Huperzia serrata · PhytoNexus

01 Identity and provenance

Accepted binomial: Huperzia serrata
Common names: Chinese Club Moss
Family (APG IV): Lycopodiaceae
Part used: Whole plant
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): Rafii MS et al. ADCS Phase II trial | Alzheimer’s Association position on huperzine A | PMC9738397 | VERIFIED 2026 (batch 5) - synthetic analogue, application, interactions, side effects and references populated from retrieved primary/regulatory sources. Interactions labelled CLINICAL vs THEORETICAL. Marketed-formulation column intentionally blank. | REGULATORY

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Lycopodium alkaloids	Huperzine A Whole plant	Donepezil, rivastigmine, galantamine (FUNCTIONAL - all reversible AChE inhibitors). Clinical impression places huperzine A at roughly 2.5-5 mg donepezil equivalence.

The analogue column is what makes the interaction reasoning tractable: where a constituent has a marketed structural counterpart, the counterpart's interaction profile is the starting hypothesis for the plant.

Looking up structures and physicochemical properties from PubChem…

03 Stated application

Reported activity: REGULATORY ASYMMETRY IS THE KEY FACT. Huperzine A is an approved DRUG in China for dementia and mild cognitive impairment, but is sold in the USA as an unregulated DIETARY SUPPLEMENT and marketed as a nootropic. The same molecule, two regulatory categories, no equivalence in oversight. Content in the plant is under 0.02% by weight, so commercial material is largely synthetic.
Reported adverse effects: EVIDENCE IS WEAKER THAN THE MARKETING. A meta-analysis of 20 RCTs (n=1823) found MMSE improvement at 8-16 weeks, but most trials carried a HIGH RISK OF BIAS. The US Alzheimer’s Disease Cooperative Study Phase II (n=210) found NO cognitive benefit at 200 micrograms twice daily; a possible signal appeared only at 400 micrograms twice daily. Transient dose-related nausea at higher doses. Long-term safety data are lacking.

04 Interaction matrix

Source column, verbatim: CLINICAL: the Alzheimer’s Association advises AGAINST taking huperzine A, particularly alongside a prescribed cholinesterase inhibitor (donepezil, rivastigmine, galantamine) - additive cholinergic toxicity. Patients may not disclose it because they regard it as a supplement rather than a drug.
Normalised onto 2 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Cholinesterase inhibitors and cholinergic drugs Autonomic	4Contraindicated	PD-additive	curated A	Cholinergic crisis: bradycardia, bronchorrhoea, bronchospasm, miosis, sei…	why ▾
Chemistry of this pair. These alkaloids inhibit acetylcholinesterase or agonise muscarinic receptors, raising synaptic acetylcholine. Class mechanism. Physostigmine-, galantamine- and arecoline-type constituents inhibit acetylcholinesterase or agonise muscarinic receptors, adding to donepezil, rivastigmine, neostigmine or pyridostigmine. Expected Cholinergic crisis: bradycardia, bronchorrhoea, bronchospasm, miosis, seizures, weakness that mimics myasthenic crisis. Management Avoid. In suspected crisis distinguish cholinergic from myasthenic weakness before giving further anticholinesterase. Onset rapid Evidence A - human data with a cited source Matched on “donepezil” Find evidence for this pair Map this mechanism
Iron, calcium and mineral supplements Nutrition	2Moderate	PK-chelation	curated A	Failure of iron-deficiency correction, unexplained non-response to oral i…	why ▾
Class mechanism. Tannins, phytates, oxalates and mucilage form insoluble complexes with divalent and trivalent cations in the gut lumen, reducing absorption of both the mineral and any co-administered chelating drug. Expected Failure of iron-deficiency correction, unexplained non-response to oral iron or calcium. Management Separate mineral doses from tannin- and fibre-rich botanicals by at least 2 hours; take iron with ascorbate instead. Onset unspecified Evidence A - human data with a cited source Matched on “supplement” Find evidence for this pair Map this mechanism

Predicted from constituent chemistry

These edges are not clinical findings. Each one is a rule inference: a constituent class in this plant is known to act on a target that the drug class also acts on. They are shown because a blank cell reads as “safe”, and for a Tier 1 entry a blank cell only means “not yet looked at”. Treat them as a literature-search agenda, not as a warning.

