Hydrastis canadensis · PhytoNexus

01 Identity and provenance

Accepted binomial: Hydrastis canadensis
Common names: Goldenseal
Family (APG IV): Ranunculaceae
Part used: Rhizome
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): BERBERINE WARNING (added batch 7, entry otherwise UNVERIFIED): goldenseal is berberine-bearing. Berberine displaces bilirubin from albumin ~10x more potently than phenylbutazone and is CONTRAINDICATED in neonates, pregnancy and breastfeeding because of kernicterus risk. LactMed flags goldenseal specifically. This row still needs full verification.
Reference not supplied - claim unverified against primary literature. | HOST FACTOR

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Isoquinoline alkaloids, Protoberberine alkaloids	Berberine, Hydrastine, Canadine, Berbamine Rhizome	Metformin (functional antidiabetic similarity), Nitrofurantoin (urinary antimicrobial activity), Quinidine (isoquinoline scaffold relationship), experimental berberine derivatives

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: Upper respiratory infections, gastrointestinal infections, antimicrobial, digestive disorders, mucosal inflammation
Marketed in: Goldenseal capsules, tinctures, immune-support formulations, herbal syrups
Reported adverse effects: Nausea, constipation, gastrointestinal irritation, elevated bilirubin (rare), uterine stimulation (avoid during pregnancy)

04 Interaction matrix

Source column, verbatim: CYP3A4 substrates, CYP2D6 substrates, cyclosporine, tacrolimus, anticoagulants, antihypertensives, antidiabetic drugs
Normalised onto 5 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Anticoagulants (vitamin-K antagonists, DOACs) Haemostasis	4Contraindicated	PD-additive + PK-CYP2C9	curated B	INR destabilisation in either direction; ecchymosis, epistaxis, gum bleed…	why ▾
Class mechanism. Coumarin-, salicylate- and coumestan-bearing botanicals add to vitamin-K-antagonist effect; several also compete for CYP2C9 and CYP3A4, raising S-warfarin exposure. Botanicals rich in vitamin K1 act in the opposite direction and blunt anticoagulation. Expected INR destabilisation in either direction; ecchymosis, epistaxis, gum bleeding, GI or intracranial haemorrhage. Management Do not start or stop the botanical without INR cover. Check INR at 3-5 days and again at 2 weeks. Document the product, batch and dose in the anticoagulation record. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “anticoagulants” Find evidence for this pair Map this mechanism
Antidiabetic drugs (insulin, sulfonylureas, biguanides, GLP-1, SGLT2) Endocrine	4Contraindicated	PD-additive	curated B	Symptomatic hypoglycaemia, sweating, tremor, confusion; severe events rep…	why ▾
Chemistry of this pair. Berberine inhibits CYP3A4 and P-glycoprotein, lowers glucose through AMPK activation, and displaces bilirubin from albumin. Class mechanism. Hypoglycaemic botanicals act through insulin secretagogue, insulin-sensitising, alpha-glucosidase-inhibiting or glucose-transport routes. Added to a titrated pharmacological regimen the effects summate rather than plateau. Expected Symptomatic hypoglycaemia, sweating, tremor, confusion; severe events reported with insulin and sulfonylureas. Management Increase self-monitoring frequency for 2 weeks after starting or stopping. Anticipate a downward dose adjustment of insulin or sulfonylurea. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “antidiabetic drugs” Find evidence for this pair Map this mechanism
Immunosuppressants (ciclosporin, tacrolimus, mycophenolate) Transplant	4Contraindicated	PK-CYP3A4/P-gp + PD-antagonistic	curated B	Acute graft rejection with inducers; nephrotoxicity, neurotoxicity and hy…	why ▾
Chemistry of this pair. Berberine inhibits CYP3A4 and P-glycoprotein, lowers glucose through AMPK activation, and displaces bilirubin from albumin. Class mechanism. These are narrow-therapeutic-index CYP3A4 and P-glycoprotein substrates. Botanical induction collapses trough levels; inhibition causes toxic accumulation. Immunostimulant botanicals separately oppose the therapeutic goal. Expected Acute graft rejection with inducers; nephrotoxicity, neurotoxicity and hypertension with inhibitors; autoimmune flare with immunostimulants. Management Treat as contraindicated in transplant recipients. Any exposure requires immediate trough level measurement and transplant team notification. Onset unspecified Evidence B - reviewed clinical column, source pending Matched on “cyclosporine” Find evidence for this pair Map this mechanism
Narrow-therapeutic-index CYP3A4 substrates Pharmacokinetic	4Contraindicated	PK-CYP3A4	curated B	Toxic accumulation or subtherapeutic failure of the co-prescribed drug, s…	why ▾
Chemistry of this pair. Berberine inhibits CYP3A4 and P-glycoprotein, lowers glucose through AMPK activation, and displaces bilirubin from albumin. 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 B - reviewed clinical column, source pending Matched on “cyp3a4 substrates” Find evidence for this pair Map this mechanism
Antihypertensives Cardiovascular	3Major	PD-additive	curated B	Orthostatic hypotension, dizziness, syncope and falls; or loss of blood-p…	why ▾
Class mechanism. Vasodilator, diuretic, ACE-inhibitory and calcium-antagonist activity in botanical extracts adds to prescribed blood-pressure lowering. A minority (ephedrine-, glycyrrhizin- and caffeine-bearing) act in the opposite direction and antagonise control. Expected Orthostatic hypotension, dizziness, syncope and falls; or loss of blood-pressure control with pressor botanicals. Management Home BP log for 2 weeks after any change. Warn about postural symptoms; review in the elderly and in those on multiple agents. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “antihypertensives” 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
Antacids, PPIs and H2 blockers Gastrointestinal	3Major	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

contraindication - berberine-bearing; kernicterus risk in neonat

06 Confusable material

No same-genus or shared-common-name entry in the corpus.

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

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marker compound

drug class

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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
Uncaria tomentosa Cat's Claw	Rubiaceae	5	0.38
Berberis vulgaris Barberry	Berberidaceae	4	0.67
Coptis chinensis Chinese Goldthread	Ranunculaceae	4	0.67
Aegle marmelos Bael	Rutaceae	5	0.83
Chlorophytum borivilianum Safed Musli	Asparagaceae	5	0.63
Phyllanthus amarus Bhui Amla	Phyllanthaceae	5	0.38

10 References and notes

No citation is on record for this entry. That is itself the finding: the audit flagged it, and it is why the entry does not carry an A evidence grade.

Curator notes

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