{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:11:06Z","timestamp":1790892666131,"version":"4.1.0"},"reference-count":159,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carol Davila University of Medicine and Pharmacy through the institutional program Publish"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance.<\/jats:p>","DOI":"10.3390\/ijms25084201","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T10:55:28Z","timestamp":1712746528000},"page":"4201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Berberine Effects in Pre-Fibrotic Stages of Non-Alcoholic Fatty Liver Disease\u2014Clinical and Pre-Clinical Overview and Systematic Review of the Literature"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9829-5035","authenticated-orcid":false,"given":"Florentina","family":"Ionita-Radu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Gastroenterology, Dr. Carol Davila Central Military Emergency University Hospital, 010242 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5541-7151","authenticated-orcid":false,"given":"Cristina","family":"Patoni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea Simona","family":"Nancoff","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Dr. Carol Davila Central Military Emergency University Hospital, 010242 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-7725","authenticated-orcid":false,"given":"Flavius-Stefan","family":"Marin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8181-1803","authenticated-orcid":false,"given":"Laura","family":"Gaman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4447-2133","authenticated-orcid":false,"given":"Ana","family":"Bucurica","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-8998","authenticated-orcid":false,"given":"Calin","family":"Socol","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-0815","authenticated-orcid":false,"given":"Mariana","family":"Jinga","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Gastroenterology, Dr. Carol Davila Central Military Emergency University Hospital, 010242 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5511-8702","authenticated-orcid":false,"given":"Madalina","family":"Dutu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Anesthesiology and Intensive Care, Dr. Carol Davila Central Military Emergency University Hospital, 010242 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-3829","authenticated-orcid":false,"given":"Sandica","family":"Bucurica","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Gastroenterology, Dr. Carol Davila Central Military Emergency University Hospital, 010242 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.jhep.2023.04.036","article-title":"Changing epidemiology, global trends and implications for outcomes of NAFLD","volume":"79","author":"Wong","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8496","DOI":"10.1038\/s41598-020-65556-2","article-title":"Histological grading evaluation of non-alcoholic fatty liver disease after bariatric surgery: A retrospective and longitudinal observational cohort study","volume":"10","author":"Chaim","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1210\/clinem\/dgac321","article-title":"Global Prevalence and Clinical Characteristics of Metabolic-associated Fatty Liver Disease: A Meta-Analysis and Systematic Review of 10 739 607 Individuals","volume":"107","author":"Chan","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s12072-022-10436-2","article-title":"Prevalence, characteristics, and mortality outcomes of obese and nonobese MAFLD in the United States","volume":"17","author":"Dao","year":"2022","journal-title":"Hepatol. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.cgh.2020.05.064","article-title":"Nonalcoholic Steatohepatitis Is the Most Rapidly Increasing Indication for Liver Transplantation in the United States","volume":"19","author":"Younossi","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1007\/s12072-023-10568-z","article-title":"Current understanding and future perspectives on the impact of changing NAFLD to MAFLD on global epidemiology and clinical outcomes","volume":"17","author":"Vaz","year":"2023","journal-title":"Hepatol. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","article-title":"Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease","volume":"75","author":"Ipsen","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Behl, T., Singh, S., Sharma, N., Zahoor, I., Albarrati, A., Albratty, M., Meraya, A.M., Najmi, A., and Bungau, S. (2022). Expatiating the Pharmacological and Nanotechnological Aspects of the Alkaloidal Drug Berberine: Current and Future Trends. Molecules, 27.","DOI":"10.3390\/molecules27123705"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bucurica, S., Radu, F.I., Bucurica, A., Socol, C., Prodan, I., Tudor, I., Sirbu, C.A., Plesa, F.C., and Jinga, M. (2022). Risk of New-Onset Liver Injuries Due to COVID-19 in Preexisting Hepatic Conditions\u2014Review of the Literature. Medicina, 59.","DOI":"10.3390\/medicina59010062"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.2174\/1385272821666170207114214","article-title":"Isoquinoline Alkaloids and Their Antiviral, Antibacterial, and Antifungal Activities and Structure-activity Relationship","volume":"21","author":"Qing","year":"2017","journal-title":"Curr. Org. