{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:36:38Z","timestamp":1785436598869,"version":"3.56.0"},"reference-count":153,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82305009"],"award-info":[{"award-number":["82305009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82305009"],"award-info":[{"award-number":["82305009"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002767","name":"Department of Science and Technology of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ5225"],"award-info":[{"award-number":["2024JJ5225"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024JJ5225"],"award-info":[{"award-number":["2024JJ5225"]}],"id":[{"id":"https:\/\/ror.org\/04qgr7x96","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Metabolic syndrome (MetS) is a pressing global health challenge comprising obesity, hyperglycemia, hypertension, and hyperlipidemia. Conventional polypharmacy often presents long-term compliance issues and side effects. Eucommia ulmoides Oliv., a traditional medicinal and edible plant rich in iridoids, lignans, flavonoids, and polysaccharides, has emerged as a promising natural intervention. This review aims to systematically summarize the bioavailability and multifaceted pharmacological mechanisms of E. ulmoides and its bioactive components in alleviating MetS. Methods: We comprehensively reviewed the recent in vitro and in vivo literature to map the functional evidence, specific signaling pathways, and gut microbiota\u2013host interactions associated with E. ulmoides extracts and its key phytochemicals (e.g., asperuloside) against various metabolic dysfunctions. Results: Current evidence indicates that E. ulmoides operates through a \u201cmulti-component, multi-target, and multi-pathway\u201d paradigm. For hyperlipidemia and obesity, it activates hepatic lipid metabolism (PPAR\u03b1\/CPT1A, FXR\/CYP7A1) and mitigates oxidative stress (Nrf2\/ARE). Furthermore, it dose-dependently reshapes the gut microbiota by enriching beneficial bacteria like Akkermansia and increasing butyrate production, exerting profound gut\u2013liver axis regulation. It also ameliorates hypertension by activating the ACE2-Ang-(1\u20137)-Mas axis, improves insulin resistance via the AMPK\/PI3K\/Akt cascade, and manages hyperuricemia by modulating XOD and renal transporters. Notably, the low oral bioavailability of its glycosides highlights the crucial role of gut microbial hydrolysis in its efficacy. Conclusions: E. ulmoides holds substantial therapeutic potential as a multi-target natural supplement for MetS. However, future translational applications necessitate large-scale randomized clinical trials, multi-omics studies to further clarify host\u2013microbiome interactions, and the development of standardized formulations to ensure clinical efficacy.<\/jats:p>","DOI":"10.3390\/metabo16060411","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:59:47Z","timestamp":1781503187000},"page":"411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Targeted Intervention of Eucommia ulmoides and Its Bioactive Constituents Against Metabolic Syndrome: From Molecular Mechanisms and Gut Microbiota Modulation to Clinical Translation"],"prefix":"10.3390","volume":"16","author":[{"given":"Fanjia","family":"Cheng","sequence":"first","affiliation":[{"name":"Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-2720","authenticated-orcid":false,"given":"Chenghao","family":"Lv","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Liver Visceral Manifestation in Traditional Chinese Medicine, Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Yi","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Liver Visceral Manifestation in Traditional Chinese Medicine, Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Liver Visceral Manifestation in Traditional Chinese Medicine, Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan Institute of Agricultural Product Processing and Quality Safety, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9370-3592","authenticated-orcid":false,"given":"Runze","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qili","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan Institute of Agricultural Product Processing and Quality Safety, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-2099","authenticated-orcid":false,"given":"Si","family":"Qin","sequence":"additional","affiliation":[{"name":"Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1038\/s41433-025-03910-2","article-title":"Association between metabolic syndrome and cataract: A meta-analysis","volume":"39","author":"Liu","year":"2025","journal-title":"Eye"},{"key":"ref_2","first-page":"351","article-title":"Metabolic syndrome and possible treatments (consecutive therapies): A literature review","volume":"18","author":"Sorout","year":"2022","journal-title":"Int. J. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13479","DOI":"10.3892\/mmr.2025.13479","article-title":"Metabolic syndrome in patients with schizophrenia: Underlying mechanisms and therapeutic approaches (Review)","volume":"31","author":"Manta","year":"2025","journal-title":"Mol. Med. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, B., Shi, H., Cai, W., Yang, B., and Xiu, W. (2025). Metabolic syndrome in children and adolescents: Definitions, epidemiology, pathophysiology, interventions, and challenges. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1512642"},{"key":"ref_5","first-page":"91478","article-title":"Assessing the impact of concurrent high-fructose and high-saturated fat diets on pediatric metabolic syndrome: A review","volume":"13","year":"2024","journal-title":"World J. Clin. