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BACOPA

*Botanical Names:*	Bacopa monnieri, Bacopa monniera^#, Herpestis monnieri^#
*Family:*	Scrophulariaceae
*Plant Part Used:*	Aerial parts

# Alternative name.

PRESCRIBING INFORMATION

Actions	Cognition enhancing, nervine tonic, mild sedative, mild anticonvulsant, anxiolytic, possibly adaptogenic
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing Bacopa in formulations in the context of: • Improving concentration in healthy individuals (4) • Improving mental performance and memory (3) • Nervous disorders, nervous debility (5) • Insomnia (4,6) • Epilepsy, anxiety (4,5)

Contraindications None known. Warnings and Precautions None required. Interactions None known. Use in Pregnancy and Lactation No adverse effects expected. Side Effects As with all saponin-containing herbs, oral use may cause irritation of the gastric mucous membranes and reflux. Dosage Dose per day^* Dose per week^* 5–13 ml of 1:2 liquid extract 35–90 ml of 1:2 liquid extract

* This dose range is extrapolated from traditional Ayurvedic medicine ⁴ and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Ayurvedic uses include: • As a nervine tonic for the treatment of nervous disorders, especially nervous breakdown, epilepsy, insanity; debility, aphonia (loss of voice), hoarseness; for a supposed direct cardiac tonic activity,²^–⁴ for urinary incontinence, particularly accompanied by constipation¹ • As a tonic for diseases of the skin, nervous system, and blood ²
Traditional Prescribing	Brahmi oil, which consists mainly of brahmi juice, coconut oil, and other medicinal plants, is considered a most effective brain tonic. Brahmi oil is said to strengthen memory and revive hair growth and is used as a cooling remedy instead of ice in epidemic fevers. Brahmi oil is also employed in headache, insomnia, and epilepsy.^3,⁴
Pharmacologic Research	• An early study demonstrated Bacopa to have cardiotonic, vasoconstricting, and sedative activities.⁵ • A laboratory study using a formulation containing Bacopa (known as Brahmi Rasayan) found high doses have sedative (without affecting motor coordination), analgesic, and anticonvulsant activities.⁶ • Standardized extract of Bacopa (25% bacoside A) produced an anxiolytic effect in vivo that was qualitatively comparable with that of lorazepam (a benzodiazepine drug). Statistically significant results were elicited with higher doses of Bacopa, which, unlike lorazepam, did not produce any significant motor deficit.⁷ • An early study compared the effects of an alcohol extract of Bacopa and the tranquilizer chlorpromazine on the learning process in rats. Both substances reduced errors and improved performance in the learning phase, but the effect of Bacopa was more marked. Chlorpromazine depressed motor efficiency, but no such deleterious effect was observed with Bacopa treatment. In fact, Bacopa improved motor efficiency compared with controls.⁸ In later studies, learning and memory retention were improved in rats in a number of experimental models after oral and intraperitoneal administration of Bacopa.^9,¹⁰ • Oral doses of Brahmi Rasayan were found to suppress experimentally induced inflammation in an animal model. The activity was comparable to that of the NSAID indomethacin. The herbal formula did not produce gastric irritation.¹¹
Clinical Studies	• In an uncontrolled trial, 35 patients with anxiety neurosis were treated with the equivalent of 12 g per day of dried Bacopa for 1 month. A significant reduction occurred in anxiety, as well as improvements in mental performance and memory. This result was accompanied by a reduction in mental fatigue, a general feeling of enhanced well being, improved sleep and appetite, and an increase in body weight.^12,¹³ • Bacopa had a positive effect on concentration, but not on short-term memory, in a small number of volunteers tested in the mid-1960s.¹⁴ Bacopa (1 g/day for 3 months) improved intellectual functions such as visual motor function, short-term memory, and mental reaction times in children. Unlike individuals who were treated with Bacopa, the placebo group did not improve from baseline values.¹⁵ • An uncontrolled clinical study on 13 patients with epilepsy using a defatted ethanolic extract of Bacopa (2 to 4 mg/kg body weight/day) demonstrated reductions in the frequency of fitting over 2 to 5 months. The onset of epileptic fits was completely checked in five cases.¹⁶ • An Australian clinical trial examined the long-term effects of a Bacopa extract on cognitive function in 46 healthy human volunteers.¹⁷ The study was of double-blind, placebo-controlled design in which subjects were randomly allocated to receive Bacopa or placebo. Neuropsychologic testing was conducted before treatment and at 5 and 12 weeks after treatment. After 12 weeks, the largest cognitive change from Bacopa treatment (which was also statistically significant compared with placebo, p < 0.05) was a time reduction for the inspection time (IT) test (64.5 16.7 min vs.75.9 25.3 min). IT is regarded as a measure of the integrity of the early stages of information processing and may act as a rate-limiting factor for cognition. This finding indicates that Bacopa significantly improved the speed of visual information processing. Verbal learning rate and memory consolidation as assessed by the Rey Auditory Verbal Learning Test were also some-what improved against placebo at 12 weeks (p < 0.05). However, the most striking finding was the highly significant (p = 0.001) reduction in anxiety in volunteers receiving Bacopa. The percentage of adverse effects was similar for both groups, except that a higher incidence of nausea, dry mouth, and fatigue occurred in the Bacopa group.

REFERENCES

1 Kapoor LD. CRC handbook of Ayurvedic medicinal plants. Boca Raton, Fla: CRC Press, 1990.

2 Chopra RN, et al. Chopra’s indigenous drugs of India, ed 2. Calcutta: Academic Publishers, 1958. reprinted 1982

3 Sandu DV. Indian therapeutics, ed 2. Delhi: Sri Satguru Publications, 1987.

4 A Panel of Vaidyas. Clinical application of Ayurvedic remedies, ed 4. Delhi: Sri Satguru Publications, 1998.

5 Malhotra CL, Das PK. Indian J Med Res. 1959;47:294-305.

6 Shukia B, Khanna NK, Godhwani JL. J Ethnopharmacol. 1987;21(1):65-74.

7 Bhattacharya SK, Ghosal S. Phytomed. 1998;5(2):77-82.

8 Prakash JC, Sirsi M. J Sci Ind Res. 1962;21C:93-96.

9 Singh HK, Dhawan BN. J Ethnopharmacol. 1982;5:205-214.

10 Singh HK, Dhawan BN. Indian J Pharmacol. 1978;10:72.

11 Jain P, et al. Indian J Exp Biol. 1994;32(9):633-636.

12 Udupa KN, Singh RH. Clinical and experimental studies on rasayana drugs and Pancakarma therapy, ed 2. New Delhi: Central Council for Research in Ayurveda and Siddha, 1995.

13 Singh RH, Singh L. J Res Ayurveda Siddha. 1980;1:133-148.

14 Ghosh S, Kar SK. J Exp Med Sci. 1966;10(1):12-13.

15 Sharma R, Chaturvedi C, Tewari PV. J Res Educ Indian Med. 1987;6:1-10.

16 Mukherjee GD, Dey CD. J Exp Med Sci. 1968;11(4):82-85.

17 Stough C, et al. Psychopharmacol. 2001;156(4):481-484.

BAICAL SKULLCAP

*Botanical Name:*	Scutellaria baicalensis
*Family:*	Labiatae
*Plant Part Used:*	Root

PRESCRIBING INFORMATION

Actions	Antiinflammatory, antiallergic, antibacterial
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing Baical skullcap in formulations in the context of: • Chronic inflammatory conditions, allergy, asthma, arthritis (7) • Hypertension (4,5) • Infections, including bronchitis, the common cold, bacillary dysentery, scarlet fever (4) • High fevers, cough with thick sputum, pneumonia (5) • Nausea, vomiting, hemoptysis, jaundice, diarrhea, or dysentery-like diseases (5) • Hepatitis (6) • Adjuvant therapy for cancer (4)

Contraindications Contraindicated in cold conditions (Chinese traditional understanding).¹ Warnings and Precautions None required. Interactions None known. Use in Pregnancy and Lactation No adverse effects expected. Side Effects None expected if taken within the recommended dose range. Dosage Dose per day^* Dose per week^* 4.5–8.5 ml of 1:2 liquid extract 30–60 ml of 1:2 liquid extract

* This dose range is adapted from dried plant dose administered by decoction in TCM.³ The author’s experience and the fact that ethanol-water is a more effective solvent than is water for many phytochemicals are taken into account.