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1007\/s10620-020-06269-4","article-title":"How Good Are Controlled Attenuation Parameter Scores from Fibroscan to Assess Steatosis, NASH, and Fibrosis?","volume":"66","author":"Trowell","year":"2020","journal-title":"Dig. Dis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1002\/hep.29607","article-title":"Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science","volume":"67","author":"Siddiqui","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) (2016). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol., 64, 1388\u20131402.","DOI":"10.1016\/j.jhep.2015.11.004"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/jgh.13857","article-title":"Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 1: Definition, risk factors and assessment","volume":"33","author":"Wong","year":"2018","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1007\/s10620-018-5398-4","article-title":"Nonalcoholic Fatty Liver Disease Demonstrates a Pre-fibrotic and Premalignant Molecular Signature","volume":"64","author":"Almanza","year":"2018","journal-title":"Dig. Dis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1159\/000533328","article-title":"Liver Biopsy: To Do or Not to Do\u2014A Single-Center Study","volume":"41","author":"Androutsakos","year":"2023","journal-title":"Dig. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1053\/j.gastro.2005.03.084","article-title":"Sampling Variability of Liver Biopsy in Nonalcoholic Fatty Liver Disease","volume":"128","author":"Ratziu","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1055\/s-0032-1306421","article-title":"Nonalcoholic Fatty Liver Disease: Pathologic Patterns and Biopsy Evaluation in Clinical Research","volume":"32","author":"Kleiner","year":"2012","journal-title":"Semin. Liver Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.jhep.2019.12.008","article-title":"Clinical validation of the FLIP algorithm and the SAF score in patients with non-alcoholic fatty liver disease","volume":"72","author":"Nascimbeni","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.jhep.2021.05.025","article-title":"EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis\u20142021 update","volume":"75","author":"Berzigotti","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_24","first-page":"5","article-title":"From liver biopsy to non-invasive markers in evaluating fibrosis in chronic liver disease","volume":"118","author":"Diaconu","year":"2015","journal-title":"Rom. J. Mil. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1148\/radiol.10091790","article-title":"Assessment of Hepatic Steatosis in Patients Undergoing Liver Resection: Comparison of US, CT, T1-weighted Dual-Echo MR Imaging, and Point-resolved1H MR Spectroscopy","volume":"256","author":"Marsman","year":"2010","journal-title":"Radiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.3748\/wjg.v25.i40.6053","article-title":"Ultrasound-based techniques for the diagnosis of liver steatosis","volume":"25","author":"Ferraioli","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ibacahe, C., Correa-Burrows, P., Burrows, R., Barrera, G., Kim, E., Hirsch, S., Jofr\u00e9, B., Blanco, E., Gahagan, S., and Bunout, D. (2020). Accuracy of a Semi-Quantitative Ultrasound Method to Determine Liver Fat Infiltration in Early Adulthood. Diagnostics, 10.","DOI":"10.3390\/diagnostics10060431"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1111\/j.1572-0241.2007.01526.x","article-title":"The Severity of Ultrasonographic Findings in Nonalcoholic Fatty Liver Disease Reflects the Metabolic Syndrome and Visceral Fat Accumulation","volume":"102","author":"Hamaguchi","year":"2007","journal-title":"Am. J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1016\/j.ultrasmedbio.2018.07.008","article-title":"Liver Ultrasound Elastography: An Update to the World Federation for Ultrasound in Medicine and Biology Guidelines and Recommendations","volume":"44","author":"Ferraioli","year":"2018","journal-title":"Ultrasound Med. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1053\/j.gastro.2019.01.042","article-title":"Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease","volume":"156","author":"Eddowes","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S240","DOI":"10.1093\/ecco-jcc\/jjx002.448","article-title":"P323 Fatty liver assessment in inflammatory bowel disease patients using controlled attenuation parameter","volume":"11","author":"Balaban","year":"2017","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.jhep.2013.12.018","article-title":"Controlled attenuation parameter (CAP) for the diagnosis of steatosis: A prospective study of 5323 examinations","volume":"60","author":"Vergniol","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/j.gastro.2018.12.036","article-title":"Noninvasive Assessment of Liver Disease in Patients with Nonalcoholic Fatty Liver Disease","volume":"156","author":"Castera","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1002\/hep.29797","article-title":"Noninvasive, Quantitative Assessment of Liver Fat by MRI-PDFF as an Endpoint in NASH Trials","volume":"68","author":"Caussy","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s41824-023-00173-6","article-title":"The effect of hepatic steatosis on 18F-FDG uptake in PET-CT examinations of cancer Egyptian patients","volume":"7","author":"Ali","year":"2023","journal-title":"Eur. J. Hybrid Imaging"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/cpf.12651","article-title":"FDG PET\/CT of the non-malignant liver in an increasingly obese world population","volume":"40","author":"Keramida","year":"2020","journal-title":"Clin. Physiol. Funct. Imaging"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Honka, M.