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Galv\u00e1n, B., Enriquez Del Castillo, L.A., Flores, L.A., Quintana-Mendias, E., Torres-Rojo, F.I., Villegas-Balderrama, C.V., and Cervantes-Hern\u00e1ndez, N. (2025). Effectiveness of Physical Exercise on Indicators of Metabolic Syndrome in Adults: A Systematic Review with Meta-Analysis of Clinical Trials. J. Funct. Morphol. Kinesiol., 10.","DOI":"10.3390\/jfmk10030244"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rondanelli, M., Borromeo, S., Cavioni, A., Gasparri, C., Gattone, I., Genovese, E., Lazzarotti, A., Minonne, L., Moroni, A., and Patelli, Z. (2025). Therapeutic Strategies to Modulate Gut Microbial Health: Approaches for Chronic Metabolic Disorder Management. Metabolites, 15.","DOI":"10.3390\/metabo15020127"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Xie, W., Xiao, Y., Xu, P., Zheng, H., Zeng, X., Wu, Y., Jiang, J., Jia, F., Yan, J., and Zheng, T. (2026). From Traditional Medicinal Plant to Modern Pharmacotherapy: A Comprehensive Review of the Bioactive Compounds and Health Applications of Eucommia ulmoides. Nutrients, 18.","DOI":"10.3390\/nu18020234"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"120555","DOI":"10.1016\/j.indcrop.2025.120555","article-title":"Analysis of global trade patterns and industrial layout in medicinal plants: A case study of Eucommia ulmoides oliver","volume":"225","author":"Luo","year":"2025","journal-title":"Ind. Crops Prod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104811","DOI":"10.1016\/j.yrtph.2020.104811","article-title":"Safety evaluation of Eucommia ulmoides extract","volume":"118","author":"Luo","year":"2020","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_11","first-page":"338","article-title":"A clinical trial testing the safety and efficacy of a standardized Eucommia ulmoides Oliver bark extract to treat hypertension","volume":"16","author":"Greenway","year":"2011","journal-title":"Altern. Med. Rev."},{"key":"ref_12","first-page":"263","article-title":"Pharmacokinetic study about compatibility of Eucommia ulmoides and Psoralea corylifolia","volume":"15","author":"Huang","year":"2023","journal-title":"Chin. Herb. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Shi, P., Zhang, M., Qian, C., Lin, L., Liu, Q., Xue, J., and Liang, S. (2025). Effects of Sweating and Drying Processes on Chemical Components, Antioxidant Activity, and Anti-Acute Liver Injury Mechanisms of Eucommia ulmoides Based on the Spectrum\u2013Effect Relationship. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178686"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105667","DOI":"10.1016\/j.fitote.2023.105667","article-title":"Pharmacokinetics, anti-rheumatoid arthritis activity, and active ingredient contents of Eucommia ulmoides Oliv","volume":"170","author":"Yang","year":"2023","journal-title":"Fitoterapia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e24851","DOI":"10.1016\/j.heliyon.2024.e24851","article-title":"A review of \u201cplant gold\u201d Eucommia ulmoides Oliv.: A medicinal and food homologous plant with economic value and prospect","volume":"10","author":"Bao","year":"2024","journal-title":"Heliyon"},{"key":"ref_16","first-page":"1","article-title":"Metabolic syndrome: A closer look at the growing epidemic and its associated pathologies","volume":"16","year":"2015","journal-title":"Obes. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.cell.2012.02.017","article-title":"Mechanisms for insulin resistance: Common threads and missing links","volume":"148","author":"Samuel","year":"2012","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrm1837","article-title":"Critical nodes in signalling pathways: Insights into insulin action","volume":"7","author":"Taniguchi","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.atherosclerosis.2015.01.039","article-title":"New insights into the pathophysiology of dyslipidemia in type 2 diabetes","volume":"239","author":"Taskinen","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","article-title":"The Global Epidemic of the Metabolic Syndrome","volume":"20","author":"Saklayen","year":"2018","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s12265-019-09879-0","article-title":"Adipokine Dysregulation and Insulin Resistance with Atherosclerotic Vascular Disease: Metabolic Syndrome or Independent Sequelae?","volume":"12","author":"Satish","year":"2019","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/s41392-024-01916-y","article-title":"Hyperuricemia and its related diseases: Mechanisms and advances in therapy","volume":"9","author":"Du","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e70163","DOI":"10.1002\/edm2.70163","article-title":"Serum Uric Acid as a Mediator of Insulin Resistance: Molecular Mechanisms and Metabolic Pathways","volume":"9","author":"Ali","year":"2026","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.jhep.2015.11.022","article-title":"Uric acid regulates hepatic steatosis and insulin resistance through the NLRP3 inflammasome-dependent mechanism","volume":"64","author":"Wan","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1002\/art.41779","article-title":"Assessing the Causal Relationships Between Insulin Resistance and Hyperuricemia and Gout Using Bidirectional Mendelian Randomization","volume":"73","author":"McCormick","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1142\/S0192415X19500137","article-title":"Ethnobotany, Phytochemistry and Pharmacological Properties of Eucommia ulmoides: A Review","volume":"47","author":"Wang","year":"2019","journal-title":"Am. J. Chin. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yang, Y., Li, F., Guo, Q., Wang, W., Zhang, L., Yin, Y., Gong, S., Han, M., and Yin, Y. (2021). Effects of Different Supplemental Levels of Eucommia ulmoides Leaf Extract in the Diet on Carcass Traits and Lipid Metabolism in Growing-Finishing Pigs. