Herbal Supplements
Part III
An Overview of the Pharmacognosy,
Pharmacology, Clinical Therapeutics and Use
of Selected Herbal Products
Scott F. Long, R.Ph., Ph.D.
Assistant Professor of Pharmacology & Toxicology
Genito-urinary System
Selected Herbs
Saw Palmetto
Botany
• Source -- Serenoa repens Bartram. -- Native to
the Southern Atlantic coast through the Gulf coast from South Carolina
through Texas. The Palm achieves a height of 6-10 feet. Fruit are
irregularly spherical to oblong, ranging in length from 1/2 to 1 inches
and 1/2 inch diametre, are deep red-brown and wrinkled.
• Active Part
Ŕ Berry
Saw Palmetto
Miscellany
• Alternate Names
Ŕ American Dwarf Palm, Cabbage Palm
• Trade Names
Ŕ Permixon®, Propalmex ®, Strogen ®
• Dosage Forms
Ŕ Tablets, Capsules, Tea, Berries, Liquid Extract
Saw Palmetto
Chemical Constituents
• n-Hexane liposterolic extract, containing
Ŕ lauric acid and other fatty acids
Ŕ phytosterols
Ŕ polysaccharides
Ŕ monoacylglycerides
Saw Palmetto
Proposed Uses
• Saw Palmetto is claimed to be effective in
the treatment of genitourinary problems,
including benign prostatic hypertrophy (BPH)
• Other purported uses
Ŕ to increase sperm production
Ŕ to increase breast size in women
Ŕ to increase libido
Ŕ mild diuresis
Saw Palmetto
Pharmacology
• Inhibition of 5-alpha reductase (in vitro)
• Antagonism of DHT at androgen receptors
• Some evidence exists for
Ŕ Anti-inflammatory actions (MOA unknown)
Ŕ Inhibition of prolactin (MOA unknown)
Ŕ Inhibition of prostatic cell proliferation
Saw Palmetto
Clinical Trials
• Men, 60-70 years old
• Criteria
Ŕ Urinary frequency
Ŕ Urine flow rate
• Significant improvement relative to placebo
Ŕ Champault et al. 1984
• Similar in efficacy relative to finasteride
Ŕ Carraro et al. 1996
• Less (though not significantly) effective than alpha 1
adrenergic blockade
Saw Palmetto
Dosing Recommendations
• Human clinical trials have used 320 mg p.o.
in divided doses, twice daily
• Herbal Usage
Ŕ 1 to 2 G fresh saw palmetto berries
Ŕ 0.5 to 1 G dried berries
Ŕ in a decoction or tea p.o. t.i.d.
Saw Palmetto
Adverse Reactions
• Abdominal and back pain
• Constipation or diarrhœa
• Decreased libido or impotence
• Dysuria and urinary retention
• Headache
• Hypertension
• Nausea
Saw Palmetto
Contraindications
• Pregnancy
• Women of child-bearing age
• Due to actions potentially similar to those
produced by finasteride
Saw Palmetto
Clinical Considerations
• Saw Palmetto does not apparently alter
prostate size
• May produce a false-negative prostate-
specific antigen (PSA) result -- baseline
measurements should be made prior to
initiation of therapy
• Take with meals to minimise GI side effects
Saw Palmetto
Summary
• Some active constituent of saw palmetto does
appear to have beneficial effects in the treatment
of BPH, although the exact mechansim is
unknown
• Use should be controlled and supervised by health
care professionals to minimise potential risks and
to judge efficacy of treatment
• Approved by the German Commission E for use in
BPH-related urinary problems.
Nettle
Botany
• Source -- Urtica dioica L., a perennial of the nettle family (Urticaceæ),
native world-wide. The plant grows 2-3 feet high with heart-shaped,
serrated leaves. Plants are gender specific, with flowers in
long,branched clusters appearing June-September. The plant is hirsute,
with each hair serving as a small, hollow, needle-like form of
protection.
• Active Parts -- Leaves, Stems, Roots
Nettle
Miscellany
• Alternate Names
Ŕ Common nettle, Greater nettle, Stinging nettle
• Trade Names
Ŕ Nettle Capsules, Nettle Liquid Extract
• Dosage Forms
Ŕ Capsules, Dried Leaf and Root Extract,
Tincture
Nettle
Chemical Constituents
• Stems (non-therapeutic) --
Ŕ Histamine, serotonin, choline, formic acid
• Roots --
Ŕ Phenylpropanes and lignans
• Roots and Flowers --
Ŕ Scopoletin, steryl derivatives, lignan glycosides,
flavonol glycosides
• Whole Plant --
Ŕ B, C, and K vitamins, sitosterol and other steroid
related compounds
Nettle
Proposed Uses
• Diuresis -- hypertension, heart failure, and
urinary, bladder, and kidney dysfunction
• Benign Prostatic Hypertrophy
• Other Uses -- Rheumatoid arthritis,
antispasmodic, expectorant, asthma, cough,
tuberculosis, locally for alopecia, epistaxis,
uterine bleeding, diabetes, gout, cancer,
eczema, wound healing.
Nettle
Pharmacology
• Nettle apparently does possess some
diuretic activity, although the mechanism is
not known.
• Shown to stimulate uterine contractions in
rabbits.
• Possesses immunostimulant (lectin protein)
and anti-inflammatory actions (scopoletin)
• Inhibits BPH in mice.
Nettle
Clinical Trials
• Nettle extracts have been shown to reduce
urine flow, nocturia, and residual urine in
humans.
• Use as a bladder irrigant in humans resulted
in reduces postoperative blood loss,
bacteriuria, and inflammation.
• Use in humans has shown some efficacy in
the treatment of allergic rhinitis.
Nettle
Dosing Recommendations
• Allergic rhinitis
Ŕ 150 or 300 mg capsules as needed
• Tea
Ŕ 1-2 teaspoonfuls of dried herb in 1 cup of
boiling water, up to twice daily
• Tincture
Ŕ 1/4 to 1 teaspoonful up to twice daily
Nettle
Adverse Reactions
• Contact dermatitis (especially fresh)
• Decreased urine volume, frequency
• Diarrhœa
• Œdema
• GI irritation
Nettle
Contraindications
• Pregnancy
• Children under 2 years old
• Elderly patients
Drug Interactions
• Diuretics
Nettle
Clinical Considerations
• Contact dermatitis associated with cutaneous
exposure may cause intense burning for 12 hours
or longer. Following exposure, the individual
should wash thoroughly with soap and water and
medicate with antihistamines and steroid cream as
needed.
