1 Potential Drug–Herb Interactions

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1	Appendix 1
	Potential Drug–Herb Interactions

Until the emergence of reports of important interactions between St John's wort (Hypericum perforatum L.) and certain conventional drugs (see St John's Wort), very few interactions involving herbal products had been reported in the medical literature. Furthermore, there has been very little experimental and clinical research in this area.

The following list of potential drug–herb interactions has been compiled on the basis of known herbal constituents and their reported pharmacological actions. It should be emphasised that many drug interactions are harmless and many of those that are

potentially harmful occur only in a small proportion of patients and may then vary in severity from patient to patient. Healthcare professionals should be alert to undeclared use of herbal medicines as a possible cause of unexplained toxicity or lack of effect of conventional medicines.

Suspected drug–herb interactions involving licensed or unlicensed herbal products should be reported to the regulatory authorities, as for any other suspected adverse reaction to herbal or 'conventional' medicines.

Table 1 Potential drug–herb interactions

Drug/therapeutic category affected	Herbal ingredients interacting	Possible effects

Gastrointestinal system
Antacids, ulcer-healing drugs	Herbal ingredients irritant to gastrointestinal	Exacerbation of symptoms. Risk of
	tract. See Appendix 2, Table 12	systemic side-effects
Antidiarrhoeal drugs	Herbal ingredients with laxative activity.	Antagonism
	See Appendix 2, Table 1
Laxatives	Herbal ingredients with laxative activity.	Potentiation; increased risk of side-effects
	See Appendix 2, Table 1
Cardiovascular system
Cardiac glycosides	Cardioactive herbal ingredients. See Appendix	Potentiation; increased risk of side-effects
	2, Table 2
	Herbal ingredients containing	Potentiation; increased risk of side-effects
	hydroxyanthracene laxatives. See Appendix 2,
	Table 1
	St John’s wort	Risk of reduced therapeutic effect of
		digoxin
Diuretics	Herbal ingredients containing	Potentiation; increased risk of
	hydroxyanthracene laxatives. See Appendix 2,	hypokalaemia
	Table 1
	Herbal ingredients with diuretic activity.	Potentiation; increased risk of
	See Appendix 2, Table 3	hypokalaemia
	Herbal ingredients with hypotensive activity.	Difficulty in controlling diuresis;
	See Appendix 2, Table 4	hypotension
Anti-arrhythmic activity	Herbal ingredients containing	Interference with existing therapy;
	hydroxyanthracene laxatives. See Appendix 2,	increased risk of hypokalaemia
	Table 1
	Cardioactive herbal ingredients. See Appendix	Interference/antagonism with existing
	2, Table 2	therapy
	Herbal ingredients with diuretic activity.	Antagonism if hypokalaemia occurs
	See Appendix 2, Table 3
Beta-adrenoceptor blocking drugs	Cardioactive herbal ingredients. See Appendix	Potential antagonism
	2, Table 2
		table continues

612

	Potential Drug–Herb Interactions		613
Table 1 continued

Drug/therapeutic category affected	Herbal ingredients interacting	Possible effects		1
Drug/therapeutic category affected	Herbal ingredients interacting	Possible effects

	Herbal ingredients with significant amine	Potential risk of severe hypertension
	content or sympathomimetic activity.
	See Appendix 2, Table 15

Antihypertensive therapy	Herbal ingredients with hypertensive activity.	Antagonism
	See Appendix 2, Table 4
	Herbal ingredients with mineralocorticoid	Antagonism
	activity See Appendix 2, Table 9
	Herbal ingredients with hypotensive activity.	Potentiation
	See Appendix 2, Table 4
	Herbal ingredients with significant amine	Antagonism
	content or sympathomimetic activity.
	See Appendix 2, Table 15
	Herbal ingredients with diuretic activity.	Risk of potentiation/ interference with
	See Appendix 2, Table 3	existing therapy

Lipid-lowering drugs	Herbal ingredients with hypolipidaemic	Additive effect
	activity. See Appendix 2, Table 6

Nitrates and calcium-channel blockers	Cardioactive ingredients. See Appendix 2,	Interference with therapy
	Table 2
	Herbal ingredients with hypertensive activity.	Antagonism
	See Appendix 2, Table 4
	Herbal ingredients with anticholinergic activity	Reduced sublingual absorption of glyceryl
		trinitrate

Sympathomimetics	Herbal ingredients with significant	Potentiation; increased risk of
	sympathomimetic amine content.	hypertension
	See Appendix 2, Table 15
	Herbal ingredients with hypertensive activity.	Increased risk of hypertension
	See Appendix 2, Table 4
	Herbal ingredients with hypotensive activity.	Antagonism
	See Appendix 2, Table 4

Anticoagulants	Herbal ingredients with coagulant/	Risk of antagonism or potentiation
	anticoagulant activity. See Appendix 2, Table 5
	Herbal ingredients containing coumarins with	Risk of potentiation
	anticoagulant activity. See Appendix 2, Table
	16
	Herbal ingredients with significant salicylate	Risk of potentiation
	concentrations. See Appendix 2, Table 5
	Cranberry juice	Raised INR reported in patients receiving
		warfarin
	Garlic	Raised INR reported in patients receiving
		warfarin
	Ginkgo	Antiplatelet activity; increased risk of
		bleeding, particularly in patients receiving
		warfarin and other anticoagulant or
		antiplatelet agents
	Horse-chestnut	Plasma protein binding
	St John’s wort	Risk of reduced therapeutic effect of
		warfarin

