{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:41:39Z","timestamp":1793306499383,"version":"4.5.0"},"reference-count":106,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology &amp; Therapeutics"],"published-print":{"date-parts":[[2020,5]]},"DOI":"10.1016\/j.pharmthera.2020.107496","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T11:15:40Z","timestamp":1580123740000},"page":"107496","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":85,"special_numbering":"C","title":["Berberine in the treatment of metabolism-related chronic diseases: A drug cloud (dCloud) effect to target multifactorial disorders"],"prefix":"10.1016","volume":"209","author":[{"given":"Wei-Jia","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Vernieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Foiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Dong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.pharmthera.2020.107496_bb0005","doi-asserted-by":"crossref","first-page":"383","DOI":"10.2174\/18715273113126660151","article-title":"A possible link of gut microbiota alteration in type 2 diabetes and Alzheimer's disease pathogenicity: An update","volume":"13","author":"Alam","year":"2014","journal-title":"CNS & Neurological Disorders Drug Targets"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0010","doi-asserted-by":"crossref","first-page":"R97","DOI":"10.1530\/JOE-15-0447","article-title":"Current understanding of metformin effect on the control of hyperglycemia in diabetes","volume":"228","author":"An","year":"2016","journal-title":"The Journal of Endocrinology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0015","doi-asserted-by":"crossref","DOI":"10.1186\/s13643-018-0779-5","article-title":"Blood pressure reduction and clinical outcomes with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: Protocol for a systematic review and meta-regression analysis","volume":"7","author":"Batty","year":"2018","journal-title":"Systematic Reviews"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0020","article-title":"Risk of bias in systematic reviews of non-randomized studies of adverse cardiovascular effects of thiazolidinediones and cyclooxygenase-2 inhibitors: Application of a new cochrane risk of bias tool","volume":"13","author":"Bilandzic","year":"2016","journal-title":"PloSMed"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0025","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.jep.2013.07.025","article-title":"Berberine metabolites exhibit triglyceride-lowering effects via activation of AMP-activated protein kinase in Hep G2 cells","volume":"149","author":"Cao","year":"2013","journal-title":"Journal of Ethnopharmacology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0030","first-page":"197","article-title":"Modulation of gut microbiota by berberine improves steatohepatitis in high-fat diet-fed BALB\/C mice","volume":"19","author":"Cao","year":"2016","journal-title":"Archives of Iranian Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0035","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ceb.2017.01.005","article-title":"AMPK signalling in health and disease","volume":"45","author":"Carling","year":"2017","journal-title":"Current Opinion in Cell Biology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0040","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.bcp.2012.07.031","article-title":"Clinical perspectives for irreversible tyrosine kinase inhibitors in cancer","volume":"84","author":"Carmi","year":"2012","journal-title":"Biochemical Pharmacology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0045","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.bbrc.2010.05.153","article-title":"Berberine inhibits PTP1B activity and mimics insulin action","volume":"397","author":"Chen","year":"2010","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0050","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.yexcr.2018.04.018","article-title":"Butyrate ameliorated-NLRC3 protects the intestinal barrier in a GPR43-dependent manner","volume":"368","author":"Cheng","year":"2018","journal-title":"Experimental Cell Research"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0055","doi-asserted-by":"crossref","first-page":"526","DOI":"10.2119\/molmed.2015.00148","article-title":"Aspirin's active metabolite salicylic acid targets high mobility group box 1 to modulate inflammatory responses","volume":"21","author":"Choi","year":"2015","journal-title":"Molecular Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0060","doi-asserted-by":"crossref","first-page":"801","DOI":"10.3389\/fphar.2018.00801","article-title":"Polypharmacology of berberine based on multi-target binding motifs","volume":"9","author":"Chu","year":"2018","journal-title":"Frontiers in Pharmacology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0065","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.pharmthera.2016.01.002","article-title":"The anti-dementia drug candidate, (\u2212)-clausenamide, improves memory impairment through its multi-target effect","volume":"162","author":"Chu","year":"2016","journal-title":"Pharmacology & Therapeutics"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0070","first-page":"510","article-title":"The anti-platelet effect of berberine and its mechanism","volume":"14","author":"Chu","year":"1994","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0075","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":"Advances in Experimental Medicine and