SUPPORTING INFORMATION

Traditional Prescribing	Uses and properties from TCM include: • Clearing heat and draining damp heat¹ • High fevers, cough with thick sputum, pneumonia; nausea, vomiting, hemoptysis, jaundice,¹^–³ viral hepatitis⁴ • Diarrhea or dysentery-like diseases, painful urinary dysfunction, hypertension, restless fetus, carbuncles ¹^–³
Pharmacologic Research	Baical skullcap root contains a number of flavone derivatives, including baicalin, wogonin, and baicalein.⁵ • Flavones and flavonols inhibited the release of histamine by mast cells in vitro.⁶ Baicalin and baicalein demonstrated antiallergic and antiasthmatic activity in vivo.² • Oral doses of an extract of Baical skullcap and baicalin, baicalein, and wogonin demonstrated mild antiinflammatory activity and decreased long-term bone destruction in adjuvant-induced arthritis.⁷ • Baicalin and baicalein have demonstrated significant antiplatelet activity after oral doses in an experimental model, but not anticoagulant activity.⁸ • Baicalein demonstrated antioxidant activity in vitro.⁹ Baicalein demonstrated antiepileptic and neuronal protective effects in vivo (by injection), probably because of free radical quenching and antioxidant activity.¹⁰ Baicalein reduced oxidative stress during hypoxia, ischemia, and reperfusion in vitro.¹¹ • A combination of baicalin and licorice extract dramatically reduced sorbitol levels in red blood cells in experimental models without affecting blood glucose levels.¹² This finding has implications for preventing diabetic complications. • Baical skullcap reduced the toxicity of anticancer drugs and decreased cancer cell viability in experimental tumors.¹³
Clinical Studies	• Baical skullcap extract promoted an increase in the immunoregulation index (increased immunoglobulin A [IgA] at stable IgG levels) of patients with lung cancer who were receiving antineoplastic chemotherapy.¹⁴ • Positive results have been demonstrated in uncontrolled trials for acute bronchitis, the common cold, bacillary dysentery, scarlet fever, hepatitis (baicalin;route unknown), and cholecystitis (baicalin;by injection). The daily dose for respiratory disorders ranged from 6 ml to 8 to 10 ml of a 50% decoction depending on the age of the child.² A 70% success rate was shown in chronic hepatitis with improvements in symptoms and liver function tests (route and preparation undefined).¹⁵ • In an uncontrolled trial involving 255 patients in China with allergic rhinitis, Baical skullcap and Paeonia suffructicosa were added to the TCM herbal prescription for patients with nasal inflammation.¹⁶ • An antihypertensive effect was demonstrated in an uncontrolled study involving 51 cases.²

REFERENCES

1 Bensky D, Gamble A. Chinese herbal medicine materia medica. Seattle: Eastland Press, 1986.

2 Chang HM, But PP. Pharmacology and applications of Chinese materia medica. Singapore: World Scientific, 1987.

3 Pharmacopoeia Commission of the People’s Republic of China. Pharmacopoeia of the People’s Republic of China, English ed. Beijing: Chemical Industry Press, 1997.

4 Lu LX. Shaanxi J Chin Trad Med. 1987;8(5):228-229.

5 Tang W, Eisenbrand G. Chinese drugs of plant origin. Berlin: Springer-Verlag, 1992.

6 Amella M, et al. Planta Med. 1985;51(1):16-20.

7 Kubo M, et al. Chem Pharm Bull (Tokyo). 1984;32(7):2724-2729.

8 Kubo M, et al. Chem Pharm Bull (Tokyo). 1985;33(6):2411-2415.

9 Hara H, et al. Eur J Pharmacol. 1992;221(2-3):193-198.

10 Hamada H, et al. Arch Biochem Biophys. 1993;306(1):261-266.

11 Shao ZH, et al. Acad Emerg Med. 2001;8(5):562-563.

12 Zhou YP, Zhang JQ. Chin Med J (Eng). 1989;102:203-206.

13 Razina TG, et al. Vopr Onkol. 1987;33(2):80-84.

14 Smol’ianinov ES, et al. Eksp Klin Farmacol. 1997;60(6):49-51.

15 Chang HM, et al, editors. Advances in Chinese medicinal materials research. Singapore: World Scientific, 1985.

16 Lin WS. Shanghai J Trad Chin Med. 1987;1:22-24.

BAPTISIA

*Other Common Name:*	Wild indigo
*Botanical Name:*	Baptisia tinctoria
*Family:*	Leguminosae
*Plant Part Used:*	Root

PRESCRIBING INFORMATION

Actions	Depurative, antipyretic, immune enhancing
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing Baptisia in formulations in the context of: • Treating and preventing nonspecific upper respiratory tract infections, in combination with a number of herbs, including Echinacea spp. root and Thuja (2) • Sinusitis, in combination with a number of herbs, including Echinacea spp. root and Thuja (3) • Tonsillitis, pharyngitis, pneumonia, fevers, the common cold, influenza (5) • Septic conditions, boils, mouth ulcers, inflammation of the mouth or teeth (5)

Contraindications None known. Warnings and Precautions None required. Interactions None known. Use in Pregnancy and Lactation No adverse effects expected. Side Effects None expected if taken within the recommended dose range. Dosage Dose per day^* Dose per week^* 2–6 ml of 1:2 liquid extract 15–40 ml of 1:2 liquid extract

* This dose range is extrapolated from the British Pharmaceutical Codex 1934, the British Herbal Pharmacopoeia 1983, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Infections of the upper respiratory tract, particularly tonsillitis, pharyngitis; diphtheria, acute catarrhal infection, lymphadenitis, fevers, pneumonia ^1,² • Sepsis, furunculosis, typhoid conditions, enfeebled circulation, mouth ulcers, gingivitis, stomatitis ^1,²
	Native Americans administered Baptisia to children who seemed drowsy and lifeless and at the point of becoming sick. Externally,
	Baptisia was used to bathe wounds and cuts. Baptisia was official in the United States Pharmacopeia (USP) from 1831 to 1842, the National Formulary (NF) from 1916 to 1936, and was used as an emetic, cathartic, stimulant, astringent, and antiseptic.³
Pharmacologic Research	• Glycoprotein derivatives from Baptisia root have demonstrated immunomodulating activity in vitro by provoking the stimulation of B lymphocytes with a concomitant increase of interferon release.⁴ • Fractions of Baptisia extract have demonstrated immune-enhancing activity in vitro and in vivo (by injection).⁵
Clinical Studies	No clinical studies have been conducted using Baptisia alone. • Three herbal formulations containing Baptisia have been used successfully for treating and preventing nonspecific upper respiratory tract infections in randomized, double-blind, placebo-controlled trials.^6,⁷ These formulations consisted of:(a) Baptisia, Echinacea spp. root, and Thuja;(b) these same herbs combined with homeopathic remedies; and (c) E. angustifolia aerial parts and root with boneset, Baptisia, and homeopathic Arnica. In most of these trials, the daily dose of herbs was below the normal therapeutic limit (and was similar to a homeopathic protocol). Only in trials conducted with the last formulation did patients receive herbs approaching the normal therapeutic range. The daily dose in these trials ranged from 1.2 to 3.0 g of the total formulation (dry weight equivalent), including homeopathic Arnica, for periods ranging from several days in treatment trials to 8 weeks in a prevention trial.^6,⁸ • A controlled trial found combined use of the first formulation previously listed with the antibiotic doxycycline had better success than did doxycycline alone in the treatment of acute sinusitis.⁹

