Herbal SupplementsPart III

An Overview of the Pharmacognosy, Pharmacology, Clinical Therapeutics and Use

of Selected Herbal ProductsScott F. Long, R.Ph., Ph.D.

Assistant Professor of Pharmacology & Toxicology

Genito-urinary SystemSelected Herbs

Saw PalmettoBotany

• 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 PalmettoMiscellany

• Alternate Names– American Dwarf Palm, Cabbage Palm

• Trade Names– Permixon®, Propalmex ®, Strogen ®

• Dosage Forms– Tablets, Capsules, Tea, Berries, Liquid Extract

Saw PalmettoChemical Constituents

• n-Hexane liposterolic extract, containing– lauric acid and other fatty acids– phytosterols– polysaccharides– monoacylglycerides

Saw PalmettoProposed 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 PalmettoPharmacology

• 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 PalmettoClinical 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 PalmettoDosing 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 PalmettoAdverse Reactions

• Abdominal and back pain

• Constipation or diarrhœa

• Decreased libido or impotence

• Dysuria and urinary retention

• Headache

• Hypertension

• Nausea

Saw PalmettoContraindications

• Pregnancy

• Women of child-bearing age

• Due to actions potentially similar to those produced by finasteride

Saw PalmettoClinical 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 PalmettoSummary

• 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.

NettleBotany

• 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

NettleMiscellany

• Alternate Names– Common nettle, Greater nettle, Stinging nettle

• Trade Names– Nettle Capsules, Nettle Liquid Extract

• Dosage Forms– Capsules, Dried Leaf and Root Extract,

Tincture

NettleChemical 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

NettleProposed 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.

NettlePharmacology

• 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.

NettleClinical 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.

NettleDosing 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

NettleAdverse Reactions

• Contact dermatitis (especially fresh)

• Decreased urine volume, frequency

• Diarrhœa

• Œdema

• GI irritation

NettleContraindications

• Pregnancy

• Children under 2 years old

• Elderly patients

Drug Interactions• Diuretics

NettleClinical 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.

NettleSummary

• 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.

PumpkinBotany

• Source -- Cucurbitaceæ family, Cucurbita pepo L., C. moschata., widely cultivated in North America and Australia.

• Active Parts -- Seeds

PumpkinMiscellany

• 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

PumpkinChemical 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

PumpkinProposed 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.

PumpkinPharmacology

• 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.

PumpkinClinical 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.

PumpkinDosing 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.

PumpkinAdverse Effects

• Electrolyte Imbalance (from the mild diuretic actions)

Drug Interactions

• Diuretics (potentiation of fluid loss and electrolyte imbalance)

PumpkinContraindications

• Pumpkin should not be used in prostatic hypertrophy of unknown etiology. Neither should it be used in patients who are pregnancy or are breastfeeding.

PumpkinClinical 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.

PumpkinSummary

• 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.

GoldensealBotany

• 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)

GoldensealMiscellany

• Alternate Names– Eye balm, Indian tumeric, Jaundice root,

Yellow root

• Trade Names– Various, all incorporating “Golden Seal”

• Dosage Forms– Capsules, Tablets, Alcoholic and Aqueous extracts,

Dried ground root powder, Tinctures, Teas

GoldensealChemical Constituents

• Alkaloids– hydrastine, berberine, hydrastinine, canadine,

berberastine, candaline, canadaline

• Meconin• Chlorogenic Acid• Fatty Acids• Carbohydrates• Volatile Oils• Resins

GoldensealProposed Uses

• Diuresis

• Other Reported Uses Include– Gastritis, Peptic ulceration, Anorexia,

Postpartum hæmorrhage, Dysmenorrhœa, Eczema, Pruritus, Tuberculosis, Cancer, Mouth ulcerations, Otorrhœa, Tinnitus, Conjunctivitis, Wound antiseptic, Laxative, Anti-inflammatory

GoldensealPharmacology

• 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

GoldensealClinical 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

GoldensealDosing Recommendations

• Various Doses have been recommended

• Dried Root– 0.5 to 1 G t.i.d.

• Liquid Extracts– 250 mg p.o. t.i.d.

GoldensealAdverse 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

GoldensealContraindications

• Any patient with cardiovascular disease, especially hypertension, cardiac failure, and arrhythmias.

• Pregnancy

GoldensealDrug Interactions

• CNS Depressants– depressants effects may be additive

• Antihypertensives– typically, may cause additive hypotensive

effects, however, hydrastinine may offset beneficial effects of antihypertensives

• Anti-coagulants– effects may be reduced by goldenseal

GoldensealClinical 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.

GoldensealSummary

• 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.

BearberryBotany

• 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

BearberryMiscellany

• Alternate Names – Bear’s grape, Crowberry, Kinnikinnick, Uva-

ursi

• Trade Names – In combination in Arctuvan®, Solvefort®,

Uroflox®, Uvalyst®

• Dosage Forms – Tablets, Tea, Drops

BearberryChemical Constituents

• Hydroquinones – Primarily arbutin, also hydroquinone

monoglucoside and methylarbutin

• Other Constituents– gallotannin, arbutin gallic acid ester,

triterpenes, iridoid glycoside monotropein, piceoside, phenol carboxylic acids, paracoumaric flavonoids, syringic acids

BearberryProposed Uses

• Mild diuretic

• Mild urinary antiseptic

BearberryPharmacology

• 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.

BearberryClinical 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.

BearberryDosing 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.

