meta-Analysis and Systematic Review","volume":"2018","author":"Li","year":"2018","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_274","doi-asserted-by":"crossref","unstructured":"Shi, L., Wang, W., Jing, C., Hu, J., and Liao, X. (2025). Berberine and health outcomes: An overview of systematic reviews. BMC Complement. Med. Ther., 25.","DOI":"10.1186\/s12906-025-04872-4"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.amjcard.2020.05.011","article-title":"Limitations of Randomized Clinical Trials","volume":"129","author":"Kostis","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"10135","DOI":"10.18632\/oncotarget.20807","article-title":"Metformin and berberine, two versatile drugs in treatment of common metabolic diseases","volume":"9","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_277","doi-asserted-by":"crossref","unstructured":"Xie, W., Su, F., Wang, G., Peng, Z., Xu, Y., Zhang, Y., Xu, N., Hou, K., Hu, Z., and Chen, Y. (2022). Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1015045"},{"key":"ref_278","doi-asserted-by":"crossref","unstructured":"Yang, F., Gao, R., Luo, X., Liu, R., and Xiong, D. (2023). Berberine influences multiple diseases by modifying gut microbiota. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1187718"},{"key":"ref_279","doi-asserted-by":"crossref","unstructured":"Solnier, J., Zhang, Y., Kuo, Y.C., Du, M., Roh, K., Gahler, R., Wood, S., and Chang, C. (2023). Characterization and Pharmacokinetic Assessment of a New Berberine Formulation with Enhanced Absorption In Vitro and in Human Volunteers. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15112567"},{"key":"ref_280","first-page":"1099","article-title":"Berberine: Ins and outs of a nature-made PCSK9 inhibitor","volume":"21","author":"Ataei","year":"2022","journal-title":"EXCLI J."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"114754","DOI":"10.1016\/j.biopha.2023.114754","article-title":"Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases","volume":"163","author":"Guo","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1002\/ptr.7806","article-title":"Berberine and health outcomes: An umbrella review","volume":"37","author":"Li","year":"2023","journal-title":"Phytother. Res."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"585","DOI":"10.4239\/wjd.v14.i5.585","article-title":"Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes","volume":"14","author":"Sayedali","year":"2023","journal-title":"World J. Diabetes"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00228-011-1108-2","article-title":"Repeated administration of berberine inhibits cytochromes P450 in humans","volume":"68","author":"Guo","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"e45007","DOI":"10.1097\/MD.0000000000045007","article-title":"Comprehensive analysis of metformin-associated lactic acidosis: Insights from the FDA Adverse Event Reporting System (FAERS)","volume":"104","author":"Jin","year":"2025","journal-title":"Medicine"},{"key":"ref_286","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Guo, L., Huang, J., Sun, Y., He, F., Zloh, M., and Wang, L. (2019). Inhibitory Effect of Berberine on Broiler P-glycoprotein Expression and Function: In Situ and In Vitro Studies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081966"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"e2462195","DOI":"10.1001\/jamanetworkopen.2024.62195","article-title":"A Berberine Derivative for Treatment of Type 2 Diabetes","volume":"8","author":"Mathioudakis","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_288","doi-asserted-by":"crossref","unstructured":"Panigrahi, A., and Mohanty, S. (2023). Efficacy and safety of HIMABERB\u00ae Berberine on glycemic control in patients with prediabetes: Double-blind, placebo-controlled, and randomized pilot trial. BMC Endocr. Disord., 23.","DOI":"10.1186\/s12902-023-01442-y"},{"key":"ref_289","first-page":"e21781","article-title":"Study on the Effect of Berberine, Myoinositol, and Metformin in Women with Polycystic Ovary Syndrome: A Prospective Randomised Study","volume":"14","author":"Mishra","year":"2022","journal-title":"Cureus"},{"key":"ref_290","doi-asserted-by":"crossref","unstructured":"Rasool, S., Al Meslmani, B., and Alajlani, M. (2023). Determination of Hypoglycemic, Hypolipidemic and Nephroprotective Effects of Berberis Calliobotrys in Alloxan-Induced Diabetic Rats. 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