BARBERRY AND INDIAN BARBERRY

*Common Name:*	Barberry
*Other Common Names:*	Common barberry, European barberry
*Botanical Name:*	Berberis vulgaris
*Family:*	Berberidaceae
*Plant Parts Used:*	Root, stem bark, or both
*Common Name:*	Indian barberry
*Botanical Name:*	Berberis aristata
*Family:*	Berberidaceae
*Plant Parts Used:*	Root, stem bark, or both

Practitioners should also consider prescribing barberry for:

• Improving digestive function (bile production and release) (5)

• Gallbladder inflammation, gallstones, intestinal dyspepsia (5)

• Topical treatment for lip sores, chronic ophthalmia (5)

Practitioners should also consider prescribing Indian barberry for:

• Improving digestive function (bile production and release) (5)

• Enlargement of the liver and spleen, colitis (5)

• Topical treatment for skin ulcers and abrasions, hemorrhoids, boils, acne (5)

Contraindications Berberine-containing plants are not recommended for use during pregnancy or for jaundiced neonates. Warnings and Precautions None required. Interactions Berberine may reinforce the effects of other drugs that displace the protein binding of bilirubin. Rather than possible uterine-contracting effects, this activity might explain the traditional contraindication for berberine-containing herbs in pregnancy. Use in Pregnancy and Lactation Contraindicated in pregnancy. Side Effects At daily doses higher than 0.5 g, berberine may cause dizziness, nose-bleeds, dyspnea, skin and eye irritation, gastrointestinal irritation, nausea, diarrhea, nephritis, and urinary tract disorders. Such doses of berberine will not be reached using the liquid doses recommended here. Dosage

It is preferable to use liquid extracts quantified for their berberine content.

Barberry:

Dose per day^* Dose per week^* 3–6 ml of 1:2 liquid extract 20–40 ml of 1:2 liquid extract Indian barberry: Dose per day^† Dose per week^† 2.0–4.5 ml of 1:1 liquid extract 15–30 ml of 1:1 liquid extract For topical use of berberine-containing herbs (such as for treatment of ophthalmia), a solution of about 5 to 6 drops of a 1:2 extract is prepared in an eye bath of recently boiled water or saline. The liquid should be allowed to cool before applying to the eye. (Allowing the alcohol to evaporate through this process is important before applying to the eye.)

* This dose range is extrapolated from the British Herbal Pharmacopoeia 1983 and the author’s education and experience.

† This dose range is extrapolated from traditional Ayurvedic medicine ^4,⁵ and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses of barberry root, stem bark, or both include: • Gallbladder inflammation, gallstones,¹ jaundice,^1,² chronic diarrhea, dysentery, cholera infantum, intestinal dyspepsia² • Renal calculi, soreness and burning of the urinary tract ² • Leishmaniasis, malaria,¹ fever² • As a tea for blood purification, as a tonic ² • Topically as a decoction for mouth ulcers and lip sores, chronic ophthalmia ²
	Barberry was used by Native Americans to treat sore throat, ulcerated gums, and ulcerated stomach. Barberry was official in the USP from 1863 to 1882.³
	Traditional Ayurvedic uses of Indian barberry root bark include: • Debility, remittent and intermittent fever,⁴ especially malarial fever^4,⁶ • Skin diseases, inflammation ⁷ • Neuralgia, dysentery, colitis ⁴ • Enlargement of the liver and spleen, jaundice ⁴ • Diseases of the eye, ear, and face ⁴ • Topically for oriental sores, mouth sores, skin ulcers and abrasions, pimples, boils, affections of the eyelids, chronic ophthalmia, piles,⁴ muscular or rheumatic pain⁸
Pharmacologic Research	Key constituents of barberry bark include alkaloids, comprising those of the isoquinoline group:protoberberines (berberine, jateorrhizine, and palmatine) and bisbenzylisoquinolines (including oxyacanthine). The principal alkaloid is berberine. Indian barberry root bark also contains berberine.⁹ The root bark is the preferred plant part for therapeutic use for both barberry and Indian barberry. The root bark has been preferred traditionally and is higher in alkaloids than the stem bark. However, given that the entire plant is killed in the harvesting process, the stem bark is a more environmentally sustainable option. The stem bark also contains the active alkaloids, albeit at lower concentrations, and is a valid therapeutic option. Several other plant parts of Indian barberry have been used in Ayurvedic medicine, including the fruit. The following information pertains to the root bark (except when the plant part has not been defined in the study, as noted). Pharmacologic information on berberine, the signature component of barberry and Indian barberry, has also been provided when relevant. • In vitro and in vivo studies have demonstrated that berberine has antimicrobial activity against a wide variety of microorganisms, including bacteria, fungi, and parasites. Barberry tincture was better than was berberine chloride (0.2%) at inhibiting the growth of various microorganisms in vitro. Indian barberry extract (part undefined) displayed inhibitory activity against Salmonella typhi in vitro.¹⁰ • Pustular skin lesions from Staphylococcus aureus and S. pyogenes infection were healed within 2 weeks when a combination of Indian barberry (part undefined) and Cedrus deodora was taken internally and also applied as a gel in an experimental model. The combined treatment was more beneficial than was the topical application alone.¹¹ • Berberine combined with Geranium leaf extract (oral doses) significantly inhibited diarrhea. Oral berberine significantly reduced intestinal fluid accumulation triggered by Escherichia coli enterotoxin in vivo. • Berberine increased thrombocytes, decreased factor XIII activity, inhibited platelet aggregation and adhesiveness, and inhibited clot retraction in vivo (route unknown). Indian barberry root extract inhibited platelet activating factor (PAF) aggregation of platelets in a dose-dependent manner and binding of radiolabeled PAF to platelets in vitro. • Berberine has demonstrated cytotoxic activity in several in vitro models. Indian barberry extract (part undefined) demonstrated anticancer activity against human epidermal carcinoma of the nasopharynx in vitro.¹² • Intraperitoneal administration of barberry extract demonstrated higher antiinflammatory activity than did isolated berberine and three different alkaloidal fractions in experimental models of acute and chronic inflammation. • Barberry tincture increased contractions in isolated intestinal tissue and demonstrated cholagogue and cholekinetic activity in experimental models. Oral administration of berberine hydrochloride significantly increased bilirubin excretion in experimental hyperbilirubinemia without affecting the functional capacity of the liver. • Oral pretreatment or posttreatment with berberine (4 mg/kg) prevented chemical-induced liver damage, indicating hepatoprotective activity.¹³ • Berberine prolonged pentobarbital-induced sleeping time and increased strychnine-induced toxicity after oral administration, suggesting an inhibitory effect on liver drug metabolizing enzymes (cytochrome P-450).¹³ • Lipogenesis was suppressed in isolated sebaceous glands by berberine. • Berberine significantly decreased scopolamine-induced amnesia in an experimental model. • Indian barberry root extract demonstrated hypoglycemic activity in an experimental model (route unknown).¹²
Pharmacologic Research	For more information on the pharmacologic parameters of berberine, see the monograph on golden seal (Hydrastis canadensis).
Clinical Studies	No clinical studies using barberry or Indian barberry have been found. Clinical trials using berberine are outlined here. The berberine doses used in many of these trials were higher than what could be achieved using herbal liquid extracts. • Berberine (100 mg/day) demonstrated an antidiarrheal action and compared well against standard antidiarrheal drugs in an uncontrolled study involving children with gastroenteritis. In randomized, controlled trials, berberine has exhibited benefit in treating diarrhea caused by Escherichia coli infection but was of little value against Vibrio cholerae infectious diarrhea (cholera). The trials with positive outcomes for E. coli diarrhea were conducted using either untreated controls (active therapy: 400 mg of berberine sulfate as a single dose) or compared rehydration therapy against only rehydration therapy with berberine (200 mg). In another trial, neither berberine (400 mg/day) nor tetracycline exhibited any benefit over placebo in patients with noncholera diarrhea. • Berberine (900 mg/day) was more efficacious than was ranitidine in clearing Helicobacter pylori and improving gastritis in H. pylori-associated duodenal ulcer in a randomized, comparative clinical trial. Ranitidine was the superior treatment for ulcer healing. • In two controlled trials, berberine (5 to 10 mg/kg/day for 6 to 10 days) was superior to placebo and compared favorably with established drugs in treating giardiasis in children. • In an uncontrolled trial, berberine (600 to 800 mg/day) corrected hypertyraminemia and prevented the elevation of serum tyramine after tyramine stimulation in patients with liver cirrhosis. (Hypertyraminemia [i.e., elevated blood levels of tyramine] is common in hepatic cirrhosis.) • In an uncontrolled trial berberine (0.9 to 1.5 g/day for 1 to 3 months) in combination with a therapeutic diet improved the major symptoms of patients with non-insulin–dependent diabetes. Berberine treatment improved patients’ strength, normalized blood pressure, decreased blood lipids, and in 60% of patients, normalized fasting glycemic levels. • Berberine bisulfate (15 mg/day for 15 days) increased platelet counts in patients with primary and secondary thrombocytopenia in an uncontrolled clinical trial. • In a randomized, controlled trial, berberine chloride (1.5 g/day) was more efficacious than were both tetracycline and a sulfamethoxazole-trimethoprim combination in clearing asexual parasitemia in patients with chloroquine-resistant malaria (all agents were used in conjunction with pyrimethamine). • Weekly intralesional injection of berberine salt solution (1%) healed cutaneous leishmaniasis after 4 to 8 weeks in a small, uncontrolled trial. (Cutaneous leishmaniasis is a protozoal skin infection caused by species of Leishmania.)