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.828165"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jep.2013.11.023","article-title":"Eucommia ulmoides Oliv.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine","volume":"151","author":"He","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s10600-019-02815-3","article-title":"Gliotoxin Analogues from Endophytic Penicillium sp. of Eucommia ulmoides and Their Antimicrobial Activity","volume":"55","author":"Zhang","year":"2019","journal-title":"Chem. Nat. Compd."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tang, W., and Eisenbrand, G. (1992). Eucommia ulmoides Oliv. Chinese Drugs of Plant Origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine, Springer.","DOI":"10.1007\/978-3-642-73739-8"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1248\/cpb.38.267","article-title":"New iridoid trimers and tetramers from seeds of eucommia ulmoides","volume":"38","author":"Yahara","year":"1990","journal-title":"Chem. Pharm. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119200","DOI":"10.1016\/j.molliq.2022.119200","article-title":"Polarity-controlled deep eutectic solvents-based biphasic system for the selective separation of geniposidic acid and aucubin from Eucommia ulmoides male flowers","volume":"358","author":"Wang","year":"2022","journal-title":"J. Mol. Liq."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13020-024-00981-3","article-title":"Geniposide for treating atherosclerotic cardiovascular disease: A systematic review on its biological characteristics, pharmacology, pharmacokinetics, and toxicology","volume":"19","author":"Li","year":"2024","journal-title":"Chin. Med."},{"key":"ref_35","first-page":"469","article-title":"LC\/MS\/MS determination and pharmacokinetic studies of six compounds in rat plasma following oral administration of the single and combined extracts of Eucommia ulmoides and Dipsacus asperoides","volume":"12","author":"Huang","year":"2014","journal-title":"Chin. J. Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Tan, D.C., Peng, B., Yang, L., Zhang, S.Y., Shi, R.P., Chong, C.M., Zhong, Z.F., Wang, S.P., and Liang, Q.L. (2022). Neuroendocrine-Immune Regulatory Network of Eucommia ulmoides Oliver. Molecules, 27.","DOI":"10.3390\/molecules27123697"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13020-021-00482-7","article-title":"Traditional application and modern pharmacological research of Eucommia ulmoides Oliv","volume":"16","author":"Huang","year":"2021","journal-title":"Chin. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"435","DOI":"10.4103\/0973-1296.141813","article-title":"Simultaneous quantification of eleven bioactive components of male flowers of Eucommia ulmoides oliver by HPLC and their quality evaluation by chemical fingerprint analysis with hierarchical clustering analysis","volume":"10","author":"Ding","year":"2014","journal-title":"Pharmacogn. Mag."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1365\/s10337-005-0520-0","article-title":"Simultaneous Determination of Nine Flavonoids in Dalbergia odorifera by LC","volume":"61","author":"Liu","year":"2005","journal-title":"Chromatographia"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Meesakul, P., Shea, T., Fenstemacher, R., Wong, S.X., Kuroki, Y., Wada, A., and Cao, S. (2023). Phytochemistry and Biological Studies of Endemic Hawaiian Plants. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216323"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1753-4887.1998.tb01670.x","article-title":"Polyphenols: Chemistry, Dietary Sources, Metabolism, and Nutritional Significance","volume":"56","author":"Bravo","year":"1998","journal-title":"Nutr. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wu, D., Yu, D., Zhang, Y., Dong, J., Li, D., and Wang, D. (2018). Metabolite Profiles, Bioactivity, and HPLC Fingerprint of Different Varieties of Eucommia ulmoides Oliv.: Towards the Utilization of Medicinal and Commercial Chinese Endemic Tree. Molecules, 23.","DOI":"10.3390\/molecules23081898"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17406","DOI":"10.1039\/D3RA00800B","article-title":"Enrichment of the flavonoid fraction from Eucommia ulmoides leaves by a liquid antisolvent precipitation method and evaluation of antioxidant activities in vitro and in vivo","volume":"13","author":"Wu","year":"2023","journal-title":"RSC Adv."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Balakrishnan, R., Cho, D.-Y., Su-Kim, I., and Choi, D.-K. (2020). Dendropanax Morbiferus and Other Species from the Genus Dendropanax: Therapeutic Potential of Its Traditional Uses, Phytochemistry, and Pharmacology. Antioxidants, 9.","DOI":"10.3390\/antiox9100962"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chen, W., Lu, J., Zhang, J., Wu, J., Yu, L., Qin, L., and Zhu, B. (2021). Traditional Uses, Phytochemistry, Pharmacology, and Quality Control of Dendrobium officinale Kimura et. Migo. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.726528"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1248\/cpb.35.1785","article-title":"The Constituents of Eucommia ulmoides OLIV. V. Isolation of Dihydroxydehydrodiconiferyl Alcohol Isomers and Phenolic Compounds","volume":"35","author":"Deyama","year":"1987","journal-title":"Chem. Pharm. Bull."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/BF02892014","article-title":"Phenolic compounds of the leaves of Eucommia ulmoides","volume":"14","author":"Young","year":"1991","journal-title":"Arch. Pharmacal Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1093\/jn\/131.1.66","article-title":"Chlorogenic acid and caffeic acid are absorbed in humans","volume":"131","author":"Olthof","year":"2001","journal-title":"J. