{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:11:31Z","timestamp":1789992691626,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSC 106\u20102320\u2010B\u2010264\u2010001\u2010"],"award-info":[{"award-number":["NSC 106\u20102320\u2010B\u2010264\u2010001\u2010"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004946","name":"National Chung-Hsing University","doi-asserted-by":"publisher","award":["108GP04376"],"award-info":[{"award-number":["108GP04376"]}],"id":[{"id":"10.13039\/501100004946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp; Nutrition"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Rheumatoid arthritis (RA) is an inflammatory disease caused by an autoimmune reaction. Only immunomodulators or related medicines can decrease RA progression. Ling\u2010Zhi\u20108 (LZ\u20108) is a small\u2010molecule protein in Ganoderma lucidum that inhibits inflammation. This study aimed to investigate the anti\u2010inflammatory function and immunomodulatory activity of LZ\u20108 in RA. Rat RA animal and cell models were used to examine the anti\u2010inflammatory efficacy of LZ\u20108 in inhibiting arthritis. Experimental results indicated that LZ\u20108 inhibited the production of interleukin (IL)\u20106 and the over\u2010expression of cyclooxygenase\u20102 in lipopolysaccharide\u2010stimulated macrophages. This suppressive effect may be associated with the potential inhibitory effect of LZ\u20108 on the MyD88\u2010mediated Jun N\u2010terminal kinase\u2010mitogen\u2010activated protein kinase signaling pathway. Administration of lower doses (3.125\u2009mg\/kg) of LZ\u20108 injections for 9\u2009days reduced inflammation and swelling in the soles of the feet in the RA animal model. The pathological lesion of the limb digits of rats in the LZ\u20108 lower doses (3.125\u2009mg\/kg) group was relatively milder than those of the medium\u2010 and high\u2010dose groups. Comparing the histological lesions, the LZ\u20108 high\u2010dose group showed reduced synovial hyperplasia, and all three doses of LZ\u20108 mitigated damage to the articular cartilage. The reduced spleen weight and the distribution of CD4\n                    <jats:sup>+<\/jats:sup>\n                    IL\u20104\n                    <jats:sup>+<\/jats:sup>\n                    , CD4\n                    <jats:sup>+<\/jats:sup>\n                    IL\u201017\n                    <jats:sup>+<\/jats:sup>\n                    , CD4\n                    <jats:sup>+<\/jats:sup>\n                    IFN\u2010\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    , and CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell immune populations were observed. In conclusion, this study demonstrates that LZ\u20108 attenuates inflammatory and immunological responses in a CFA (complete Freund's adjuvant)\u2010 induced arthritis model, supporting its potential as an immunomodulatory agent for arthritis\u2010associated inflammatory conditions.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71825","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:04:18Z","timestamp":1777446258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Evaluation of the Anti\u2010Inflammatory Activity of Ling\u2010Zhi\u20108 (\n                    <scp>LZ<\/scp>\n                    \u20108) In\u00a0Vitro and a Rheumatoid Arthritis Animal Model"],"prefix":"10.1002","volume":"14","author":[{"given":"Shao\u2010Wen","family":"Hung","sequence":"first","affiliation":[{"name":"Division of Sustainable Agriculture, Agricultural Facilities and Environment Research Center Agricultural Technology Research Institute  Hsinchu City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010Jung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Human Development and Family Studies National Taiwan Normal University  Taipei City Taiwan"},{"name":"Program of Nutritional Science, School of Life Science National Taiwan Normal University  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8694-9561","authenticated-orcid":false,"given":"Cheng\u2010Yao","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Veterinary Pathobiology National Chung Hsing University  Taichung City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u2010Te","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Pharmaceutical Technology Yuanpei University of Medical Technology  Hsinchu City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906\u2010020\u20102864\u20102"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/09540105.2017.1346062"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.12703\/p6\u201097"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00666"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300679u"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.12057"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114524001144"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00400340"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(17)31282\u20106"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262\u2010011\u20101016\u20104"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0708441"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.5MA0420\u2010453R"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2487"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804239"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172669"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010103019\u2010085803"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(07)60784\u20103"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)30173\u20108"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20991"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00816-x"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.13360"},{"key":"e_1_2_13_26_1","first-page":"91","article-title":"Preventive Effects of Borage Oil and Ling\u2010Zhi\u20108 Protein on Carbon Tetrachloride\u2010Induced Acute Hepatic Toxicity in Rats","volume":"12","author":"Yang C.\u2010Y.","year":"2014","journal-title":"Current Topics in Nutraceutical Research"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00731"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111764"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6312"}],"container-title":["Food Science &amp; 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