{"id":"cd8ced4d-a4da-5669-ad2b-2f4dc40dc557","stable_key":"96d9034a-2550-5f3c-b767-1767c982533c:p38-required-for-the-nrf2-response","predicate":"enables","statement":"The p38 inhibitor SB239063 suppressed the (+)-lariciresinol-induced response, placing p38 upstream of it.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"f34b477f-c6df-5246-b431-5dc82c4c3d05","mechanism_event_label":"The p38 inhibitor SB239063 suppressed the (+)-lariciresinol-induced response, placing p38 upstream of it.","subject":{"id":"8e62ed16-0010-5b56-acf2-f0684433098d","slug":"p38-mapk","display_name":"p38 mitogen-activated protein kinase family","entity_type_key":"protein_family"},"object":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"f34b477f-c6df-5246-b431-5dc82c4c3d05","stable_key":"96d9034a-2550-5f3c-b767-1767c982533c:p38-required-for-the-nrf2-response-event","event_type":"observed_relationship","label":"The p38 inhibitor SB239063 suppressed the (+)-lariciresinol-induced response, placing p38 upstream of it.","description":"The p38 inhibitor SB239063 suppressed the (+)-lariciresinol-induced response, placing p38 upstream of it.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8e62ed16-0010-5b56-acf2-f0684433098d","slug":"p38-mapk","display_name":"p38 mitogen-activated protein kinase family","entity_type_key":"protein_family"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"09e8fc4d-e8f7-569b-a427-4c271f523a30","slug":"plus-lariciresinol","display_name":"(+)-Lariciresinol","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Acute","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"RAW 264.7 murine macrophages","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"SB239063 with (+)-lariciresinol","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Inhibitor dependence establishes that p38 is required, not that lariciresinol binds or acts on p38 directly.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"RAW 264.7 murine macrophages","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The p38 inhibitor SB239063 suppressed the (+)-lariciresinol-induced response, placing p38 upstream of it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"p38 dependence of the antioxidant response","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c6b531d3-d9a1-5c9f-9f85-bb167fa8488b","evidence_kind":"source_excerpt","locator":"Lines 22-31","start_line":22,"end_line":31,"excerpt":"## p38-required-for-the-nrf2-response\nThe p38 inhibitor SB239063 suppressed the (+)-lariciresinol-induced response, placing p38 upstream of it.\nModel/species: RAW 264.7 murine macrophages\nTissue/system: p38 dependence of the antioxidant response\nExposure: SB239063 with (+)-lariciresinol\nRoute: In vitro\nDuration: Acute\nLimits: Inhibitor dependence establishes that p38 is required, not that lariciresinol binds or acts on p38 directly.\nPrimary reference: Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"48c58761-0291-5bad-a926-75e904b2d802","stable_key":"import-96d9034a-2550-5f3c-b767-1767c982533c","title":"Lariciresinol: five molecules under one name, and the mechanisms each one carries (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies, every abstract read and all DOIs cross-checked against live PubMed metadata. Mechanism edges only, with no conclusion or claim of benefit recorded. Three author clusters account for eight of the twelve and carry shared laboratory keys. Study-specific concentrations, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"6bf0015b7ff727b7a80d693dd18ffdd227d0e16ae45d9e85a5f81fa733edd3a4","revision_id":"219d9b0c-1a71-5e27-8d6c-7b3e77a594c6","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}