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TCM Gout Compound Triage — Computational Analysis (comp-013)

Frozen analysis archived to ./etc/experiments/comp-013-tcm-gout-compound-triage/wiki-archive.md (409 lines). This wiki stub remains so cross-references resolve and the page stays discoverable. Computational analyses are write-once artifacts; the daemon does not need to re-read them on every sweep, so the long content lives next to the experiment that produced it at etc/experiments/comp-013-tcm-gout-compound-triage/.

Question: Which Traditional Chinese Medicine (TCM) compounds with documented gout indication are mechanistically viable when triaged via the comp-004 IC50 occupancy + comp-007 composite scoring frameworks?

Where the analysis lives: - Full archived analysis: ./etc/experiments/comp-013-tcm-gout-compound-triage/wiki-archive.md - Experiment directory (inputs, scripts, outputs): ./etc/experiments/comp-013-tcm-gout-compound-triage/ - Computational experiments index: computational-experiments.md

Addendum — 2026-05-19 traditional-name re-scan corrections + additions

This addendum captures the marker-correction batch surfaced by the 2026-05-19 traditional-formula-name re-scans (URAT1 rescan, XO rescan). These are formula-anchored + species-anchored findings that the original comp-013 herb-by-herb query framing missed. Per CLAUDE.md §"Global-multilingual research by default", the discipline upgrade is to seed compound lists from traditional formula composition + traditional pathology term (e.g., 痛风 / 痹证 / 湿热痹) in addition to mechanism-name queries.

1. Mangiferin → Zhi Mu / Anemarrhena asphodeloides (new tier-1 entry). Mangiferin (CHEMBL3611008) is the cardinal anti-hyperuricemia active in A. asphodeloides. Niu 2015 + supporting series: dual-pathway URAT1 down-regulation + AQP2 modulation. Anemarrhena is a cardinal herb of Bai Hu Jia Gui Zhi Tang (BHGZ; the canonical gout-active formula in the modern Chinese RCT literature). Tier-1 promotion based on (a) mechanism, (b) BHGZ RCT context, © ChEMBL coverage of mangiferin. Adds to the comp-013 URAT1 row alongside cordycepin and astilbin. (In Vitro + Animal Model; source: urat1-classical-formula-rescan-2026-05-19.md)

2. Bai Hu Jia Gui Zhi Tang (BHGZ) — ChiCTR1900024974 RCT scope. White Tiger Plus Cinnamon Branch decoction (Anemarrhena + gypsum + cinnamon + rice + licorice) is the canonical TCM gout formula in the modern Chinese RCT literature. ChiCTR1900024974 is a registered RCT (protocol PMC9013133, 2022); outcomes paper pending. 91% pilot effectiveness in the protocol's prior-series basis is uncontrolled — wait for the RCT outcomes paper before promoting beyond mechanism-tier. A later open-access rat MSU acute-gout study supports BHGZ as an inflammation-axis candidate through reduced ankle inflammation, IL-1β/IL-6, and TLR4/MyD88/NF-kB readouts, but this is Animal Model evidence and does not establish human efficacy or urate lowering. (Clinical Trial protocol; outcomes pending + Animal Model inflammation mechanism. Sources: urat1-classical-formula-rescan-2026-05-19.md; Liu 2025, Clinics, DOI 10.1016/j.clinsp.2025.100665)

3. Coix lacryma-jobi (Yi Yi Ren) — major mechanism upgrade. Original comp-013 entry attributed activity to "atractylenolide I = MECHANISM UNCLEAR". The 2026-05-19 re-scan replaces this with Coix seed oil four-transporter mechanism (URAT1 + GLUT9 + OAT1 + ABCG2) at 73-87% SUA reduction in HUA rodent models (PMC12114407). This is a major upgrade — four-transporter coverage from a single GRAS food-grade input. (Animal Model; source: urat1-classical-formula-rescan-2026-05-19.md)

