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The activation of PPARG plays a critical role in modulating macrophage polarization and lipid metabolism, suggesting its potential as a therapeutic target for MASLD. Methods: We used UPLC-Q\/TOF-MS and network pharmacology to investigate the key components and targets of Swertia davidi Franch, focusing on Swertianin. In vitro experiments on macrophages were conducted to assess the modulation of M1 polarization, and a mouse model of MASLD was utilized to explore the therapeutic effects of Swertianin. Results: Swertianin activated PPARG, leading to significant inhibition of M1 macrophage polarization, a reduction in lipid accumulation, and decreased inflammatory marker levels both in vitro and in vivo. The treatment significantly improved liver pathology in mice, indicating its therapeutic potential for MASLD. Conclusions: Swertianin\u2019s activation of PPARG provides a novel mechanism for treating MASLD, targeting both macrophage polarization and inflammation.<\/jats:p>","DOI":"10.3390\/genes16060693","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T11:08:31Z","timestamp":1749208111000},"page":"693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Swertianin Suppresses M1 Macrophage Polarization and Inflammation in Metabolic Dysfunction-Associated Fatty Liver Disease via PPARG Activation"],"prefix":"10.3390","volume":"16","author":[{"given":"Jing","family":"Xia","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China"},{"name":"Department of Basic Medical Sciences, Chongqing Three Gorges Medical College, Chongqing 404120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China"},{"name":"Department of Basic Medical Sciences, Chongqing Three Gorges Medical College, Chongqing 404120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Yang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China"},{"name":"College of Pharmacy, Chongqing Three Gorges Medical College, Chongqing 404120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tan","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China"},{"name":"College of Clinical Medicine, Chongqing Three Gorges Medical College, Chongqing 404120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China"},{"name":"College of Pharmacy, Chongqing Three Gorges Medical College, Chongqing 404120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8797-1413","authenticated-orcid":false,"given":"Wenxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China"},{"name":"College of Pharmacy, Chongqing Three Gorges Medical College, Chongqing 404120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-Alcoholic Fatty Liver Disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","unstructured":"Rong, L., Zou, J., Ran, W., Qi, X., Chen, Y., Cui, H., and Guo, J. (2023). Advancements in the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD). Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1087260"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2174\/0115734021268893231116045914","article-title":"Cardiovascular Risk Related to Glomerular Hyperfiltration in Nondiabetic: Increasing Visibility Is Crucial","volume":"19","author":"Valtuille","year":"2023","journal-title":"Curr. Hypertens. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.cmet.2023.01.006","article-title":"The Role of Hepatokines in NAFLD","volume":"35","author":"Stefan","year":"2023","journal-title":"Cell Metab."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Xu, R., Pan, J., Zhou, W., Ji, G., and Dang, Y. (2022). Recent Advances in Lean NAFLD. Biomed. Pharmacother., 153.","DOI":"10.1016\/j.biopha.2022.113331"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e1529","DOI":"10.1002\/ctm2.1529","article-title":"DEAD-Box Helicase 17 Exacerbates Non-alcoholic Steatohepatitis via Transcriptional Repression of Cyp2c29, Inducing Hepatic Lipid Metabolism Disorder and Eliciting the Activation of M1 Macrophages","volume":"14","author":"Ning","year":"2024","journal-title":"Clin. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e17116","DOI":"10.1016\/j.heliyon.2023.e17116","article-title":"Exploring the Potential of Treating Chronic Liver Disease Targeting the PI3K\/Akt Pathway and Polarization Mechanism of Macrophages","volume":"9","author":"Yang","year":"2023","journal-title":"Heliyon"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.eprac.2022.03.010","article-title":"American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings","volume":"28","author":"Cusi","year":"2022","journal-title":"Endocr. Pract."