Biology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0080","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms4557","article-title":"Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys","volume":"5","author":"Colman","year":"2014","journal-title":"Nature Communications"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0085","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/591654","article-title":"Berberine in the treatment of type 2 diabetes mellitus: A systemic review and meta-analysis","volume":"2012","author":"Dong","year":"2012","journal-title":"Evidence-based Complementary and Alternative Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0090","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pharmthera.2016.04.008","article-title":"Polyphenols: Potential source of drugs for the treatment of ischaemic heart disease","volume":"162","author":"Du","year":"2016","journal-title":"Pharmacology & Therapeutics"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0095","first-page":"480","article-title":"Multi-target and multi-component pattern, a superficial understanding of the action mechanism of Traditional Chinese Medicine","volume":"11","author":"Du","year":"2009","journal-title":"Modernization of Traditional\u202fChinese Medicine\u202fand\u202fMateria Medica-World Science and Technology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0100","article-title":"Transforming berberine into its intestine-absorbable form by the gut microbiota","volume":"5","author":"Feng","year":"2015","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0105","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3389\/fphar.2018.00214","article-title":"Gut microbiota-regulated pharmacokinetics of berberine and active metabolites in beagle dogs after oral administration","volume":"9","author":"Feng","year":"2018","journal-title":"Frontiers in Pharmacology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0110","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fnmol.2018.00267","article-title":"Trilobatin protects against oxidative injury in neuronal PC12 cells through regulating mitochondrial ROS homeostasis mediated by AMPK\/Nrf2\/Sirt3 signaling pathway","volume":"11","author":"Gao","year":"2018","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0115","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0140-6736(15)60692-4","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 2013","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0120","doi-asserted-by":"crossref","first-page":"996","DOI":"10.3109\/00498254.2011.597456","article-title":"CYP2D plays a major role in berberine metabolism in liver of mice and humans","volume":"41","author":"Guo","year":"2011","journal-title":"Xenobiotica"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0125","doi-asserted-by":"crossref","DOI":"10.1186\/s12906-016-1367-7","article-title":"Dose-response effect of berberine on bile acid profile and gut microbiota in mice","volume":"16","author":"Guo","year":"2016","journal-title":"BMC Complementary and Alternative Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0130","doi-asserted-by":"crossref","first-page":"RA164","DOI":"10.12659\/MSM.881842","article-title":"Modulating gut microbiota as an anti-diabetic mechanism of berberine","volume":"17","author":"Han","year":"2011","journal-title":"Medical Science Monitor"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0135","doi-asserted-by":"crossref","first-page":"E955","DOI":"10.1152\/ajpendo.90599.2008","article-title":"Berberine suppresses proinflammatory responses through AMPK activation in macrophages","volume":"296","author":"Jeong","year":"2009","journal-title":"American Journal of Physiology. Endocrinology and Metabolism"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0140","series-title":"Beberine","author":"Jiang","year":"2018"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0145","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.phymed.2018.09.212","article-title":"Efficacy and safety of berberine for dyslipidaemias: A systematic review and meta-analysis of randomized clinical trials","volume":"50","author":"Ju","year":"2018","journal-title":"Phytomedicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0150","doi-asserted-by":"crossref","first-page":"E812","DOI":"10.1152\/ajpendo.90710.2008","article-title":"Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity","volume":"296","author":"Kim","year":"2009","journal-title":"American Journal of Physiology. Endocrinology and Metabolism"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0155","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1038\/nm1135","article-title":"Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins","volume":"10","author":"Kong","year":"2004","journal-title":"Nature Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0160","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00109-005-0717-6","article-title":"Human low-density lipoprotein receptor gene and its regulation","volume":"84","author":"Kong","year":"2006","journal-title":"Journal of Molecular Medicine (Berlin, Germany)"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0165","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.metabol.2008.01.037","article-title":"Combination of simvastatin with berberine improves the lipid-lowering