• The FDA consideres nettle to be of undefined
safety.
• Approved by the German Commission E to treat
urinary inflammation and prevent urinary calculi.
Nettle
Summary
• There is both scientific and clinical evidence to
support the use of nettle as a mild diuretic, urinary
anti-inflammatory, and anti-allergic.
• Oral dosing rarely results in severe adverse
reactions and the herb is generally considered safe.
• Further research is required to confidently
recommend nettle as an alternative therapy.
• Approved by German Commission E for urinary
inflammation and prevention of urinary gravel.
Also externally for rheumatism.
Pumpkin
Botany
• Source -- Cucurbitaceæ family, Cucurbita pepo
L., C. moschata., widely cultivated in North
America and Australia.
• Active Parts -- Seeds
Pumpkin
Miscellany
• Alternate Names
Ŕ Cucurbita, Pumpkinseed oil, Vegetable marrow
• Trade Names
Ŕ Available in combination with palmetto as
Ultimate Oil®, Proleve 40® and others.
• Dosage Forms
Ŕ seeds (whole or crushed), seed extract or oil,
tablets, tea
Pumpkin
Chemical Constituents
• Cucurbitin ((-)-3-amino-3-
carboxypyrrolidine) a water soluble amino
acid.
• Pumpkin Seed Oil -- Unsaturated fatty acids
(c. 25% oleic and 55% linoleic acids),
phytosterols
Pumpkin
Proposed Uses
• The current lay recommendations for the
use of pumpkin is in the treatment of benign
prostatic hypertrophy.
• Historically, pumpkin has been used to treat
tape and other intestinal parasitic helminthic
infections.
Pumpkin
Pharmacology
• Cucurbitin exhibits anthelminthic activity
against pinworms and tapeworms in mice.
It has also been shown to inhibit the growth
of immature Schistosoma.
• The beneficial effects in BPH are purported
to be due to the fatty acids and phytosterols,
however this claim has not been
substantiated.
Pumpkin
Clinical Trials
• Clinical trials of pumpkin as a single entity
have not been performed. In combination
with saw palmetto, patients have shown an
improvement in urinary flow, micturition
time and frequency, and reduced residual
urine. No changes in prostate size have
been noted.
Pumpkin
Dosing Recommendations
• Anthelminthic -- Doses vary from 60 to 500
G of pumpkin seed in three divided doses
daily, either as a tea or an emulsion of
crushed seeds in powdered sugar and milk
or water.
• Many cultures report the ingestion of a
handful of seeds daily for the treatment of
both helminthic infections and BPH.
Pumpkin
Adverse Effects
• Electrolyte Imbalance (from the mild
diuretic actions)
Drug Interactions
• Diuretics (potentiation of fluid loss and
electrolyte imbalance)
Pumpkin
Contraindications
• Pumpkin should not be used in prostatic
hypertrophy of unknown etiology. Neither
should it be used in patients who are
pregnancy or are breastfeeding.
Pumpkin
Clinical Considerations
• Patients taking pumpkin should be
monitored for electrolyte imbalances.
• If used as an anthelminthic, the patients
should be monitored to ensure efficacy.
• Caution should be taken to monitor urine
output. As with any diuretic, forced
diuresis with urinary obstruction may cause
nephrotoxicity.
Pumpkin
Summary
• There is no evidence, either scientific or clinical,
to support the use of pumpkin in the treatment of
BPH. The potential benefit from the diuretic
effects of the fatty acids is, at best, mild and
minor. Better agents with known side effect and
toxicity profiles provide better choices for the
treatment of prostatic hypertrophy.
• Approved by German Commission E for urinary
irritation and BPH related problems.
Goldenseal
Botany
• Source -- Hydrastis canadensis L., Native to Canada and
the Eastern U.S.A. A small, perennial herb, growing 6-12 inches high.
The stalk and dark, green leaves are hirsute. The plant flowers in April
and produces oblong, crimson fruit.
• Active Part -- Rhizome (root stock)
Goldenseal
Miscellany
• Alternate Names
Ŕ Eye balm, Indian tumeric, Jaundice root,
Yellow root
• Trade Names
Ŕ Various, all incorporating “Golden Seal”
• Dosage Forms
Ŕ Capsules, Tablets, Alcoholic and Aqueous extracts,
Dried ground root powder, Tinctures, Teas
Goldenseal
Chemical Constituents
• Alkaloids
Ŕ hydrastine, berberine, hydrastinine, canadine,
berberastine, candaline, canadaline
• Meconin
• Chlorogenic Acid
• Fatty Acids
• Carbohydrates
• Volatile Oils
• Resins
Goldenseal
Proposed Uses
• Diuresis
• Other Reported Uses Include
Ŕ Gastritis, Peptic ulceration, Anorexia,
Postpartum hæmorrhage, Dysmenorrhœa,
Eczema, Pruritus, Tuberculosis, Cancer, Mouth
ulcerations, Otorrhœa, Tinnitus, Conjunctivitis,
Wound antiseptic, Laxative, Anti-inflammatory
Goldenseal
Pharmacology
• Alkaloid components have been reported to inhibit smooth
muscle contraction and to have an oxytocic effect.
Extracts have been shown to attentuate hyperphagia and
polydipsia associated with diabetes mellitus in mice.
• Berberine exerts anticoagulant, cardiac stimulant (low
doses), cardiodepressant (high doses), antipyretic,
antimuscarinic, antihistaminic, antitumour, antimicrobial,
anthelminthic, and hypotensive effects as well as
increasing cardiac perfusion
• Hydrastinine is reported to cause vasoconstriction with
subsequent increases in blood pressure
Goldenseal
Clinical Trials
• Very Few Clinical Trials have been performed to date on
Goldenseal extracts
• Goldenseal is apparently less effective than ergot alkaloids in
reducing postpartum hæmorrhage
• Antipyretic actions of berberine have been shown to be greater
than aspirin
• Berberine has been shown to correct laboratory abnormalities
and improve biliary flow in patients with cirrhosis
• Berberine hase been shown to shorten/decrease episodes of
diarrhœa associated with cholera, giardiasis, salmonellosis,
shigellosis, and some enterobacteriosis
Goldenseal
Dosing Recommendations
• Various Doses have been recommended
• Dried Root
Ŕ 0.5 to 1 G t.i.d.