4. Plantago seed (Che Qian Zi) — attribution correction. Original comp-013 attributed Plantago activity to aucubin. The 2026-05-19 re-scan replaces aucubin attribution with acteoside + apigenin + geniposidic acid via PPAR pathway → URAT1 + GLUT9 (Liu 2024 PMC11313179). Apigenin specifically deserves a separate URAT1 mechanism entry per Li 2021 PMID 34044255. (In Vitro + Animal Model; source: urat1-classical-formula-rescan-2026-05-19.md)

5. Si Miao San (SMS) — phytoecdysteroid + estrone arms missed. The original comp-013 SMS row captured the main flavonoid + alkaloid contributions. The 2026-05-19 re-scan surfaced two additional axes: (a) Phytoecdysteroids from Achyranthes bidentata / Niu Xi (one of the four SMS cardinal herbs) — independent ecdysteroid-pathway anti-inflammatory mechanism. (b) Estrone-family signaling — multiple SMS components engage estrogen-receptor-mediated downstream effects relevant to bone + inflammation. Both axes are mechanism-additive to the existing flavonoid arm. (Mechanistic Extrapolation; source: urat1-classical-formula-rescan-2026-05-19.md)

6. Rhein / Emodin split in Rheum palmatum (Da Huang) — mechanism separation. Original comp-013 framing treated rhein + emodin as a co-acting anthraquinone class. The 2026-05-19 re-scan separates them: rhein → direct XO inhibition (Meng 2015, Animal Model); emodin → transporter-mediated UA excretion, NO XO inhibition (Hou 2023 PMC10304951, already cited but mechanism not separated in narrative). Treat as two distinct chokepoint engagements rather than one. (Animal Model; source: xo-classical-formula-rescan-2026-05-19.md)

7. Acacetin → Agastache rugosa / Huo Xiang (new tier-1 XO chokepoint candidate). Yuk 2023 PMC9914411: acacetin XO IC50 = 0.58 μM. Most potent flavonoid in panel, beats luteolin. Classical formula context: Huo Xiang Zheng Qi. GRAS culinary status in Korea + Japan. Tier-1 XO chokepoint entry. (In Vitro; source: xo-classical-formula-rescan-2026-05-19.md)

8. Kaempferol → Chrysanthemum morifolium / Ju Hua (new tier-1 XO chokepoint candidate). Wee 2023 PMC9864848: kaempferol XO IC50 = 2.18 μM. Lee 2018 PMC6213378 DKB114 formula 38.3% UA ↓ at 200 mg/kg, XO IC50 104.4 μg/mL. Tier-1 XO chokepoint entry. (In Vitro + Animal Model; source: xo-classical-formula-rescan-2026-05-19.md)

9. Chlorogenic acid as a compound-class entry (not per-herb). Chlorogenic acid family is XO-active across Wu Mei (Prunus mume), Lonicera japonica, and likely Crataegus pinnatifida (Shan Zha) and others. Reframe as a compound-class entry rather than per-herb redundant entries. (In Vitro; source: xo-classical-formula-rescan-2026-05-19.md)

10. H04 falsification card partial closure. Comp-013's H04 hypothesis card flagged "ChEMBL coverage gap" — 5/9 compounds had no ChEMBL data. The 2026-05-19 traditional-name-first scan partially closes this: mangiferin (CHEMBL3611008), apigenin (well-cataloged), acteoside (curated). The methodology gap isn't ChEMBL coverage — it's seed-list construction at the herb level rather than the formula + marker level. Update H04 with this diagnosis: the falsification was query-framing, not database coverage.

Cross-references for this addendum: - urat1-classical-formula-rescan-2026-05-19.md - xo-classical-formula-rescan-2026-05-19.md - lit-scan-query-framing-retrospective-audit-2026-05-19.md — the audit triggering both re-scans - hypotheses/H04-tcm-rigor-intersection.md — needs marker-correction update incorporating items 1, 3, 4 above - gout-pathophysiology.md §"multi-track urate transporter coverage" — XO row updated with acacetin + kaempferol + rhein - abcg2-modulators.md §"Tier 2 — Solid mechanism, modest evidence" — Poria cocos added (sister rescan finding, mushroom-hdac6-q141k-rescan-2026-05-19.md)