Ruta graveolens · PhytoNexus

01 Identity and provenance

Accepted binomial: Ruta graveolens
Common names: Rue
Family (APG IV): Rutaceae
Part used: Herb
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): INCHEM PIM 475, Ruta graveolens | Eickhorst K et al. (Ruta-associated phytophototoxicity in children) | Heskel NS et al. Contact Dermatitis 1983 | VERIFIED 2026 (batch 6) - synthetic analogue, application, interactions, side effects and references populated from retrieved primary/regulatory sources. Interactions labelled CLINICAL vs THEORETICAL. Marketed-formulation column intentionally blank. | ROUTE

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Flavonol glycosides	Rutin Herb	none listed

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 emmenagogue, antispasmodic and remedy for headache and joint pain. WIDELY USED AS A FOLK ABORTIFACIENT, which is the dominant source of serious poisoning. Rigorous human efficacy trials are absent.
Reported adverse effects: TWO DISTINCT HAZARDS. (1) PHYTOPHOTODERMATITIS: 5-methoxypsoralen (bergapten) and 8-methoxypsoralen react with UVA to cause erythema, blistering and lasting hyperpigmentation. It is PHOTOIRRITANT, NOT ALLERGIC - it happens to anyone, needs no prior sensitisation, and follows mere handling of the fresh plant followed by sunlight. Reported in whole families including children aged 5 and 6, and in gardeners pruning on sunny days. (2) SYSTEMIC POISONING IN ATTEMPTED ABORTION: methyl-nonyl-ketone induces uterine contraction and pelvic congestion; South American poison-centre data show elevated rates of hepatic injury, renal impairment and haematological abnormality in women taking high-dose rue tea. Presentation is often confounded by concurrent sepsis from unsafe abortion. CONTRAINDICATED IN PREGNANCY. Tincture is mutagenic in Salmonella TA98 and photomutagenic; increases sister chromatid exchange in human lymphocytes. EMA notes the essential oil is no longer recommended.

