{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:57:36Z","timestamp":1780545456705,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1D1A1B03029050"],"award-info":[{"award-number":["2017R1D1A1B03029050"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2015R1D1A1A01057695"],"award-info":[{"award-number":["2015R1D1A1A01057695"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A6A1A03023718"],"award-info":[{"award-number":["2018R1A6A1A03023718"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1I1A1A01061117"],"award-info":[{"award-number":["2019R1I1A1A01061117"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002573","name":"Yonsei University","doi-asserted-by":"publisher","award":["2019-12-0013"],"award-info":[{"award-number":["2019-12-0013"]}],"id":[{"id":"10.13039\/501100002573","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lupus nephritis (LN) is the most frequent phenotype in patients with systemic lupus erythematosus (SLE) and has a high rate of progression to end-stage renal disease, in spite of intensive treatment and maintenance therapies. Recent evidence suggests that protease-activated receptor-2 (PAR2) is a therapeutic target for glomerulonephritis. In this study, we performed a cell-based high-throughput screening and identified a novel potent PAR2 antagonist, punicalagin (PCG, a major polyphenol enriched in pomegranate), and evaluated the effects of PCG on LN. The effect of PCG on PAR2 inhibition was observed in the human podocyte cell line and its effect on LN was evaluated in NZB\/W F1 mice. In the human podocyte cell line, PCG potently inhibited PAR2 (IC50 = 1.5 \u00b1 0.03 \u00b5M) and significantly reduced the PAR2-mediated activation of ERK1\/2 and NF-\u03baB signaling pathway. In addition, PCG significantly decreased PAR2-induced increases in ICAM-1 and VCAM-1 as well as in IL-8, IFN-\u03b3, and TNF-\u03b1 expression. Notably, the intraperitoneal administration of PCG significantly alleviated kidney injury and splenomegaly and reduced proteinuria and renal ICAM-1 and VCAM-1 expression in NZB\/W F1 mice. Our results suggest that PCG has beneficial effects on LN via inhibition of PAR2, and PCG is a potential therapeutic agent for LN.<\/jats:p>","DOI":"10.3390\/ijms21144975","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T11:03:23Z","timestamp":1594724603000},"page":"4975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2"],"prefix":"10.3390","volume":"21","author":[{"given":"Yohan","family":"Seo","sequence":"first","affiliation":[{"name":"College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea"},{"name":"New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin Hee","family":"Mun","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Hyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-6388","authenticated-orcid":false,"given":"Dongkyu","family":"Jeon","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"BK21 Plus Project, Department of Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taejun","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"BK21 Plus Project, Department of Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunhee","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"BK21 Plus Project, Department of Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwoo","family":"Jo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Beom","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"BK21 Plus Project, Department of Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03772, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Namkung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea"},{"name":"Interdisciplinary Program of Integrated OMICS for Biomedical Science Graduate School, Yonsei University, Seoul 03772, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03772, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1056\/NEJMra1100359","article-title":"Systemic lupus erythematosus","volume":"365","author":"Tsokos","year":"2011","journal-title":"N. 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