Drug class	Severity	Mechanism type	Provenance	Expected effect
Anticholinergics Autonomic	4Contraindicated	PD-additive	predicted D	Anticholinergic toxidrome: dry mouth, urinary retention, blurred vision, …	why ▾
Chemistry of this pair. These alkaloids inhibit acetylcholinesterase or agonise muscarinic receptors, raising synaptic acetylcholine. Class mechanism. Tropane alkaloids (atropine, hyoscine, hyoscyamine) are competitive muscarinic antagonists; added to prescribed anticholinergics, antihistamines or tricyclics the burden summates. Expected Anticholinergic toxidrome: dry mouth, urinary retention, blurred vision, tachycardia, delirium, hyperthermia. Management Calculate total anticholinergic burden. Avoid in older adults, prostatism and narrow-angle glaucoma. Onset rapid Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Narrow-therapeutic-index CYP3A4 substrates Pharmacokinetic	4Contraindicated	PK-CYP3A4	predicted D	Toxic accumulation or subtherapeutic failure of the co-prescribed drug, s…	why ▾
Chemistry of this pair. Alkaloidal bases have pH-dependent absorption and commonly interact with hepatic CYP isoenzymes and efflux transporters. Class mechanism. Furanocoumarins, bergamottin, piperine, glabridin and berberine inhibit CYP3A4; hyperforin, andrographolide and several diterpenes induce it through PXR. Because CYP3A4 handles roughly half of marketed drugs, the affected list is broad and the direction is product-specific. Expected Toxic accumulation or subtherapeutic failure of the co-prescribed drug, sometimes fatal for antiarrhythmics, immunosuppressants and oncology agents. Management Screen the full regimen for 3A4 substrates. Where the substrate has a narrow index, avoid rather than monitor. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Antacids, PPIs and H2 blockers Gastrointestinal	2Moderate	PK-absorption	predicted D	Reduced or erratic absorption of alkaloids; heartburn and reflux from pre…	why ▾
Chemistry of this pair. Alkaloidal bases have pH-dependent absorption and commonly interact with hepatic CYP isoenzymes and efflux transporters. Class mechanism. Gastric pH elevation alters the dissolution and ionisation of alkaloidal and enteric-coated botanical products; menthol- and peppermint-oil products lose their enteric protection at high pH and can be released prematurely. Expected Reduced or erratic absorption of alkaloids; heartburn and reflux from premature release of volatile-oil preparations. Management Separate administration by 2 hours. Avoid non-enteric peppermint oil in reflux disease. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism

05 Hazard register

jurisdictional asymmetry - approved drug in China, unregulated s

06 Confusable material

These entries could be mistaken for this one in trade, in the herbarium, or in a prescription. Powdered material is often indistinguishable, so the check is macroscopic, microscopic and chromatographic rather than nominal.

Coptis chinensis

Chinese Goldthread

Ranunculaceae

Shares the common name "chinese"

07 Mechanism map

Chemistry sorts to the left, pharmacology to the right. Dashed edges are predicted. Drag nodes, scroll to zoom, export at 3× for a figure.

species

chemical class

marker compound

drug class

expected effect

hazard

08 Open literature

Abstract-scoped query built from this binomial, its common names and its marker compounds, run live against Europe PMC, PubMed and OpenAlex, then ranked locally against an evidence hierarchy.

Checking openFDA spontaneous reports…

09 Isomechanistic neighbours

Species whose interaction profile overlaps this one, ranked by shared severity weight rather than by count — a shared contraindication counts for more than a shared minor signal. Practical use: these are the plants you should not stack with this one, because the mechanisms summate.

Species	Family	Shared classes	Jaccard
Duboisia myoporoides Corkwood	Solanaceae	4	0.57
Physostigma venenosum Calabar Bean	Fabaceae	4	0.44
Areca catechu Areca Nut	Arecaceae	4	0.80
Galanthus nivalis Snowdrop	Amaryllidaceae	4	0.67
Atropa belladonna Belladonna	Solanaceae	3	0.43
Hyoscyamus niger Henbane	Solanaceae	3	0.43

10 References and notes

Source column: Yang G et al. PLoS One 2013;8:e74916 (meta-analysis, 20 RCTs)

8:e74916 (meta-analysis, 20 RCTs)

Systematic review / meta-analysis manual

Yang G et al. PLoS One 2013

Yang G et al. PLoS One 2013 manual

BibTeX for all 2 records

@article{anon,
  title = {8:e74916 (meta-analysis, 20 RCTs)},
}

@article{YangGetal2013,
  title = {Yang G et al. PLoS One 2013},
  author = {Yang G et al.},
  journal = {PLoS One},
  year = {2013},
}

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