{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:32:39Z","timestamp":1787164359711,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,1,7]],"date-time":"2005-01-07T00:00:00Z","timestamp":1105056000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Chebulagic acid (CHE) from the immature seeds of\n                      <jats:italic>Terminalia chebula<\/jats:italic>\n                      was identified from a natural product library as a potent suppressor of T cell activity. This study examined the effectiveness of CHE against the onset and progression of collagen\u2010induced arthritis (CIA) in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Arthritis was induced in DBA\/1J mice by subcutaneous immunization with bovine type II collagen on days 0 and 21. CHE was administered intraperitoneally for 3 weeks, either as prophylaxis (10 or 20 mg\/kg) before disease onset or as therapy (20 mg\/kg) after disease onset. Clinical scores, serum antibody levels, and cytokines were measured, and flow cytometric analysis and real\u2010time reverse transcription\u2013polymerase chain reaction were performed to evaluate the knee joints of mice with CIA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In both the prophylactic and therapeutic CHE dosing models, all clinical scores, serum levels of total and anticollagen IgG, and levels of interleukin\u201010 (IL\u201010) and IL\u20106 were reduced, while serum levels of transforming growth factor \u03b2 (TGF\u03b2) were markedly elevated. The number of granulocytes was reduced, but the proportion of CD4+,CD25+ T cells was greater in the knee joints of CHE\u2010treated CIA mice. Expression of Foxp3 and TGF\u03b2 messenger RNA was also augmented significantly in the knee joints of CHE\u2010treated CIA mice in the therapeutic dosing model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CHE significantly suppressed the onset and progression of CIA in mice. Immune suppression via the induction of TGF\u03b2 and CD4+,CD25+ T cells may represent a new strategy in the development of therapies for managing rheumatoid arthritis and other inflammatory diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.20715","type":"journal-article","created":{"date-parts":[[2005,1,7]],"date-time":"2005-01-07T16:49:58Z","timestamp":1105116598000},"page":"345-353","source":"Crossref","is-referenced-by-count":41,"title":["Suppression of the onset and progression of collagen\u2010induced arthritis by chebulagic acid screened from a natural product library"],"prefix":"10.1002","volume":"52","author":[{"given":"Sang\u2010Ik","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pung\u2010Mi","family":"Hyun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Hyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung\u2010Shin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang\u2010Keun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung\u2010Soo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pil Jae","family":"Maeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Soon","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,1,7]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200012)43:12<2668::AID-ANR6>3.0.CO;2-E"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11131"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035075"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780311003"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1358\/dot.1998.34.7.485263"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-003-0444-1"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80195-8"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.6.3105"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.295"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3008"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/10.12.1969"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(01)00273-4"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(03)00003-0"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80170-3"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.7.1187"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1996.0026"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.8.4760"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-37024"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1159\/000049017"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.20.1017"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10591"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01330296"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200309000-00010"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-8741(02)00099-5"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/np50082a001"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/np50069a008"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-32070"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/np50086a002"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2001.01267.x"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri702"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115073"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1999.0339"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11063"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030152"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104521200"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079490"},{"key":"e_1_2_5_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni909"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.4.2227"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200464120-00001"}],"container-title":["Arthritis 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