Respiratory system
	St John’s wort	Risk of reduced therapeutic effect of
		theophylline
	Herbal ingredients that are potentially	Risk of allergic reaction
	allergenic. See Appendix 2, Table 11

Terfenadine	Cardioactive herbal ingredients. See Appendix	May increase arrhythmogenic potential of
	2, Table 2	terfenadine
	Herbal ingredients with diuretic activity.	Electrolyte imbalance may increase
	See Appendix 2, Table 3	arrhythmogenic potential of terfenadine

	614		Appendix 1
	Table 1 continued
1
1		Drug/therapeutic category affected		Herbal ingredients interacting	Possible effects
		Drug/therapeutic category affected		Herbal ingredients interacting	Possible effects

		Allergic disorders		Herbal ingredients claimed to have sedative	Potentiation of drowsiness associated with
				activity. See Appendix 2, Table 7	antihistamines

		Central nervous system

		Hypnotics and anxiolytics		Herbal ingredients claimed to have sedative	Potentiation
				activity. See Appendix 2, Table 7

Antipsychotics	Herbal ingredients with diuretic activity.
	See Appendix 2, Table 3

Potentiation of lithium therapy; increased risk of toxicity; diuretics reported to reduce lithium clearance

	Herbal ingredients with anticholinergic activity	Risk of interference with therapy;
		anticholinergic drug reported to reduce
		plasma phenothiazine concentrations

	Evening primrose	Potential risk of seizures

Antidepressants	Herbal ingredients containing	Risk of hypertensive crisis with
	sympathomimetic amines. See Appendix 2,	monoamine-oxidase inhibitors (MAOIs)
	Table 15

	Ginseng (Panax)	Suspected phenelzine interaction

	Herbal ingredients containing tryptophan	Risk of CNS excitation and confusional
		states with MAOIs

	White horehound	5-Hydroxytryptamine antagonism, in vitro,
		in vivo

	Herbal ingredients with sedative activity.	May potentiate sedative side-effects
	See Appendix 2, Table 7

	St John’s wort	Risk of increased serotonergic effects in
		patients taking selective serotonin
		reuptake inhibitors (SSRIs)

Drugs used in nausea and vertigo	Herbal ingredients with sedative activity.	May potentiate sedative side-effects
	See Appendix 2, Table 7

	Herbal ingredients with anticholinergic activity	Antagonism

Analgesics	Herbal ingredients with diuretic activity.	Increased risk of toxicity with anti-
	See Appendix 2, Table 3	inflammatory analgesics

	Herbal ingredients with corticosteroid activity.	Possible reduction in plasma-aspirin
	See Appendix 2, Table 9	concentrations

	Herbal ingredients with sedative activity.	May potentiate sedative side-effects
	See Appendix 2, Table 7

	St John’s wort	Risk of increased serotonergic effects, with
		possibility of increased risk of side-effects

Antiepileptics	Herbal ingredients with sedative activity.	May potentiate sedative side-effects
	See Appendix 2, Table 7

	Borage	May increase risk of seizure

	Evening primrose oil	May increase risk of seizure

	Sage	May increase risk of seizure

	Herbal ingredients with significant salicylate	Transient potentiation of phenytoin
	content. See Appendix 2, Table 5	therapy may occur

	Herbal ingredients with significant folic acid	Plasma phenytoin concentration may be
	content	reduced

	St John’s wort	Risk of reduced therapeutic effect of
		anticonvulsants (carbamazepine,
		phenobarbitone, phenytoin)

Drugs for parkinsonism	Herbal ingredients with anticholinergic activity	Potentiation; increased risk of side-effects

	Herbal ingredients with cholinergic activity	Antagonism

Infections

Antifungal drugs	Herbal ingredients with anticholinergic activity	Risk of reduced absorption of
		ketoconazole

		Potential Drug–Herb Interactions		615
Table 1 continued

	Drug/therapeutic category affected	Herbal ingredients interacting	Possible effects		1
	Drug/therapeutic category affected	Herbal ingredients interacting	Possible effects

	HIV protease inhibitorsHIV non-nucleoside	St John’s wort	Risk of reduced blood concentrations of
	reverse transcriptase inhibitors		anti-HIV drugs, with possible loss of HIV
			suppression

	Endocrine system

	Antidiabetics	Herbal ingredients with hypoor	Potentiation/antagonism of activity
		hyperglycaemic activity. See Appendix 2,
		Table 8

		Herbal ingredients with diuretic activity.	Antagonism
		See Appendix 2, Table 3

	Drugs for hypoand hyperthyroidism	Herbal ingredients with significant iodine	Interference with therapy
		content.