• Liquid Extracts
Ŕ 250 mg p.o. t.i.d.
Goldenseal
Adverse Effects
• Bradycardia, asystole, heart block,
• CNS depression, paræsthesias, seizures; paralysis
and respiratory depression (higher doses)
• Contact dermatitis
• GI cramping/pain, diarrhœa, constipation,
vomiting
• Leucocytosis
• Mouth ulcerations
Goldenseal
Contraindications
• Any patient with cardiovascular disease,
especially hypertension, cardiac failure, and
arrhythmias.
• Pregnancy
Goldenseal
Drug Interactions
• CNS Depressants
Ŕ depressants effects may be additive
• Antihypertensives
Ŕ typically, may cause additive hypotensive
effects, however, hydrastinine may offset
beneficial effects of antihypertensives
• Anti-coagulants
Ŕ effects may be reduced by goldenseal
Goldenseal
Clinical Considerations
• Goldenseal may inhibit absorption of
dietary B vitamins. Deficiencies have been
reported.
• Tolerance to the effects of the herb are
reported to develop relatively quickly.
• The use of goldenseal to mask urine drug
tests does not appear to have any validity.
Goldenseal
Summary
• Although the constituents of goldenseal
have been found to have some
pharmacologic actions, the numerous
adverse effects and lack of either basic
laboratory or clinical research do not
support its use for any reason.
• Goldenseal has not been reviewed by
German Commission E.
Bearberry
Botany
• Source -- Arctostaphylos uva-ursi L. Sprengel, A.
coactylis, A. adenotricha; a low, trailing evergreen shrub,
native to the Northern portion of the Northern Hemisphere.
Plant is evergreen with branches, irregular stems and red
berries.
• Active Part -- leaves
Bearberry
Miscellany
• Alternate Names
Ŕ Bear’s grape, Crowberry, Kinnikinnick, Uva-
ursi
• Trade Names
Ŕ In combination in Arctuvan®, Solvefort®,
Uroflox®, Uvalyst®
• Dosage Forms
Ŕ Tablets, Tea, Drops
Bearberry
Chemical Constituents
• Hydroquinones
Ŕ Primarily arbutin, also hydroquinone
monoglucoside and methylarbutin
• Other Constituents
Ŕ gallotannin, arbutin gallic acid ester,
triterpenes, iridoid glycoside monotropein,
piceoside, phenol carboxylic acids,
paracoumaric flavonoids, syringic acids
Bearberry
Proposed Uses
• Mild diuretic
• Mild urinary antiseptic
Bearberry
Pharmacology
• A hydroquinone metabolite of arbutin has
been shown to have antiseptic and
astringent actions.
• The triterpene ursolic acid and the flavonoid
isoquercetin both have demonstrated
diuretic activity.
Bearberry
Clinical Trials
• No controlled humans studies have been
performed.
• Studies in mice have demonstrated that bearberry
may attentuate weight loss in diabetes without
altering glycemic control.
• Other studies have demonstrated an ability to
accentuate the antiinflammatory/anti-allergic
actions of dexamethasone, prednisone and
indomethacin.
Bearberry
Dosing Recommendations
• Doses for bearberry vary greatly, ranging
from 1 to 10 G daily.
• Anecdotal evidence indicates that as much
as 20 G may be taken without adverse
reaction and as little as 1 G may cause
toxicity in sensitive individuals.
Bearberry
Adverse Effects
• Cyanosis
• Green-coloured urine
• Nausea
• Vomiting
• High Doses
Ŕ Tinnitus, Seizures, Cardiovascular collapse
Bearberry
Contraindications
• Pregnancy
• Diuretics
Ŕ May potentiate electrolyte imbalance
Bearberry
Drug Interactions
• Diuretics
Ŕ potentiation of actions
• Urinary Acidifiers
Ŕ may inactivate bearberry
Bearberry
Clinical Considerations
• Discolourisation of Urine
• An alkaline urinary pH is believed to be
necessary to support the antiseptic actions
of bearberry
Bearberry
Summary
• While some components of bearberry may possess
pharmacologic action, the lack of clinical evidence
for efficacy and the danger of excessive
electrolyte imbalance preclude its use for any
disease state.
• The existence of affordable and specific diuretics
do not support the use of bearberry.
• Approved by German Commission E for urinary
irritation.
Buchu
Botany
• Source -- Barosma betulina
Bartl & Wendl. (Agathosma
betulina), B. serratifolia, B.
crenulata, low lying shrubs
endigenous to South Africa.
• Active Part -- leaves from
flowering or fruit bearing
plants.
Buchu
Miscellany
• Alternate Names
Ŕ Agathosma, Betuline, Bocco
• Trade Names
Ŕ None
• Dosage Forms
Ŕ Dried Leaves for infusion
Ŕ Tincture
Buchu
Chemical Constituents
• The active compounds are found primarily
in volatile oils obtained from leaves.
• Diosphenol (buchu camphor)
• Pulegone
• Terpene-4-ol
• Various Flavonoids
Buchu
Proposed Uses
• Diuretic
• Urogenital Tract Infections
Buchu
Pharmacology
• Very little research has been performed on
buchu or its constituents.
• Diosmin, one of the flavonoids of buchu has
been shown to possess anti-inflammatory
actions in rats.
• No Clinical Trials have been
performed.
Buchu
Dosing Recommendations
• Infusion
Ŕ 1 oz. dried leaves infused in 1 pint boiling
water
• Tincture
Ŕ 1 - 2 ml p.o. three to four times daily
Buchu
Adverse Effects
• Volatile Oil
Ŕ Diarrhœa, Nausea, Vomiting
Ŕ Nephritis
• Pulegone
Ŕ Hepatotoxicity
Ŕ Hypermenorrhœa
Ŕ Spontaneous Abortion
Buchu
Contraindications
• Pregnancy
• Kidney Infection
• Kidney Disease
• Liver Disease
Buchu
Drug Interactions
• Buchu may enhance the actions of oral anti-
coagulants
Buchu
Clinical Considerations
• Any patient taking buchu should be
monitored for hepatotoxicity and
nephrotoxicity.
