{"id":"926709d8-8332-5ce0-810f-ae73b52764e4","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:hair-creb","predicate":"increases_in_recorded_experiment","statement":"SA increased CREB phosphorylation in human dermal papilla cells.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"da06503a-18e8-5e91-9872-d478d0617e47","mechanism_event_label":"SA increased CREB phosphorylation in human dermal papilla cells.","subject":{"id":"67ad4a8f-1bf6-59e5-90a6-97b7709024d3","slug":"shikimic-acid","display_name":"Shikimic acid","entity_type_key":"small_molecule"},"object":{"id":"4651e07f-f3b9-591c-b0f3-9142cc1b3744","slug":"human-creb1","display_name":"Human cAMP response element-binding protein 1 / CREB1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"da06503a-18e8-5e91-9872-d478d0617e47","stable_key":"31b1baa4-4113-5541-b9e7-fe44a5253a07:hair-creb-event","event_type":"experimental_observation","label":"SA increased CREB phosphorylation in human dermal papilla cells.","description":"**Hair-follicle findings include human tissue, not a human treatment trial.** In isolated human hair follicles, 1 or 10 µM shikimic acid increased shaft elongation during 12-day culture. Dermal papilla cells showed higher MTT readouts, and 1 µM exposure increased MYC, HGF, KGF and VEGF transcripts at 24 h and p38/CREB phosphorylation at 15 min. Transcript increases are not proof of increased secreted growth-factor flux. Mannose-receptor staining establishes receptor presence, not that this receptor was necessary for the response. Topical 10–100 mM exposure also affected anagen-related measurements in mice; neither system establishes oral human hair regrowth. [Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle.](https://pubmed.ncbi.nlm.nih.gov/31740717/)","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","sequence_order":0,"notes":""},{"entity":{"id":"4651e07f-f3b9-591c-b0f3-9142cc1b3744","slug":"human-creb1","display_name":"Human cAMP response element-binding protein 1 / CREB1","entity_type_key":"protein"},"role":"measured outcome","stoichiometry":null,"state_label":"increase","sequence_order":1,"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_contrast","value_text":"{\"intervention\": \"SA\", \"comparator\": \"Vehicle\", \"endpoint\": \"SA increased CREB phosphorylation in human dermal papilla cells.\", \"effect_direction\": \"increase\", \"combination\": \"single\", \"conditions\": []}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Human cells; 1 µM SA, 15 min.","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":"Signaling readout, not demonstrated direct receptor or kinase binding.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"SA increased CREB phosphorylation in human dermal papilla cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle. | 2019 | DOI 10.1038/s41598-019-53612-5 | PMID 31740717 | https://pubmed.ncbi.nlm.nih.gov/31740717/ | https://doi.org/10.1038/s41598-019-53612-5 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6861222/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 75-75; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0b173251-9c9d-5034-851c-c2756d115c21","evidence_kind":"source_excerpt","locator":"Lines 75-75","start_line":75,"end_line":75,"excerpt":"**Hair-follicle findings include human tissue, not a human treatment trial.** In isolated human hair follicles, 1 or 10 µM shikimic acid increased shaft elongation during 12-day culture. Dermal papilla cells showed higher MTT readouts, and 1 µM exposure increased MYC, HGF, KGF and VEGF transcripts at 24 h and p38/CREB phosphorylation at 15 min. Transcript increases are not proof of increased secreted growth-factor flux. Mannose-receptor staining establishes receptor presence, not that this receptor was necessary for the response. Topical 10–100 mM exposure also affected anagen-related measurements in mice; neither system establishes oral human hair regrowth. [Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle.](https://pubmed.ncbi.nlm.nih.gov/31740717/)","model_system":"Human cells; 1 µM SA, 15 min.","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}