Herbal Supplements
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
Endocrine 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
– Berry
Saw Palmetto
Miscellany
• Alternate Names
– American Dwarf Palm, Cabbage Palm
• Trade Names
– Permixon®, Propalmex ®, Strogen ®
• Dosage Forms
– Tablets, Capsules, Tea, Berries, Liquid Extract
Saw Palmetto
Chemical Constituents
• n-Hexane liposterolic extract, containing
–
–
–
–
lauric acid and other fatty acids
phytosterols
polysaccharides
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
–
–
–
–
to increase sperm production
to increase breast size in women
to increase libido
mild diuresis
Saw Palmetto
Pharmacology
• Inhibition of 5-alpha reductase (in vitro)
• Antagonism of DHT at androgen receptors
• Some evidence exists for
– Anti-inflammatory actions (MOA unknown)
– Inhibition of prolactin (MOA unknown)
– Inhibition of prostatic cell proliferation
Saw Palmetto
Clinical Trials
• Men, 60-70 years old
• Criteria
– Urinary frequency
– Urine flow rate
• Significant improvement relative to placebo
– Champault et al. 1984
• Similar in efficacy relative to finasteride
– Carraro et al. 1996
• Less (though not significantly) effective than alpha1
adrenergic blockade
Saw Palmetto
Dosing Recommendations
• Human clinical trials have used 320 mg p.o.
in divided doses, twice daily
• Herbal Usage
– 1 to 2 G fresh saw palmetto berries
– 0.5 to 1 G dried berries
– 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 prostatespecific 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
– Common nettle, Greater nettle, Stinging nettle
• Trade Names
– Nettle Capsules, Nettle Liquid Extract
• Dosage Forms
– Capsules, Dried Leaf and Root Extract,
Tincture
Nettle
Chemical Constituents
• Stems (non-therapeutic) -– Histamine, serotonin, choline, formic acid
• Roots -– Phenylpropanes and lignans
• Roots and Flowers -– Scopoletin, steryl derivatives, lignan glycosides,
flavonol glycosides
• Whole Plant -– 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
– 150 or 300 mg capsules as needed
• Tea
– 1-2 teaspoonfuls of dried herb in 1 cup of
boiling water, up to twice daily
• Tincture
– 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
– Cucurbita, Pumpkinseed oil, Vegetable marrow
• Trade Names
– Available in combination with palmetto as
Ultimate Oil®, Proleve 40® and others.
• Dosage Forms
– seeds (whole or crushed), seed extract or oil,
tablets, tea
Pumpkin
Chemical Constituents
• Cucurbitin ((-)-3-amino-3carboxypyrrolidine) 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.
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
– Black snakeroot, Bugbane, Bugwort,
Rattleweed, Rattleroot, Squaw root
• Trade Names
– Estroven®, Femtrol®, Remifemin®
• Dosage Forms
– 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 vagalmediated 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 nonsignificant 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
– 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 postmenopause.
Evening Primrose
Botany
• Source -- Œnethera biennis L., a biennial,
flowering herb that grows in North America
and Europe.
– 3-4 feet high
– 3-5 inch leaves, 1 inch wide
– yellow flower (June) typically
opening around 6:00-7:00 P.M.
• Active Part -- Seeds
Evening Primrose
Miscellany
• Alternate Names
– King’s Cure All
• Trade Names
– Efamol®, Epogram®
• Dosage Forms
– Capsules, Gelcaps
Evening Primrose
Chemical Constituents
• Primarily Essential Fatty Acids
–
–
–
–
–
Linoleic acid
gamma-Linoleic acid
Oleic acid
Palmitic acid
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 antiemetics
– 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
– Devil’s shrub (Siberian)
• Trade Names
– Vigoran® (Siberian)
• Dosage Forms
– 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, immunostimulant, 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
– Lion’s tooth, Swine’s snout, Priest’s crown,
Wild endive
• Trade Names
– Various, all incorporating “dandelion”
• Dosage Forms
– 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, nonspecific 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.