REFERENCES

Except when specifically referenced, the following book was referred to in the compilation of the pharmacologic and clinical informationMills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Edinburgh: Churchill Livingstone, 2000.

1 British Herbal Medicine Association’s Scientific Committee. British Herbal Pharmacopoeia. Bournemouth: BHMA, 1983.

2 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983

3 Vogel VJ. American Indian medicine. Norman, Okla: University of Oklahoma Press, 1970.

4 Thakur RS, Puri HS, Husain A. Major medicinal plants of India. Lucknow, India: Central Institute of Medicinal and Aromatic Plants, 1989.

5 Kapoor LD. CRC handbook of Ayurvedic medicinal plants. Boca Raton, Fla: CRC Press, 1990.

6 Chopra RN, et al. Chopra’s indigenous drugs of India, ed 2. Calcutta: Academic Publishers, 1958. reprinted 1982

7 Kumar S, et al. J Ethnopharmacol. 2000;70(3):191-195.

8 Joshi AR, Joshi K. J Ethnopharmacol. 2000;73:175-183.

9 Chauhan SK, Singh BP, Agrawal S. Indian Drugs. 1998;35(8):468-470.

10 Sohni YR, Padmaja K, Bhatt RM. J Ethnopharmacol. 1995;45(2):141-147.

11 Chakkrabarti A, Guha C, Sen TB. Indian Vet J. 1999;76(5):432-434.

12 Dhar ML, et al. Indian J Exp Biol. 1968;6(4):232-247.

13 Janbaz KH, Gilani AH. Fitoterapia. 2000;71:25-33.

BILBERRY

*Botanical Name:*	Vaccinium myrtillus
*Family:*	Ericaceae
*Plant Part Used:*	Fruit

PRESCRIBING INFORMATION

Actions	Vasoprotective, antiedema, antioxidant, antiinflammatory
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing bilberry that contains anthocyanins (e.g., fresh or dried fruit, standardized tablets) as part of an overall treatment program in the context of: • Vision disorders, myopia, retinitis, hemeralopia, simple glaucoma (4) • Venous insufficiency, especially of the lower limbs (1) • Peripheral vascular disorders, diabetic retinopathy (3) • Hypertensive retinopathy, nosebleed caused by capillary fragility (3) • Chronic primary dysmenorrhea (3) • Raynaud’s syndrome (4) • Venous disorders during pregnancy, including hemorrhoids (4) • Postoperative complications from nose surgery (4) • Decreased capillary resistance (bruising, petechiae, fecal occult blood) (4) • Nonspecific, acute diarrhea (4) • Topical treatment for mild inflammation of the mouth and throat (4)

Based on appropriate evaluation of the patient, practitioners should consider prescribing bilberry that contains no anthocyanins (e.g., liquid extracts) in formulations in the context of digestive disorders, including diarrhea, dyspepsia, gastrointestinal infections, and inflammations; scurvy, urinary complaints, vaginal discharges (6) Contraindications None known. Warnings and Precautions Very high doses of the standardized tablets should be used cautiously in patients with hemorrhagic disorders and in those taking warfarin or antiplatelet drugs. (Inhibition of platelet aggregation was demonstrated from the blood of healthy volunteers after oral administration of an extract containing 173 mg/day of anthocyanins for 30 to 60 days.) Interactions Possible interaction may occur with warfarin and antiplatelet drugs but only for very high doses. Use in Pregnancy and Lactation No adverse effects expected. Side Effects A surveillance study reported mild side effects in a small percentage of patients affecting the gastrointestinal, cutaneous, or nervous systems. Dosage Dose per day^* Dose per week^* 3–6 ml of 1:1 liquid extract 20–40 ml of 1:1 liquid extract Tablets providing 50 to 120 mg per day of anthocyanins (equivalent to about 20 to 50 g of fresh fruit) have been typically used in clinical trials.

* This dose range is extrapolated from traditional herbal texts ¹ and pharmacologic and clinical trial data.

SUPPORTING INFORMATION

Traditional Prescribing

Traditional Western herbal medicine uses include:

• Digestive disorders (diarrhea, dyspepsia, gastrointestinal infections, and inflammations), hemorrhoids ¹

• Scurvy, urinary complaints ¹

• Vaginal discharges, to dry up breast milk ¹

Pharmacologic Research

Bilberry fruit contains a range of anthocyanins, some of which are blue pigments responsible for the color of the ripe berries.

• Bilberry extract has demonstrated vasoprotective and antiedema effects in vivo.

• In vitro studies have demonstrated the antioxidant activity of bilberry and its anthocyanins.

• Antiplatelet activity has been demonstrated in vitro, in vivo, and ex vivo. The mechanism of action may depend on an increase in the concentration of cAMP, a decrease in the concentration of platelet thromboxane, or both.

