1. Where’s the proof these TCM compounds actually bind VDR? No crystallography, no binding assays, just mRNA/protein level changes. Couldn’t this just be downstream noise?
2. Doses in cell studies (e.g., 50 μM emodin) are absurdly high. Show me pharmacokinetics proving these levels are reachable in humans, or this is just another ‘in vitro fantasy.
3. If VDR is mutated in rickets, do any TCM compounds rescue function? Gln152Xaa is mentioned, but zero data showing TCM fixes it. Overpromising without evidence.
4. Sepsis ‘protection’ via astragalus polysaccharide, how do we know it’s VDR and not just general anti-inflammation? Did they test VDR-KO mice? No? Then it’s speculation.
5. Psoriasis-1 formula ‘inhibits VDR/STAT4’—but other papers say VDR suppresses STATs.** Contradiction ignored. Which is it?”
6. **”Clinical relevance? Nowhere.** Xenografts? Patient samples? Most data are cells or rats. Call me when there’s a human trial.
7. Bufalin ‘stabilizes VDR’; at what cost? It’s a cardiotoxin. Where’s the therapeutic window? Or is this just another cytotoxic compound masquerading as targeted therapy?
8. No structural insights. If vitexin ‘binds VDR,’ show me the docking model or competitive assays. Otherwise, it’s hand-waving.
9. Polymorphisms matter, but zero functional links to TCM. If FokI SNP changes VDR activity, do TCM compounds work better/worse in these patients? Silence.
10. Safety? Ignored. Chronic VDR modulation risks hypercalcemia, immune dysfunction. Where’s the tox data? Nowhere; just hype.