Buchu
Summary
• No scientific or clinical evidence supports
the use of buchu as a diuretic.
• The risk of hepato- and nephro-toxicity
precludes its use at any dose for any disease
state.
• German Commission E does not support the
use of buchu for any purpose. Its use is not
approved.
Cardiovascular System
Selected Herbs
Garlic
Botany
• Source -- Allium sativum L., a member of the
same family as the onion, the monocotyledenous lilies.
• Active Part -- Bulb/cloves
Garlic
Miscellany
• Alternate Names
Ŕ Allium, Stinking Rose, Da-suan
• Trade Names
Ŕ Kwai®, Kyolic®, Garlique®
• Dosage Forms
Ŕ Tablets, Powder, Fresh bulb, and Oil
Garlic
Chemical Constituents
• Alliin is thought to be the primary
beneficial constituent. It is converted to
allicin (via alliinase) which is thought to
provide garlics major effect. Allicin also
provides the characteristic smell.
• Other constituents include numerous
sulphur-containing compounds; ajoene; A,
B, and C vitamins; and minerals.
Garlic
Proposed Uses
• Historically, garlic has been used to treat
blood disorders, heal wounds, treat
infections, and ward off evil spirits.
• Currently, garlic is heavily promoted to
treat hyperlipidæmia and high blood
pressure.
• Other reported used include AIDS, asthma,
diabetes, inflammation, heavy metal poisoning,
constipation, and athlete’s foot.
Garlic
Pharmacology
• The exact mechanism of action of garlic is not known.
Pharmacodynamic effects include:
Ŕ decreased total cholesterol, triglycerides, and LDL and increased
HDL
Ŕ hypotensive actions (animals and humans)
Ŕ decreased blood glucose (rabbits)
Ŕ anti-infective actions in vitro and in vivo
Ŕ methylallyltrisulphide and ajoene inhibit platelet aggregation
Ŕ decreased nitrosamine and nitrite accumulation and prolonged
survival in cancer cell-dosed mice
Ŕ decreased GI hypermotility in rodents
Garlic
Clinical Trials
• The cholesterol-lowering effects of garlic have
indicated effects no better than the HMG CoA
reductase inhibitors. No evaluations of
morbidity/mortality have been performed.
• Anti-infective properties occur only at extremely
high concentrations.
• Significant reductions in diastolic pressure with
little change in systolic pressure.
• Preliminary studies indicate possible reduction in
morbidity in AIDS patients.
Garlic
Dosing Recommendations
• Anti-hyperlipidæmic -- 600-900 mg daily or
4 G fresh garlic or 8 mg garlic oil daily
Garlic
Adverse Effects
• Contact dermatitis, other allergic reactions
• Diaphoresis
• Dizziness
• Garlic odour
• Hypothyroidism
• Irritation of mouth, œsophagus, stomach
• Nausea and vomiting
Garlic
Contraindications
• Known hypersensitivity to garlic or any
member of the lily family
• Peptic ulcer disease
• GERD
• Pregnancy
Garlic
Drug Interactions
• Anticoagulants
Ŕ may increase the bleeding tendencies in patients
receiving heparin or warfarin
• Antiplatelet Drugs
Ŕ may produce synergistic actions with the anti-
thrombotic actions of aspirin, tirofiban,
dipyridamole, and other inhibitors of platelet
function.
Garlic
Clinical Considerations
• Patients should be monitored for potential
adverse effects and drug interactions.
• Baseline and periodic lipid profiles should
be obtained to ensure efficacy.
• It is generally thought that efficacy is
dependent upon alliin/allicin -- the odourous
components of garlic. “Odour-less”
compounds probably lack any efficacy.
Garlic
Summary
• Scientific and clinical data support some efficacy
in lowering lipids and blood pressure. However,
the data are conflicting.
• No evidence exists for many of the other
purported uses of garlic.
• Garlic is approved by German Commission E as
an adjunct to dietary intervention in elevated
cholesterol and to prevent age-related vascular
disease.
Horse Chestnut
Botany
• Source -- Æsculus hippocastanum L., Native
to Northern and Central Asia. The tree has smooth, grey
bark and soft wood.
• Active Part
Ŕ Seed
Horse Chestnut
Miscellany
• Alternate Names
Ŕ æscin, escine, hippocastani semen (extract)
• Trade Names
Ŕ Venostatin Retard®, Venostat®
• Dosage Forms
Ŕ Extract
Horse Chestnut
Chemical Constituents
• Triterpene glycosides
Ŕ Æscin
• Flavonoids
Ŕ Quercetin, Kæmpferol, Astragalin,
Isoquercetin, Rutin
• Coumarins
Ŕ Æsculetin, Fraxin, Scopolin)
• Other constituents
Ŕ Allantoin, Choline, Citric acid, Phytosterols
Horse Chestnut
Proposed Uses
• Purported uses for horse chestnut include
Ŕ varicose veins
Ŕ diarrhœa
Ŕ fever
Ŕ phlebitis
Ŕ hæmorrhoids
Ŕ prostatic hypertrophy
Horse Chestnut
Pharmacology
• Anti-inflammatory
• Reduced transcapillary filtration
• Increases prostaglandin F2alpha
• Stabilises lysosomal membranes
• Anti-viral
• Anti-diarrhœal (quercetin)
Horse Chestnut
Clinical Trials
• Stabilisation of lysosomal membranes has
been associated with reduced enzyme levels
responsible for varicose veins in humans.
• Three additional clinical trials have
demonstrated improvement in vascular
insufficiency with reduced lower leg
œdema, mean lower leg volume, heaviness,
tenseness, fatigue, and paræsthesias.