• Anthocyanins from bilberry protected collagen against nonenzymatic proteolytic activity in vitro and therefore may protect collagen from degradation during inflammatory processes.

• Bilberry extract demonstrated significant dose-dependent antiulcer activity in vivo.

Clinical Studies

All clinical studies have been conducted using bilberry preparations that were standardized for anthocyanin content. The oral doses used in the following clinical studies ranged from 54 to 288 mg per day of anthocyanins, with doses of 115 mg/day and 173 mg/day of anthocyanins most commonly administered.

• A review of uncontrolled trials from 1979 to 1985 concluded that bilberry extract caused rapid disappearance of symptoms and improvements in venous microcirculation and lymph drainage for patients with venous insufficiency.

• In a double-blind, placebo-controlled trial, patients with peripheral vascular disorders of various causes experienced a reduction in subjective symptoms, including paresthesia, pain, heaviness, and edema, after treatment with bilberry for 30 days. Mobilization of finger joints was improved in patients with Raynaud’s syndrome.

• Bilberry extract provided relief for patients with venous disorders, including hemorrhoids during pregnancy in an open trial lasting 2 to 3 months.

• In a double-blind, placebo-controlled trial, bilberry significantly reduced symptoms of dysmenorrhea, such as pelvic and lumbosacral pain, mammary tension, headache, nausea, and heaviness of the lower limbs.

• In uncontrolled trials, bilberry extract improved symptoms caused by decreased capillary resistance and reduced the microcirculatory changes induced by cortisone therapy in patients with asthma and chronic bronchitis after 6 months’ treatment and improved diabetic retinopathy with a marked reduction or even disappearance of retinic hemorrhages. Other controlled studies support the use of bilberry for the treatment of both diabetic and hypertensive retinopathy.

• In a placebo-controlled trial, bilberry extract reduced nosebleed caused by abnormal capillary fragility of the mucous membranes.

• Studies have also shown the benefits of bilberry in patients with visual disorders, such as myopia, defective vision in bright light, simple glaucoma (in combination with retinol), and poor darkness adaptation. Bilberry also improved night vision in healthy volunteers, although a small double-blind, placebo-controlled trial published in 2000 cast doubt on this aspect of its efficacy.²

• Postoperative complications from surgery of the nose were reduced in patients who received bilberry extract administered for 7 days before and 10 days after surgery.

• In Germany, the Commission E supports the use of bilberry dried fruit and preparations to treat nonspecific acute diarrhea and externally for local therapy of mild inflammation of the mucous membranes of the mouth and throat.³

REFERENCES

1 Grieve M. A modern herbal. New York: Dover Publications, 1971.

2 Muth ER, Laurent JM, Jasper P. Altern Med Rev. 2000;5(2):164-173.

3 Blumenthal M, et al, editors. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council, 1998.

BLACK COHOSH

*Botanical Names:*	Cimicifuga racemosa, Actaea racemosa^#^{^}
*Family:*	Ranunculaceae
*Plant Part Used:*	Root and rhizome

# Alternative name.

^ Adopted by the American Herbal Products Association as the new botanical name.¹

PRESCRIBING INFORMATION

Actions	Antirheumatic, spasmolytic, estrogen modulating, uterine tonic
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing black cohosh in formulations in the context of: • Symptoms associated with menopause (2,4) • Dysmenorrhea (4,5) • Premenstrual syndrome (4) • Ovarian dysfunction and ovarian insufficiency (4) • Amenorrhea, ovarian pain, female infertility; arthritis, rheumatism, neuralgia, myalgia, sciatica; whooping cough, tinnitus (5)

Contraindications Black cohosh should not be taken during pregnancy or lactation² except during the last month to assist with birth.³ Until more information is available, women with estrogen-dependent tumors such as breast cancer should avoid using black cohosh. Warnings and Precautions Traditional sources note that overdose has caused nausea and vomiting and may produce vertigo, as well as visual and nervous disturbance. Interactions The antiproliferative effect of black cohosh extract in combination with tamoxifen was assessed in vitro on 17β-estradiol–stimulated MCF-7 human breast cancer cells. Black cohosh augmented the antiproliferative action of tamoxifen. Whether this interaction also applies in vivo has not been established. Use in Pregnancy and Lactation Contraindicated in pregnancy and lactation, except for assisting birth during the last month. Side Effects High doses cause frontal headache. Stomach complaints have been observed with a low frequency in clinical trials. Dosage Dose per day^* Dose per week^* 1.5–3.0 ml of 1:2 liquid extract 10–20 ml of 1:2 liquid extract Black cohosh may be taken long term within the recommended dose, although the Commission E recommends not more than 6 months, perhaps because controlled studies over longer periods are lacking.

* This dose range is extrapolated from the British Pharmaceutical Codex 1934, the British Herbal Pharmacopoeia 1983, clinical trial information, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Myalgia, chorea, arthritis, rheumatism, neuralgia, sciatica ^3,⁴ • Female reproductive disorders, dysmenorrhea, amenorrhea, ovarian pain, female infertility, partus preparator, leukorrhea ^4,⁵ • Whooping cough, tinnitus ⁴
Pharmacologic Research	• Experimental studies have shown the luteinizing hormone (LH) suppressive effect of black cohosh when the extract was given both orally and via injection (the latter route produced greater activity). At least three compounds were found to be involved. Black cohosh extract has also increased LH secretion in vivo (oral route).⁶ • Although estrogenic compounds are present in black cohosh, no estrogenic activity was found in vivo after oral or subcutaneous administration. Black cohosh extracts reduced the number of skin flushes in an experimental menopausal model, which was considered to be indicative of an estrogenic effect.⁷ Research presented in 2000 highlights the debate concerning the nature of any estrogenic activity of black cohosh.⁸ • Black cohosh is not overtly estrogenic, but the compounds within it act as phyto-SERMs (plant substances that act as selective estrogen-receptor modulators) that interact with certain types of estrogen receptors such as Erβ, which is present in many tissues. • Black cohosh had no effect on uterine weight in vivo or on any of the estrogen-regulated genes in the uterus, whereas it mimicked many of the effects of estradiol in bone, liver, and the aorta. • Oral administration of black cohosh extract did not promote estro-gen-dependent mammary gland tumors in vivo.⁹ • Black cohosh extract inhibited monoamine oxidase in the striatum after long-term pretreatment in vivo.¹⁰
Clinical Studies	The clinical studies outlined here were conducted using a German pro-prietary medicine and reflect lower doses compared with those used traditionally. The tablets are quoted as containing 1 mg of a marker triterpene glycoside (27-deoxyactein). Current regulatory information indicates that these tablets now contain 24.8 to 42.7 mg dried herb equivalent and 0.8 to 1.2 mg triterpene glycosides. • A review of clinical data indicates that black cohosh appears to have therapeutic efficacy for moderate to severe neurovegetative symptoms of menopause. Good tolerability and a low risk of side effects have been confirmed.¹¹ The data reviewed includes case reports dating back to the 1950s, a drug-monitoring study of over 700 individuals and clinical trials. Three of the trials were randomized and controlled and administered a dose containing 4 mg/day of marker triterpene glycoside. In the randomized, double-blind, placebo-controlled trial, black cohosh was superior in efficacy to that of conjugated estrogens (0.625 mg/day) after 3 months. In this trial, the black cohosh treatment group also showed significant improvement in the proliferation status of vaginal epithelium. However, the administered dose of estrogens was considered too low. A pharmacologic study involving menopausal women observed that black cohosh (4 tablets/day) significantly reduced the mean serum LH level compared with a placebo group. This statistical reduction of LH was not observed in an earlier randomized, controlled trial using the same dose. • Treatment with a high dose of black cohosh extract was not associated with changes in endometrial thickness, vaginal cell status, or hormone levels in a drug-monitoring study involving 28 menopausal women. Hormones measured included LH, follicle-stimulating hormone (FSH), prolactin, and estradiol. Approximately 80% of patients demonstrated good or very good efficacy in relation to the menopausal symptoms measured. The dosage of extract (similar to that discussed here) was 136 mg/day. The mean duration of treatment was 98 days.¹² • Treatment with black cohosh (2 tablets/day) was not significantly better than was placebo for most menopausal symptoms in a randomized, double-blind trial involving women with a history of breast cancer. Of the seven menopausal symptoms assessed, sweating was the only symptom for which the improvement reported by the treatment group was statistically significant from placebo.¹³ The dose administered was lower than that used in other clinical trials. • In an open, multicenter, postmarketing surveillance study, a combination of St. John’s wort and black cohosh demonstrated improvement in 90% of patients for the psychologic complaints experienced in menopause, with improved concentration and a reduction in hot flashes.¹⁴ The same St. John’s wort and black cohosh combination significantly reduced menopausal symptoms compared with placebo in a randomized, double-blind trial involving 179 women. The daily dose contained 0.5 mg of total hypericin and 2 mg of 27-deoxyactein (the active compound in black cohosh).¹⁵ • In Germany, the Commission E supports using black cohosh to treat premenstrual discomfort, dysmenorrhea, and menopausal symptoms.¹⁶

