Hypericum perforatum · PhytoNexus

01 Identity and provenance

Accepted binomial: Hypericum perforatum
Common names: St. John's Wort
Family (APG IV): Hypericaceae
Part used: Flowering tops
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): Reference not supplied - claim unverified against primary literature.

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Naphthodianthrones,flavonoids	Hypericin, Hyperforin Flowering tops	None

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: Depression, Anxiety, Anti inflammatory, Anti viral
Marketed in: Perika tablet, Jarsin tablets, hypericun capsules
Reported adverse effects: Dizziness, fatigue, serotonin syndrome, gastrointestinal upset

04 Interaction matrix

Source column, verbatim: Antidepressants, antiviral drugs, antiepileptic drugs
Normalised onto 3 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Antidepressants (SSRI, SNRI, TCA) CNS	4Contraindicated	PD-additive serotonergic + PK-CYP2D6	curated B	Serotonin syndrome (agitation, clonus, hyperthermia, autonomic instabilit…	why ▾
Chemistry of this pair. Hyperforin is a potent PXR agonist, inducing CYP3A4, CYP2C19 and intestinal P-glycoprotein, while also inhibiting monoamine reuptake. Class mechanism. Hypericin- and hyperforin-type constituents inhibit monoamine reuptake and induce CYP3A4/2C19 and P-glycoprotein; others inhibit CYP2D6, raising tricyclic and SSRI concentrations. Expected Serotonin syndrome (agitation, clonus, hyperthermia, autonomic instability) or loss of antidepressant effect on withdrawal of an inducer. Management Screen for serotonergic burden before adding. Taper rather than stop abruptly. Consider therapeutic drug monitoring for tricyclics. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “antidepressants” Find evidence for this pair Map this mechanism
Antivirals and antiretrovirals Infection	4Contraindicated	PK-CYP3A4/P-gp induction	curated B	Virological breakthrough and selection of resistant virus - a permanent l…	why ▾
Chemistry of this pair. Hyperforin is a potent PXR agonist, inducing CYP3A4, CYP2C19 and intestinal P-glycoprotein, while also inhibiting monoamine reuptake. Class mechanism. Protease inhibitors, NNRTIs and direct-acting antivirals are CYP3A4 and P-glycoprotein substrates with steep concentration-effect relationships. Botanical induction produces sustained subtherapeutic exposure. Expected Virological breakthrough and selection of resistant virus - a permanent loss of treatment options. Management Absolute contraindication with antiretroviral therapy. Ask about supplements at every viral-load review. Onset delayed Evidence B - reviewed clinical column, source pending Matched on “antiviral drugs” Find evidence for this pair Map this mechanism
Antiepileptics CNS	3Major	PK-CYP induction + PD-antagonistic	curated B	Breakthrough seizures, status epilepticus, or additive sedation and ataxi…	why ▾
Class mechanism. Enzyme-inducing botanicals lower plasma anticonvulsant concentrations, while GABAergic constituents add sedation and a few (thujone, camphor, beta-asarone, pinene-rich oils) are directly proconvulsant and lower seizure threshold. Expected Breakthrough seizures, status epilepticus, or additive sedation and ataxia. Management Measure anticonvulsant levels before and 2-4 weeks after any change. Avoid proconvulsant essential oils entirely in epilepsy. Onset delayed Evidence B - reviewed clinical column, source pending Matched on “antiepileptic drugs” 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. Ribosome-inactivating toxalbumins depurinate 28S rRNA and halt protein synthesis at extremely low doses. 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
Hepatotoxic drugs Organ toxicity	4Contraindicated	Organ-toxicity additive	predicted D	Transaminase elevation, cholestasis, sinusoidal obstruction syndrome, acu…	why ▾
Chemistry of this pair. Ribosome-inactivating toxalbumins depurinate 28S rRNA and halt protein synthesis at extremely low doses. Class mechanism. Pyrrolizidine alkaloids, high-dose anthraquinones, kava constituents and germander-type diterpenes cause hepatocellular or sinusoidal injury that adds to the risk from paracetamol, isoniazid, methotrexate, azoles and statins. Expected Transaminase elevation, cholestasis, sinusoidal obstruction syndrome, acute liver failure. Management Baseline and 4-weekly ALT and bilirubin. Stop the botanical at any transaminase rise above three times the upper reference limit. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Hormonal therapy, oral contraceptives and HRT Endocrine	4Contraindicated	PK-CYP3A4 induction + PD-oestrogenic	predicted D	Breakthrough bleeding and contraceptive failure; unpredictable effect in …	why ▾
Chemistry of this pair. Hyperforin is a potent PXR agonist, inducing CYP3A4, CYP2C19 and intestinal P-glycoprotein, while also inhibiting monoamine reuptake. Class mechanism. CYP3A4-inducing botanicals accelerate ethinylestradiol and progestin clearance. Separately, isoflavone, lignan and coumestan phyto-oestrogens bind oestrogen receptors and may add to or compete with prescribed hormones. Expected Breakthrough bleeding and contraceptive failure; unpredictable effect in hormone-sensitive malignancy. Management Advise a second, non-hormonal contraceptive method. Avoid phyto-oestrogens in oestrogen-receptor-positive breast cancer without oncology advice. Onset delayed Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Immunosuppressants (ciclosporin, tacrolimus, mycophenolate) Transplant	4Contraindicated	PK-CYP3A4/P-gp + PD-antagonistic	predicted D	Acute graft rejection with inducers; nephrotoxicity, neurotoxicity and hy…	why ▾
Chemistry of this pair. Hyperforin is a potent PXR agonist, inducing CYP3A4, CYP2C19 and intestinal P-glycoprotein, while also inhibiting monoamine reuptake. 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 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. Hyperforin is a potent PXR agonist, inducing CYP3A4, CYP2C19 and intestinal P-glycoprotein, while also inhibiting monoamine reuptake. 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
Nephrotoxic drugs Organ toxicity	4Contraindicated	Organ-toxicity additive	predicted D	Rising creatinine, tubulointerstitial nephritis, urothelial carcinoma wit…	why ▾
Chemistry of this pair. Ribosome-inactivating toxalbumins depurinate 28S rRNA and halt protein synthesis at extremely low doses. Class mechanism. Aristolochic acid, high oxalate loads and anthraquinone-driven volume depletion add to aminoglycoside, NSAID, contrast and calcineurin-inhibitor nephrotoxicity. Expected Rising creatinine, tubulointerstitial nephritis, urothelial carcinoma with aristolochic acid, oxalate nephropathy. Management Check creatinine and urinalysis. Aristolochia-containing material must never be dispensed; verify identity of any Fangchi or Mu Tong substitute. Onset unspecified 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	2Moderate	PK-CYP3A4/OATP	predicted D	Myalgia, raised creatine kinase, rhabdomyolysis, hepatic transaminase ele…	why ▾
Chemistry of this pair. Flavonoids inhibit CYP3A4, CYP1A2, OATP1B1 and UGT to a variable extent and have measurable antiplatelet activity. 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

The audit recorded no hazard beyond the interaction profile. The controlled-vocabulary field reads not assessed, which means the assessment has not been done rather than that it came back clear.

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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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	6	0.35
Echinacea purpurea Echinacea	Asteraceae	6	0.35
Centella asiatica Mandukaparni	Apiaceae	6	0.43
Achillea millefolium Yarrow	Asteraceae	6	0.35
Actaea racemosa Black Cohosh	Ranunculaceae	6	0.46
Sambucus nigra Elderberry	Adoxaceae	5	0.45

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.

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