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/s41574-021-00507-z","article-title":"Emerging Therapeutic Approaches for the Treatment of NAFLD and Type 2 Diabetes Mellitus","volume":"17","author":"Ferguson","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.jhep.2021.09.007","article-title":"NAFLD-Driven HCC: Safety and Efficacy of Current and Emerging Treatment Options","volume":"76","author":"Foerster","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41392-022-01119-3","article-title":"Targeted Therapeutics and Novel Signaling Pathways in Non-Alcohol-Associated Fatty Liver\/Steatohepatitis (NAFL\/NASH)","volume":"7","author":"Xu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1093\/cvr\/cvad095","article-title":"Non-Alcoholic Fatty Liver Disease: Pathophysiological Concepts and Treatment Options","volume":"119","author":"Grander","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vancells Lujan, P., Vi\u00f1as Esmel, E., and Sacanella Meseguer, E. (2021). Overview of Non-Alcoholic Fatty Liver Disease (NAFLD) and the Role of Sugary Food Consumption and Other Dietary Components in Its Development. Nutrients, 13.","DOI":"10.3390\/nu13051442"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5681","DOI":"10.7150\/ijbs.65044","article-title":"Mouse Models of Nonalcoholic Fatty Liver Disease (NAFLD): Pathomechanisms and Pharmacotherapies","volume":"18","author":"Fang","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.2147\/DDDT.S315724","article-title":"Non-Alcoholic Steatohepatitis (NASH)\u2014A Review of a Crowded Clinical Landscape, Driven by a Complex Disease","volume":"15","author":"Fraile","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_17","unstructured":"Su, Z.Z., He, Y.Y., and Chen, G. (1993). Clinical and Experimental Study on Effects of Man-Shen-Ling Oral Liquid in the Treatment of 100 Cases of Chronic Nephritis. Zhongguo Zhong Xi Yi Jie He Za Zhi., 13."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kumar, V., and Van Staden, J. (2016). A Review of Swertia Chirayita (Gentianaceae) as a Traditional Medicinal Plant. Front. Pharmacol., 6.","DOI":"10.3389\/fphar.2015.00308"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.tips.2023.11.004","article-title":"PPAR Agonists for the Treatment of Neuroinflammatory Diseases","volume":"45","author":"Titus","year":"2024","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tahri-Joutey, M., Andreoletti, P., Surapureddi, S., Nasser, B., Cherkaoui-Malki, M., and Latruffe, N. (2021). Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid \u03b2-Oxidation by PPAR\u03b1. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168969"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"156043","DOI":"10.1016\/j.metabol.2024.156043","article-title":"Comparative Efficacy of THR-\u03b2 Agonists, FGF-21 Analogues, GLP-1R Agonists, GLP-1-Based Polyagonists, and Pan-PPAR Agonists for MASLD: A Systematic Review and Network Meta-Analysis","volume":"161","author":"Lin","year":"2024","journal-title":"Metabolism"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1021\/acs.jmedchem.4c02803","article-title":"Identification of Novel Organo-Se BTSA-Based Derivatives as Potent, Reversible, and Selective PPAR\u03b3 Covalent Modulators for Antidiabetic Drug Discovery","volume":"68","author":"Chen","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e002548","DOI":"10.1136\/jitc-2021-002548","article-title":"S100A4 Enhances Protumor Macrophage Polarization by Control of PPAR-\u03b3-Dependent Induction of Fatty Acid Oxidation","volume":"9","author":"Liu","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"118011","DOI":"10.1016\/j.jep.2024.118011","article-title":"Rujifang Inhibits Triple-Negative Breast Cancer Growth via the PI3K\/AKT Pathway","volume":"327","author":"Jia","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155073","DOI":"10.1016\/j.phymed.2023.155073","article-title":"Network Pharmacology Analysis and Animal Experiment Validation of Neuroinflammation Inhibition by Total Ginsenoside in Treating CSM","volume":"126","author":"Li","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Miao, Z., Wang, W., Miao, Z., Cao, Q., and Xu, S. (2024). Role of Selenoprotein W in Participating in the Progression of Non-Alcoholic Fatty Liver Disease. Redox Biol., 71.","DOI":"10.1016\/j.redox.2024.103114"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, H., Cheng, W., Hu, P., Ling, T., Hu, C., Chen, Y., Zheng, Y., Wang, J., Zhao, T., and You, Q. (2024). Integrative Analysis Identifies Oxidative Stress Biomarkers in Non-Alcoholic Fatty Liver Disease via Machine Learning and Weighted Gene Co-Expression Network Analysis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1335112"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.biopha.2018.09.067","article-title":"PMA Treated THP-1-Derived-IL-6 Promotes EMT of SW48 through STAT3\/ERK-Dependent Activation of Wnt\/\u03b2-Catenin Signaling Pathway","volume":"108","author":"Gao","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tedesco, S., De Majo, F., Kim, J., Trenti, A., Trevisi, L., Fadini, G.P., Bolego, C., Zandstra, P.W., Cignarella, A., and Vitiello, L. (2018). Convenience versus Biological Significance: Are PMA-Differentiated THP-1 Cells a Reliable Substitute for Blood-Derived Macrophages When Studying in Vitro Polarization?. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00071"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ye, J., Coulouris, G., Zaretskaya, I., Cutcutache, I., Rozen, S., and Madden, T.L. (2012). Primer-BLAST: A Tool to Design Target-Specific Primers for Polymerase Chain Reaction. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-134"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14791","DOI":"10.18632\/aging.205301","article-title":"IGFBPL1 Inhibits Macrophage Lipid Accumulation by Enhancing the Activation of IGR1R\/LXR\u03b1\/ABCG1 Pathway","volume":"15","author":"Hou","year":"2023","journal-title":"Aging"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Liu, L., Guo, H., Song, A., Huang, J., Zhang, Y., Jin, S., Li, S., Zhang, L., Yang, C., and Yang, P. (2020). Progranulin Inhibits LPS-Induced Macrophage M1 Polarization via NF-KB and MAPK Pathways. BMC Immunol., 21.","DOI":"10.1186\/s12865-020-00355-y"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"473","DOI":"10.21037\/atm.2019.07.103","article-title":"The Pathways and Mechanisms of Muramyl Dipeptide Transcellular Transport Mediated by PepT1 in Enterogenous Infection","volume":"7","author":"Ma","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1161\/ATVBAHA.117.309114","article-title":"Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits","volume":"37","author":"Zhang","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Flessa, C.-M., Nasiri-Ansari, N., Kyrou, I., Leca, B.M., Lianou, M., Chatzigeorgiou, A., Kaltsas, G., Kassi, E., and Randeva, H.S. (2022). Genetic and Diet-Induced Animal Models for Non-Alcoholic Fatty Liver Disease (NAFLD) Research. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415791"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1080\/13880209.2022.2127153","article-title":"Swertia Mussotii Prevents High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats by Inhibiting Expression the TLR4\/MyD88 and the Phosphorylation of NF-\u039aB","volume":"60","author":"Si","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/hep.24127","article-title":"Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score and the Histopathologic Diagnosis in NAFLD: Distinct Clinicopathologic Meanings \u00a7\u0394","volume":"53","author":"Brunt","year":"2011","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1080\/13880209.2023.2292256","article-title":"Nicotinamide Mononucleotide Alleviates Endotoxin-Induced Acute Lung Injury by Modulating Macrophage Polarization via the SIRT1\/NF-\u039aB Pathway","volume":"62","author":"He","year":"2023","journal-title":"Pharm. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13073-020-00773-y","article-title":"FOXC1-Mediated LINC00301 Facilitates Tumor Progression and Triggers an Immune-Suppressing Microenvironment in Non-Small Cell Lung Cancer by Regulating the HIF1\u03b1 Pathway","volume":"12","author":"Sun","year":"2020","journal-title":"Genome Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1158\/0008-5472.CAN-17-1636","article-title":"MUC1-C Induces PD-L1 and Immune Evasion in Triple-Negative Breast Cancer","volume":"78","author":"Maeda","year":"2018","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e000826","DOI":"10.1136\/jitc-2020-000826","article-title":"Combination of Radiotherapy and Suppression of Tregs Enhances Abscopal Antitumor Effect and Inhibits Metastasis in Rectal Cancer","volume":"8","author":"Ji","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1080\/14786419.2011.592836","article-title":"Activity-Guided Isolation of Antioxidant Xanthones from Swertia Chirayita (Roxb.) H. Karsten (Gentianaceae)","volume":"26","author":"Singh","year":"2011","journal-title":"Nat. Prod. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"113182","DOI":"10.1016\/j.intimp.2024.113182","article-title":"Swertianin Promotes Anti-Tumor Activity by Facilitating Macrophage M1 Polarization via STING Signaling","volume":"142","author":"Cao","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, L., Jiang, Y., Yu, Q., Xiao, C., Sun, J., Weng, L., and Qiu, Y. (2023). Gentiopicroside Improves High-Fat Diet-Induced NAFLD in Association with Modulation of Host Serum Metabolome and Gut Microbiome in Mice. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1145430"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.biopha.2017.10.022","article-title":"Mangiferin Ameliorates Fatty Liver via Modulation of Autophagy and Inflammation in High-Fat-Diet Induced Mice","volume":"96","author":"Wang","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1053\/j.gastro.2016.09.017","article-title":"Estrogen Signals Through Peroxisome Proliferator-Activated Receptor\u2212\u03b3 Coactivator 1\u03b1 to Reduce Oxidative Damage Associated With Diet-Induced Fatty Liver Disease","volume":"152","author":"Oropeza","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1080\/15548627.2020.1834711","article-title":"TXNIP\/VDUP1 Attenuates Steatohepatitis via Autophagy and Fatty Acid Oxidation","volume":"17","author":"Park","year":"2020","journal-title":"Autophagy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/s41588-022-01078-z","article-title":"A Multiancestry Genome-Wide Association Study of Unexplained Chronic ALT Elevation as a Proxy for Nonalcoholic Fatty Liver Disease with Histological and Radiological Validation","volume":"54","author":"Vujkovic","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, C., Ma, C., Gong, L., Guo, Y., Fu, K., Zhang, Y., Zhou, H., and Li, Y. (2021). Macrophage Polarization and Its Role in Liver Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.803037"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.7150\/ijbs.73890","article-title":"Covalent Inhibition of Pyruvate Kinase M2 Reprograms Metabolic and Inflammatory Pathways in Hepatic Macrophages against Non-Alcoholic Fatty Liver Disease","volume":"18","author":"Fan","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dong, X.C. (2023). Sirtuin 6\u2014A Key Regulator of Hepatic Lipid Metabolism and Liver Health. Cells, 12.","DOI":"10.3390\/cells12040663"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"K\u00f6k\u00e9ny, G., Calvier, L., and Hansmann, G. (2021). PPAR\u03b3 and TGF\u03b2\u2014Major Regulators of Metabolism, Inflammation, and Fibrosis in the Lungs and Kidneys. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910431"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"153048","DOI":"10.1016\/j.tox.2021.153048","article-title":"Resveratrol Protected Acrolein-Induced Ferroptosis and Insulin Secretion Dysfunction via ER-Stress- Related PERK Pathway in MIN6 Cells","volume":"465","author":"Zhang","year":"2022","journal-title":"Toxicology"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"He, Y., Zhang, R., Yu, L., Zahr, T., Li, X., Kim, T.-W., and Qiang, L. (2023). PPAR\u03b3 Acetylation in Adipocytes Exacerbates BAT Whitening and Worsens Age-Associated Metabolic Dysfunction. Cells, 12.","DOI":"10.3390\/cells12101424"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"108391","DOI":"10.1016\/j.pharmthera.2023.108391","article-title":"PPAR-\u03b3 Signaling in Nonalcoholic Fatty Liver Disease: Pathogenesis and Therapeutic Targets","volume":"245","author":"Chen","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.bbrc.2019.04.144","article-title":"Hepatocellular INOS Protects Liver from NASH through Nrf2-Dependent Activation of HO-1","volume":"514","author":"Qiao","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"105796","DOI":"10.1016\/j.phrs.2021.105796","article-title":"Dioscin Ameliorates Murine Ulcerative Colitis by Regulating Macrophage Polarization","volume":"172","author":"Wu","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11882-021-01022-x","article-title":"The Role of PPAR-\u03b3 in Allergic Disease","volume":"21","author":"Stark","year":"2021","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/978-1-4939-7837-3_12","article-title":"Polarizing Macrophages In Vitro","volume":"1784","author":"Huang","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1016\/j.cellsig.2011.06.003","article-title":"INOS\/NO Signaling Regulates Apoptosis Induced by Glycochenodeoxycholate in Hepatocytes","volume":"23","author":"Wang","year":"2011","journal-title":"Cell Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.immuni.2019.08.017","article-title":"Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche","volume":"51","author":"Bonnardel","year":"2019","journal-title":"Immunity"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/6\/693\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:47:58Z","timestamp":1760032078000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/6\/693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":61,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["genes16060693"],"URL":"https:\/\/doi.org\/10.3390\/genes16060693","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,6]]}}}