-J., Rebelos, E., Malaspina, S., and Nuutila, P. (2022). Hepatic Positron Emission Tomography: Applications in Metabolism, Haemodynamics and Cancer. Metabolites, 12.","DOI":"10.3390\/metabo12040321"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pouwels, S., Sakran, N., Graham, Y., Leal, A., Pintar, T., Yang, W., Kassir, R., Singhal, R., Mahawar, K., and Ramnarain, D. (2022). Non-alcoholic fatty liver disease (NAFLD): A review of pathophysiology, clinical management and effects of weight loss. BMC Endocr. Disord., 22.","DOI":"10.1186\/s12902-022-00980-1"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1254014","DOI":"10.1155\/2022\/1254014","article-title":"Advance of Serum Biomarkers and Combined Diagnostic Panels in Nonalcoholic Fatty Liver Disease","volume":"2022","author":"Zeng","year":"2022","journal-title":"Dis. Markers"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1097\/MEG.0000000000002176","article-title":"Predictive value of cytokeratin-18 fragment levels for diagnosing steatohepatitis in patients with nonalcoholic fatty liver disease","volume":"33","author":"Tada","year":"2021","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e27325","DOI":"10.1016\/j.heliyon.2024.e27325","article-title":"Non-invasive diagnosis of non-alcoholic fatty liver disease: Current status and future perspective","volume":"10","author":"Wang","year":"2024","journal-title":"Heliyon"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1097\/CM9.0000000000000989","article-title":"Non-invasive fibrosis assessment in non-alcoholic fatty liver disease","volume":"133","author":"Rios","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1177\/2050640619868352","article-title":"Individualized risk prediction of significant fibrosis in non-alcoholic fatty liver disease using a novel nomogram","volume":"7","author":"Zhou","year":"2019","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s12967-015-0552-7","article-title":"Progression of non-alcoholic steatosis to steatohepatitis and fibrosis parallels cumulative accumulation of danger signals that promote inflammation and liver tumors in a high fat\u2013cholesterol\u2013sugar diet model in mice","volume":"13","author":"Ganz","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bucurica, S., Lupanciuc, M., Ionita-Radu, F., Stefan, I., Munteanu, A.E., Anghel, D., Jinga, M., and Gaman, E.L. (2023). Estrobolome and Hepatocellular Adenomas\u2014Connecting the Dots of the Gut Microbial \u03b2-Glucuronidase Pathway as a Metabolic Link. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216034"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1002\/hep.32324","article-title":"Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD","volume":"76","author":"Moore","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1016\/j.cmet.2022.09.020","article-title":"Leptin increases hepatic triglyceride export via a vagal mechanism in humans","volume":"34","author":"Metz","year":"2022","journal-title":"Cell Metab."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Li, X. (2024). Fibroblast Growth Factors, Elsevier.","DOI":"10.1016\/B978-0-443-15793-6.00001-9"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"601349","DOI":"10.3389\/fendo.2020.601349","article-title":"FGF19 and FGF21 for the Treatment of NASH\u2014Two Sides of the Same Coin? Differential and Overlapping Effects of FGF19 and FGF21 From Mice to Human","volume":"11","author":"Henriksson","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1194\/jlr.M027094","article-title":"Dual actions of fibroblast growth factor 19 on lipid metabolism","volume":"54","author":"Wu","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Tian, H., Zhang, S., Liu, Y., Wu, Y., and Zhang, D. (2023). Fibroblast Growth Factors for Nonalcoholic Fatty Liver Disease: Opportunities and Challenges. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054583"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3389\/fphys.2019.00419","article-title":"FGF21 as Modulator of Metabolism in Health and Disease","volume":"10","author":"Tezze","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"970292","DOI":"10.3389\/fphys.2022.970292","article-title":"The AMPK pathway in fatty liver disease","volume":"13","author":"Fang","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"248","DOI":"10.37349\/emed.2020.00017","article-title":"Role of acetylation in nonalcoholic fatty liver disease: A focus on SIRT1 and SIRT3","volume":"1","author":"Nassir","year":"2020","journal-title":"Explor. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.biochem.77.061307.091829","article-title":"Fat and Beyond: The Diverse Biology of PPAR\u03b3","volume":"77","author":"Tontonoz","year":"2008","journal-title":"Annu. Rev. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.biochi.2016.11.009","article-title":"PPARs and nonalcoholic fatty liver disease","volume":"136","author":"Liss","year":"2017","journal-title":"Biochimie"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.2147\/DMSO.S316096","article-title":"MAFLD Criteria May Overlook a Subtype of Patient with Steatohepatitis and Significant Fibrosis","volume":"14","author":"Huang","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1002\/hep.31843","article-title":"Saroglitazar, a PPAR-\u03b1\/\u03b3 Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial","volume":"74","author":"Gawrieh","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2309000","article-title":"A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis","volume":"390","author":"Harrison","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1016\/S0140-6736(19)32517-6","article-title":"Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: A multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"394","author":"Harrison","year":"2019","journal-title":"Lancet"},{"key":"ref_61","first-page":"60","article-title":"Resmetirom: An Orally Administered, Small-molecule, Liver-directed, \u03b2-selective THR Agonist for the Treatment of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis","volume":"19","author":"Karim","year":"2023","journal-title":"Eur. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/apt.17734","article-title":"Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis","volume":"59","author":"Harrison","year":"2023","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/s41591-021-01425-3","article-title":"Efruxifermin in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled, phase 2a trial","volume":"27","author":"Harrison","year":"2021","journal-title":"Nat. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"100661","DOI":"10.1016\/j.jhepr.2022.100661","article-title":"Effect of pegbelfermin on NASH and fibrosis-related biomarkers and correlation with histological response in the FALCON 1 trial","volume":"5","author":"Brown","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1002\/hep.31108","article-title":"Cenicriviroc Treatment for Adults with Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study","volume":"72","author":"Ratziu","year":"2020","journal-title":"Hepatology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"105922","DOI":"10.1016\/j.cct.2019.105922","article-title":"Cenicriviroc for the treatment of liver fibrosis in adults with nonalcoholic steatohepatitis: AURORA Phase 3 study design","volume":"89","author":"Anstee","year":"2019","journal-title":"Contemp. Clin. Trials"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/hep.29514","article-title":"The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial","volume":"67","author":"Loomba","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5503","DOI":"10.1038\/s41467-021-25701-5","article-title":"A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes","volume":"12","author":"Harrison","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Yan, H.-M., Xia, M.-F., Wang, Y., Chang, X.-X., Yao, X.-Z., Rao, S.-X., Zeng, M.-S., Tu, Y.-F., Feng, R., and Jia, W.-P. (2015). Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134172"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1177\/09564624231196600","article-title":"Pilot study on the efficacy and safety of berberine in people with metabolic syndrome and human immunodeficiency virus infection","volume":"34","year":"2023","journal-title":"Int. J. STD AIDS"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s12967-016-0982-x","article-title":"Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease","volume":"14","author":"Chang","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1080\/00325481.2022.2063568","article-title":"Effect of berberine and bicyclol on Chinese patients with nonalcoholic fatty liver disease: A retrospective study","volume":"134","author":"Geng","year":"2022","journal-title":"Postgrad. Med."},{"key":"ref_73","first-page":"294","article-title":"The Effect of Berberine on Lipid Profile, Liver Enzymes, and Fasting Blood Glucose in Patients with Non-alcoholic Fatty Liver Disease (NAFLD): A Randomized Controlled Trial","volume":"36","author":"Nejati","year":"2022","journal-title":"Med. J. Islam. Repub. Iran"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Yan, H., Wu, W., Chang, X., Xia, M., Ma, S., Wang, L., and Gao, J. (2021). Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism. Biol. Sex Differ., 12.","DOI":"10.1186\/s13293-020-00344-1"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Cossiga, V., Lembo, V., Guarino, M., Tuccillo, C., Morando, F., Pontillo, G., Fiorentino, A., Caporaso, N., and Morisco, F. (2019). Berberis aristata, Elaeis guineensis and Coffea canephora Extracts Modulate the Insulin Receptor Expression and Improve Hepatic Steatosis in NAFLD Patients: A Pilot Clinical Trial. Nutrients, 11.","DOI":"10.3390\/nu11123070"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/s41419-019-1706-y","article-title":"Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans","volume":"10","author":"Wu","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kohli, K., Mujtaba, A., Malik, R., Amin, S., Alam, S., Ali, A., Barkat, A., and Ansari, M.J. (2021). Development