Horse Chestnut
Dosing Recommendations
• Most clinical trials have employed 100 -
200 mg æscin in one to two doses daily
Horse Chestnut
Adverse Effects
• Muscle spasm
• Nausea and vomiting
• Nephropathy
• Hepatotoxicity
• Pruritus
• Urticaria
• Hypersensitivity
Horse Chestnut
Contraindications
• Pregnant and breast-feeding patients
• Patients on anti-coagulants/anti-thrombotics
• Patients with bleeding disorders
• Patients with demonstrated hypersensitivity
Horse Chestnut
Drug Interactions
• Anti-coagulants
• Anti-thrombotics
• Increased risk of bleeding due to the
coumarins present in crude extracts
Horse Chestnut
Clinical Considerations
• Patients should be monitored for bleeding,
nephrotoxicity and hepatotoxicity
• May discolour urine red
• Whole fruit, leaves, and older bark of horse
chestnut is poisonous
• Should not be confused with buckeye,
which is also called horse chestnut
Horse Chestnut
Summary
• Given the inadequate pharmacologic therapy for
venous insufficiency, the temptation to use horse
chestnut is strong. However, further clinical trials
are needed and a single-agent æscin preparation
would likely be preferred.
• Horse chestnut is approved by German
Commission E for the treatment of chronic venous
insufficiency, pedal œdema, and nocturnal leg
cramps
Angelica
Botany
• Source -- Angelica archangelica L, also A. acutiloba, A.
atropurpurea, A. dahurica, A. edulis, A. gigas, A. keiskei,
A. koerana, A. polymorpha, and A. sinensis -- A native of
Syria, but naturalised as far north as Lapland and Iceland. The plant is
biennial and grows to a height of 4-6 feet with long, hollow stems and serrated
leaves. The roots are long, thick to spindly and fleshy.
• Active Part -- Root and rhizome
Angelica
Miscellany
• Alternate Names
Ŕ Angelica root, Angelica radix, Dong quai
• Trade Names
Ŕ Various trade names, often incorporating
angelica or dong quai
• Dosage Forms
Ŕ Fluid extract, Tincture, Essential Oil, and Cut,
Dried, and Powdered Root
Angelica
Chemical Constituents
• Coumarins -- angelicin, osthol, bergaptan,
imperatorin, oreoselon, oxypeucidanin,
umbelliferone, xanthotoxol, and xanthotoxin
• Phenols -- ferulic acid
• Chalcones -- xanthoangelol and 4-hydroxyderricin
• Others -- terpene hydrocarbons, alcohols, esters,
lactones, aliphatic carbonyls, polysaccharides,
palmitic acid, archangelone, various volatile oils,
and macrocycline lactones
Angelica
Proposed Uses
• Historically, angelica has the reputation of a
“cure-all” with use in post-menopausal
women, menstrual discomfort, anæmia,
poor circulation, headache, backache,
osteoporosis, hay fever, asthma, & eczema.
• Current trends for angelica use include
peripheral vascular disease, GI disorders,
and cancer.
Angelica
Pharmacology
• Inhibition of platelet activity in vitro and in vivo, may inhibit
thromboxane A2 formation and increase prostaglandin I2
production.
• Stimulate hæmatopoiesis (mice)
• Reduced myocardial injury and arrhythmias in cultured murine
cells
• Anti-tumour actions (mice) due to the chalcones, may increase
tumour necrosis factor
• Anti-inflammatory/analgesic actions (mice)
• Anti-bacterial actions (primarily against Gram positive organisms)
• Stimulate uterine contractions and relaxation of tracheal smooth
muscle (mice)
Angelica
Clinical Trials
• No human clinical trials for angelica alone exists.
• Angelica in combination with nifedipine has been
shown to decrease pulmonary hypertension in
humans.
• Angelica in combination with other unidentified
compounds decreased antibody production in
asthmatics
• Numerous Chinese studies involving poly-herbal
therapy report improvent in gynecological
disorders.
Angelica
Dosing Recommendations
• There appears to be little aggreement in the
appropriate dose of angelica.
• German Commission E recommends
Ŕ 4.5 G of crude drug
Ŕ 1.5-3 G of fluid extract
Ŕ 1.5 G tincture
Ŕ 10-20 drops of essential oil
Angelica
Adverse Effects
• Photodermatitis
• Phototoxicity
• Other allergic reactions
• Hypotenstion
Angelica
Contraindications
• Pregnant and Breast-feeding Patients
• Diabetics
• Patients with bleeding disorders or who are
taking anti-coagulants/anti-thrombotics
Angelica
Drug Interactions
• Anti-coagulants
• Anti-thrombotics
• Due to the anti-platelet actions, may see a
potentiation of effects
Angelica
Clinical Considerations
• Patients should be monitored for bleeding.
• Patients should avoid excess and direct
sunlight.
• Given the anti-tumour and cytotoxic actions
of the herb, the risk of cancer is greater with
angelica than with some other herbal
products.
Angelica
Summary
• Although long used in traditional Chinese medicine,
the is little evidence other than anecdotal for its
efficacy. Animal studies indicate that some
pharmacologic actions may support the use of
angelica, the risk should be weighed against any
benefit. The lack of clinical support and risk of
toxicity do not justify the use of angelica.
• German Commission E has approved angelica for the
treatment of anorexia, GI spasm and discomfort,
including feelings of fullness and flatulence.
Broom
Botany
• Source -- Cytisus scoparius L. Link
(Sarothamnus scoparius), native to Europe and
Northern Asia. The plant grows to a height of 3-5 feet
with long, straight branches and alternate oblate leaves
• Active Part
Ŕ Twigs
Ŕ Flowers
Ŕ Ærial parts
Broom
Miscellany
• Alternate Names
Ŕ Cytisi scoparii herba, Scotch broom, Hogweed,
Bannal
• Trade Names
Ŕ No single ingredient trade names
• Dosage Forms
Ŕ Tea, Extract, Cigarettes, Root
Broom
Chemical Constituents
• Alkaloids -- Sparteine
• Flavone glycosides -- Oxysparteine,
scoparoside, spiræoside, lupanine,
genitoside, isoquercetin
• Others -- Kæmpferol, Sarothamnoside,
Caffeic acid derivatives, Essential oils,
lectins (phytohæmagglutinins)
Broom
Proposed Uses
• Antiarrhythmic
• Cathartic
• Diuretic
• Emetic
• Relaxation
• Euphoria
Broom
Pharmacology
• Blocks sodium and potassium channels in
myocardial cells (rodents)
• Negative inotropy and chronotropy
• Oxytocic-like action
• Diuretic (scoparoside)
• Metabolised by CYP2D6 pathway of the
Cytochrome P450 system
Broom
Clinical Trials
• No clinical trials exist for the efficacy of
broom in humans
• Scientifically, the lectins are used as
pharmacologic markers, to classify red cell
polyagglutinability, and sparteine is used to
characterise metabolisers of hepatic
CYP2D6 system.
