{"id":"3f25638e-40d3-5c09-b6ef-fee15530cd9e","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:avermectin-nfkb-mapk-inflammation","predicate":"reduces","statement":"Avermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"a7cf67ba-90be-557a-905d-28cdfccb43c4","mechanism_event_label":"Avermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages.","subject":{"id":"1bafa49b-3d92-5083-bff2-ab29cab57cb4","slug":"avermectin","display_name":"Avermectin","entity_type_key":"chemical_species"},"object":{"id":"298f597e-d720-5f42-8cca-44e91c8ea42e","slug":"raw2647-nfkb-translocation","display_name":"NF-kappa-B p65 nuclear translocation in RAW 264.7 macrophages","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a7cf67ba-90be-557a-905d-28cdfccb43c4","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:avermectin-nfkb-mapk-inflammation-event","event_type":"observed_relationship","label":"Avermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages.","description":"Avermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1bafa49b-3d92-5083-bff2-ab29cab57cb4","slug":"avermectin","display_name":"Avermectin","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"298f597e-d720-5f42-8cca-44e91c8ea42e","slug":"raw2647-nfkb-translocation","display_name":"NF-kappa-B p65 nuclear translocation in RAW 264.7 macrophages","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"30 minutes after lipopolysaccharide","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":"Mouse RAW 264.7 macrophages","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Avermectin 0.625, 1.25 or 5 mg/L for one hour before 1 mg/L lipopolysaccharide","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The compound tested was avermectin, the parent macrocyclic lactone, not ivermectin, and tumour necrosis factor alpha, interleukin-1 beta and interleukin-10 were regulated while interleukin-6 was not significantly affected.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mouse RAW 264.7 macrophages","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Avermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway. (2009). https://pubmed.ncbi.nlm.nih.gov/19453757/ DOI: 10.1111/j.1472-8206.2009.00684.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"NF-kappa-B and MAP kinase signalling, cytokine output","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ad8dd943-2d95-5ca3-a327-af0867937da9","evidence_kind":"source_excerpt","locator":"Lines 222-231","start_line":222,"end_line":231,"excerpt":"## avermectin-nfkb-mapk-inflammation\nAvermectin inhibited NF-kappa-B p65 translocation into the nucleus and inhibited JNK and p38 phosphorylation in lipopolysaccharide-stimulated mouse macrophages.\nModel/species: Mouse RAW 264.7 macrophages\nTissue/system: NF-kappa-B and MAP kinase signalling, cytokine output\nExposure: Avermectin 0.625, 1.25 or 5 mg/L for one hour before 1 mg/L lipopolysaccharide\nRoute: In vitro\nDuration: 30 minutes after lipopolysaccharide\nLimits: The compound tested was avermectin, the parent macrocyclic lactone, not ivermectin, and tumour necrosis factor alpha, interleukin-1 beta and interleukin-10 were regulated while interleukin-6 was not significantly affected.\nPrimary reference: Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway. (2009). https://pubmed.ncbi.nlm.nih.gov/19453757/ DOI: 10.1111/j.1472-8206.2009.00684.x\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":"20818ddd-7b37-5226-a24b-7de007e80eb2","stable_key":"import-e0801c92-7fd3-5cb2-82b7-dd82f010f3ed","title":"Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. 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