	Corticosteroids	Herbal ingredients with diuretic activity.	Risk of increased potassium loss
		See Appendix 2, Table 3

		Herbal ingredients with corticosteroid activity.	Increased risk of side-effects, e.g. water
		See Appendix 2 Table 9	and sodium retention

	Sex hormones	Herbal ingredients with hormonal activity.	Possible interaction with existing therapy
		See Appendix 2, Table 9

Obstetrics and gynaecology

Oral contraceptives	Herbal ingredients with hormonal activity.
	See Appendix 2, Table 9

Possible interaction with existing therapy; may reduce effectiveness of oral contraceptive

	St John’s wort	Risk of reduced blood concentrations of
		oral contraceptives, breakthrough
		bleeding and unintended pregnancy

Malignant disease and immunosuppression

Irinotecan	St John’s wort	Risk of altered irinotecan pharmacokinetics

Methotrexate	Herbal ingredients with significant salicylate	Increased risk of toxicity
	content. See Appendix 2, Table 5

Drugs affecting immune response	Herbal ingredients with immunomodulatory	Potentiation or antagonism
	activity. See Appendix 2, Table 10

	St John’s wort	Risk of reduced therapeutic effect of
		ciclosporin

Musculoskeletal and joint diseases

Systemic lupus erythematosus	Alfalfa	Antagonism; contra-indicated

Probenecid	Herbal ingredients with significant salicylate	Risk of inhibition of probenecid
	content. See Appendix 2, Table 5

Eye

Acetazolamide	Herbal ingredients with significant salicylate	Increased risk of toxicity
	content. See Appendix 2, Table 5

Skin	Herbal ingredients with potential allergenic	Allergic reaction; exacerbation of existing
	activity. See Appendix 2, Table 11	symptoms

	Herbal ingredients with phototoxic activity.	Phototoxic reaction; exacerbation of
	See Appendix 2, Table 11	existing symptoms

Anaesthetics

General anaesthetics	Herbal ingredients with hypotensive activity.	Potentiation of hypotensive effect
	See Appendix 2, Table 4

Competitive muscle relaxants	Herbal ingredients with diuretic activity.	Risk of potentiation if hypokalaemia occurs
	See Appendix 2, Table 3

Depolarising muscle relaxants	Cardioactive herbal ingredients.	Risk of arrhythmias
	See Appendix 2, Table 2

	Appendix 2
2	Pharmacological Activities and
2	Constituents of Herbal Ingredients

Table 1		Laxatives

	Drug		Comment

	Aloes		Hydroxyanthracene constituents
	Cascara		Hydroxyanthracene constituents
	Frangula		Hydroxyanthracene constituents
	Horehound, White		Large doses
	Ispaghula		Bulk laxative
	Plantain		Bulk laxative
	Rhubarb		Hydroxyanthracene constituents
	Senna		Hydroxyanthracene constituents
	Yellow Dock		Hydroxyanthracene constituents

Table 2		Cardioactive agents

	Drug		Comment

	Broom		Alkaloid constituents: cardiac depressant
			activity
	Butterbur		S-petasin: negative chronotropic activity
			in vivo, negative inotropic activity ex vivo
	Calamus		Anti-arrhythmic activity
	Cereus		Tyramine: cardiotonic amine
	Cola		Caffeine
	Coltsfoot		Cardiac calcium-channel blocking activity
	Devil’s Claw		Activity in vivo
	Fenugreek		Activity in vitro
	Figwort		Cardioactive glycoside constituents,
			activity in vitro
	Fumitory		Alkaloid constituent: cardioactive
	Ginger		Activity in vivo
	Ginseng, Panax		Activity in vivo
	Golden Seal		Berberine: cardioactive alkaloid
	Hawthorn		Tyramine: cardiotonic amine; activity in
			vivo
	Horehound, White		Activity in vivo
	Lime Flower		Activity reputed with excessive ingestion
	Mate´		Caffeine
	Mistletoe		Viscotoxin, negative inotropic effect in vivo
	Motherwort		Cardiac glycoside constituents; activity in
			vitro

table continues

Table 2 continued

	Drug	Comment


	Pleurisy Root	Cardenolides, active in vitro and in vivo
	Prickly Ash, Northern	Interaction with NaþKþ ATPase
	Prickly Ash, Southern	Interaction with NaþKþ ATPase
	Quassia	Activity in vitro
	Rhodiola	Inotropic, anti-arrhythmic and other
		cardiac effects ex vivo, confirmation
		required
	Shepherd’s Purse	Activity in vitro
	Squill	Cardiac glycoside constituents
	Wild Carrot	Depressant activity in vivo

Table 3 Diuretics

	Drug	Comment

	Agrimony	Activity in vivo
	Artichoke	Reputed action
	Boldo	Reputed action, oil
	Broom	Reputed action
	Buchu	Reputed action
	Burdock	Reputed action
	Celery	Reputed action
	Corn Silk	Reputed action
	Couchgrass	Activity in vivo
	Dandelion	Activity in vivo
	Elder	Activity in vivo
	Guaiacum	Reputed action
	Java Tea	Activity in vivo
	Juniper	Reputed action; terpinen-4-ol
	Nettle	Activity in humans
	Pokeroot	Activity in vivo
	Shepherd’s Purse	Activity in vivo
	Squill	Activity in vivo
	Uva-Ursi	Reputed action
	Yarrow	Activity in vivo