of Natural Polysaccharide\u2013Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment. Polymers, 13.","DOI":"10.3390\/polym13213833"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1124\/dmd.106.011361","article-title":"Pharmacokinetics of Berberine and Its Main Metabolites in Conventional and Pseudo Germ-Free Rats Determined by Liquid Chromatography\/Ion Trap Mass Spectrometry","volume":"34","author":"Zuo","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Majidzadeh, H., Araj-Khodaei, M., Ghaffari, M., Torbati, M., Dolatabadi, J.E.N., and Hamblin, M.R. (2020). Nano-based delivery systems for berberine: A modern anti-cancer herbal medicine. Colloids Surf. B Biointerfaces, 194.","DOI":"10.1016\/j.colsurfb.2020.111188"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"884","DOI":"10.7150\/thno.18219","article-title":"Edaravone-Encapsulated Agonistic Micelles Rescue Ischemic Brain Tissue by Tuning Blood-Brain Barrier Permeability","volume":"7","author":"Jin","year":"2017","journal-title":"Theranostics"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Azadi, R., Mousavi, S.E., Kazemi, N.M., Yousefi-Manesh, H., Rezayat, S.M., and Jaafari, M.R. (2021). Anti-inflammatory efficacy of Berberine Nanomicelle for improvement of cerebral ischemia: Formulation, characterization and evaluation in bilateral common carotid artery occlusion rat model. BMC Pharmacol. Toxicol., 22.","DOI":"10.1186\/s40360-021-00525-7"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s40199-020-00335-y","article-title":"Fabrication, characterization and optimization of berberine-loaded PLA nanoparticles using coaxial electrospray for sustained drug release","volume":"28","author":"Ghaffarzadegan","year":"2020","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.2174\/1389201024666230112141330","article-title":"Nanocarrier Based Delivery of Berberine: A Critical Review on Pharmaceutical and Preclinical Characteristics of the Bioactive","volume":"24","author":"Hafeez","year":"2023","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.21873\/invivo.13308","article-title":"Comparing the Influences of Metformin and Berberine on the Intestinal Microbiota of Rats With Nonalcoholic Steatohepatitis","volume":"37","author":"Chen","year":"2023","journal-title":"In Vivo"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Dai, Y., Zhu, W., Zhou, J., and Shen, T. (2022). The combination of berberine and evodiamine ameliorates high-fat diet-induced non-alcoholic fatty liver disease associated with modulation of gut microbiota in rats. Braz. J. Med. Biol. Res., 55.","DOI":"10.1590\/1414-431x2022e12096"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Wang, Y., Tai, Y.-L., Zhao, D., Zhang, Y., Yan, J., Kakiyama, G., Wang, X., Gurley, E.C., Liu, J., and Liu, J. (2021). Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways. Cells, 10.","DOI":"10.3390\/cells10020210"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"750826","DOI":"10.3389\/fphar.2021.750826","article-title":"Berberine Alleviates Non-alcoholic Steatohepatitis Through Modulating Gut Microbiota Mediated Intestinal FXR Activation","volume":"12","author":"Shu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_88","first-page":"451","article-title":"The therapeutic effects of berberine plus sitagliptin in a rat model of fatty liver disease","volume":"24","author":"Mehrdoost","year":"2021","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"153550","DOI":"10.1016\/j.phymed.2021.153550","article-title":"Therapeutic effect of oxyberberine on obese non-alcoholic fatty liver disease rats","volume":"85","author":"Li","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Cossiga, V., Lembo, V., Nigro, C., Mirra, P., Miele, C., D\u2019argenio, V., Leone, A., Mazzone, G., Veneruso, I., and Guido, M. (2021). The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice. Nutrients, 13.","DOI":"10.3390\/nu13041281"},{"key":"ref_91","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":"2021","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00210-020-01914-1","article-title":"Berberine attenuates non-alcoholic steatohepatitis by regulating chemerin\/CMKLR1 signalling pathway and Treg\/Th17 ratio","volume":"394","author":"Lu","year":"2020","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.7150\/ijbs.54604","article-title":"Berberine alleviates lipid metabolism disorders via inhibition of mitochondrial complex I in gut and liver","volume":"17","author":"Yu","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.3892\/etm.2021.10543","article-title":"Berberine ameliorates nonalcoholic fatty liver disease by decreasing the liver lipid content via reversing the abnormal expression of MTTP and LDLR","volume":"22","author":"Chen","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Lu, Z., He, B., Chen, Z., Yan, M., and Wu, L. (2020). Anti-inflammatory activity of berberine in non-alcoholic fatty liver disease via the Angptl2 pathway. BMC Immunol., 21.","DOI":"10.1186\/s12865-020-00358-9"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1016\/j.jksus.2020.03.019","article-title":"Berberine ameliorates intestinal mucosal barrier dysfunction in nonalcoholic fatty liver disease (NAFLD) rats","volume":"32","author":"Wang","year":"2020","journal-title":"J. King Saud Univ.-Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11596-019-1997-3","article-title":"Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats via Activation of SIRT3\/AMPK\/ACC Pathway","volume":"39","author":"Zhang","year":"2019","journal-title":"Curr. Med. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"7289","DOI":"10.1096\/fj.201802316R","article-title":"Berberine alleviates nonalcoholic fatty liver induced by a high-fat diet in mice by activating SIRT3","volume":"33","author":"Xu","year":"2019","journal-title":"FASEB J."},{"key":"ref_99","first-page":"2668","article-title":"Berberine prevents non-alcoholic steatohepatitis-derived hepatocellular carcinoma by inhibiting inflammation and angiogenesis in mice","volume":"11","author":"Luo","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_100","first-page":"2091","article-title":"Berberine attenuates hepatic oxidative stress in rats with non-alcoholic fatty liver disease via the Nrf2\/ARE signalling pathway","volume":"17","author":"Deng","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_101","first-page":"4635","article-title":"Inhibition of CCL19 benefits non-alcoholic fatty liver disease by inhibiting TLR4\/NF-\u03baB-p65 signaling","volume":"18","author":"Zhao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.biopha.2018.01.071","article-title":"Natural products berberine and curcumin exhibited better ameliorative effects on rats with non-alcohol fatty liver disease than lovastatin","volume":"99","author":"Feng","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Zhao, L., Cang, Z., Sun, H., Nie, X., Wang, N., and Lu, Y. (2017). Berberine improves glucogenesis and lipid metabolism in nonalcoholic fatty liver disease. BMC Endocr. Disord., 17.","DOI":"10.1186\/s12902-017-0165-7"},{"key":"ref_104","first-page":"4134","article-title":"Berberine ameliorates non-alcoholic steatohepatitis in ApoE-\/- mice","volume":"14","author":"Yang","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3892\/etm.2015.2846","article-title":"Effects of a combination of puerarin, baicalin and berberine on the expression of proliferator-activated receptor-\u03b3 and insulin receptor in a rat model of nonalcoholic fatty liver disease","volume":"11","author":"Zhao","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_106","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":"Arch. Iran. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.2147\/IJN.S84565","article-title":"Berberine-loaded solid lipid nanoparticles are concentrated in the liver and ameliorate hepatosteatosis in db\/db mice","volume":"10","author":"Xue","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12944-015-0087-1","article-title":"Effect of a high fat, high sucrose diet on the promotion of non-alcoholic fatty liver disease in male rats: The ameliorative role of three natural compounds","volume":"14","author":"Ragab","year":"2015","journal-title":"Lipids Health Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"S429","DOI":"10.12980\/APJTB.4.2014C474","article-title":"Metabolic effects of berberine on liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: An additional mechanism for the hypolipidemic effects of berberine","volume":"4","author":"Heidarian","year":"2014","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.mito.2013.09.002","article-title":"Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: A possible role for SirT3 activation","volume":"13","author":"Teodoro","year":"2013","journal-title":"Mitochondrion"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11655-011-0668-4","article-title":"Effect of berberine on expressions of uncoupling protein-2 mRNA and protein in hepatic tissue of non-alcoholic fatty liver disease in rats","volume":"17","author":"Yang","year":"2011","journal-title":"Chin. J. Integr. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.ejphar.2011.07.036","article-title":"Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver","volume":"668","author":"Xing","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1194\/jlr.M001958","article-title":"Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats","volume":"51","author":"Chang","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"117238","DOI":"10.1016\/j.jep.2023.117238","article-title":"Berberine-silybin salt achieves improved anti-nonalcoholic fatty liver disease effect through regulating lipid metabolism","volume":"319","author":"Ma","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Ye, C., Zhang, Y., Lin, S., Chen, Y., Wang, Z., Feng, H., Fang, G., and Quan, S. (2023). Berberine Ameliorates Metabolic-Associated Fatty Liver Disease Mediated Metabolism Disorder and Redox Homeostasis by Upregulating Clock Genes: Clock and Bmal1 Expressions. Molecules, 28.","DOI":"10.3390\/molecules28041874"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Guo, H.-H., Shen, H.-R., Wang, L.-L., Luo, Z.-G., Zhang, J.-L., Zhang, H.-J., Gao, T.-L., Han, Y.-X., and Jiang, J.-D. (2023). Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases. Biomed. Pharmacother., 163.","DOI":"10.1016\/j.biopha.2023.114754"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"121595","DOI":"10.1016\/j.lfs.2023.121595","article-title":"LCN2 contributes to the improvement of nonalcoholic steatohepatitis by 8-Cetylberberine","volume":"321","author":"He","year":"2023","journal-title":"Life Sci."