REFERENCES

1 McGuffin M, editor. Herbs of Commerce, ed 2, Bethesda, Md: American Herbal Products Association, 1998. [draft 3.3]

2 British Herbal Medicine Association. British herbal compendium. Bournemouth: BHMA, 1992.

3 Felter HW. The eclectic materia medica, pharmacology and therapeutics. Portland: Eclectic Medical Publications, 1922. reprinted 1983

4 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.

5 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983

6 Knuvener E, Korte B, Winterhoff H. Phytomed. 2000;7(supp 2):12.

7 Lohning A, Verspohl EJ, Winterhoff H: International Conference: 2000 Years of Natural Product Research – Past, Present and Future, Amsterdam, July 26-30, 1999; Abstract 327.

8 Third International Congress on Phytomedicine, Munich, October 11-13, 2000. Phytomed. 2000;7(supp 2):11-12.

9 Freundenstein J, Dasenbrock C, Nisslein T. Phytomed. 2000;7(supp 2):13.

10 Lohning A, Winterhoff H. Phytomed. 2000;7(supp 2):13.

11 Liske E. Adv Ther. 1998;15(1):45-53.

12 Nesselhut T, Liske E: 10th Annual Meeting of the North American Menopause Society, New York, September 23-25, 1999; Poster 8.

13 Jacobson JS, et al. J Clin Oncol. 2001;19(10):2739-2745.

14 Gerhard I, Liske E, Wustenberg P. Z Phytother Abstractband. 1995:21-22.

15 Boblitz N, et al. Focus Alternat Complement Ther. 1995;5(1):85-86.

16 Blumenthal M, et al, editors. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council, 1998.

BLACK HAW

*Botanical Name:*	Viburnum prunifolium
*Family:*	Caprifoliaceae
*Plant Part Used:*	Bark

PRESCRIBING INFORMATION

Actions	Uterine sedative, bronchospasmolytic, antiasthmatic, hypotensive, astringent
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing black haw in formulations in the context of: • Dysmenorrhea (5) • False labor pains, threatened miscarriage, postpartum hemorrhage (5) • Asthma, hiccup, leg cramps (5)

Contraindications None known. Warnings and Precautions According to the American Herbal Products Association,¹ individuals with a history of kidney stones are cautioned against using black haw because of the presence of oxalate or oxalic acid in the dried bark. Oxalate, as the potassium or calcium salt, is present in the cell sap of many plants and vegetables. Calcium oxalate is practically insoluble in water² and is unlikely to be present in aqueous ethanolic liquid extracts of black haw in sufficient quantities to justify this precaution. Interactions Black haw contains scopoletin (a coumarin), and suggestions are that it may potentiate the effects of anticoagulant medications or cause hemorrhagic problems.³ However, no evidence has been found to suggest that anticoagulant activity in vivo⁴ and simple plant coumarins do not necessarily increase the risk of bleeding. Use in Pregnancy and Lactation No adverse effects expected. Side Effects None expected if taken within the recommended dose range. A traditional text reports that nausea and vomiting may occur with large doses.⁵ Dose per day^* Dose per week^* 1.5–4.5 ml of 1:2 liquid extract 10–30 ml of 1:2 liquid extract

* This dose range is extrapolated from the British Pharmaceutical Codex 1949, the British Herbal Pharmacopoeia 1983, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • As a uterine tonic, for uterine irritation and inflammation ^5,⁶ • Dysmenorrhea, severe lumbar and bearing-down pains; cramplike, expulsive menstrual pains ^5,⁶ • Threatened miscarriage,^5,⁶ especially with a rise in blood pressure⁶ • False labor pains,^5,⁶ postpartum hemorrhage; menorrhagia, uterine hemorrhage in menopause, amenorrhea⁵ • Nervous disorders associated with menses, including epilepsy ⁵ • Leg cramps, especially at night ⁵ • Asthma,⁶ hiccup, heart palpitations⁵ • Diarrhea, dysentery, jaundice ⁵ • Sterility, spermatorrhea ⁵ • Alcoholic hangover ⁵ • Topically for indolent ulcers and ophthalmic disorders ⁵
Traditional Prescribing	Native Americans used black haw for stomach troubles, dysentery, female reproductive problems, before and during parturition, and as an antispasmodic, diaphoretic, and tonic. Black haw was official in the USP from 1882 to 1926 and NF from 1926 to 1960.^3,⁷
Pharmacologic Research	Black haw bark contains flavonoids (including the biflavone amentoflavone), iridoid glycosides, triterpenes and triterpenic acids, and coumarins (including scopoletin).³
Pharmacologic Research	The value of published research conducted before 1940 on Viburnum spp. must be questioned because of possible improper identification of the various species and possible adulteration with other species.⁸ • Early studies investigating the uterine spasmolytic effect for black haw had varying results.⁹^–¹⁵ Two reviews of these studies concluded that the findings were scientifically invalid because of significant design limitations.^16,¹⁷ More recent studies have confirmed the uterine spasmolytic activity of black haw ethanolic extracts in vitro.¹⁸^–²¹ • Black haw has also demonstrated spasmolytic activity in isolated intestinal tissues.²¹ • Hypotensive and hypertensive effects have been reported for black haw. An indirect, dose-dependent, vasoconstricting effect was observed in isolated aortic tissue.²² Intravenous administration of the total extract induced a slow but prolonged increase in mean blood pressure in vivo.²² Conversely, early in vivo studies demonstrated a hypotensive effect for black haw (intravenous route).^15,²³ Theories suggest that the hypotensive effect was a result of the absence of iridoid compounds in the extracts used in the early studies.²¹ Moreover, because the herb was administered by injection in all these studies, their relevance is questionable. • In an early study, dietary black haw root bark did not have a significant appetite-enhancing effect in an experimental model, suggesting a lack of bitter action.²⁴ (This finding is not surprising because modern herbal clinicians do not regard black haw as a bitter tonic.)
Clinical Studies	No clinical studies using black haw have been found.