616

Pharmacological Activities and Constituents of Herbal Ingredients

617

Table 4 Hypotensives and hypertensives

	Drug	Comment

	Hypotensive
	Agrimony	Hypotensive, in vivo
	Asafoetida	Hypotensive, in vivo
	Avens	Hypotensive, in vivo
	Butterbur	Hypotensive, in vivo; S-petasin, iso-S-
		petasin
	Calamus	Hypotensive, in vivo
	Cat’s Claw	Hypotensive, in vivo
	Corn Silk	Hypotensive, in vivo
	Cowslip	Hypotensive, then hypertensive in vivo
	Devil’s Claw	Hypotensive, in vivo
	Elecampane	Hypotensive, in vivo
	Fenugreek	Hypotensive
	Fucus	Hypotensive
	Fumitory	Hypotensive, in vivo
	Garlic	Hypotensive, human and in vivo
	Ginger	Hypotensive
	Ginseng, Panax	Hypotensive, human and in vivo
	Golden Seal	Hypotensive, alkaloid effect
	Hawthorn	Hypotensive, in vivo
	Horehound, White	Vasodilator (volatile oil)
	Horse-chestnut	Hypotensive, in vivo
	Horseradish	Hypotensive, in vivo
	Java Tea	Hypotensive, in vivo
	Juniper	Hypotensive, in vivo
	Mistletoe	Hypotensive, in vivo
	Nettle	Hypotensive, in vivo
	Parsley	Hypotensive, in vivo
	Plantain	Hypotensive, in vivo
	Pokeroot	Hypotensive, in vivo
	Prickly Ash, Northern	Hypotensive, in vivo
	Prickly Ash, Southern	Hypotensive, in vivo
	Sage	Hypotensive
	Shepherd’s Purse	Hypotensive
	Squill	Vasodilator, in vivo
	St John’s Wort	Hypotensive, in vivo
	Thyme	Hypotensive, in vivo
	Vervain	Hypotensive
	Wild Carrot	Hypotensive, in vivo
	Yarrow	Hypotensive, in vivo
	Hypertensive
	Bayberry	Hypertensive, myricitrin mineralocorticoid
		side-effect
	Broom	Hypertensive, alkaloid effect
	Capsicum	Hypertensive, increased catecholamine
		secretion
	Cohosh, Blue	Hypertensive, alkaloid effect

Table 4 continued

	Drug	Comment

	Cola	Hypertensive, caffeine	2
	Coltsfoot	Hypertensive, pressor activity	2
	Coltsfoot	Hypertensive, pressor activity
	Ephedra	Hypertensive, human and in vivo
	Ginger	Hypertensive
	Ginseng, Panax	Hypertensive, human and in vivo
	Liquorice	Hypertensive, mineralocorticoid side-
		effect
	Mate´	Hypertensive, caffeine
	Vervain	Hypertensive

Table 5 Anticoagulants and coagulants

	Drug	Comment

	Anticoagulants
	Bilberry	Inhibits platelet aggregation, human, in
		vivo, in vitro
	Cat’s Claw	Inhibits platelet aggregation, in vitro
	Clove	Eugenol inhibitor of platelet activity
	Feverfew	Inhibits platelet aggregation
	Fucus	Anticoagulant action
	Garlic	Inhibits platelet aggregation, humans in
		vivo
	Ginger	Inhibition of platelet activity
	Ginkgo	Inhibition of platelet activity
	Ginseng, Panax	Reduction of blood coagulation
	Horseradish	Peroxidase stimulates synthesis of
		arachidonic acid metabolites
	Liquorice	Inhibition of platelet activity
	Meadowsweet	Salicylate constituents
	Poplar	Salicylate constituents
	Willow	Salicylate constituents
	Coagulants
	Golden Seal	Heparin antagonist
	Mistletoe	Lectins, agglutinating activity
	Yarrow	Coagulant, in vivo

Table 6 Hypolipidaemic and hyperlipidaemic agents

Drug Comment

Hypocholesterolaemic

Alfalfa	Hypocholesterolaemic, in vivo

Artichoke	Hypocholesterolaemic, human, in vivo

Bilberry	Hypocholesterolaemic, in vivo

Capsicum	Hypocholesterolaemic, in vivo

Cohosh, Black	Hypocholesterolaemic, in vivo

Fenugreek	Hypocholesterolaemic, human, in vivo

Garlic	Hypocholesterolaemic, human, in vivo

table continues

	618		Appendix 2
	Table 6 continued

		Drug		Comment

2		Ginger		Hypocholesterolaemic, in vivo
2		Ispaghula		Hypocholesterolaemic, human
		Ispaghula		Hypocholesterolaemic, human
		Milk thistle		Hypocholesterolaemic, in vivo
		Myrrh		Hypolipidaemic, human, in vivo
		Plantain		Hypocholesterolaemic, in vivo
		Scullcap		Hypocholesterolaemic, in vivo
		Senega		Hypolipidaemic, in vivo
		Tansy		Hypocholesterolaemic, in vivo
				Hypercholesterolaemic
		Hydrocotyle		Hypercholesterolaemic, in vivo

