{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:21Z","timestamp":1785422721631,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"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":["82003762"],"award-info":[{"award-number":["82003762"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82003762"],"award-info":[{"award-number":["82003762"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Shanghai","award":["22ZR1473700"],"award-info":[{"award-number":["22ZR1473700"]}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["21S11907700"],"award-info":[{"award-number":["21S11907700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"award":["21S11907700"],"award-info":[{"award-number":["21S11907700"]}],"id":[{"id":"https:\/\/ror.org\/03kt66j61","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province of China","doi-asserted-by":"publisher","award":["2025AFB467"],"award-info":[{"award-number":["2025AFB467"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Idiopathic inflammatory myopathies (IIMs), characterized by muscle weakness and chronic inflammation, currently lack highly effective therapies. This study investigated the therapeutic potential and underlying mechanism of (5R)-5-hydroxytriptolide (LLDT-8), a triptolide derivative with reduced toxicity, using an experimental autoimmune myositis (EAM) mouse model and in vitro assays. Methods: Forty female BALB\/c mice were randomly assigned to five groups: normal, vehicle, methylprednisolone (MP), LLDT-8 (0.0625 mg\/kg), and LLDT-8 (0.125 mg\/kg). EAM mice were treated with LLDT-8 (0.0625 or 0.125 mg\/kg) or methylprednisolone as a positive control. Cellular experiments and molecular docking were performed to investigate potential mechanisms of LLDT-8. Results: LLDT-8 significantly attenuated clinicopathological features, including muscle weakness and pain sensitivity, while reducing serum levels of aspartate aminotransferase and lactate dehydrogenase. Histological analysis revealed that LLDT-8 reduced inflammatory cell infiltration and the presence of CD4+ and CD8+ T cells in muscle tissues. Mechanistically, LLDT-8 inhibited the expression of nucleotide-binding oligomerization domain receptor caspase recruitment domain 5 (NLRC5), a key transcriptional regulator of major histocompatibility complex-I (MHC-I). This suppression extended to downstream antigen presentation-related molecules, including the transporter associated with antigen processing and proteasome 20S subunit beta. Molecular docking further confirmed the high binding affinity of LLDT-8 to both NLRC5 and MHC-I. Conclusions: LLDT-8 alleviates inflammatory muscle injury by targeting the NLRC5\/MHC-I signaling axis, suggesting it may be a promising therapeutic candidate for IIMs.<\/jats:p>","DOI":"10.3390\/ph19040631","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:11:04Z","timestamp":1776420664000},"page":"631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["(5R)-5-Hydroxytriptolide (LLDT-8) Ameliorates Experimental Autoimmune Myositis via Suppression of the NLRC5\/MHC-I Signaling Pathway"],"prefix":"10.3390","volume":"19","author":[{"given":"Tingting","family":"Hao","sequence":"first","affiliation":[{"name":"Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Qi","sequence":"additional","affiliation":[{"name":"School of International Equestrianism, Wuhan Business University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cancan","family":"Xie","sequence":"additional","affiliation":[{"name":"Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijuan","family":"Shao","sequence":"additional","affiliation":[{"name":"Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Que","family":"Wang","sequence":"additional","affiliation":[{"name":"Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3665-874X","authenticated-orcid":false,"given":"Zemin","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghua","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijun","family":"He","sequence":"additional","affiliation":[{"name":"Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Zuo","sequence":"additional","affiliation":[{"name":"Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1056\/NEJMra1402225","article-title":"Inflammatory muscle diseases","volume":"372","author":"Dalakas","year":"2015","journal-title":"N. 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