Upstream Complement Literature Inventory — Legacy COMP-020 Provenance¶

MSU crystals activate complement and generate C5a, making upstream complement interference a plausible way to weaken flare priming. This literature re-run identifies assay-specific natural-product leads; it does not rank them, establish gout activity, or show that any reaches a useful compartment.

Evidence that survives¶

Rosmarinic acid covalently modified activated C3b and reduced C3b deposition in the Sahu 1999 biochemical system (In Vitro; PMID 10353266). Englberger 1988 and Peake 1991 used different complement formats and conditions (In Vitro; PMIDs 3198307 and 1761351). Their reported concentrations are descriptive records from non-interchangeable assays, not a combined potency range or an operative gout concentration.
Helicteres angustifolia benzofuran lignans inhibited complement in the Yin 2016 hemolytic and depletion-rescue experiments (In Vitro, single-paper anchor; PMID 27834928 / PMC6273495). Independent matched-material replication is required before priority or translation claims.
Luteolin and other flavonoids, Bupleurum polysaccharides, marine sulfated polysaccharides, and heparin-derived oligosaccharides have complement-assay evidence in the cited primary records (In Vitro). The materials, assay formats, units, and safety constraints differ, so cross-paper ordering is not justified.

The legacy scan preserves those source observations but supplies no threshold-qualified hit set, headline compound, tier, assay-format causality, comparative potency, dietary efficacy, ChEMBL coverage rate, exhaustive absence conclusion, or platform priority. Its artifact predates the current reproducible lifecycle and is quarantined as literature-mining provenance, not a completed COMP or quantitative model.

Sourcing and delivery¶

Rosmarinic acid and luteolin occur in multiple plants; Helicteres lignans require exact compound isolation or a qualified botanical material; polysaccharide activity depends on the exact extracted material. Botanical name alone is not a product specification.

The proposed gout-relevant compartment is unresolved. Oral availability, metabolism, protein binding, intestinal concentration, and access to MSU-associated complement can differ sharply among small molecules and polysaccharides. Plasma exposure does not establish gut-luminal activity, and gut-luminal exposure does not establish joint exposure.

Experiment that changes the decision¶

Choose a candidate from its independently verified evidence home, qualify one exact material, and test it in a preregistered concentration series using complement-competent serum with vehicle and positive controls. Measure an MSU-associated endpoint such as C5a or C5b-9, plus material stability and recovery under the same conditions. Replicate the exact material independently before comparing it with another class or making a sourcing decision.

A positive result advances only that material, assay, and compartment hypothesis. A negative result redirects that candidate without rejecting upstream complement as an exploitable gout weakness.