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5735","DOI":"10.1021\/jf0257547","article-title":"Absorption of phenolic acids in humans after coffee consumption","volume":"50","author":"Nardini","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1093\/jn\/133.6.1853","article-title":"Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats","volume":"133","author":"Gonthier","year":"2003","journal-title":"J. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Osredkar, J. (2023). Pharmacokinetics of Quercetin. Quercetin\u2014Effects on Human Health, IntechOpen.","DOI":"10.5772\/intechopen.1005227"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5202908","DOI":"10.1155\/2016\/5202908","article-title":"Health-Promoting Properties of Eucommia ulmoides: A Review","volume":"2016","author":"Hussain","year":"2016","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1080\/14786419.2019.1700250","article-title":"Lignans and phenolic constituents from Eucommia ulmoides Oliver","volume":"35","author":"Huang","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1248\/cpb.33.3651","article-title":"The Constituents of Eucommia ulmoides OLIV. II. Isolation and Structures of Three New Lignan Glycosides","volume":"33","author":"Deyama","year":"1985","journal-title":"Chem. Pharm. Bull."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1248\/cpb.31.2993","article-title":"The Constituents of Eucommia ulmoides OLIV. I. Isolation of (+)-Medioresinol Di-O-\u03b2-D-glucopyranoside","volume":"31","author":"Deyama","year":"1983","journal-title":"Chem. Pharm. Bull."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pu, Y., Cai, Y., Zhang, Q., Hou, T., Zhang, T., Zhang, T., and Wang, B. (2021). Comparison of Pinoresinol and its Diglucoside on their ADME Properties and Vasorelaxant Effects on Phenylephrine-Induced Model. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.695530"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1248\/cpb.51.508","article-title":"Biotransformation of pinoresinol diglucoside to mammalian lignans by human intestinal microflora, and isolation of Enterococcus faecalis strain PDG-1 responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol","volume":"51","author":"Xie","year":"2003","journal-title":"Chem. Pharm. Bull."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Senizza, A., Rocchetti, G., Mosele, J.I., Patrone, V., Callegari, M.L., Morelli, L., and Lucini, L. (2020). Lignans and Gut Microbiota: An Interplay Revealing Potential Health Implications. Molecules, 25.","DOI":"10.3390\/molecules25235709"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1017\/S0954422407249704","article-title":"Bioavailability of lignans in human subjects","volume":"19","author":"Clavel","year":"2006","journal-title":"Nutr. Res. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9250485","DOI":"10.26599\/FSHW.2025.9250485","article-title":"Research Progress of Polysaccharide Structure-activity Relationship","volume":"15","author":"Zhou","year":"2025","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Liu, X., Xing, Y., Liu, G., Bao, D., Zhang, Z., Bi, H., and Wang, M. (2025). Physicochemical properties, biological activities, applications, and protective potential of the skeletal system of Eucommia ulmoides polysaccharides: A review. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1570095"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s40538-023-00495-4","article-title":"Structural characterization, physicochemical property, and antioxidant activity of polysaccharide components from Eucommia ulmoides leaves","volume":"10","author":"Liu","year":"2023","journal-title":"Chem. Biol. Technol. Agric."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"He, Y., Li, L., Chang, H., Cai, B., Gao, H., Chen, G., Hou, W., Jappar, Z., and Yan, Y. (2022). Research progress on extraction, purification, structure and biological activity of Dendrobium officinale polysaccharides. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.965073"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2503753","DOI":"10.1080\/10495398.2025.2503753","article-title":"Eucommia ulmoides and its inhibitory effects on prevotella in piglet gut microbiome through metagenomic and metabolomic analysis","volume":"36","author":"Han","year":"2025","journal-title":"Anim. Biotechnol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yan, S., Liu, X., Wang, Y., Yang, X., Bai, L., Sun, L., Zhou, Y., and Cui, S. (2023). Structural characterization and antioxidant activity of pectic polysaccharides from Veronica peregrina L. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1217862"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Yang, Y., Yin, X., Zhang, D., Zhang, B., Lu, J., and Wang, X. (2022). Structural Characteristics, Antioxidant, and Immunostimulatory Activities of an Acidic Polysaccharide from Raspberry Pulp. Molecules, 27.","DOI":"10.3390\/molecules27144385"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1016\/j.crfs.2022.08.016","article-title":"Structure-immunomodulatory activity relationships of dietary polysaccharides","volume":"5","author":"Chen","year":"2022","journal-title":"Curr. Res. Food Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"154652","DOI":"10.1016\/j.phymed.2023.154652","article-title":"Eucommia bark\/leaf extract improves HFD-induced lipid metabolism disorders via targeting gut microbiota to activate the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis","volume":"110","author":"Wang","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/0300-9629(88)90668-8","article-title":"Fermentation of polysaccharides and absorption of short chain fatty acids in the mammalian hindgut","volume":"90","author":"Rechkemmer","year":"1988","journal-title":"Comp. Biochem. Physiol. A Comp. