Berberis vulgaris · PhytoNexus

01 Identity and provenance

Accepted binomial: Berberis vulgaris
Common names: Barberry
Family (APG IV): Berberidaceae
Part used: Root bark
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): NCCIH berberine safety communication | LactMed, goldenseal/berberine | MotherToBaby berberine fact sheet | VERIFIED 2026 (batch 7) - synthetic analogue, application, interactions, side effects and references populated from retrieved primary/regulatory sources. Interactions labelled CLINICAL vs THEORETICAL. Marketed-formulation column intentionally blank. | HOST FACTOR

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Berberine, Palmatine, Jatrorrhizine, Berbamine	Berberine Root bark	Metformin (functional similarity)

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: Traditional use for digestive complaints, biliary disorders and infection; root bark is a commercial berberine source.
Reported adverse effects: NEONATAL KERNICTERUS - THE DEFINING RISK, AND IT IS NOT DOSE-RELATED IN THE USUAL SENSE. Berberine displaces bilirubin from albumin; in vitro it is about TENFOLD more potent as a displacer than phenylbutazone and about a hundredfold more than papaverine. Displaced free bilirubin crosses the blood-brain barrier and can cause kernicterus - permanent injury with hearing loss, movement disorder and developmental delay. Berberine also appears to slow bilirubin clearance. CONTRAINDICATED IN NEONATES, IN PREGNANCY (crosses the placenta; possible uterine stimulation) AND IN BREASTFEEDING (transfers into milk). PARTICULARLY RELEVANT IN SOUTH ASIA: neonatal jaundice affects a large share of term babies, G6PD deficiency is prevalent and independently raises kernicterus risk, and berberine-containing herbs are given traditionally. Other effects: GI upset, hypoglycaemia when stacked on antidiabetic therapy.

04 Interaction matrix

Source column, verbatim: CLINICAL: additive hypoglycaemia with metformin, sulfonylureas, insulin and GLP-1 agonists. Berberine inhibits CYP3A4 and P-glycoprotein - interaction with ciclosporin is documented, and narrow-therapeutic-index CYP3A4 substrates need caution. ABSOLUTE: do not co-administer with anything else that displaces bilirubin (e.g. sulfonamides) in a jaundiced neonate.
Normalised onto 3 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Antidiabetic drugs (insulin, sulfonylureas, biguanides, GLP-1, SGLT2) Endocrine	4Contraindicated	PD-additive	curated A	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 A - human data with a cited source Matched on “glp-1 agonists” Find evidence for this pair Map this mechanism
Immunosuppressants (ciclosporin, tacrolimus, mycophenolate) Transplant	4Contraindicated	PK-CYP3A4/P-gp + PD-antagonistic	curated A	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 A - human data with a cited source Matched on “ciclosporin” Find evidence for this pair Map this mechanism
Narrow-therapeutic-index CYP3A4 substrates Pharmacokinetic	4Contraindicated	PK-CYP3A4	curated A	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 A - human data with a cited source Matched on “cyp3a4 substrates” 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 displaces bilirubin from albumin -

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.

Berberis aristata

Daruharidra

Berberidaceae

Same genus (Berberis)

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
Hydrastis canadensis Goldenseal	Ranunculaceae	4	0.67
Coptis chinensis Chinese Goldthread	Ranunculaceae	4	1.00
Tinospora cordifolia Giloy	Menispermaceae	4	1.00
Chelidonium majus Greater Celandine	Papaveraceae	4	0.80
Stephania tetrandra Han Fang Ji	Menispermaceae	4	1.00
Corydalis yanhusuo Yan Hu Suo	Papaveraceae	4	1.00

10 References and notes

Source column: Chan E. Biol Neonate 1993;63:201-8 (displacement of bilirubin from albumin by berberine). PubMed 8513024

Chan E. Biol Neonate 1993

Chan E 1993 manual

63:201-8 (displacement of bilirubin from albumin by berberine). PubMed 8513024

manual

BibTeX for all 2 records

@article{ChanE1993,
  title = {Chan E. Biol Neonate 1993},
  author = {Chan E},
  year = {1993},
}

@article{anon,
  title = {63:201-8 (displacement of bilirubin from albumin by berberine). PubMed 8513024},
}

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