REFERENCES

1 McGuffin M, et al, editors. American Herbal Products Association’s botanical safety handbook. Boca Raton, Fla: CRC Press, 1997.

2 Budavari S, et al, editors. The Merck index: an encyclopedia of chemicals, drugs and biologicals, ed 12, Whitehouse Station, N.J.: Merck and Co., 1996.

3 American Herbal Pharmacopoeia. Black haw bark – Viburnum prunifolium: analytical, quality control, and therapeutic monograph. Santa Cruz, Calif: American Herbal Pharmacopoeia, June 2000.

4 Patterson DSP, Roberts BA, O’Neill PA. Vet Rec. 1971;89(20):544-545.

5 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983

6 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.

7 Vogel VJ. American Indian medicine. Norman, Okla: University of Oklahoma Press, 1970.

8 American Herbal Pharmacopoeia. Cramp bark–Viburnum opulus: analytical, quality control, and therapeutic monograph. Santa Cruz, Calif: American Herbal Pharmacopoeia, February 2000.

9 Pilcher JD, Delzell WR, Burman GE. Arch Intern Med. 1916;18(5):557-583.

10 Pilcher JD, Delzell WR, Burman GE. J Am Med Assoc. 1916;67(7):490-492.

11 Pilcher JD. Arch Int Med. 1917;19(9):53-55.

12 Pilcher JD, Mauer RT. Surgery Gynecol Obstet. 1918;27:97-99.

13 Hager BH, Becht FC. J Pharmacol ExpTher. 1919;13(1):61-70.

14 Munch JC. J Am Pharm Assoc. 1939;28(11):886-887.

15 Munch JC, Pratt HJ. Pharm Arch. 1941;12:88-91.

16 Woodbury RA. Drug Stand. 1951;19(7-9):143-151.

17 Baldini L, Brambilla G, Parodi S. Arch Ital Sci Farmacolog. 1963;3(14):55-63.

18 Balansard G, et al. Med Plants Phytother. 1983;17(3):123-132.

19 Jarboe CH, et al. Nature. 1966;212(64):837.

20 Jarboe CH, et al. J Med Chem. 1967;10:488-489.

21 Tomassini L, et al. Proceedings of the Societa Italiana di Fitochimica 9th National Congress. Florence: Societa Italiana di Fitochimica, May 27-30, 1988.

22 Cometa MF, Tomassini L, Palmery M. Fitoterapia. 1998;69(5):23.

23 Evans WEJr, Harne WG, Krantz JCJr. J Pharmacol. 1942;75:174-177.

24 Garb S, Cattell M. Drug Stand. 1956;24(3):94-99.

BLADDERWRACK

*Other Common Name:*	Kelp (this common name is applied to several seaweed species, including bladderwrack)
*Botanical Name:*	Fucus vesiculosus
*Family:*	Fucaceae
*Plant Part Used:*	Thallus (plant body)

PRESCRIBING INFORMATION

Actions	Weight reducing, thyroid stimulant, demulcent
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing bladderwrack in formulations in the context of: • Obesity associated with iodine deficiency (3,5) • Thyroid conditions resulting from iodine deficiency (5,7) • Rheumatic conditions, including arthritis (5)

Contraindications Hyperthyroidism, pregnancy, lactation, and cardiac problems associated with hyperthyroidism¹ Warnings and Precautions None required. Interactions Bladderwrack may interact with thyroid replacement therapies (thyroxine). Use in Pregnancy and Lactation Contraindicated in pregnancy and lactation. Side Effects

Kelp (species undefined) has caused transient hyperthyroidism (estimated iodine intake of 2.8 to 4.2 mg/day)^2,³ and raised levels of thyroid stimulating hormone (dose undefined).⁴

When consumed as a food, kelp (probably not bladderwrack) has caused subclinical hypothyroidism ⁵ and Hashimoto’s thyroiditis.⁶ Rare extrathyroidal effects may also occur in susceptible individuals as a result of iodine intake, such as the allergic reactions of edema (doses up to 25 mg/day iodine), iodine fever (50 to 500 mg/day iodine), and eosinophilia (dose not defined). However, iodine intake from iodine-rich foods and supplements are unlikely to reach these high levels.⁷

Other cases of side effects from bladderwrack or kelp ingestion have been recorded (including kidney damage) and were attributed to high levels of heavy metals, particularly arsenic. In one case, the ingested kelp tablets contained 20 g of arsenic per tablet (27.8 g/g). The dose taken was not indicated. Physicians linked a case of severe dyserythropoiesis and autoimmune thrombocytopenia to ingestion of a kelp tablet (probably not bladderwrack). Analysis of the tablets showed that they contained 1.3 μ g/g of arsenic. The patient had been ingesting 2.2 g of arsenic daily from this source.⁸^–¹⁰ The reader should note that marine organisms, including bladderwrack, naturally accumulate arsenic.

However, the arsenic is mainly organically bound and rapidly excreted. For this reason, the World Health Organization has established a tolerable weekly intake for inorganic arsenic only, which is present in bladderwrack at considerably lower levels.¹¹

Dosage Dose per day^* Dose per week^* 4.5–8.5 ml of 1:1 liquid extract 30–60 ml of 1:1 liquid extract

* This dose range is extrapolated from the British Herbal Pharmacopoeia 1983, the British Herbal Compendium 1992, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Obesity, particularly associated with hypothyroidism.¹² (Eclectic texts note that bladderwrack may be beneficial for treating obesity but only in cases when the diet is deficient, presumably of the iodine that bladderwrack contains.¹³) • Myxedema (a condition resulting from advanced hypothyroidism), lymphadenoid goiter (most likely of the simple type resulting from iodine deficiency, rather than the exophthalmic type, which is indicative of hyperthyroidism)¹² • Rheumatism and rheumatoid arthritis (internally and topically)¹²
Traditional Prescribing	Bladderwrack was thought by the Eclectics to tone muscular fibers, to act powerfully on the glandular system as a depurative, and to reduce renal congestion and bladder inflammation.¹³
Pharmacologic Research	Bladderwrack thallus contains trace minerals (particularly free and protein-bound iodide) and polysaccharides of several types (including alginic acid and fucans such as fucoidan). Other constituents include polyphenols, lipids, and sterols.¹ • Experimental studies conducted and reported in 1910 found oral doses of bladderwrack have a stimulatory activity on the thyroid gland.¹⁴ • When administered by injection, a polysaccharide fraction of bladder-wrack demonstrated hypoglycemic activity in a normoglycemic model and lowered serum lipid levels in hyperlipidemia.^15,¹⁶ • Bladderwrack extract promoted collagen gel contraction by increasing the expression of integrin molecules on the surface of fibroblasts in an in vitro model of dermal tissue.¹⁷ Polysaccharides from bladderwrack demonstrated strong adhesion to epithelial tissue in vitro.¹⁸ • Low molecular weight fucoidan fraction from bladderwrack demonstrated potent anticoagulant and fibrinolytic properties in vitro, with only minor platelet-activating effects.¹⁹ • Fractions of bladderwrack extract demonstrated anti-HIV activity in vitro.²⁰
Clinical Studies	• A clinical trial investigating several weight-reducing treatments in moderately overweight Swedish women was conducted over a 2-year period. Most of the treatments, including the kelp-lecithin-vitamin combination, produced poor results.²¹ (The species used was probably not bladderwrack.) • A hypocaloric diet combined with spirulina, bladderwrack, and gelatin did not change any of the measured parameters in hypertensive obese patients.²² • In a controlled clinical trial, obese volunteers taking bladderwrack extract in addition to a controlled diet achieved a significantly greater average weight loss than did those on diet alone.²³

REFERENCES

1 British Herbal Medicine Association. British herbal compendium. Bournemouth: BHMA, 1992.

2 Eliason BC. J Am Board Fam Pract. 1998;11(6):478-480.

3 Shilo S, Hirsch HJ. Postgrad Med J. 1986;62:661-662.

4 Key TJA, et al. J Hum Nutr Diet. 1992;5:323-326.

5 Konno N, et al. J Clin Endocrinol Metab. 1994;78(2):393-397.

6 Okamura K, Inoue K, Omae T. Acta Endocrinol. 1978;88:703-712.

7 de Smet PAGM, et al, editors. Adverse effects of herbal drugs. Berlin: Springer-Verlag, 1997.

