{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:08:37Z","timestamp":1785431317617,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012544","name":"China Medical University, Taiwan","doi-asserted-by":"crossref","award":["CMU112-S-07"],"award-info":[{"award-number":["CMU112-S-07"]}],"id":[{"id":"10.13039\/501100012544","id-type":"DOI","asserted-by":"crossref"}]},{"award":["CMU112-S-07"],"award-info":[{"award-number":["CMU112-S-07"]}],"id":[{"id":"https:\/\/ror.org\/032d4f246","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Buddhist Tzuchi Medical Foundation of the Taichung Tzu Chi Hospital, Taiwan","award":["TTCRD 114-11"],"award-info":[{"award-number":["TTCRD 114-11"]}]},{"name":"the National Science and Technology Council, Taipei, Taiwan","award":["109-2314-B-039-043-MY3"],"award-info":[{"award-number":["109-2314-B-039-043-MY3"]}]},{"award":["109-2314-B-039-043-MY3"],"award-info":[{"award-number":["109-2314-B-039-043-MY3"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Phillygenin (PHI), a natural lignan derived from Forsythia suspensa, has garnered attention for its potential to alleviate chronic diseases, including chronic colitis, pulmonary fibrosis, and diabetes. Chronic kidney disease (CKD) poses a global health challenge, characterized by high morbidity and mortality rates and associated with a spectrum of secondary complications. In this study, we aim to investigate the therapeutic effectiveness of PHI on CKD and also identify molecular signals by using a unilateral ureteral obstruction (UUO) mouse model and in vitro experiments. Methods: C57BL\/6 mice were administered PHI at 50 mg\/kg\/day to assess its therapeutic effectiveness. In vitro, lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were used to induce pyroptosis, also known as pyroptosis, in renal proximal tubular cells (NRK52E). Results: After PHI treatment for 14 consecutive days, the collagen deposition and extracellular matrix (ECM) accumulation, the expression of oxidative stress response proteins (catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), pro-inflammatory markers (TNF-\u03b1 and Cyclooxygenase-2(COX-2), and infiltration of neutrophils and macrophages were significantly ameliorated in the UUO mice. Interestingly, the pyroptosis-related proteins (NLRP3\/Caspase-1\/GSDMD\/IL-1\u03b2) and cell apoptotic death were also conspicuously relieved after treatment with PHI. Furthermore, PHI administration significantly attenuated the ATP\/LPS-induced NF-\u03baB\/NLRP3\/Caspase-1\/GSDMD pyroptosis signal pathway in NRK52E cells. Conclusions: These results demonstrate, for the first time, that PHI treatment ameliorates inflammation and the related pyroptosis via inhibitory regulation of the NF-\u03baB\/NLRP3\/Caspase-1\/GSDMD axis, leading to attenuated renal fibrosis and progressive CKD in UUO mice and in vitro. Our findings suggest that PHI could be a nutraceutical candidate for attenuating CKD progression.<\/jats:p>","DOI":"10.3390\/nu18091421","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:47:28Z","timestamp":1777546048000},"page":"1421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phillygenin, a Plant-Derived Lignan, Attenuates Renal Inflammation, Fibrosis, and Pyroptosis in a Unilateral Ureteral Obstruction Model"],"prefix":"10.3390","volume":"18","author":[{"given":"Yu-Syuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Nutrition, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-7927","authenticated-orcid":false,"given":"Shun-Fa","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Liang","family":"Kuo","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, Taichung 40402, Taiwan"},{"name":"School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan"},{"name":"Clinical Nutrition, China Medical University Hospital, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haw-Ling","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Emergency, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Mu","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery, College of Medicine and Hospital, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ssu-Chia","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yu","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0122-0043","authenticated-orcid":false,"given":"Chun-Fa","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Nursing, College of Medical and Health Science, Asia University, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0447-5084","authenticated-orcid":false,"given":"Siao-Syun","family":"Guan","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan 32546, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-1197","authenticated-orcid":false,"given":"Shing-Hwa","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"},{"name":"Department of Pediatrics, College of Medicine and Hospital, National Taiwan University, Taipei 10051, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40447, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7240-8465","authenticated-orcid":false,"given":"Cheng-Tien","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-981-13-8871-2_1","article-title":"Prevalence and Disease Burden of Chronic Kidney Disease","volume":"Volume 1165","author":"Lv","year":"2019","journal-title":"Renal Fibrosis: Mechanisms and Therapies; 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