	Table 7		Sedatives

		Drug		Comment

		Calamus		Potentiates barbiturate sleeping time
		Celery		In vivo
		Centaury		Reputed action
		Chamomile, German		Human
		Couchgrass		In vivo
		Elecampane		In vivo
		Ginseng,		CNS depressant and stimulant
		Eleutherococcus;
		Ginseng, Panax
		Golden Seal		In vivo
		Hawthorn		CNS depressant; potentiates barbiturate
				sleeping time
		Hops		In vivo
		Hydrocotyle		In vivo
		Jamaica Dogwood		In vivo
		Kava		Conflicting results in vivo
		Nettle		CNS depression, in vivo
		Passionflower		In vivo
		Sage		In vivo
		Scullcap		Reputed action
		Senega		CNS depressant, in vivo
		Shepherd’s Purse		Potentiates barbiturate sleeping time
		Valerian		Human, in vivo
		Wild Carrot		In vivo
		Wild Lettuce		In vivo, related species

	Table 8 Hypoglycaemics and hyperglycaemics

		Drug		Comment

		Hypoglycaemic
		Agrimony		Hypoglycaemic, in vivo
		Alfalfa		Manganese, human
		Aloes/Aloe vera		In vivo

Table 8 continued

	Drug	Comment

	Burdock	In vivo
	Celery	In vivo
	Corn Silk	In vivo
	Damiana	In vivo
	Dandelion	In vivo
	Devil’s Claw	In vivo
	Elecampane	In vivo
	Eucalyptus	In vivo
	Fenugreek	Human
	Garlic	Human, in vivo,
	Ginger	In vivo
	Ginseng,	In vivo
	Eleutherococcus
	Ginseng, Panax	Human
	Ispaghula	Human
	Java Tea	In vivo
	Juniper	In vivo
	Marshmallow	Human, in vivo
	Myrrh	In vivo
	Nettle	In vivo
	Sage	In vivo
	Senega	In vivo
	Tansy	In vivo
	Hyperglycaemic
	Elecampane	In vivo
	Ginseng, Panax	Human, in vivo
	Hydrocotyl	Human
	Rosemary	In vivo

Table 9 Hormonally active agents

	Drug	Comment

	Agnus Castus	Oestrogenic, in vitro; conflicting results
	Alfalfa	Oestrogenic, in vivo
	Aniseed	Oestrogenic, in vivo
	Bayberry	Mineralocorticoid, in vivo
	Butterbur	S-petasin, inhibition of testosterone
		release, in vivo, in vitro
	Cohosh, Black	Oestrogenic, in vivo, in vitro; conflicting
		results
	Fucus	Hyper-/hypothyroidism reported
	Ginkgo	Oestrogenic, in vitro
	Ginseng,	Oestrogenic, in vivo, in vitro
	Eleutherococcus;
	Ginseng, Panax
	Horseradish	May depress thyroid activity; conflicting
		results

table continues

Pharmacological Activities and Constituents of Herbal Ingredients

619

Table 9 continued

	Drug	Comment

	Liquorice	Mineralocorticoid activity, human;
		oestrogenic in vivo, in vitro
	Motherwort	Oxytocic, in vitro; conflicting results
	Pleurisy Root	Oestrogenic, in vivo; conflicting results
	Red Clover	Oestrogenic in vivo; conflicting results
	Saw Palmetto	Oestrogenic and anti-androgenic in vivo;
		human use in prostate cancer
	Vervain	Inhibition of gonadotrophic activity;
		conflicting results
	Wild Carrot	Oestrogenic, in vivo

Table 10 Immunomodulating agents

	Drug	Comments

	Alfalfa	In vitro
	Boneset	In vitro
	Calendula	In vitro
	Cat’s Claw	In vitro
	Celandine, Greater	In vitro
	Chamomile, German	In vitro
	Drosera	In vitro
	Echinacea	In vitro, in vivo, conflicting results in
		humans
	Ephedra	Inhibits complement pathway, in vitro
	Ginseng,	Human in vivo, in vitro
	Eleutherococcus
	Mistletoe	Human, in vivo, in vitro
	Saw Palmetto	In vivo

Table 11 Allergenic and photosensitising agents

	Drug	Comment

	Agnus Castus	Allergic effects reported
	Angelica	Furanocoumarins, photosensitivity,
		contact allergy
	Aniseed	Furanocoumarins, photosensitivity,
		contact allergy
	Apricot	Contact allergy, kernels
	Arnica	Contact allergy
	Artichoke	Sesquiterpene lactone constituents
	Asafoetida	Irritant gum, contact allergy
	Boneset	Sesquiterpene lactone constituents
	Calendula	Individuals sensitive to plants from the
		Compositae/Asteraceae families
	Cassia	Allergic reactions, mainly contact
		dermatitis
	Celery	Furanocoumarins, photosensitivity
	Chamomile, German	Sesquiterpene lactone constituents
	Chamomile, Roman	Sesquiterpene lactone constituents