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Zhou, L.-M., Fan, J.-H., Xu, M.-M., Xiong, M.-Y., Wang, Q.-J., Chai, X., Li, X.-D., Li, X.-G., and Ye, X.-L. (2023). Epiberberine regulates lipid synthesis through SHP (NR0B2) to improve non-alcoholic steatohepatitis. Biochim. Biophys. Acta (BBA)-Mol. Basis Dis., 1869.","DOI":"10.1016\/j.bbadis.2023.166639"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"goad032","DOI":"10.1093\/gastro\/goad032","article-title":"Berberine alleviates non-alcoholic hepatic steatosis partially by promoting SIRT1 deacetylation of CPT1A in mice","volume":"11","author":"Wang","year":"2022","journal-title":"Gastroenterol. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Chen, Y., Jiang, Z., Xu, J., Zhang, J., Sun, R., Zhou, J., Lu, Y., Gong, Z., Huang, J., and Shen, X. (2021). Improving the ameliorative effects of berberine and curcumin combination via dextran-coated bilosomes on non-alcohol fatty liver disease in mice. J. Nanobiotechnology, 19.","DOI":"10.1186\/s12951-021-00979-1"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"913378","DOI":"10.3389\/fphar.2022.913378","article-title":"Berberrubine, a Main Metabolite of Berberine, Alleviates Non-Alcoholic Fatty Liver Disease via Modulating Glucose and Lipid Metabolism and Restoring Gut Microbiota","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"843872","DOI":"10.3389\/fphar.2022.843872","article-title":"Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease","volume":"13","author":"Li","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"552","DOI":"10.21037\/atm-22-1753","article-title":"Methyltransferase SETD2 mediates hepatoprotection of berberine against steatosis","volume":"10","author":"Dai","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"119778","DOI":"10.1016\/j.lfs.2021.119778","article-title":"Demethylenetetrahydroberberine alleviates nonalcoholic fatty liver disease by inhibiting the NLRP3 inflammasome and oxidative stress in mice","volume":"281","author":"Zhang","year":"2021","journal-title":"Life Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.21037\/atm-20-8106","article-title":"Berberine attenuates atherosclerotic lesions and hepatic steatosis in ApoE-\/- mice by down-regulating PCSK9 via ERK1\/2 pathway","volume":"9","author":"Ma","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3389\/fphar.2020.00185","article-title":"Berberine Inhibits Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation and Pyroptosis in Nonalcoholic Steatohepatitis via the ROS\/TXNIP Axis","volume":"11","author":"Mai","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.freeradbiomed.2019.06.019","article-title":"Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway","volume":"141","author":"Zhu","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/bph.14079","article-title":"Berberine attenuates hepatic steatosis and enhances energy expenditure in mice by inducing autophagy and fibroblast growth factor 21","volume":"175","author":"Sun","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.bbrc.2018.03.003","article-title":"Berberine alleviates hepatic lipid accumulation by increasing ABCA1 through the protein kinase C \u03b4 pathway","volume":"498","author":"Liang","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_130","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_131","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.taap.2016.12.019","article-title":"Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice","volume":"316","author":"Choi","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_132","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_133","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.bbrc.2016.03.019","article-title":"Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress","volume":"472","author":"Qiang","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1530\/JME-16-0139e","article-title":"ERK-dependent mTOR pathway is involved in berberine-induced autophagy in hepatic steatosis","volume":"59","author":"He","year":"2017","journal-title":"J. Mol. Endocrinol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"22612","DOI":"10.1038\/srep22612","article-title":"Berberine Ameliorates Hepatic Steatosis and Suppresses Liver and Adipose Tissue Inflammation in Mice with Diet-induced Obesity","volume":"6","author":"Guo","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_136","first-page":"7535","article-title":"Berberine reverses abnormal expression of L-type pyruvate kinase by DNA demethylation and histone acetylation in the livers of the non-alcoholic fatty disease rat","volume":"8","author":"Zhang","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12967-015-0383-6","article-title":"Berberine ameliorates nonalcoholic fatty liver disease by a global modulation of hepatic mRNA and lncRNA expression profiles","volume":"13","author":"Yuan","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1234300","DOI":"10.3389\/fphar.2023.1234300","article-title":"Development of a novel human triculture model of non-alcoholic fatty liver disease and identification of berberine as ameliorating steatosis, oxidative stress and fibrosis","volume":"14","author":"Rafiei","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.joim.2021.09.003","article-title":"Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis","volume":"19","author":"Shan","year":"2021","journal-title":"J. Integr. Med."