04 Interaction matrix

Source column, verbatim: CLINICAL: additive with photosensitising drugs (tetracyclines, fluoroquinolones, thiazides, retinoids, St John’s wort). Furanocoumarins inhibit CYP3A4 - the grapefruit-juice effect - so caution with CYP3A4 substrates. Avoid alongside phototherapy.
Normalised onto 4 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
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. Coumarin and furanocoumarin nuclei interfere with vitamin-K-dependent clotting-factor synthesis and inhibit CYP3A4 and CYP2C9 at the intestinal wall. 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
Diuretics Renal	3Major	PD-additive + electrolyte-mediated	curated A	Hypokalaemia, hyponatraemia, dehydration, muscle weakness, cramps, arrhyt…	why ▾
Class mechanism. Aquaretic and saluretic botanicals add to renal potassium and sodium loss. Anthraquinone laxatives compound this through colonic potassium loss, and glycyrrhizin causes mineralocorticoid-like retention of sodium with kaliuresis. Expected Hypokalaemia, hyponatraemia, dehydration, muscle weakness, cramps, arrhythmia; potentiation of digoxin toxicity through low potassium. Management Check potassium, sodium and creatinine 1-2 weeks after starting. Avoid the combination entirely in patients also on digoxin. Onset rapid Evidence A - human data with a cited source Matched on “thiazides” Find evidence for this pair Map this mechanism
Antibacterials and anthelmintics Infection	2Moderate	PK-chelation + PK-CYP	curated A	Treatment failure from subtherapeutic antibiotic concentrations, or raise…	why ▾
Class mechanism. Cation- and tannin-rich botanicals chelate tetracyclines and fluoroquinolones; efflux-pump-inhibiting and CYP-modulating constituents alter macrolide, rifamycin and azole exposure. Anthelmintic botanicals add to praziquantel and albendazole effect. Expected Treatment failure from subtherapeutic antibiotic concentrations, or raised toxicity of azoles and macrolides. Management Separate doses by 2-3 hours. Do not rely on botanical antimicrobials in place of an indicated antibiotic. Onset unspecified Evidence A - human data with a cited source Matched on “fluoroquinolones” Find evidence for this pair Map this mechanism
Topical antiseptics, keratolytics and irritants Dermatology	2Moderate	PD-additive local	curated A	Contact dermatitis, chemical burn, photoirritation, unexpected systemic a…	why ▾
Class mechanism. Essential-oil terpenes, capsaicinoids and phorbol-type diterpenes add to the barrier disruption caused by topical antiseptics, retinoids and keratolytics, and increase percutaneous absorption of anything applied with them. Expected Contact dermatitis, chemical burn, photoirritation, unexpected systemic absorption from broken skin. Management Patch test first. Never apply undiluted essential oils to broken or freshly shaved skin, or with occlusion. Onset rapid Evidence A - human data with a cited source Matched on “retinoids” 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
Cytotoxic and targeted anticancer drugs Oncology	4Contraindicated	PK-CYP3A4/UGT + PD-antagonistic	predicted D	Neutropenic sepsis and severe diarrhoea from over-exposure, or reduced an…	why ▾
Chemistry of this pair. Flavonoids inhibit CYP3A4, CYP1A2, OATP1B1 and UGT to a variable extent and have measurable antiplatelet activity. Class mechanism. Botanical CYP3A4 and UGT1A1 modulation alters exposure to irinotecan, taxanes, vinca alkaloids and kinase inhibitors. High-dose antioxidant botanicals may also oppose the oxidative mechanism of some cytotoxics and of proteasome inhibitors. Expected Neutropenic sepsis and severe diarrhoea from over-exposure, or reduced antitumour effect; boronic-acid proteasome inhibitors are directly antagonised by polyphenols. Management No botanical should be taken during active cytotoxic therapy without oncology sign-off. Record all supplements in the chemotherapy chart. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Anticoagulants (vitamin-K antagonists, DOACs) Haemostasis	3Major	PD-additive + PK-CYP2C9	predicted D	INR destabilisation in either direction; ecchymosis, epistaxis, gum bleed…	why ▾
Chemistry of this pair. Coumarin and furanocoumarin nuclei interfere with vitamin-K-dependent clotting-factor synthesis and inhibit CYP3A4 and CYP2C9 at the intestinal wall. 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 D - in silico rule prediction only Find evidence for this pair Map this mechanism
Antiplatelet agents Haemostasis	3Major	PD-additive	predicted D	Prolonged bleeding time, surgical and post-procedural bleeding, bruising,…	why ▾
Chemistry of this pair. Flavonoids inhibit CYP3A4, CYP1A2, OATP1B1 and UGT to a variable extent and have measurable antiplatelet activity. Class mechanism. Organosulfur compounds, gingerols, salicylates, ginkgolides and eugenol inhibit thromboxane A2 synthesis, platelet aggregation and PAF-mediated activation, duplicating the pharmacology of aspirin and P2Y12 blockers. Expected Prolonged bleeding time, surgical and post-procedural bleeding, bruising, haematuria. Management Stop the botanical 7-14 days before elective surgery or neuraxial anaesthesia. Record it on the pre-operative medicines list. Onset rapid Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Statins and lipid-lowering drugs Cardiovascular	3Major	PK-CYP3A4/OATP	predicted D	Myalgia, raised creatine kinase, rhabdomyolysis, hepatic transaminase ele…	why ▾
Chemistry of this pair. Coumarin and furanocoumarin nuclei interfere with vitamin-K-dependent clotting-factor synthesis and inhibit CYP3A4 and CYP2C9 at the intestinal wall. Class mechanism. CYP3A4 and OATP1B1 inhibition by furanocoumarin- and flavonoid-rich botanicals raises simvastatin, atorvastatin and lovastatin exposure. Some botanicals themselves contain monacolin K, which is chemically lovastatin. Expected Myalgia, raised creatine kinase, rhabdomyolysis, hepatic transaminase elevation. Management Ask specifically about red-yeast-rice type products. Check CK and ALT if muscle symptoms appear; prefer a non-3A4 statin. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism

05 Hazard register

phototoxic contact - Photoirritant not allergic - affects anyone

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.

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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
Achillea millefolium Yarrow	Asteraceae	7	0.54
Senna alexandrina Senna	Fabaceae	6	0.43
Ginkgo biloba Ginkgo	Ginkgoaceae	6	0.60
Vaccinium myrtillus Bilberry	Ericaceae	6	0.55
Saraca asoca Ashoka	Fabaceae	6	0.55
Cyperus rotundus Nagarmotha	Cyperaceae	6	0.55

10 References and notes

Source column: EMA/CVMP summary report, Ruta graveolens

EMA/CVMP summary report, Ruta graveolens

manual

BibTeX for all 1 records

@article{anon,
  title = {EMA/CVMP summary report, Ruta graveolens},
}

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