efficacy","volume":"57","author":"Kong","year":"2008","journal-title":"Metabolism"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0170","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.metabol.2008.08.013","article-title":"Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression","volume":"58","author":"Kong","year":"2009","journal-title":"Metabolism"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0175","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ejphar.2015.05.068","article-title":"Current knowledge and pharmacological profile of berberine: An update","volume":"761","author":"Kumar","year":"2015","journal-title":"European Journal of Pharmacology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0180","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.tiv.2013.04.011","article-title":"Melamine activates NF\u03baB\/COX-2\/PGE2 pathway and increases NADPH oxidase-dependent ROS production in macrophages and human embryonic kidney cells","volume":"27","author":"Kuo","year":"2013","journal-title":"Toxicology In Vitro"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0185","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jep.2014.09.049","article-title":"Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension","volume":"161","author":"Lan","year":"2015","journal-title":"Journal of Ethnopharmacology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0190","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":"10.1016\/j.pharmthera.2020.107496_bb0195","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1194\/jlr.M800375-JLR200","article-title":"Identification of mRNA binding proteins that regulate the stability of LDL receptor mRNA through AU-rich elements","volume":"50","author":"Li","year":"2009","journal-title":"Journal of Lipid Research"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0200","doi-asserted-by":"crossref","first-page":"28885","DOI":"10.1074\/jbc.M109.052407","article-title":"Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine","volume":"284","author":"Li","year":"2009","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0205","doi-asserted-by":"crossref","DOI":"10.1186\/s12967-016-0987-5","article-title":"Integrative analysis of metabolome and gut microbiota in diet-induced hyperlipidemic rats treated with berberine compounds","volume":"14","author":"Li","year":"2016","journal-title":"Journal of Translational Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0210","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/1479-5876-9-62","article-title":"Bioactivities of berberine metabolites after transformation through CYP450 isoenzymes","volume":"9","author":"Li","year":"2011","journal-title":"Journal of Translational Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0215","first-page":"4066","article-title":"Effects of berberine on serum inflammatory factors and carotid atherosclerotic plaques in patients with acute cerebral ischemic stroke","volume":"41","author":"Li","year":"2016","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0220","doi-asserted-by":"crossref","first-page":"6422","DOI":"10.1016\/j.bmc.2010.06.106","article-title":"Design, synthesis, and cholesterol-lowering efficacy for prodrugs of berberrubine","volume":"18","author":"Li","year":"2010","journal-title":"Bioorganic & Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0225","article-title":"Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus","volume":"2014","author":"Li","year":"2014","journal-title":"Evidence-based Complementary and Alternative Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0230","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1248\/bpb.b14-00412","article-title":"Berberine up-regulates hepatic low-density lipoprotein receptor through Ras-independent but AMP-activated protein kinase-dependent Raf-1 activation","volume":"37","author":"Li","year":"2014","journal-title":"Biological & Pharmaceutical Bulletin"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0235","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1507\/endocrj.EJ18-0109","article-title":"Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: A systematic literature review and a meta-analysis","volume":"66","author":"Liang","year":"2019","journal-title":"Endocrine Journal"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0240","first-page":"163","article-title":"Antibacterial activity of berberine","volume":"53","author":"Lin","year":"2018","journal-title":"Acta Pharmaceutica Sinica"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0245","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1055\/s-0043-125066","article-title":"Berberine modulates gut microbiota and reduces insulin resistance via the TLR4 signaling pathway","volume":"126","author":"Liu","year":"2018","journal-title":"Experimental and Clinical Endocrinology & Diabetes"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0250","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.cmet.2013.12.008","article-title":"Fasting: Molecular mechanisms and clinical applications","volume":"19","author":"Longo","year":"2014","journal-title":"Cell Metabolism"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0255","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1677\/JOE-08-0419","article-title":"Berberine promotes glucagon-like peptide-1 (7-36) amide secretion in streptozotocin-induced diabetic rats","volume":"200","author":"Lu","year":"2009","journal-title":"The Journal of Endocrinology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0260","doi-asserted-by":"crossref","first-page":"9337","DOI":"10.1074\/jbc.M513000200","article-title":"Active