{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T21:06:22Z","timestamp":1781816782261,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030122"],"award-info":[{"award-number":["82030122"]}],"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":["82474548"],"award-info":[{"award-number":["82474548"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012152","name":"National Postdoctoral Program for Innovative Talents","doi-asserted-by":"publisher","award":["GZC20233128"],"award-info":[{"award-number":["GZC20233128"]}],"id":[{"id":"10.13039\/501100012152","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Jianpi\u2010Huogu Prescription (JHP), integrating the classic Chinese herbal formulas Linggui\u2010Zhugan Decoction and Si\u2010Wu Decoction, has shown clinical efficacy in treating early nontraumatic osteonecrosis of the femoral head (NONFH). In this study, 299 chemical constituents of JHP were identified using ultra\u2010performance liquid chromatography\u2013quadrupole\u2010time of flight mass spectrometry. Pharmacological evaluations in rats with early NONFH demonstrated that JHP attenuated femoral head pathological changes, improved gait parameters, increased mechanical pain thresholds, reduced serum levels of triglycerides, total cholesterol, low\u2010density lipoprotein, very\u2010low\u2010density lipoprotein, and the TXB\u2082\/6\u2010keto\u2010PGF\u2081\u03b1 ratio while elevating high\u2010density lipoprotein, decreased serum inflammatory cytokines (IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1) and the RANKL\/OPG ratio, and restored bone trabecular morphology and reduced the number of bone marrow adipocytes. Mechanistically, through transcriptomic profiling, network calculations and experimental validation, JHP downregulated NMNAT1, NMNAT3, and NAMPT in the femoral head, thereby reducing NAD\n                    <jats:sup>+<\/jats:sup>\n                    synthesis, increased ATP production (evidenced by a decreased ADP\/ATP ratio) and upregulated STK11 expression, activated p\u2010HMGCR while suppressing ACAT1 thus inhibiting cholesterol synthesis and lipid accumulation, and surface plasmon resonance confirmed direct binding of its active components (ligustilide, 5,6,4\u2032\u2010trihydroxy\u20107,3\u2032\u2010dimethoxyflavone, (Z)\u20103\u2010butylidenephthalide, senkyunolide H, ferulic acid, guanosine) to NMNAT1. In conclusion, JHP ameliorates early NONFH by regulating lipid metabolism, improving hypercoagulability, and restoring bone homeostasis through the NMNAT1\/NMNAT3\/NAMPT\/STK11\/HMGCR\/ACAT1 axis.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.70858","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T04:16:53Z","timestamp":1758687413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Jianpi\u2010Huogu Prescription Repairs Nontraumatic Osteonecrosis of the Femoral Head by Inhibiting\n                    <scp>NAMPT<\/scp>\n                    \/\n                    <scp>STK11<\/scp>\n                    \/\n                    <scp>HMGCR<\/scp>\n                    \/\n                    <scp>ACAT1<\/scp>\n                    Axis\u2010Mediated Lipid Production"],"prefix":"10.1111","volume":"29","author":[{"given":"Tao","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaochen","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangrong","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jia","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Beijing University of Chinese Medicine; Engineering Research Center\u00a0of\u00a0Chinese\u00a0Orthopaedics\u00a0and\u00a0Sports\u00a0Rehabilitation\u00a0Artificial\u00a0Intelligent,\u00a0Ministry\u00a0of\u00a0Education  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Yunnan University of Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Beijing University of Chinese Medicine; Engineering Research Center\u00a0of\u00a0Chinese\u00a0Orthopaedics\u00a0and\u00a0Sports\u00a0Rehabilitation\u00a0Artificial\u00a0Intelligent,\u00a0Ministry\u00a0of\u00a0Education  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-111X","authenticated-orcid":false,"given":"Yanqiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2019.12.004"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker197"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000157539.67567.03"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.09.018"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102474\u201012\u201082"},{"key":"e_1_2_12_7_1","volume-title":"The Essentials of the Golden Chamber","author":"Zhang Z.","year":"2006"},{"key":"e_1_2_12_8_1","unstructured":"Taiping Huimin Hejiaobu \u201cTaiping Huimin Hejiaobu Fang [M] \u201d(Beijing: People's Health Publishing House (1985) 310)."},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2020.03.014"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.I.00575"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.18430"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.13422\/j.cnki.syfjx.20230506"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.13422\/j.cnki.syfjx.20230442"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky987"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.19540\/j.cnki.cjcmm.20211116.401"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0254\u20106272(14)60100\u2010x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108074"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2261758"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010021\u201001493\u20106"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12858\u2010019\u20100108\u20101"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.03.008"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.04.002"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.9b05495"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201031575\u2010y"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psj.2020.10.062"},{"issue":"8","key":"e_1_2_12_26_1","first-page":"1054","article-title":"Treating Early\u2010To\u2010Middle Stage Nontraumatic Osteonecrosis of Femoral Head Patients by Jianpi Huogu Recipe: A Retrospective Study","volume":"33","author":"Chen W.","year":"2013","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.80250"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlife.2024.12.003"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.107452"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153669"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02976451"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03708"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2022.2042327"},{"key":"e_1_2_12_33_2","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.1080\/13880209.2022.2113958].","DOI":"10.1080\/13880209.2022.2113958"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1042044"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222313163"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlife.2024.11.006"},{"issue":"3","key":"e_1_2_12_37_1","first-page":"287","article-title":"Prospective Study on Jianpihuogu Formula for Early\u2010and Mid\u2010Stage Non\u2010Traumatic Osteonecrosis of Femoral Head","volume":"7","author":"Chen W.\u2010h.","year":"2013","journal-title":"Chinese Journal of Joint Surgery"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010018\u20101001\u20102"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.19124"},{"key":"e_1_2_12_39_2","doi-asserted-by":"crossref","unstructured":"https:\/\/doi.org\/10.7150\/ijms.29056].","DOI":"10.7150\/ijms.29056"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944\u2010022\u201001696\u2010w"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113358"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.12.012"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2020.148276"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018\u2010022\u201003417\u20106"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70858","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T09:06:18Z","timestamp":1764666378000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":45,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/jcmm.70858"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70858","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70858"}}