Broom
Dosing Recommendations
• 1 - 1.5 G of active drug in aqueous or
ethanolic extracts once daily
Broom
Adverse Effects
• Arrhythmias
• Headache
• Spontaneous abortion
• Fungal pneumonia (smoking contaminated
broom top cigarettes)
• Overdose -- shock, tachycardia, changes in
mental status, vertigo, nausea, and diarrhœa
Broom
Contraindications
• Pregnancy
• Hypertension
• Congestive Heart Failure
Broom
Drug Interactions
• Antihypertensive (increased or decreased
efficacy of antihypertensive)
• Beta and Calcium Blockers (additive
negative chronotropic effects)
• Tricyclic Antidepressants (additive
arrhythmic effects)
• Monoamine Oxidase Inhibitors
(hypertensive crisis)
Broom
Clinical Considerations
• Patients with pacemakers should not take
broom, due to the increased risk of
alteration of myocardial conductive
pathways.
• Patients should be monitored for other
adverse reactions and drug interactions.
Broom
Summary
• Sparteine and other constituents may be valuable
as models for new pharmacologic agents
• Broom as a herbal compound should not be used
do to lack of clinical data and high risks of
toxicity
• The FDA considers the herb unsafe for use
• The German Commission E has approved broom
for functional heart and circulatory disorders
Guarana
Botany
• Source -- Paullinia cupana, (H. B. & K.)
P. sorbilis -- Native to South America. The plant has
divided, compound leaves, yellow flowers, and produces
pear-shaped fruit, and 3-seed pods.
• Active Part -- Seeds
Guarana
Miscellany
• Alternate Names
Ŕ Brazilian cocoa, Guarana gum, Guarana paste,
Zoom
• Trade Names
Ŕ Happy Motion®, Zoom®
• Dosage Forms
Ŕ Tea, Alcoholic extracts, Elixir, Tablets,
Capsules, Candies, Gums
Guarana
Chemical Constituents
• Caffeine (up to 10%) -- 800 mg of crude
guarana contains approximately 30 mg
caffeine
• Guarinine (a methylated xanthine)
• Tannins -- catechutannic acid, d-catechin,
tannic acid, and catechol
• Saponins -- Timbonine
Guarana
Proposed Uses
• Cardiac stimulant
• CNS stimulant
• Aphrodisiac
• Appetite suppressant
• Diarrhœa
• Prevention of malaria and dysentery
Guarana
Pharmacology
• Antagonism of adenosine and
phosphodiesterase (caffeine)
• CNS stimulant
• Cardiac stimulant
• Diuretic
• Hypoglycæmic
• Coronary/peripheral vasodilatation
• Cerebrovascular vasoconstriction
• Skeletal muscle stimulant
• Smooth muscle relaxant
• Increased gastric acid secretion
Guarana
Clinical Trials
• No clinical trials have been performed for
guarana for any medicinal use.
Guarana
Dosing Recommendations
• Various doses have been used, according to
lay literature, ranging from 200 to 800 mg
of guarana. Daily intake of the crude herb
should not exceed 3 G.
• Maximum daily intake of caffeine is
accepted as 250 mg (3-5 G guarana). Intake
over this amount may cause toxicity and
withdrawal.
Guarana
Adverse Effects
• Accepted Dose -- diuresis, insomnia
• Overdose -- agitation, anxiety, diarrhœa,
headache, irritability, nausea, arrhythmias,
seizures, tachycardia, tremors, vomiting
• Withdrawal -- anxiety, headache, irritability
Guarana
Contraindications
• Pregnancy, breast-feeding
• Arrhythmias
• Cardiovascular disease
• Hypertension
• Gastric/Peptic ulcer disease
• Chronic headache
• Diabetes
Guarana
Drug Interactions
• Adenosine (decreased response)
• Beta-adrenergic agonists (increased response)
• Cimetidine, disulfiram, fluoroquinolones,
oral contraceptives (increase serum caffeine levels)
• Iron (decreased absorption)
• Lithium (decreased clearance)
• Theophylline (additive effects)
Guarana
Clinical Considerations
• In general patients should be warned of
effects similar to those for caffeine.
• Professional should be aware of potential
toxicities and their signs/symptoms and any
drug interactions.
Guarana
Summary
• Taken in moderation, guarana is probably as safe as
coffee, tea, or caffeinated carbonated beverages for
use as a CNS stimulant.
• Patients should be educated on the potential adverse
reactions.
• Guarana should not be used to treat cardiovascular
disorders, since potentially life-threatening responses
could arise.
• The German Commission E has not evaluated guarana
for medicinal use.
Endocrine System
Selected Herbs
Black Cohosh
Botany
• Source -- Cimicifuga racemosa Nutt and other
species native to Eastern North America, they are tall (1-3 feet),
herbaceous plants that flower in June/July with feathery racemes of
white blossoms.
• Active Part -- Roots and rhizomes
Black Cohosh
Miscellany
• Alternate Names
Ŕ Black snakeroot, Bugbane, Bugwort,
Rattleweed, Rattleroot, Squaw root
• Trade Names
Ŕ Estroven®, Femtrol®, Remifemin®
• Dosage Forms
Ŕ Caplets, Capsules
Black Cohosh
Chemical Constituents
• Steroidal terpenes
• Acteina
• Cimigoside
• 27-Deoxyactein
• Others -- tannins, salicylic acid, and the
isoflavone formononetine
Black Cohosh
Proposed Uses
• Astringent
• Diuretic
• Anti-diarrhœal
• Anti-inflammatory
• Menopause
Black Cohosh
Pharmacology
• Acteina is thought to produce vagal-
mediated hypotension (animal studies)
• Black cohosh has been shown to occupy
œstrogen receptors to decrease the release
of leutinising hormone (LH) without
altering follicle stimulating hormone (FSH)
in mice
Black Cohosh
Clinical Trials
• Clinical trials have shown similar effects on
LH as those produced in the laboratory.