metabolite of atorvastatin inhibits membrane cholesterol domain formation by an antioxidant mechanism","volume":"281","author":"Mason","year":"2006","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0265","doi-asserted-by":"crossref","DOI":"10.3390\/nu9121348","article-title":"Short chain fatty acids in the colon and peripheral tissues: A focus on butyrate, colon cancer, obesity and insulin resistance","volume":"9","author":"McNabney","year":"2017","journal-title":"Nutrients"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0270","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/j.1440-1681.2012.05670.x","article-title":"Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention","volume":"39","author":"Meng","year":"2012","journal-title":"Clinical and Experimental Pharmacology & Physiology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0275","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41568-018-0061-0","article-title":"Fasting and cancer: Molecular mechanisms and clinical application","volume":"18","author":"Nencioni","year":"2018","journal-title":"Nature Reviews. Cancer"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0280","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.freeradbiomed.2018.10.453","article-title":"Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity","volume":"130","author":"Paul","year":"2019","journal-title":"Free Radical Biology & Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0285","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":"10.1016\/j.pharmthera.2020.107496_bb0290","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1007\/s00216-018-0884-2","article-title":"Combined analytical approaches to define biodistribution and biological activity of semi-synthetic berberrubine, the active metabolite of natural berberine","volume":"410","author":"Porru","year":"2018","journal-title":"Analytical and Bioanalytical Chemistry"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0295","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1007\/s00204-016-1737-4","article-title":"The current role of thiazolidinediones in diabetes management","volume":"90","author":"Rizos","year":"2016","journal-title":"Archives of Toxicology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0300","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s40264-013-0048-4","article-title":"Hepatotoxicity of tyrosine kinase inhibitors: Clinical and regulatory perspectives","volume":"36","author":"Shah","year":"2013","journal-title":"Drug Safety"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0305","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":"10.1016\/j.pharmthera.2020.107496_bb0310","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1248\/bpb.b13-00272","article-title":"Tetrandrine potentiates the hypoglycemic efficacy of berberine by inhibiting P-glycoprotein function","volume":"36","author":"Shan","year":"2013","journal-title":"Biological & Pharmaceutical Bulletin"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0315","doi-asserted-by":"crossref","DOI":"10.1177\/1470320316656481","article-title":"Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease","volume":"17","author":"Shen","year":"2016","journal-title":"Journal of the Renin-Angiotensin-Aldosterone System"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0320","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1021\/np400607k","article-title":"Berberine and its metabolites: Relationship between physicochemical properties and plasma levels after administration to human subjects","volume":"77","author":"Spinozzi","year":"2014","journal-title":"Journal of Natural Products"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0325","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12291-014-0441-5","article-title":"Stress, oxidative injury and disease","volume":"30","author":"Srivastava","year":"2015","journal-title":"Indian Journal of Clinical Biochemistry"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0330","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1161\/01.ATV.0000030360.72503.56","article-title":"Statins reduce inflammation in atheroma of nonhuman primates independent of effects on serum cholesterol","volume":"22","author":"Sukhova","year":"2002","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0335","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1089\/omi.2014.0112","article-title":"Berberine ameliorates nonbacterial prostatitis via multi-target metabolic network regulation","volume":"19","author":"Sun","year":"2015","journal-title":"OMICS"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0340","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1159\/000449507","article-title":"Modulation of microbiota-gut-brain axis by berberine resulting in improved metabolic status in high-fat diet-fed rats","volume":"9","author":"Sun","year":"2016","journal-title":"Obesity Facts"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0345","doi-asserted-by":"crossref","DOI":"10.1038\/s41387-018-0061-x","article-title":"Restoration of GLP-1 secretion by berberine is associated with protection of colon enterocytes from mitochondrial overheating in diet-induced obese mice","volume":"8","author":"Sun","year":"2018","journal-title":"Nutrition & Diabetes"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0350","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1159\/000324281","article-title":"Gut-liver axis and sensing