{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:12:34Z","timestamp":1790741554500,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82125034"],"award-info":[{"award-number":["82125034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274182"],"award-info":[{"award-number":["82274182"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82330115"],"award-info":[{"award-number":["82330115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82521104"],"award-info":[{"award-number":["82521104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) that symbolizes a primary contributor of morbidity and mortality. Dihydroartemisinin (DHA; artenimol) shows good therapeutic effects on LN. Its pharmacological target remains unclear. Proteolysis targeting chimeras (PROTAC) technology was used to identify the targets of DHA in LN treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      The activity of a novel compound termed A1 was assessed through cytotoxicity and anti\u2010inflammatory assays\n                      <jats:italic>in vitro<\/jats:italic>\n                      . The target of DHA was screened by the A1 integrating with proteomics and then validated via western blotting, co\u2010immunoprecipitation (Co\u2010IP), immunofluorescence, molecular docking, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) in vitro. Twenty\u2010four\u2010hour proteinuria, inflammatory cytokines, serum biochemical indicators, immune complex deposition and renal pathological injury were detected. Adeno\u2010associated virus\u2010mediated RNA interference in silencing CARD6 was conducted\n                      <jats:italic>in vivo<\/jats:italic>\n                      to comprehensively evaluate the effect and the target of DHA on MRL\/lpr mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      CARD6 was the most notably degraded protein affected by A1 that identified as the target of DHA. Specifically, DHA interacted with CORE\u2010CARD6 at the 481\u2013949aa region. DHA blocked CARD6 to inhibit RIP2\/NF\u2010\u03baB pathway, which manifested anti\u2010inflammatory properties\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Silencing CARD6 ameliorated the inflammatory response of MRL\/lpr mice. Notably, the inhibition effects of DHA on the MRL\/lpr mice were abrogated when CARD6 was depleted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>CARD6 was a therapeutic target of DHA for LN management. This finding highlights the great potential of using PROTAC technology to effectively identify therapeutic targets of natural products.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70510","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:49:14Z","timestamp":1779176954000},"page":"4969-4988","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Caspase Recruitment Domain 6\n                    <b>(<\/b>\n                    CARD6) is the therapeutic target of dihydroartemisinin for lupus nephritis based on Proteolysis Targeting Chimera (PROTAC) technology"],"prefix":"10.1111","volume":"183","author":[{"given":"Honglian","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Ni","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhen","family":"Rao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"},{"name":"Department of Nephrology, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital Southern University of Science and Technology  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyi","family":"Guo","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayun","family":"Chen","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"},{"name":"Department of Nephrology, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital Southern University of Science and Technology  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jigang","family":"Wang","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"},{"name":"Department of Nephrology, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital Southern University of Science and Technology  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Rao","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-5006","authenticated-orcid":false,"given":"Shuwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"},{"name":"State Key Laboratory of Multi\u2010organ Injury Prevention and Treatment Southern Medical University  Guangzhou China"},{"name":"MOE Innovation Center for Medical Basic Research on Inflammation and Immune Related Diseases Southern Medical University  Guangzhou China"},{"name":"Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.734008"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70235"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70229"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jalm\/jfac036"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0141-9"},{"issue":"108","key":"e_1_2_13_8_1","first-page":"43","article-title":"Therapeutic targeting of macrophages in lupus nephritis","volume":"20","author":"Chalmers S. A.","year":"2015","journal-title":"Discovery Medicine"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/2049-9957-3-9"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ado6492"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S220754"},{"issue":"9","key":"e_1_2_13_13_1","first-page":"676","article-title":"Effect of dihydro\u2010qinghaosu on auto\u2010antibody production, TNF alpha secretion and pathologic change of lupus nephritis in BXSB mice","volume":"23","author":"Dong Y. J.","year":"2003","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01359-07"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.8.2635"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510380103"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.07.001"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102154"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102980"},{"key":"e_1_2_13_20_1","unstructured":"Justiz V.A. Goyal A. andVaracallo M.(2024).Systemic lupus erythematosus."},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/00313020903434421"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4609"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI125116"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.211"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-043021-032611"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000662"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01223"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.03021"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2018.0093"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2np00038e"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123621"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2019.06.009"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.092379"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-00925-5"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1118180"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2019.02.022"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42863"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00588-9"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.06.014"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa403"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0304-8"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00405"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2019.102331"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2023.06.006"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102561"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107697"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1080310"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2007.04.012"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11070928"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202400753"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00966-4"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36664-0"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70510","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70510","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70510","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T08:25:15Z","timestamp":1783671915000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":54,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/bph.70510"],"URL":"https:\/\/doi.org\/10.1111\/bph.70510","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]},"assertion":[{"value":"2025-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}