• Another clinical trial resulting in significant
reductions in LH secretion and non-
significant reductions in FSH.
• Changes were not significantly different
than those produce by standard œstrogen
therapy.
Black Cohosh
Dosing Recommendations
• Doses vary and are not standardised.
• Clinical trials have utilised doses ranging
from 8 mg to 2400 mg daily
Black Cohosh
Adverse Effects
• Hypotension
• Nausea
• Vomiting
• Miscarriage at high doses
Black Cohosh
Contraindications
• Pregnancy
• Patients with low blood pressure
• Patients with œstrogen-dependent cancers
or who are at risk for developing such
cancers.
Black Cohosh
Drug Interactions
• Anti-hypertensive
Ŕ Effects may be additive to cause a precipitous
drop in blood pressure.
Black Cohosh
Clinical Considerations
• Blood pressure should be closely monitored
in patients taking black cohosh.
Black Cohosh
Summary
• Clinical evidence does exist that supports the use of
black cohosh as an alternative therapy in the treatment
of post-menopausal symptoms. However, many of
these trials used low numbers of subjects. More
extensive clinical trials are needed to better assess the
safety and efficacy of cohosh.
• German Commission E has approve black cohosh for
the treatment of premenstrual discomfort,
dysmenorrhœa, and signs and symptoms of post-
menopause.
Evening Primrose
Botany
• Source -- Œnethera biennis L., a biennial,
flowering herb that grows in North America
and Europe.
Ŕ 3-4 feet high
Ŕ 3-5 inch leaves, 1 inch wide
Ŕ yellow flower (June) typically
opening around 6:00-7:00 P.M.
• Active Part -- Seeds
Evening Primrose
Miscellany
• Alternate Names
Ŕ King’s Cure All
• Trade Names
Ŕ Efamol®, Epogram®
• Dosage Forms
Ŕ Capsules, Gelcaps
Evening Primrose
Chemical Constituents
• Primarily Essential Fatty Acids
Ŕ Linoleic acid
Ŕ gamma-Linoleic acid
Ŕ Oleic acid
Ŕ Palmitic acid
Ŕ Stearic acid
Evening Primrose
Proposed Uses
• Historically, evening primrose has been
used to treat asthmatic cough, GI
disturbances, whooping cough, eczema,
breast pain, premenstrual syndrome,
psoriasis, multiple sclerosis, rheumatoid
arthritis, hypercholesterolæmia, asthma,
Raynaud’s syndrome, Sjögren’s syndrome,
diabetic nephropathy, and as a sedative,
astringent, analgesic, and vulnerary.
Evening Primrose
Pharmacology
• No specific mechanism of action has been shown for evening
primrose.
• Supporters of its use claim that the beneficial effects are
derived from the linoleic and gamma-linoleic acid
constituents. These are essential fatty acids that must be
obtained from the diet, since they cannot be synthesised de
novo.
• Animal studies have supported its use for diabetic
neuropathy.
• Additional animal studies have shown that high levels of
linoleic and gamma linoleic acid will decrease mammary
tumours.
Evening Primrose
Clinical Trials
• No benefit was seen in two large trials using evening primrose
constituents to treat atopic dermatitis. Meta-analysis of nine
other studies indicated improvement.
• Breast pain and tenderness associated with PMS and benign
breast disease showed significant improvement with evening
primrose.
• Use with fish oils indicated a reduced need for analgesics in
arthritis, but no improvement in disease progression was seen.
• Gamma Linoleic acid has been shown to reduce serum
cholesterol and blood pressure in both humans and animals.
• One clinical trial indicated beneficial effects in the treatment of
attention deficit/ hyperactivity disorder.
Evening Primrose
Dosing Recommendations
• Most doses are based upon evening
primrose standardised to 8% gamma
linoleic acid.
• Eczema -- 320 mg to 8 G daily for adults
and 1/2 that dose for children
• Mastalgia -- 3 - 4 G daily
Evening Primrose
Adverse Effects
• Headache
• Inflammation (chronic)
• Thrombosis (chronic)
• Immunosuppression (chronic)
• Nausea
• Rash
• Temporal lobe epilepsy, especially in
schizophrenic patients or those taking
phenothiazines.
Evening Primrose
Contraindications
• Pregnancy
• Patients with schizophrenia
• Patients taking any epileptogenic drug
Evening Primrose
Drug Interactions
• Phenothiazine anti-psychotics or anti-
emetics
Ŕ the aforementioned convulsions
Evening Primrose
Clinical Considerations
• Any patient with a history of seizure
disorders should not use evening primrose.
• Despite the promise it has shown with
ADHD, it should not be indiscriminantly
used in children.
Evening Primrose
Summary
• Underlying mechanisms of fatty acid metabolism
may contribute to numerous disease states
including ADHD, DM, CV disorders,
hypercholestolæmia, cancer, and dermatologic
conditions. Evening primrose could beneficial for
these disorders. However the risk of seizures
probably outweighs any potential benefit.
• Neither the FDA nor the German Commission E
has approved the use of evening primrose for any
disease state.
Ginseng
Botany
• Source -- American Ginseng, Panax quinquifolius, Asian
or Chinese Ginseng, P. ginseng, and Siberian Ginseng,
Eleutherococcus senticosus.
• Active Part -- Root
Ginseng
Miscellany
• Alternate Names
Ŕ Devil’s shrub (Siberian)
• Trade Names
Ŕ Vigoran® (Siberian)
• Dosage Forms
Ŕ Powders, Teas, Tinctures, Capsules, Tablets,
Oils
Ginseng
Chemical Constituents
• Ginsenosides (panaxosides) -- American and Chinese
• Eleutherosides -- Siberian
• Vitamins (A, B, C, D) in varying
concentrations
• Essential oils
• Resins
Ginseng
Proposed Uses
• Although different uses exist for the various
forms of Ginseng, the numerous uses for
any may include diabetes mellitus and stress
and for their adaptogenic, immuno-
stimulant, anti-cancer, and cognitive
(American and Chinese) actions.
Ginseng
Pharmacology
• May act as agonists at mineralocorticoid,
glucocorticoid, progestin, and œstrogen
(Siberian) receptors.