microbes","volume":"28","author":"Szabo","year":"2010","journal-title":"Digestive Diseases"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0355","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0077969","article-title":"Tissue distribution of berberine and its metabolites after oral administration in rats","volume":"8","author":"Tan","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0360","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1053\/j.seminoncol.2015.09.010","article-title":"Mechanisms of nonsteroidal anti-inflammatory drugs in cancer prevention","volume":"43","author":"Umar","year":"2016","journal-title":"Seminars in Oncology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0365","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.3923\/ijp.2018.1087.1098","article-title":"Evaluation of anticoagulant and antithrombotic activities of berberine: A focus on the ameliorative effect on blood hypercoagulation","volume":"14","author":"Wang","year":"2018","journal-title":"International Journal of Pharmacology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0370","first-page":"486","article-title":"Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-IV","volume":"45","author":"Wang","year":"2016","journal-title":"Zhejiang Da Xue Xue Bao. Yi Xue Ban"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0375","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 Metabolism Reviews"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0380","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":"Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0385","article-title":"Identification of berberine as a direct thrombin inhibitor from traditional Chinese medicine through structural, functional and binding studies","volume":"7","author":"Wang","year":"2017","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0390","first-page":"659","article-title":"A new research mode of drug PK-PD mediated by the gut microbiota: Insights into the pharmacokinetics of berberine","volume":"53","author":"Wang","year":"2018","journal-title":"Acta Pharmaceutica Sinica"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0395","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.metabol.2017.02.003","article-title":"Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism","volume":"70","author":"Wang","year":"2017","journal-title":"Metabolism"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0400","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.7150\/thno.18290","article-title":"Gut microbiota-mediated personalized treatment of hyperlipidemia using berberine","volume":"7","author":"Wang","year":"2017","journal-title":"Theranostics"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0405","doi-asserted-by":"crossref","first-page":"6552","DOI":"10.1016\/j.bmc.2012.09.029","article-title":"Synthesis and structure-activity relationship of berberine analogues in LDLR up-regulation and AMPK activation","volume":"20","author":"Wang","year":"2012","journal-title":"Bioorganic & Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0410","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/ni.2022","article-title":"Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling","volume":"12","author":"Wen","year":"2011","journal-title":"Nature Immunology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0415","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.maturitas.2018.03.012","article-title":"Microbiota-drug interactions: Impact on metabolism and efficacy of therapeutics","volume":"112","author":"Wilkinson","year":"2018","journal-title":"Maturitas"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0420","author":"World Health Organization"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0425","first-page":"98","article-title":"Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion","volume":"30","author":"Wu","year":"1995","journal-title":"Yao Xue Xue Bao"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0430","first-page":"128","article-title":"Effects of atorvastatin on gut microbiota in mice with type 2 diabetes mellitus","volume":"12","author":"Wu","year":"2017","journal-title":"China Practical Medical"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0435","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s11655-010-0188-7","article-title":"Advance of studies on anti-atherosclerosis mechanism of berberine","volume":"16","author":"Wu","year":"2010","journal-title":"Chinese Journal of Integrative Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0440","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.cdtm.2015.11.006","article-title":"Study progress of berberine for treating cardiovascular disease","volume":"1","author":"Xia","year":"2016","journal-title":"Chronic Diseases and Translational Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0445","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1507\/endocrj.EJ17-0012","article-title":"Inhibition of NF-\u03baB activation improves insulin resistance of L6 cells","volume":"64","author":"Xie","year":"2017","journal-title":"Endocrine Journal"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0450","article-title":"Berberine promotes glucose consumption independently of AMP-activated protein kinase activation","volume":"9","author":"Xu","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0455","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0134172","article-title":"Efficacy of berberine in patients with non-alcoholic fatty liver