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1007\/s10600-018-2537-2","article-title":"Secondary Metabolites from Branches of Eucommia ulmoides","volume":"54","author":"Xiong","year":"2018","journal-title":"Chem. Nat. Compd."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"199803197","DOI":"10.1002\/chin.199803197","article-title":"ChemInform Abstract: A New Triterpenoid from the Leaves of Eucommia ulmoides OLIV","volume":"29","author":"Tanaka","year":"1998","journal-title":"ChemInform"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"De Stefani, C., Lodovichi, J., Albonetti, L., Salvatici, M.C., Quintela, J.C., Bilia, A.R., and Bergonzi, M.C. (2022). Solubility and Permeability Enhancement of Oleanolic Acid by Solid Dispersion in Poloxamers and \u03b3-CD. Molecules, 27.","DOI":"10.3390\/molecules27093042"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13960","DOI":"10.3390\/molecules171213960","article-title":"A new ursane-type nor-triterpenoid from the leaves of Eucommia ulmoides Oliv","volume":"17","author":"Li","year":"2012","journal-title":"Molecules"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Ota, A., and Ulrih, N.P. (2017). An Overview of Herbal Products and Secondary Metabolites Used for Management of Type Two Diabetes. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00436"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.jpha.2019.11.004","article-title":"Isoflavones\u2019 effects on pharmacokinetic profiles of main iridoids from Gardeniae Fructus in rats","volume":"10","author":"Chang","year":"2020","journal-title":"J. Pharm. Anal."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1023\/A:1015821527621","article-title":"Pharmacokinetic study of an iridoid glucoside: Aucubin","volume":"8","author":"Suh","year":"1991","journal-title":"Pharm. Res."},{"key":"ref_77","unstructured":"Scherbl, D. (2017). Influence of Breakfast Consumption on the Chlorogenic Acid Metabolism in Humans. [Ph.D. Thesis, University of Kaiserslautern-Landau]."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00394-019-02066-6","article-title":"Factors influencing the cardiometabolic response to (poly)phenols and phytosterols: A review of the COST Action POSITIVe activities","volume":"58","author":"Gibney","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1093\/jn\/135.4.795","article-title":"Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside","volume":"135","author":"Kuijsten","year":"2005","journal-title":"J. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1039\/C9NP00011A","article-title":"Synergy and antagonism in natural product extracts: When 1 + 1 does not equal 2","volume":"36","author":"Caesar","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Vaou, N., Stavropoulou, E., Voidarou, C.C., Tsakris, Z., Rozos, G., Tsigalou, C., and Bezirtzoglou, E. (2022). Interactions between Medical Plant-Derived Bioactive Compounds: Focus on Antimicrobial Combination Effects. Antibiot, 11.","DOI":"10.3390\/antibiotics11081014"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/1475-2875-10-S1-S4","article-title":"Whole plant extracts versus single compounds for the treatment of malaria: Synergy and positive interactions","volume":"10","author":"Rasoanaivo","year":"2011","journal-title":"Malar. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1006\/cyto.2002.0894","article-title":"Inhibition of TNF-alpha and IL-6 production by Aucubin through blockade of NF-kappaB activation RBL-2H3 mast cells","volume":"18","author":"Jeong","year":"2002","journal-title":"Cytokine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"113920","DOI":"10.1016\/j.jep.2021.113920","article-title":"Pinoresinol diglucoside (PDG) attenuates cardiac hypertrophy via AKT\/mTOR\/NF-\u03baB signaling in pressure overload-induced rats","volume":"272","author":"Chen","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"177003","DOI":"10.1016\/j.ejphar.2024.177003","article-title":"Asperuloside activates hepatic NRF2 signaling to stimulate mitochondrial metabolism and restore lipid homeostasis in high fat diet-induced MAFLD","volume":"983","author":"He","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"155291","DOI":"10.1016\/j.phymed.2023.155291","article-title":"Aqueous extract of fermented Eucommia ulmoides leaves alleviates hyperlipidemia by maintaining gut homeostasis and modulating metabolism in high-fat diet fed rats","volume":"128","author":"Duan","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.phymed.2008.12.018","article-title":"Synergy research: Approaching a new generation of phytopharmaceuticals","volume":"16","author":"Wagner","year":"2009","journal-title":"Phytomedicine"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Suberu, J.O., Gorka, A.P., Jacobs, L., Roepe, P.D., Sullivan, N., Barker, G.C., and Lapkin, A.A. (2013). Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract\u2013possible synergistic and resistance mechanisms. PLoS ONE, 8.","DOI":"10.1371\/annotation\/57ae25b0-d2c8-444b-ab62-f047c5f3e01e"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1021\/np200336g","article-title":"Synergy-directed fractionation of botanical medicines: A case study with goldenseal (Hydrastis canadensis)","volume":"74","author":"Junio","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9420003","DOI":"10.26599\/FMH.2024.9420003","article-title":"The food and medicinal homological resources benefiting patients with hyperlipidemia: Categories, functional components, and mechanisms","volume":"1","author":"Hao","year":"2024","journal-title":"Food Med. Homol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41574-019-0176-8","article-title":"Obesity: Global epidemiology and pathogenesis","volume":"15","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1142\/S0192415X08005606","article-title":"Du-zhong (Eucommia ulmoides Oliver) leaf extract mediates hypolipidemic action in hamsters fed a high-fat diet","volume":"36","author":"Choi","year":"2008","journal-title":"Am. J. Chin. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.neulet.2010.05.030","article-title":"Effects of Eucommia leaf extracts on autonomic nerves, body temperature, lipolysis, food intake, and body weight","volume":"479","author":"Horii","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"751854","DOI":"10.1155\/2013\/751854","article-title":"Mechanism of the Inhibitory Effects of Eucommia ulmoides Oliv. Cortex Extracts (EUCE) in the CCl4-Induced Acute Liver Lipid Accumulation in Rats","volume":"2013","author":"Jin","year":"2013","journal-title":"Int. J. Endocrinol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Lee, G.H., Lee, H.Y., Park, S.A., Shin, T.S., and Chae, H.J. (2019). Eucommia ulmoides Leaf Extract Ameliorates Steatosis Induced by High-fat Diet in Rats by Increasing Lysosomal Function. Nutrients, 11.","DOI":"10.3390\/nu11020426"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.jep.2006.03.034","article-title":"Hypoglycemic and hypolipidemic action of Du-zhong (Eucommia ulmoides Oliver) leaves water extract in C57BL\/KsJ-db\/db mice","volume":"107","author":"Park","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1017\/S0007114510002965","article-title":"Chronic administration of Eucommia leaf stimulates metabolic function of rats across several organs","volume":"104","author":"Fujikawa","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1017\/jns.2012.12","article-title":"Asperuloside stimulates metabolic function in rats across several organs under high-fat diet conditions, acting like the major ingredient of Eucommia leaves with anti-obesity activity","volume":"1","author":"Fujikawa","year":"2012","journal-title":"J. Nutr. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"114603","DOI":"10.1016\/j.jep.2021.114603","article-title":"Mechanism by which Eucommia ulmoides leaves Regulate Nonalcoholic fatty liver disease based on system pharmacology","volume":"282","author":"Gong","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1021\/acs.jafc.2c07239","article-title":"Eucommia Bark\/Leaf Extract Improves Lipid Metabolism Disorders by Affecting Intestinal Microbiota and Microbiome-Host Interaction in HFD Mice","volume":"71","author":"Wang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9428","DOI":"10.1038\/s41467-025-64477-w","article-title":"Akkermansia muciniphila Muc(T) harnesses dietary polyphenols as xenosiderophores for enhanced iron uptake","volume":"16","author":"Boeren","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Daza, M.C., and de Vos, W.M. (2022). Polyphenols as Drivers of a Homeostatic Gut Microecology and Immuno-Metabolic Traits of Akkermansia muciniphila: From Mouse to Man. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010045"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1053\/j.gastro.2022.09.040","article-title":"Bacteroides vulgatus SNUG 40005 Restores Akkermansia Depletion by Metabolite Modulation","volume":"164","author":"You","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1007\/s11427-023-2346-1","article-title":"Gut microbiota bridges dietary nutrients and host immunity","volume":"66","author":"Fan","year":"2023","journal-title":"Sci. China Life Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"24552","DOI":"10.1021\/acs.jafc.4c07429","article-title":"Akkermansia muciniphila Growth Promoted by Lychee Major Flavonoid through Bacteroides uniformis Metabolism","volume":"72","author":"Tang","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"101522","DOI":"10.1016\/j.isci.2020.101522","article-title":"Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling","volume":"23","author":"Nakamura","year":"2020","journal-title":"iScience"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12986-020-00516-1","article-title":"Gut bacteria Akkermansia is associated with reduced risk of obesity: Evidence from the American Gut Project","volume":"17","author":"Zhou","year":"2020","journal-title":"Nutr. Metab."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1080\/13880209.2019.1568510","article-title":"Molecular mechanistic insight into the anti-hyperuricemic effect of Eucommia ulmoides in mice and rats","volume":"57","author":"Fang","year":"2019","journal-title":"Pharm. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s11130-025-01332-9","article-title":"Eucommia folium can be Prepared as a Tea with the Ability to Prevent and Treat Hyperuricaemia","volume":"80","author":"Hao","year":"2025","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"110074","DOI":"10.1016\/j.cbi.2022.110074","article-title":"Aucubin ameliorates liver fibrosis and hepatic stellate cells activation in diabetic mice via inhibiting ER stress-mediated IRE1\u03b1\/TXNIP\/NLRP3 inflammasome through NOX4\/ROS pathway","volume":"365","author":"Bao","year":"2022","journal-title":"Chem. Biol. Interact."