Table 11 continued

	Drug	Comment

	Cinnamon	Contact allergy	2
	Corn Silk	Allergic reactions	2
	Corn Silk	Allergic reactions
	Cowslip	Allergic reactions
	Dandelion	Sesquiterpene lactone constituents
	Echinacea	Individuals sensitive to plants from the
		Compositae/Asteraceae families
	Elecampane	Sesquiterpene lactone constituents
	Feverfew	Sesquiterpene lactone constituents
	Fucus	Iodine may aggravate/trigger acne
	Garlic	Sulfur-containing compounds, allergic
		reaction
	Ginger	Dermatitis in sensitive individuals
	Ginkgo	Fruit pulp and seeds: severe allergic
		reactions
	Gravel Root	Sesquiterpene lactone constituents
	Guaiacum	Irritant resin
	Holy Thistle	Sesquiterpene lactone constituents
	Hops	Contact allergy
	Hydrangea	Contact allergy
	Hydrocotyle	Photosensitivity
	Ispaghula	Rare cases of allergy
	Juniper	Contact allergy
	Kava	Cases of allergic skin reactions
	Lady’s Slipper	Contact allergy
	Mistletoe	Injection site reactions, rare cases of
		anaphylactic reactions
	Motherwort	Dermatitis, photosensitisation
	Parsley	Furanocoumarins, photosensitivity
	Pilewort	Contact allergy, protanemonin
	Plantain	Contact allergy
	Pleurisy Root	Contact allergy
	Pulsatilla	Contact allergy, protoanemonin
	Rosemary	Dermatitis, photosensitisation
	St John’s Wort	Photodermatitis, hypericin
	Tansy	Sesquiterpene lactone constituents
	Wild Carrot	Furanocoumarins, photosensitivity
	Yarrow	Sesquiterpene lactone constituents

Table 12 Irritants

	Drug	Comment

	Alfalfa	Canavanine in seeds
	Arnica	Irritant to mucous membranes
	Asafoetida	Irritant gum
	Blue Flag	Irritant gum and oil
	Bogbean	Irritant to GI tract
	Boldo	Irritant oil

table continues

	620		Appendix 2
	Table 12 continued

		Drug		Comment

2		Buchu		Irritant oil
2		Capsicum		Capsaicinoids, mucosal irritants
		Capsicum		Capsaicinoids, mucosal irritants
		Cassia		Irritant to mucous membranes; oil
		Celandine, Greater		Irritant juice
		Cinnamon		Irritant to mucous membranes; oil
		Cohosh, Blue		Irritant to mucous membranes;
				spasmogenic in vitro
		Cowslip		Irritant saponins
		Drosera		Plumbagin
		Eucalyptus		Irritant oil
		False Unicorn		Large doses may cause vomiting
		Figwort		Purgative effect
		Garlic		Raw clove
		Ground Ivy		Irritant oil
		Guaiacum		Avoid if inflammatory condition
		Horse-chestnut		Saponin constituents, contra-indicated in
				existing renal disease
		Horseradish		Irritant oil
		Hydrangea		May cause gastro-enteritis, hydrangin
		Jamaica Dogwood		Irritant to humans
		Juniper		Irritant oil
		Lemon Verbena		Irritant oil
		Lime Flower		Irritant to kidney, oil
		Mistletoe		Injection site reactions
		Nettle		Tea irritant to stomach
		Parsley		Irritant oil
		Pennyroyal		Toxic and irritant oil
		Pilewort		Irritant sap
		Pleurisy Root		Gastrointestinal irritant
		Pokeroot		Irritant saponins
		Pulsatilla		Irritant to mucous membranes
		Queen’s Delight		Diterpene constituents
		Sage		Irritant oil
		Sarsaparilla		Saponins
		Senega		Saponins
		Skunk Cabbage		Inflammatory and blistering to skin
		Squill		Saponins
		Thyme		Irritant oil
		Willow		Salicylates
		Witch Hazel		Irritant to stomach

Table 13 Anti-inflammatory agents

Aloe Vera, Angelica, Arnica, Bilberry, Bloodroot, Blue Flag, Boldo, Boneset, Borage, Buchu, Butterbur, Calendula, Cassia, Cat’s Claw, Celandine (Greater), Centaury, Chamomile (German), Chamomile (Roman), Cohosh (Black), Coltsfoot, Comfrey, Cowslip, Dandelion, Devil’s Claw, Echinacea, Elder, Ephedra, Evening Primrose, Feverfew, Figwort, Gentian, Ginger, Ground Ivy, Horse-chestnut, Hydrocotyle, Java tea, Juniper, Liquorice, Milk Thistle, Myrrh, Nettle, Passionflower, Plantain, Pokeroot, Prickly Ash (Southern), Rosemary, Sarsaparilla, Shepherd’s Purse, St John’s wort, Uva-Ursi, Willow, Yarrow, Yucca

Table 14 Antispasmodics

Angelica, Aniseed, Asafoetida, Butterbur, Calendula, Capsicum, Cassia, Celandine (Greater), Celery, Chamomile (German), Cinnamon, Clove, Cohosh (Blue), Cowslip, Devil’s claw, Elecampane, Euphorbia, Hops, Jamaica Dogwood, Lime Flower, Raspberry, Chamomile (Roman), Rosemary, Sage, Scullcap, Tansy, Thyme, Valerian

Table 15 Herbal ingredients containing amines or alkaloids, or with sympathomimetic action