},{"key":"ref_140","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_141","doi-asserted-by":"crossref","first-page":"173244","DOI":"10.1016\/j.ejphar.2020.173244","article-title":"Berbamine induced AMPK activation regulates mTOR\/SREBP-1c axis and Nrf2\/ARE pathway to allay lipid accumulation and oxidative stress in steatotic HepG2 cells","volume":"882","author":"Sharma","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_142","first-page":"1921","article-title":"In-vitro Synergistic Effect of Metformin and Berberine on High Glucose-induced Lipogenesis","volume":"18","author":"Khorzoughi","year":"2019","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Rafiei, H., Omidian, K., and Bandy, B. (2019). Dietary Polyphenols Protect Against Oleic Acid-Induced Steatosis in an in Vitro Model of NAFLD by Modulating Lipid Metabolism and Improving Mitochondrial Function. Nutrients, 11.","DOI":"10.3390\/nu11030541"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1600781","DOI":"10.1002\/mnfr.201600781","article-title":"Comparison of dietary polyphenols for protection against molecular mechanisms underlying nonalcoholic fatty liver disease in a cell model of steatosis","volume":"61","author":"Rafiei","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_145","first-page":"16360","article-title":"Effect of berberine on a cellular model of non-alcoholic fatty liver disease","volume":"10","author":"Liu","year":"2017","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1194\/jlr.M600020-JLR200","article-title":"Inhibition of lipid synthesis through activation of AMP kinase: An additional mechanism for the hypolipidemic effects of berberine","volume":"47","author":"Brusq","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_147","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_148","doi-asserted-by":"crossref","first-page":"706","DOI":"10.4274\/tjps.galenos.2021.73554","article-title":"Emerging Role of Biopharmaceutical Classification and Biopharmaceutical Drug Disposition System in Dosage form Development: A Systematic Review","volume":"19","author":"Samineni","year":"2022","journal-title":"Turk. J. Pharm. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/hep.29724","article-title":"Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"68","author":"Younossi","year":"2018","journal-title":"Hepatology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000100426","article-title":"SREBP-1c Transcription Factor and Lipid Homeostasis: Clinical Perspective","volume":"68","author":"Foufelle","year":"2007","journal-title":"Horm. Res. Paediatr."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Fang, J., Yu, C.-H., Li, X.-J., Yao, J.-M., Fang, Z.-Y., Yoon, S.-H., and Yu, W.-Y. (2022). Gut dysbiosis in nonalcoholic fatty liver disease: Pathogenesis, diagnosis, and therapeutic implications. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.997018"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"982145","DOI":"10.3389\/fendo.2022.982145","article-title":"Research progress on the pharmacological effects of berberine targeting mitochondria","volume":"13","author":"Fang","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_153","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_154","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nri3452","article-title":"Activation and regulation of the inflammasomes","volume":"13","author":"Latz","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/j.bbadis.2017.04.009","article-title":"EGCG ameliorates diet-induced metabolic syndrome associating with the circadian clock","volume":"1863","author":"Mi","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1053\/j.gastro.2020.01.050","article-title":"Circadian Rhythms in the Pathogenesis and Treatment of Fatty Liver Disease","volume":"158","author":"Saran","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Choi, H.M., Doss, H.M., and Kim, K.S. (2020). Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041219"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Sasaki, Y., Ohta, M., Desai, D., Figueiredo, J.-L., Whelan, M.C., Sugano, T., Yamabi, M., Yano, W., Faits, T., and Yabusaki, K. (2015). Angiopoietin Like Protein 2 (ANGPTL2) Promotes Adipose Tissue Macrophage and T lymphocyte Accumulation and Leads to Insulin Resistance. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131176"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s13410-022-01058-3","article-title":"Lipocalin-2 levels increase in plasma of non-alcoholic fatty liver disease patients with metabolic syndrome","volume":"43","author":"Chawla","year":"2022","journal-title":"Int. J. Diabetes Dev. Ctries."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4201\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:25:52Z","timestamp":1760106352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,10]]},"references-count":159,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084201"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084201","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,10]]}}}