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.jep.2011.07.033","article-title":"Evaluation of antidiabetic potential of selected traditional Chinese medicines in STZ-induced diabetic mice","volume":"137","author":"He","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Do, M.H., Hur, J., Choi, J., Kim, M., Kim, M.J., Kim, Y., and Ha, S.K. (2018). Eucommia ulmoides Ameliorates Glucotoxicity by Suppressing Advanced Glycation End-Products in Diabetic Mice Kidney. Nutrients, 10.","DOI":"10.3390\/nu10030265"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jep.2010.03.019","article-title":"Antihypertensive effect of Eucommia ulmoides Oliv. extracts in spontaneously hypertensive rats","volume":"129","author":"Luo","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"111901","DOI":"10.1016\/j.biopha.2021.111901","article-title":"Eucommia ulmoides (Tochu) and its extract geniposidic acid reduced blood pressure and improved renal hemodynamics","volume":"141","author":"Ishimitsu","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1080\/14656566.2023.2197591","article-title":"Advances in pharmacotherapies for hyperuricemia","volume":"24","author":"Piani","year":"2023","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1097\/HJH.0000000000003807","article-title":"Asymptomatic hyperuricemia: To treat or not a threat? A clinical and evidence-based approach to the management of hyperuricemia in the context of cardiovascular diseases","volume":"42","author":"Fiori","year":"2024","journal-title":"J. Hypertens."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"700","DOI":"10.2174\/1381612825666190408122557","article-title":"Hyperuricemia and Cardiovascular Disease","volume":"25","author":"Zhang","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_118","first-page":"527","article-title":"Effect of Eucommia ulmoides leaves on hyperuricemia and kidney injury induced by a high-fat\/high-fructose diet in rats","volume":"25","author":"Gong","year":"2022","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"154124","DOI":"10.1016\/j.phymed.2022.154124","article-title":"Lignans from Eucommia ulmoides Oliver leaves exhibit neuroprotective effects via activation of the PI3K\/Akt\/GSK-3\u03b2\/Nrf2 signaling pathways in H2O2-treated PC-12 cells","volume":"101","author":"Han","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Li, X., Chen, Z., Zhang, Y., Fan, C., Chen, L., Xu, X., Chang, J., Qiang, W., Jiang, H., and Liu, C. (2025). Research progress on multidimensional intervention strategies for hyperuricemia: Western medicine, Traditional Chinese Medicine, and emerging therapies. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1722245"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.amjcard.2006.04.046","article-title":"Metabolic syndrome and hyperglycemia: Congruence and divergence","volume":"98","author":"Alexander","year":"2006","journal-title":"Am. J. Cardiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.critrevonc.2016.11.003","article-title":"Hyperglycemia, tumorigenesis, and chronic inflammation","volume":"108","author":"Chang","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2025). 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025. Diabetes Care, 48, S181\u2013S206.","DOI":"10.2337\/dc25-S009"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jep.2015.01.015","article-title":"The ethanol extract of Eucommia ulmoides Oliv. leaves inhibits disaccharidase and glucose transport in Caco-2 cells","volume":"163","author":"Zhang","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"137596","DOI":"10.1016\/j.ijbiomac.2024.137596","article-title":"Hypoglycemic activity of enzymatically extracted Eucommia ulmoides polysaccharide (EUL-w1) on IR-HepG2 cell via the AMPK\/PI3K\/Akt signaling pathway","volume":"283","author":"Gong","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ejphar.2007.12.011","article-title":"Antioxidant and pancreas-protective effect of aucubin on rats with streptozotocin-induced diabetes","volume":"582","author":"Jin","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"103702","DOI":"10.1016\/j.jff.2019.103702","article-title":"Aucubin alleviates diabetic nephropathy by inhibiting NF-\u03baB activation and inducing SIRT1\/SIRT3-FOXO3a signaling pathway in high-fat diet\/streptozotocin-induced diabetic mice","volume":"64","author":"Ma","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"8067","DOI":"10.1002\/fsn3.4413","article-title":"Eucommia ulmoides extract regulates oxidative stress to maintain calcium homeostasis and improve diabetic osteoporosis","volume":"12","author":"Shen","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.freeradbiomed.2021.05.025","article-title":"AGE\/RAGE in diabetic kidney disease and ageing kidney","volume":"171","author":"Wu","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41420-019-0198-y","article-title":"Hyperglycemia exacerbates acetaminophen-induced acute liver injury by promoting liver-resident macrophage proinflammatory response via AMPK\/PI3K\/AKT-mediated oxidative stress","volume":"5","author":"Wang","year":"2019","journal-title":"Cell Death Discov."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10557-020-07080-z","article-title":"Extracellular Vesicle-Mediated Vascular Cell Communications in Hypertension: Mechanism Insights and Therapeutic Potential of ncRNAs","volume":"36","author":"Zhang","year":"2022","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s13659-020-00281-x","article-title":"Plants Used as Antihypertensive","volume":"11","author":"Verma","year":"2021","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/ptr.6877","article-title":"Insights to potential antihypertensive activity of berry fruits","volume":"35","author":"Yousefi","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1007\/s00394-023-03145-5","article-title":"Fruit and vegetable consumption and the risk of hypertension: A systematic review and meta-analysis of prospective studies","volume":"62","author":"Madsen","year":"2023","journal-title":"Eur. J. Nutr."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2049059","DOI":"10.1155\/2020\/2049059","article-title":"Tissue Distribution Comparison of Six Active Ingredients from an Eucommiae Cortex Extract between Normal and Spontaneously Hypertensive Rats","volume":"2020","author":"Hu","year":"2020","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.jpha.2021.10.004","article-title":"Potential therapeutic effects and applications of Eucommiae Folium in secondary hypertension","volume":"12","author":"Li","year":"2022","journal-title":"J. Pharm. Anal."