	Drug	Comment

	Agnus Castus	Dopamine agonist (labdane diterpenes),
		in vitro
	Alfalfa	Alkaloids
	Aniseed	Anethole, sympathomimetic
	Arnica	Betaines, choline
	Bloodroot	Alkaloids
	Bogbean	Alkaloids
	Boldo	Alkaloids
	Borage	Alkaloids
	Broom	Alkaloids, amines
	Butterbur	Alkaloids
	Calamus	Amines
	Capsicum	Sympathomimetic
	Cat’s Claw	Alkaloids
	Celandine, Greater	Alkaloids
	Centaury	Alkaloids
	Cereus	Tyramine
	Cohosh, Black	Alkaloids
	Cohosh, Blue	Alkaloids
	Cola	Alkaloids
	Coltsfoot	Alkaloids
	Comfrey	Alkaloids
	Corn Silk	Amines
	Ephedra	Alkaloids
	Eyebright	Alkaloids
	Fenugreek	Choline, trigonelline
	Fumitory	Alkaloids
	Gentian	Alkaloids
	Ginkgo	Seed: alkaloids; leaf: MAOI activity

table continues

Pharmacological Activities and Constituents of Herbal Ingredients

621

Table 15 continued

	Drug	Comment

	Ginseng, Panax	MAOI potentiation, suspected phenelzine
		interaction
	Golden Seal	Alkaloids
	Gravel Root	Alkaloids
	Hawthorn	Tyramine
	Horehound, White	Alkaloids
	Hydrocotyle	Alkaloids
	Ispaghula	Alkaloids
	Jamaica Dogwood	Alkaloids
	Kava	Alkaloids; possible dopamine antagonist
		effects
	Liferoot	Alkaloids
	Lobelia	Alkaloids
	Mate´	Alkaloids, amines
	Mistletoe	Amines, alkaloids (possible)
	Motherwort	Alkaloids
	Nettle	Choline
	Parsley	Myristicin, sympathomimetic
	Passionflower	Alkaloids (traces or absent)
	Plantain	Alkaloids
	Pleurisy Root	Sympathomimetic
	Pokeroot	Betalains
	Prickly Ash, Northern	Alkaloids
	Prickly Ash, Southern	Alkaloids
	Quassia	Alkaloids
	Sassafras	Alkaloids
	Shepherd’s Purse	Choline, tyramine
	Skunk Cabbage	Alkaloids
	Stone Root	Alkaloids
	Valerian	Alkaloids
	Vervain	Sympathomimetic
	Yarrow	Betonicine, stachydrine, betaine

Table 16 Herbal ingredients containing coumarins(a)

Alfalfa, Angelica, Aniseed, Arnica, Asafoetida, Bogbean, Boldo, Buchu, Capsicum, Cassia, Celery, Chamomile (German), Chamomile (Roman), Dandelion, Fenugreek, Ginseng (Eleutherococcus), Horse-chestnut, Horseradish, Java tea, Liquorice, Meadowsweet, Nettle, Parsley, Prickly Ash (Northern), Quassia, Wild Carrot, Wild Lettuce

Coumarin constituents detected so far in these herbal ingredients do not possess the minimum structural requirements (a C-4 hydroxyl substituent and a C-3 non-polar carbon substituent)(G87) for anticoagulant activity.

Table 17 Herbal ingredients containing flavonoids

Agnus Castus, Agrimony, Angelica, Aniseed, Apricot, Arnica, Artichoke, Bayberry, Bilberry, Bogbean, Boldo, Boneset, Broom, Buchu, Burdock, Burnet, Butterbur, Calendula, Celandine (Greater), Celery, Cereus, Chamomile (German), Chamomile

(Roman), Chaparral, Clivers, Cohosh (Black), Coltsfoot, Corn Silk, 2 Couchgrass, Cowslip, Damiana, Dandelion, Devil’s Claw, Drosera,

Elder, Ephedra, Eucalyptus, Euphorbia, Eyebright, Fenugreek, Feverfew, Figwort, Frangula, Fumitory, Ginkgo, Gravel Root, Ground Ivy, Hawthorn, Hops, Horehound (Black), Horehound (White), Horse-chestnut, Hydrangea, Hydrocotyle, Java Tea, Juniper, Kava, Lemon Verbena, Lime Flower, Liquorice, Marshmallow, Mate´, Meadowsweet, Melissa, Milk thistle, Mistletoe, Motherwort, Nettle, Parsley, Passionflower, Plantain, Pulsatilla, Raspberry, Red Clover, Rhodiola, Rhubarb, Rosemary, Sage, Sarsaparilla, Saw Palmetto, Scullcap, Senna, Shepherd’s Purse, Squill, St John’s Wort, Stone Root, Thyme, Uva-Ursi, Wild Carrot, Wild Lettuce, Willow, Witch Hazel, Yarrow

Table 18 Herbal ingredients containing iridoids

Agnus Castus, Bilberry, Bogbean, Centaury, Clivers, Devil’s Claw, Eyebright, Figwort, Gentian, Ispaghula, Motherwort, Plantain, Scullcap, Uva-Ursi, Valerian, Vervain