BearberryAdverse Effects

• Cyanosis

• Green-coloured urine

• Nausea

• Vomiting

• High Doses– Tinnitus, Seizures, Cardiovascular collapse

BearberryContraindications

• Pregnancy

• Diuretics– May potentiate electrolyte imbalance

BearberryDrug Interactions

• Diuretics– potentiation of actions

• Urinary Acidifiers– may inactivate bearberry

BearberryClinical Considerations

• Discolourisation of Urine

• An alkaline urinary pH is believed to be necessary to support the antiseptic actions of bearberry

BearberrySummary

• 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.

BuchuBotany

• 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.

BuchuMiscellany

• Alternate Names – Agathosma, Betuline, Bocco

• Trade Names – None

• Dosage Forms – Dried Leaves for infusion– Tincture

BuchuChemical Constituents

• The active compounds are found primarily in volatile oils obtained from leaves.

• Diosphenol (buchu camphor)

• Pulegone

• Terpene-4-ol

• Various Flavonoids

BuchuProposed Uses

• Diuretic

• Urogenital Tract Infections

BuchuPharmacology

• 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.

BuchuDosing Recommendations

• Infusion– 1 oz. dried leaves infused in 1 pint boiling

water

• Tincture– 1 - 2 ml p.o. three to four times daily

BuchuAdverse Effects

• Volatile Oil– Diarrhœa, Nausea, Vomiting– Nephritis

• Pulegone– Hepatotoxicity– Hypermenorrhœa– Spontaneous Abortion

BuchuContraindications

• Pregnancy

• Kidney Infection

• Kidney Disease

• Liver Disease

BuchuDrug Interactions

• Buchu may enhance the actions of oral anti-coagulants

BuchuClinical Considerations

• Any patient taking buchu should be monitored for hepatotoxicity and nephrotoxicity.

BuchuSummary

• 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

GarlicBotany

• Source -- Allium sativum L., a member of the same family as the onion, the monocotyledenous lilies.

• Active Part -- Bulb/cloves

Garlic Miscellany

• Alternate Names– Allium, Stinking Rose, Da-suan

• Trade Names– Kwai®, Kyolic®, Garlique®

• Dosage Forms– 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:– decreased total cholesterol, triglycerides, and LDL and increased

HDL

– hypotensive actions (animals and humans)

– decreased blood glucose (rabbits)

– anti-infective actions in vitro and in vivo

– methylallyltrisulphide and ajoene inhibit platelet aggregation

– decreased nitrosamine and nitrite accumulation and prolonged survival in cancer cell-dosed mice

– 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– may increase the bleeding tendencies in patients

receiving heparin or warfarin

• Antiplatelet Drugs– 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 ChestnutBotany

• Source -- Æsculus hippocastanum L., Native to Northern and Central Asia. The tree has smooth, grey bark and soft wood.

• Active Part– Seed

Horse Chestnut Miscellany

• Alternate Names– æscin, escine, hippocastani semen (extract)

• Trade Names– Venostatin Retard®, Venostat®

• Dosage Forms– Extract

Horse Chestnut Chemical Constituents

• Triterpene glycosides– Æscin

• Flavonoids– Quercetin, Kæmpferol, Astragalin, Isoquercetin,

Rutin• Coumarins

– Æsculetin, Fraxin, Scopolin)• Other constituents

– Allantoin, Choline, Citric acid, Phytosterols

Horse Chestnut Proposed Uses

• Purported uses for horse chestnut include– varicose veins– diarrhœa– fever– phlebitis– hæmorrhoids– 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

AngelicaBotany

• 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– Angelica root, Angelica radix, Dong quai

• Trade Names– Various trade names, often incorporating

angelica or dong quai

• Dosage Forms– 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– 4.5 G of crude drug– 1.5-3 G of fluid extract– 1.5 G tincture– 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.

BroomBotany

• 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– Twigs– Flowers– Ærial parts

BroomMiscellany

• Alternate Names– Cytisi scoparii herba, Scotch broom, Hogweed,

Bannal

• Trade Names– No single ingredient trade names

• Dosage Forms– Tea, Extract, Cigarettes, Root

BroomChemical Constituents

• Alkaloids -- Sparteine

• Flavone glycosides -- Oxysparteine, scoparoside, spiræoside, lupanine, genitoside, isoquercetin

• Others -- Kæmpferol, Sarothamnoside, Caffeic acid derivatives, Essential oils, lectins (phytohæmagglutinins)

BroomProposed Uses

• Antiarrhythmic

• Cathartic

• Diuretic

• Emetic

• Relaxation

• Euphoria

BroomPharmacology

• 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

BroomClinical 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.

BroomDosing Recommendations

• 1 - 1.5 G of active drug in aqueous or ethanolic extracts once daily

BroomAdverse Effects

• Arrhythmias

• Headache

• Spontaneous abortion

• Fungal pneumonia (smoking contaminated broom top cigarettes)

• Overdose -- shock, tachycardia, changes in mental status, vertigo, nausea, and diarrhœa

BroomContraindications

• Pregnancy

• Hypertension

• Congestive Heart Failure

BroomDrug 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)

BroomClinical 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.

BroomSummary

• 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

GuaranaBotany

• 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– Brazilian cocoa, Guarana gum, Guarana paste,

Zoom

• Trade Names– Happy Motion®, Zoom®

• Dosage Forms– 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 CohoshBotany

• 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 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– 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 PrimroseBotany

• 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 anti-emetics– 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.

GinsengBotany

• 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, 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.

DandelionBotany

• Source -- Taraxacum officinale and T. lævigatum, ubiquitous in the Northern Hemisphere

• Active Part -- Leaves and Roots

DandelionMiscellany

• 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, 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.