Rosmarinic Acid + DAF SCR1-4 Combination Question (comp-029)¶
Could rosmarinic acid and active DAF SCR1-4 suppress MSU-associated complement activation more than either exact material alone?
COMP-029 cannot answer that question. It combined assumed exposure and DAF-accessibility distributions with an uncalibrated composition rule. Every numerical result, confidence interval, category, co-localization claim, complementarity claim, and routing conclusion is invalid. The COMP-029 tombstone is non-runnable; Git retains the retired implementation and outputs.
Evidence boundary¶
Rosmarinic acid changed complement readouts in biochemical assays, with material assay-format variation (In Vitro; PMIDs 10353266 and 3198307). DAF accelerates decay of complement convertases (In Vitro; PMC2187498 and PMC2189641). MSU-associated complement activation can generate downstream complement products (In Vitro; PMC8924570).
Those observations do not establish that rosmarinic acid and DAF reach the same relevant compartment, remain active together, act independently, or produce an additive or synergistic effect. COMP-012 also does not establish DAF expression, folding, protease survival, retained activity, delivery, or MSU-surface access.
Research conjecture — two-node complement suppression may outperform either arm alone
Grounded premises: Rosmarinic acid changes complement readouts in biochemical assays (In Vitro; PMID 10353266 and PMID 3198307). DAF accelerates decay of complement convertases (In Vitro; PMC2187498 and PMC2189641). MSU-associated complement activation generates measurable downstream products (In Vitro; PMC8924570).
Novel leap: If delivered in active form to the same relevant compartment, rosmarinic acid and DAF SCR1-4 may suppress MSU-associated complement activation more than either arm alone. No direct evidence establishes the exact pair, delivery geometry, exposure, or interaction.
Why it matters: A genuine combination effect could expose a multi-node weakness that neither intervention can exploit reliably alone.
Discriminating observation: Once an active DAF preparation exists, compare vehicle, rosmarinic acid, DAF SCR1-4, and their combination in one matched complement-competent-serum assay. Measure C5a, C5b-9, DAF recovery, retained function, and surface association across prespecified concentrations.
A useful result must show that each exact material remains active in the joint assay and that the combination differs reproducibly from the stronger singleton. A null result kills only the tested pairing and conditions.
Related: complement evidence · DAF construct question · H05 · validation experiments