Table 19 Herbal ingredients containing saponins

Alfalfa, Aloe Vera, Bogbean, Burnet, Calendula, Chaparral, Cohosh (Blue), Corn Silk, Cowslip, False Unicorn, Fenugreek, Ginseng (Eleutherococcus), Ginseng (Panax), Hawthorn, Horehound (White), Horse-chestnut, Hydrangea, Hydrocotyle, Jamaica Dogwood, Lime Flower, Milk Thistle, Mistletoe, Pokeroot, Pulsatilla, Red Clover, Sarsaparilla, Senega, Senna, Stone Root, Thyme, Vervain, Witch Hazel, Yucca

Table 20 Herbal ingredients containing tannins

Agrimony, Apricot, Arnica, Artichoke, Avens, Bayberry, Bilberry, Blue Flag, Boldo, Borage, Burnet, Butterbur, Calamus, Cascara, Cassia, Chamomile (German), Cinnamon, Clivers, Cola, Coltsfoot, Comfrey, Corn Silk, Cowslip, Damiana, Drosera, Elder, Ephedra, Eucalyptus, Eyebright, Feverfew, Frangula, Gentian, Ground Ivy, Hawthorn, Holy Thistle, Hops, Horse-chestnut, Ispaghula, Juniper, Lady’s Slipper, Lime Flower, Marshmallow, Meadowsweet, Motherwort, Nettle, Pilewort, Plantain, Poplar, Prickly Ash (Northern), Prickly Ash (Southern), Queen’s Delight, Raspberry, Rhubarb, Sage, Sassafras, Saw Palmetto, Scullcap, Slippery Elm, Squill, St. John’s Wort, Stone Root, Tansy, Thyme, Uva-Ursi, Valerian, Vervain, Willow, Witch Hazel, Yarrow, Yellow Dock

Table 21 Herbal ingredients containing essential oils

Agnus Castus, Agrimony, Angelica, Aniseed, Arnica, Artichoke, Asafoetida, Avens, Blue Flag, Boldo, Boneset, Buchu, Burdock, Burnet, Butterbur, Calamus, Calendula, Capsicum, Cassia, Celery, Chamomile (German), Chamomile (Roman), Chaparral, Cinnamon, Clove, Coltsfoot, Couchgrass, Damiana, Elder, Elecampane, Ephedra, Eucalyptus, Eyebright, Feverfew, Garlic, Gentian, Ginger, Ginseng (Eleutherococcus), Ginseng (Panax), Golden Seal, Ground Ivy, Holy Thistle, Hops, Horehound (Black), Horseradish, Hydrocotyle, Java Tea, Juniper, Lemon Verbena, Lime Flower, Liquorice, Lobelia, Meadowsweet, Melissa, Motherwort, Myrrh, Parsley, Pennyroyal, Prickly Ash (Northern), Queen’s Delight, Red Clover, Rhodiola, Rosemary, Sage, Sassafras, Saw Palmetto, Senna (trace), Skunk Cabbage, Squill, St John’s Wort, Stone Root, Tansy, Thyme, Uva-Ursi, Valerian, Vervain, Wild Carrot, Witch Hazel, Yarrow

Appendix 3

Council of Europe – Categories for

Natural Sources of Flavourings

Table 1 Council of Europe. categories for natural sources of flavourings (Report No. 1. Strasbourg: Council of Europe, 2000)(a)

Category Natural source of flavouring

1Plants, animals and other organisms, and parts of these or products thereof, normally consumed as food items, herbs or spices in Europe for which it is considered that there should be no restrictions on use.Flavouring preparations, which are not themselves consumed as food but which are derived from plants, animals and other organisms, and parts of these or products thereof, normally consumed as food items, herbs or spices in Europe. These preparations, on the basis of the information available, are not considered a risk to health in the quantities used.

2Plants, animals and other organisms, and parts of these or products thereof, and preparations derived therefrom, not normally consumed as food items, herbs or spices in Europe.These source materials and preparations, on the basis of the information available, are not considered to constitute a risk to health in the quantities used.

3Plants, animals and other organisms, and parts of these or products thereof, normally consumed as food items, herbs or spices in Europe which contain defined ’active principles’ or ’other chemical components’ requiring limits on use levels.Flavouring preparations, which are not themselves consumed as food but which are derived from plants, animals and other organisms, and parts of these or products thereof, normally consumed as food items, herbs or spices in Europe which contain defined ’active principles’ or ’other chemical components’ requiring limits on use levels.

These source materials and preparations are not considered to constitute a risk to health in the quantities used provided that the limits set for the ’active principles’ or ’other chemical components’ are not exceeded.

4Plants, animals and other organisms, and parts of these or products thereof, and preparations derived therefrom, not normally consumed as food items, herbs or spices in Europe which contain defined ’active principles’ or ’other chemical components’ requiring limits on use levels.These source materials and preparations are not considered to constitute a risk to health in the quantities used provided that the limits set for the ’active principles’ or ’other chemical components’ are not exceeded.

5Plants, animals and other organisms, and parts of these or products thereof, and preparations derived therefrom, for which additional toxicological and/or chemical information is required.These could temporarily be acceptable provided that any limits set for the ’active principles’ or the ’other chemical components’ are not exceeded.

6Plants, animals and other organisms, and parts of these or products thereof, and preparations derived therefrom, which are considered to be unfit for human consumption in any amount.

Reproduced with permission of Council of Europe.

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