{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:56:07Z","timestamp":1790708167732,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intervertebral disc degeneration (IDD) is driven by macrophage\u2010mediated inflammation involving the p38MAPK\/NF\u2010\u03baB signaling pathway and impaired autophagic flux. Juanbi Tang (JBT), a classical eleven\u2010herb Chinese formula documented since 1732 CE for the treatment of Bi syndrome (a traditional diagnosis encompassing painful musculoskeletal obstruction conceptually corresponding to degenerative spinal conditions), demonstrates clinical anti\u2010inflammatory activity; however, its molecular mechanism in IDD remains uncharacterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>JBT chemical composition was characterized by HPLC fingerprinting with osthole as quantitative reference standard (inter\u2010batch RSD 2.3%) in accordance with the 2020 Chinese Pharmacopoeia, and quality control was extended beyond a single marker constituent by multi\u2010component fingerprint similarity analysis using the cosine angle and correlation coefficient methods. A male Sprague\u2013Dawley rat annular puncture IDD model (five groups: Sham, IDD, IDD\u2009+\u2009JBT, IDD\u2009+\u20093\u2010methyladenine [3\u2010MA], and IDD\u2009+\u2009JBT\u2009+\u20093\u2010MA) was evaluated by MRI, CT, Safranin O\u2013Fast Green, Masson trichrome and hematoxylin and eosin staining. LPS\u2010stimulated (1\u2009\u03bcg\/mL) primary rat nucleus pulposus (NP) cells and murine RAW264.7 macrophages \u2014 including Atg5\u2010overexpressing (Atg5\u2010OE) and knockdown (Atg5\u2010KD) variants \u2014 were used for in vitro mechanistic studies. Endpoints included apoptosis, mitochondrial membrane potential (\u0394\u03a8m), reactive oxygen species (ROS), macrophage M1\/M2 polarization, ELISA cytokine quantification and Western blot pathway analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In vivo, JBT significantly improved Pfirrmann grade, disc height index, Safranin O staining intensity, Masson\u2010stained collagen content and Thompson grade, with concomitant suppression of serum TNF\u2010\u03b1 and restoration of IL\u201010; all benefits were partially abrogated by 3\u2010MA co\u2010administration. JBT suppressed p\u2010p38MAPK and p\u2010NF\u2010\u03baB p65 and restored the COL II\/MMP\u201013 balance in disc tissue. In NP cells, JBT reduced total apoptosis from 29.1% to 14.5%, restored \u0394\u03a8m, attenuated ROS accumulation, reversed the Bax\/Bcl\u20102 ratio, and activated autophagy (LC3\u2010II\u2009\u2191\u2009, p62\u2009\u2193\u2009). In RAW264.7 macrophages, JBT promoted M2 polarization (CD206\n                      <jats:sup>+<\/jats:sup>\n                      : 28.1% to 49.7%) and suppressed M1 polarization (CD197\n                      <jats:sup>+<\/jats:sup>\n                      : 52.4% to 18.9%) under LPS stimulation, with concurrent autophagy activation. Western blot analysis across normal, Atg5\u2010OE and Atg5\u2010KD macrophages demonstrated that Atg5 expression level bidirectionally modulates p62 clearance and consequent NF\u2010\u03baB suppression, consistent with the autophagy\u2013p62\u2013NF\u2010\u03baB regulatory module contributing to JBT's pharmacological activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>JBT attenuates IDD through coordinated suppression of macrophage\u2010driven inflammation and activation of autophagy, providing mechanistic support for its clinical application in musculoskeletal disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70498","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:59:53Z","timestamp":1789045193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Juanbi Tang Attenuates Intervertebral Disc Degeneration by Suppressing p38MAPK\/NF\u2010\u03baB Signaling and Activating Atg5\u2010Dependent Autophagy to Promote Macrophage M2 Polarization: In Vivo and In Vitro Evidence"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4951-2026","authenticated-orcid":false,"given":"Ye\u2010Hui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Spine and Neurosurgery Sichuan Province Orthopedic Hospital Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Spine and Neurosurgery Sichuan Province Orthopedic Hospital Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010Sheng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Spine and Neurosurgery Sichuan Province Orthopedic Hospital Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan\u2010Geng","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Spine and Neurosurgery Sichuan Province Orthopedic Hospital Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Mao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Spine and Neurosurgery Sichuan Province Orthopedic Hospital Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Spine and Neurosurgery Sichuan Province Orthopedic Hospital Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Spine and Neurosurgery Sichuan Province Orthopedic Hospital Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"e316","article-title":"Global, Regional, and National Burden of Low Back Pain, 1990\u20102020, its Attributable Risk Factors, and Projections to 2050","volume":"5","author":"GBD 2021 Low Back Pain Collaborators","year":"2023","journal-title":"Lancet Rheumatology"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00733-9"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021367"},{"key":"e_1_2_12_5_1","first-page":"8","article-title":"Role of Macrophage in Intervertebral Disc Degeneration","volume":"13","author":"Zhao Y.","year":"2025","journal-title":"Bone Research"},{"key":"e_1_2_12_6_1","first-page":"27","article-title":"Mechanisms and Therapeutic Strategies of Macrophage Polarization in Intervertebral Disc Degeneration","volume":"52","author":"Hu Z.","year":"2025","journal-title":"Journal of Orthopaedic Translation"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13057"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1324561"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200507002"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.023"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00045"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.5.3127"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf102812t"},{"key":"e_1_2_12_14_1","first-page":"23","article-title":"Osthole Improves Collagen\u2010Induced Arthritis in a Rat Model Through Inhibiting Inflammation and Cellular Stress","volume":"23","author":"Hu P. 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