{"id":"c7270250-58d4-5acf-97f7-f05ec4deba6e","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:raw-inflammatory","predicate":"decreases_in_recorded_experiment","statement":"SA reduced nitrite and selected cytokine responses in LPS-challenged RAW264.7 cells.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ead0d251-4a1d-5a84-bbf7-d3c3b711a514","mechanism_event_label":"SA reduced nitrite and selected cytokine responses in LPS-challenged RAW264.7 cells.","subject":{"id":"67ad4a8f-1bf6-59e5-90a6-97b7709024d3","slug":"shikimic-acid","display_name":"Shikimic acid","entity_type_key":"small_molecule"},"object":{"id":"2178b2b9-74ba-5524-b56e-f3d06fc2cef2","slug":"mouse-raw2647-inflammatory-response","display_name":"Mouse RAW264.7 LPS-induced cytokine/nitrite response","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ead0d251-4a1d-5a84-bbf7-d3c3b711a514","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:raw-inflammatory-event","event_type":"experimental_observation","label":"SA reduced nitrite and selected cytokine responses in LPS-challenged RAW264.7 cells.","description":"**Other inflammatory models are separate evidence.** Rabelo 2016 reported lower nitrite, TNF and IL-1β responses and reduced ERK/p38 phosphorylation in LPS-exposed mouse RAW264.7 macrophages. Rodent pain outcomes were also reported at 50–200 mg/kg depending on the test. Only the indexed abstract was available for this extraction, so unverified route, cell dose and timing are not invented. Lower p38 signaling here and higher p38 phosphorylation in hair cells are different conditions, not automatically conflicting studies. [Shikimic acid inhibits LPS-induced cellular pro-inflammatory cytokines and attenuates mechanical hyperalgesia in mice.](https://pubmed.ncbi.nlm.nih.gov/27454847/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"67ad4a8f-1bf6-59e5-90a6-97b7709024d3","slug":"shikimic-acid","display_name":"Shikimic acid","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"SA plus LPS","sequence_order":0,"notes":""},{"entity":{"id":"2178b2b9-74ba-5524-b56e-f3d06fc2cef2","slug":"mouse-raw2647-inflammatory-response","display_name":"Mouse RAW264.7 LPS-induced cytokine/nitrite response","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"e96aad69-74fb-55c6-8378-7d5c281003eb","slug":"lipopolysaccharide","display_name":"Lipopolysaccharide","entity_type_key":"chemical_species"},"role":"stimulus","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary indexed abstract reviewed; full results, tables and supplements not independently extracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"stimulus","comparator":"LPS without SA","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"lipopolysaccharide","display_name":"Lipopolysaccharide","entity_type_key":"chemical_species"}},{"dimension":"experimental_condition","value_text":"added","comparator":"LPS without SA","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"shikimic-acid","display_name":"Shikimic acid","entity_type_key":"small_molecule"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"SA plus LPS\", \"comparator\": \"LPS without SA\", \"endpoint\": \"SA reduced nitrite and selected cytokine responses in LPS-challenged RAW264.7 cells.\", \"effect_direction\": \"decrease\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"shikimic-acid\", \"state\": \"added\"}, {\"entity_slug\": \"lipopolysaccharide\", \"state\": \"stimulus\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Mouse RAW264.7; accessible abstract, cell dose not independently extracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"SA reduced nitrite and selected cytokine responses in LPS-challenged RAW264.7 cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Shikimic acid inhibits LPS-induced cellular pro-inflammatory cytokines and attenuates mechanical hyperalgesia in mice. | 2016 | DOI 10.1016/j.intimp.2016.07.016 | PMID 27454847 | https://pubmed.ncbi.nlm.nih.gov/27454847/ | https://doi.org/10.1016/j.intimp.2016.07.016","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 67-67; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"81a3ea58-42a2-5264-8e5c-0eed1dead273","evidence_kind":"source_excerpt","locator":"Lines 67-67","start_line":67,"end_line":67,"excerpt":"**Other inflammatory models are separate evidence.** Rabelo 2016 reported lower nitrite, TNF and IL-1β responses and reduced ERK/p38 phosphorylation in LPS-exposed mouse RAW264.7 macrophages. Rodent pain outcomes were also reported at 50–200 mg/kg depending on the test. Only the indexed abstract was available for this extraction, so unverified route, cell dose and timing are not invented. Lower p38 signaling here and higher p38 phosphorylation in hair cells are different conditions, not automatically conflicting studies. [Shikimic acid inhibits LPS-induced cellular pro-inflammatory cytokines and attenuates mechanical hyperalgesia in mice.](https://pubmed.ncbi.nlm.nih.gov/27454847/)","model_system":"Mouse RAW264.7; accessible abstract, cell dose not independently extracted.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. Not a verbatim quotation from a primary paper.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e6ae59de-0369-5c2f-8262-57d91302671c","stable_key":"import-31b1baa4-4113-5541-b9e7-fe44a5253a07","title":"Shikimic acid: detailed mechanisms of action (reviewed 5 October 2026)","document_type":"imported_text","citation_label":"Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication.","file_path":"","sha256":"95b1f9e9577661312d67f36e156d2e49326b207f296c1c0e801a5b007fd8e283","revision_id":"cd3237f1-131a-557d-84b5-7543259807b0","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}