disease","volume":"10","author":"Yan","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0460","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1007\/s11427-013-4568-z","article-title":"Learning from berberine: Treating chronic diseases through multiple targets","volume":"58","author":"Yao","year":"2015","journal-title":"Science China. Life Sciences"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0465","doi-asserted-by":"crossref","first-page":"E148","DOI":"10.1152\/ajpendo.00211.2007","article-title":"Berberine improves glucose metabolism through induction of glycolysis","volume":"294","author":"Yin","year":"2008","journal-title":"American Journal of Physiology. Endocrinology and Metabolism"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0470","article-title":"Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice","volume":"13","author":"Yu","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0475","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mce.2010.07.022","article-title":"Protein kinase D activation stimulates the transcription of the insulin receptor gene","volume":"330","author":"Zhang","year":"2010","journal-title":"Molecular and Cellular Endocrinology"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0480","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.metabol.2009.07.029","article-title":"Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression","volume":"59","author":"Zhang","year":"2010","journal-title":"Metabolism"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0485","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.3892\/etm.2017.4402","article-title":"Berberine alleviates dextran sodium sulfate-induced colitis by improving intestinal barrier function and reducing inflammation and oxidative stress","volume":"13","author":"Zhang","year":"2017","journal-title":"Experimental and Therapeutic Medicine"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0490","article-title":"Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats","volume":"5","author":"Zhang","year":"2015","journal-title":"Scientific Reports"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0495","article-title":"Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats","volume":"7","author":"Zhang","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0500","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s11427-017-9047-4","article-title":"Prevention and treatment of cancer targeting chronic inflammation: Research progress, potential agents, clinical studies and mechanisms","volume":"60","author":"Zhang","year":"2017","journal-title":"Science China. Life Sciences"},{"issue":"12","key":"10.1016\/j.pharmthera.2020.107496_bb0505","first-page":"1664","article-title":"Sodium butyrate in combination with berberine improves nonalcoholic fatty liver disease in C57BL\/6J mice","volume":"35","author":"Zhang","year":"2019","journal-title":"Chinese Pharmacological Bulletin"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0510","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.biopha.2008.01.007","article-title":"Reduction of blood lipid by berberine in hyperlipidemic patients with chronic hepatitis or liver cirrhosis","volume":"62","author":"Zhao","year":"2008","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0515","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.biopha.2017.03.003","article-title":"Berberine inhibits palmitate-induced NLRP3 inflammasome activation by triggering autophagy in macrophages: A new mechanism linking berberine to insulin resistance improvement","volume":"89","author":"Zhou","year":"2017","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0520","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.fitote.2013.11.010","article-title":"Berberine metabolites could induce low density lipoprotein receptor up-regulation to exert lipid-lowering effects in human hepatoma cells","volume":"92","author":"Zhou","year":"2014","journal-title":"Fitoterapia"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0525","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\u2212\/\u2212 mice","volume":"268","author":"Zhu","year":"2018","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.pharmthera.2020.107496_bb0530","doi-asserted-by":"crossref","DOI":"10.3390\/molecules21101336","article-title":"The potential mechanisms of berberine in the treatment of nonalcoholic fatty liver disease","volume":"21","author":"Zhu","year":"2016","journal-title":"Molecules"}],"container-title":["Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725820300243?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725820300243?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T22:02:51Z","timestamp":1759010571000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0163725820300243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5]]},"references-count":106,"alternative-id":["S0163725820300243"],"URL":"https:\/\/doi.org\/10.1016\/j.pharmthera.2020.107496","relation":{},"ISSN":["0163-7258"],"issn-type":[{"value":"0163-7258","type":"print"}],"subject":[],"published":{"date-parts":[[2020,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Berberine in the treatment of metabolism-related chronic diseases: A drug cloud (dCloud) effect to target multifactorial disorders","name":"articletitle","label":"Article Title"},{"value":"Pharmacology & Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pharmthera.2020.107496","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"107496"}}