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1159\/000447900","article-title":"Lignans Extracted from Eucommia ulmoides Oliv. Protects Against AGEs-Induced Retinal Endothelial Cell Injury","volume":"39","author":"Liu","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"21971","DOI":"10.3390\/molecules201219826","article-title":"The Restorative Effects of Eucommia ulmoides Oliver Leaf Extract on Vascular Function in Spontaneously Hypertensive Rats","volume":"20","author":"Hosoo","year":"2015","journal-title":"Molecules"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13020-024-01022-9","article-title":"The role of Chinese herbal medicine in the regulation of oxidative stress in treating hypertension: From therapeutics to mechanisms","volume":"19","author":"Jin","year":"2024","journal-title":"Chin. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"6432173","DOI":"10.1155\/2020\/6432173","article-title":"Antihypertensive Activity of Eucommia ulmoides Oliv: Male Flower Extract in Spontaneously Hypertensive Rats","volume":"2020","author":"Ding","year":"2020","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Xu, X., Tian, W., Duan, W., Pan, C., Huang, M., Wang, Q., Yang, Q., Wen, Z., Tang, Y., and Xiong, Y. (2022). Quanduzhong capsules for the treatment of grade 1 hypertension patients with low-to-moderate risk: A multicenter, randomized, double-blind, placebo-controlled clinical trial. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1014410"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"5598055","DOI":"10.1155\/ijne\/5598055","article-title":"An Exploratory Single-Arm Clinical Trial on Eucommia ulmoides Leaf Extract Effects on Blood Pressure, Oxidative Stress, and Atrial Natriuretic Peptide (ANP) in Individuals With and Without Chronic Kidney Disease","volume":"2025","author":"Satonaka","year":"2025","journal-title":"Int. J. Nephrol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Nishibe, S., Oikawa, H., Mitsui-Saitoh, K., Sakai, J., Zhang, W., and Fujikawa, T. (2023). The Differences of Mechanisms in Antihypertensive and Anti-Obesity Effects of Eucommia Leaf Extract between Rodents and Humans. Molecules, 28.","DOI":"10.3390\/molecules28041964"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.foodchem.2011.04.092","article-title":"Estrogenic properties of six compounds derived from Eucommia ulmoides Oliv. and their differing biological activity through estrogen receptors \u03b1 and \u03b2","volume":"129","author":"Wang","year":"2011","journal-title":"Food Chem."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Yan, J., Hu, R., Li, B., Tan, J., Wang, Y., Tang, Z., Liu, M., Fu, C., He, J., and Wu, X. (2022). Effect of Eucommia ulmoides Leaf Extract on Growth Performance, Carcass Traits, Parameters of Oxidative Stress, and Lipid Metabolism in Broiler Chickens. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.945981"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Peng, Y., Yang, Y., Tian, Y., Zhang, M., Cheng, K., Zhang, X., Zhou, M., Hui, M., and Zhang, Y. (2024). Extraction, Characterization, and Antioxidant Activity of Eucommia ulmoides Polysaccharides. Molecules, 29.","DOI":"10.3390\/molecules29204793"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S2221-1691(13)60060-X","article-title":"Bioavailability enhancers of herbal origin: An overview","volume":"3","author":"Kesarwani","year":"2013","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e27870","DOI":"10.1016\/j.heliyon.2024.e27870","article-title":"Biological properties and potential application of extracts and compounds from different medicinal parts (bark, leaf, staminate flower, and seed) of Eucommia ulmoides: A review","volume":"10","author":"Peng","year":"2024","journal-title":"Heliyon"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Meng, Y., Du, Q., Du, H., Wang, Q., Wang, L., Du, L., and Liu, P. (2022). Analysis of chemotypes and their markers in leaves of core collections of Eucommia ulmoides using metabolomics. Front. Plant Sci., 13.","DOI":"10.3389\/fpls.2022.1029907"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.aninu.2023.07.008","article-title":"Dietary Eucommia ulmoides leaf extract improves laying performance by altering serum metabolic profiles and gut bacteria in aged laying hens","volume":"15","author":"Liang","year":"2023","journal-title":"Anim. Nutr."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Wang, P.L., You, J.L., Hua, Q.M., Li, H.Q., Shi, Q., Li, W.L., Sheng, Y.J., Liu, K.H., He, B.Q., and Zhang, Q.Y. (2025). Integrated metabolomics and transcriptomics analysis comprehensively revealed the underlying metabolite mechanism difference between Male and Female Eucommia ulmoides Oliver. BMC Plant Biol., 25.","DOI":"10.1186\/s12870-025-06575-x"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Du, Q., Song, K., Wang, L., Du, L., Du, H., Li, B., Li, H., Yang, L., Wang, Y., and Liu, P. (2024). Integrated Transcriptomics and Metabolomics Analysis Promotes the Understanding of Adventitious Root Formation in Eucommia ulmoides Oliver. Plants, 13.","DOI":"10.3390\/plants13010136"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/6\/411\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:19:11Z","timestamp":1782361151000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/6\/411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":153,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["metabo16060411"],"URL":"https:\/\/doi.org\/10.3390\/metabo16060411","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]}}}