• Decrease both fasting and post-prandial blood
glucose levels
• Has been shown to increase T lymphocyte cell
counts.
• American ginseng has been shown to have
numerous opposing effects
Ginseng
Clinical Trials
• Numerous large and small human trials
have been performed to evaluate the
numerous claims of ginseng.
• There are no consistent results that indicate
definitive therapeutic benefits.
• Many studies contradict other studies.
Ginseng
Dosing Recommendations
• Wide ranges of doses have been used for
ginseng.
• Ranges from 200 mg to 2 G daily.
Ginseng (Siberian)
Adverse Effects
• Diarrhœa
• Difficulting in concentrating
• Dizziness
• Euphoria
• Hypertension
• Increased Agitation
• Nervousness
• Skin Eruptions
• Vaginal bleeding and other œstrogenic effects
Ginseng
Contraindications
• Pregnancy
• Children
• Known Hypersensitivity
Ginseng (Siberian)
Drug Interactions
• Digoxin -- elevates digoxin levels
• Barbiturates -- inhibits barbiturate
metabolism
• B and C Vitamins -- increases vitamin
excretion
• Oral Hypoglycæmics -- synergistic actions,
potential hypoglycæmia
Ginseng
Clinical Considerations
• Most literature, including herbal literature,
recommend use for no more than three (3)
weeks
• Patients should be monitored for any
changes in stress response for electrolyte
abnormalities
Ginseng
Summary
• Many of the purported claims for ginseng have not
been supported with laboratory data.
• Endocrine effects, including ability to lower
glucose and effects on steroid receptors, may
represent pharmacologic effect, but the
risk:benefit analysis precludes indiscriminat use.
• German Commission E has approved ginseng for
use to increase vigour and fortitude.
Dandelion
Botany
• Source -- Taraxacum officinale and T.
lævigatum, ubiquitous in the Northern Hemisphere
• Active Part -- Leaves and Roots
Dandelion
Miscellany
• Alternate Names
Ŕ Lion’s tooth, Swine’s snout, Priest’s crown,
Wild endive
• Trade Names
Ŕ Various, all incorporating “dandelion”
• Dosage Forms
Ŕ Capsules, Extracts, Teas
Dandelion
Chemical Constituents
• Acids -- Caffeic acid, Parahydroxyphenylacetic
acid, Chlorgenic acid
• Essential Fatty Acids -- Linoleic, Linolinic, Oleic,
and Palmitic acids
• Others -- Taraxasterol, Taraxacin, Taraxacum,
Taraxerin, Taraxerol, Taraxanthin (a carotenoid)
• Trace elements, vitamins (A, B, C, D), resins,
terpenes, and phytosterols.
Dandelion
Proposed Uses
• Herbalists recommend dandelion for liver
and gall bladder disorders, cholecystitis,
digestive problems, constipation, and as a
diuretic.
• Currently, it is recommended for diabetes
mellitus and as a stomach aid.
• It is claimed to possess laxative, diuretic,
bile-stimulant, and anti-rheumatic actions.
Dandelion
Pharmacology
• Taraxacum has been shown to increase salivary, gastric,
and biliary secretions and laxative actions.
• Dandelion has been shown to decrease blood glucose
levels.
• Both diuretic and anti-inflammatory actions have been
shown in rodents.
• Dandelion extracts have been shown to inhibit tumour cell
growth.
• Broad “beneficial” effects in jaundice, liver congestion,
gallstones, hepatitis, and cholecystitis have been claimed
but not convincingly substantiated.
Dandelion
Clinical Trials
• Very few clinical trials have been
performed using dandelion.
• One study in a small group of patients
indicated that dandelion could successfully
treat abdominal pain, constipation, and
diarrhœa associated with chronic, non-
specific colitis.
Dandelion
Dosing Recommendations
• Dried root -- 2-8 G by infusion or decoction
thrice daily
• Dried leaf -- 4-10 G infusion thrice daily
• Fluid extract (1:1 in 25% ethanol) -- 4-8 ml
thrice daily
• Tincture of root (1:5 in 45% ethanol) -- 5-10
ml thrice daily
• Juice of root -- 4-8 ml thrice daily
Dandelion
Adverse Effects
• Hypoglycæmia
• Gastrointestinal obstruction
• Biliary obstruction
• Contact dermatitis
• Other allergic reactions
• Cholecystitis
• Cholelithiasis
Dandelion
Contraindications
• Pregnancy
• Breast-feeding
• Known hypersensitivity
Dandelion
Drug Interactions
• Anti-diabetic agents -- synergistic actions,
resulting in hypoglycæmia
• Anti-hypertensives -- synergistic actions,
resulting in hypotension
• Diuretics -- synergistic actions, contributing
to drops in blood pressure and potentially
dangerous electrolyte imbalances.
Dandelion
Clinical Considerations
• Patients should be monitored for changes in
blood glucose, blood pressure, and
electrolyte imbalances.
• Dandelion, used as a food source, contains
more vitamin A and carotenoids than
carrots.
Dandelion
Summary
• Dandelion has long been used and recently enjoyed a
resurgence as a food product, especially in salads.
Taken in these small amounts, dandelion appears
relatively safe and free of adverse effects.
• Clinical evidence is lacking to support its use as a
herbal medication. Dandelion should not be taken in
quantities greater that those ingested as food.
• German Commission E has approved dandelion to
stimulate appetite and to treat dyspepsia and
flatulence.
Selected Bibliography
• Professional’s Handbook of Complementary and Alternative
Medicines, C. W. Fetrow and J. R. Avila, Eds. Springhouse
Corporation, Springhouse PA, 1999
• Medicinal Plants of the World, I. A. Ross, Humana Press,
Totawa NJ, 1999
• The Complete German Commission E Monographs:
Therapeutic Guide to Herbal Medicines, M. Blumenthal et al.
Eds., American Botanical Council, Austin TX, 1998
• A Modern Herbal: The medicinal, culinary, cosmetic, and
economic properties, cultivation, and folklore of herbs, grasses,
fungi, shrubs, and trees with all their modern scientific uses. M.
Grieve, Jonathan Cape, Ltd., Chatham Kent, 1931.