{"id":"e8098219-8b72-54b4-8ff7-2a7a31202f5b","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:mk2206-nrf2","predicate":"decreases_in_recorded_experiment","statement":"MK2206 attenuated shikimic-acid-associated Nrf2 accumulation.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"54a5912c-2193-53a1-87ae-bd9f49904896","mechanism_event_label":"MK2206 attenuated shikimic-acid-associated Nrf2 accumulation.","subject":{"id":"f4be1e35-7918-56fe-a5be-95b880a1521c","slug":"mk2206","display_name":"MK2206","entity_type_key":"small_molecule"},"object":{"id":"83e40444-8c9b-59bf-a54f-0ed04f43bfb0","slug":"mouse-bv2-nrf2-nuclear","display_name":"Mouse BV2 nuclear Nrf2 accumulation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"54a5912c-2193-53a1-87ae-bd9f49904896","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:mk2206-nrf2-event","event_type":"experimental_observation","label":"MK2206 attenuated shikimic-acid-associated Nrf2 accumulation.","description":"**AKT and Nrf2 involvement does not identify the binding target.** BV2 experiments recorded increased AKT phosphorylation and nuclear Nrf2. MK2206 pretreatment attenuated Nrf2 activation and partially reversed redox/nitrite responses. A reagent labeled RA also attenuated the Nrf2 response; its identity and selectivity are not independently resolved here, so no vitamin-A or retinoic-acid interaction is created from that abbreviation. Pharmacological perturbation supports pathway involvement while leaving the initiating target and off-target alternatives open. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced <i>in vitro</i> and <i>in vivo</i> model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f4be1e35-7918-56fe-a5be-95b880a1521c","slug":"mk2206","display_name":"MK2206","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"MK2206 pretreatment with shikimic acid","sequence_order":0,"notes":""},{"entity":{"id":"83e40444-8c9b-59bf-a54f-0ed04f43bfb0","slug":"mouse-bv2-nrf2-nuclear","display_name":"Mouse BV2 nuclear Nrf2 accumulation","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"67ad4a8f-1bf6-59e5-90a6-97b7709024d3","slug":"shikimic-acid","display_name":"Shikimic acid","entity_type_key":"small_molecule"},"role":"joint exposure","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text retrieved; relevant methods/results/figures reviewed. Selective extraction, not raw-data reanalysis or exhaustive supplemental extraction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"pretreatment","comparator":"Shikimic acid without MK2206","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"mk2206","display_name":"MK2206","entity_type_key":"small_molecule"}},{"dimension":"experimental_condition","value_text":"present","comparator":"Shikimic acid without MK2206","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\": \"MK2206 pretreatment with shikimic acid\", \"comparator\": \"Shikimic acid without MK2206\", \"endpoint\": \"MK2206 attenuated shikimic-acid-associated Nrf2 accumulation.\", \"effect_direction\": \"decrease\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"mk2206\", \"state\": \"pretreatment\"}, {\"entity_slug\": \"shikimic-acid\", \"state\": \"present\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Mouse BV2; MK2206 10 µM for 4 h before pathway assay.","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":"Pharmacological pathway perturbation; not proof of direct SA–AKT binding or perfect inhibitor specificity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"MK2206 attenuated shikimic-acid-associated Nrf2 accumulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced <i>in vitro</i> and <i>in vivo</i> model. | 2023 | DOI 10.3389/fphar.2023.1265571 | PMID 38026972 | https://pubmed.ncbi.nlm.nih.gov/38026972/ | https://doi.org/10.3389/fphar.2023.1265571 | https://pmc.ncbi.nlm.nih.gov/articles/PMC10652795/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 61-61; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"56babeeb-6bdb-59f0-8d79-0cbf8f2d1f2e","evidence_kind":"source_excerpt","locator":"Lines 61-61","start_line":61,"end_line":61,"excerpt":"**AKT and Nrf2 involvement does not identify the binding target.** BV2 experiments recorded increased AKT phosphorylation and nuclear Nrf2. MK2206 pretreatment attenuated Nrf2 activation and partially reversed redox/nitrite responses. A reagent labeled RA also attenuated the Nrf2 response; its identity and selectivity are not independently resolved here, so no vitamin-A or retinoic-acid interaction is created from that abbreviation. Pharmacological perturbation supports pathway involvement while leaving the initiating target and off-target alternatives open. [Shikimic acid (SA) inhibits neuro-inflammation and exerts neuroprotective effects in an LPS-induced <i>in vitro</i> and <i>in vivo</i> model.](https://pubmed.ncbi.nlm.nih.gov/38026972/)","model_system":"Mouse BV2; MK2206 10 µM for 4 h before pathway assay.","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. 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