8 Conz PA, et al. Nephrol Dial Transplant. 1998;13:526-527.

9 Walkiw O, Douglas DE. Clin Toxicol. 1975;8(3):325-331.

10 Pye KG, et al. Lancet. 1992;339(8808):1540.

11 de Smet PAGM, et al, editors. Adverse effects of herbal drugs. Berlin: Springer-Verlag, 1992.

12 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.

13 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983

14 Hunt R, Seidell A. J Pharmacol. 1910;2:15-47.

15 Vazquez-Freire MJ, Lamela M, Calleja JM. Phytother Res. 1996;10(supp 1):S184-S185.

16 Lamela M, Vazquez-Freire MJ, Calleja JM. Phytother Res. 1996;10(supp 1):S175-S176.

17 Fujimura T, et al. Biol Pharm Bull. 2000;23(3):291-297.

18 Schmidgall J, Schnetz E, Hensel A. Planta Med. 2000;66(1):48-53.

19 Durig J, et al. Thromb Res. 1997;85(6):479-491.

20 Beress A, et al. J Nat Prod. 1993;56(4):478-485.

21 Bjorvell H, Rossner S. Int J Obes. 1987;11(1):67-71.

22 Monego ET, et al. Arq Bras Cardiol. 1996;66(6):343-347.

23 Curro F, Amadeo A. Arch Med Interna. 1976;28:1343-1349.

BLUE COHOSH

*Botanical Name:*	Caulophyllum thalictroides
*Family:*	Berberidaceae
*Plant Part Used:*	Root

PRESCRIBING INFORMATION

Actions	Spasmolytic, uterine and ovarian tonic, emmenagogue, oxytocic
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing blue cohosh in formulations in the context of: • Disorders of the female reproductive tract including amenorrhea, dysmenorrhea, menorrhagia, ovarian or uterine pain or inflammation, uterine prolapse or atony (5) • Spasmodic conditions of smooth muscle, including abdominal cramping (5) • Rheumatic conditions, muscular weakness, nervous debility (5)

Contraindications Because of possible teratogenic effects, blue cohosh is contraindicated in early pregnancy and lactation. Traditional texts such as the British Herbal Pharmacopoeia 1983 support this contraindication by recommending that only small doses are advisable during the first trimester of pregnancy. Use in late pregnancy has been linked to adverse events and should be undertaken only by clinicians experienced with blue cohosh for this application. Warnings and Precautions None required. Interactions None known. Use in Pregnancy and Lactation Contraindicated in pregnancy and lactation. Side Effects

High levels of the isolated alkaloid anagyrine in goat’s milk have been associated with teratogenic effects in animals and in one human.¹ The relevance of this finding to use of blue cohosh is unclear.

Several adverse events have been associated with maternal ingestion of blue cohosh. A midwife attempted the induction of labor using a combination of blue cohosh and black cohosh given orally (dose undefined) at around 42 weeks of gestation.² After normal labor, the female baby was unable to breathe spontaneously and sustained central nervous system hypoxic-ischemic damage.³ Profound neonatal congestive heart failure was linked to maternal consumption of blue cohosh tablets about 1 month before delivery. The dosage and content of the tablets was undefined. The woman had been advised to take 1 tablet per day, but she took three times that dose (3 tablets/day) for 3 weeks before delivery.⁴ The infant exhibited signs of severe cardiac injury and was hospitalized. Follow-up at 2 years of age indicated that cardiomegaly and mildly reduced left ventricular function were evident.

The U. S. Food and Drug Administration’s (FDA) Special Nutritionals Adverse Event Monitoring System database (which lists adverse events but is not subject to preconditions, analysis, or peer review) also contains two cases possibly associated with blue cohosh, including stroke in an infant.

Toxic effects have occurred from overdose of blue cohosh tincture (cited as 10 to 20 doses/day in relation to attempted abortion). Symptoms included hyperthermia, hypertension, tachycardia, hyperventilation, diaphoresis, and weakness.⁵

The presence of oxytocic quinolizidine alkaloids such as sparteine or N-methylcytisine in blue cohosh might explain both its oxytocic activity and its occasional toxicity. Adverse effects may be the result of an inability by some people to metabolize sparteine and alkaloids of related structure. About 5% of male and female subjects studied in a trial were unable to metabolize sparteine by N-oxidation,⁶ and this defect appears to have a genetic basis.⁷

Dosage Dose per day^* Dose per week^* 1.5–3.0 ml of 1:2 liquid extract 10–20 ml of 1:2 liquid extract

* This dose range is extrapolated from the British Herbal Pharmacopoeia 1983 and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Uterine pain, amenorrhea, dysmenorrhea, irregular menstruation; threatened miscarriage, false labor pains, as a partus preparator; uterine atony ^8,⁹ • Rheumatic pain, muscular weakness, debility of the nervous system, epilepsy ⁹ • Abdominal cramping, indigestion; dull frontal headache ⁹
Traditional Prescribing	Blue cohosh was used by Native Americans to expedite parturition and menstruation, for lingering parturition, and for suppressing profuse menstruation, genitourinary complaints in both sexes, colic, sore throat, rheumatism, and dropsy. However, the modern understanding argues against using blue cohosh to facilitate labor except perhaps in practitioners already experienced with its use in this context. Blue cohosh was considered an effective fever remedy. Blue cohosh was official in the USP from 1882 to 1905 and the NF from 1916 to 1950 and was used for antispasmodic, emmenagogue, and diuretic purposes.¹⁰
Pharmacologic Research	Blue cohosh root contains quinolizidine alkaloids, including sparteine, methylcytisine, and anagyrine.¹¹ Blue cohosh also contains saponins such as caulosaponin.¹² • Uterine stimulant effects were observed for the liquid extract, hot water extract and saponin fraction, and isolated caulosaponin in vitro.¹²^–¹⁴ • Methylcytisine has demonstrated hypertensive activity when administered by injection. Caulosaponin demonstrated vasoconstrictive activity on isolated arteries and a cardiotoxic effect on cardiac muscle.¹² • Nicotinic activity was observed after oral ingestion of methylcytisine by a human subject.⁵
Clinical Studies	• A survey published in 2000 reported that herbal therapy was recommended by 73.2% of 82 North Carolina–certified midwives for pregnant and postpartum patients. Blue cohosh was among the herbs commonly prescribed for women past their due dates.¹⁵ Similar findings were obtained in a survey conducted a year earlier in which 64% of 90 midwives reported using blue cohosh. This survey recorded the following dosages: 5 drops of tincture every 4 hours for induction of labor or 10 drops of tincture every 2 hours in hot water.¹⁶

REFERENCES

1 Ortega JA, Lazerson J. J Pediatr. 1987;111(1):87-89.

2 Gunn TR, Wright IM. N Z Med J. 1996;109(1032):410-411.

3 Wright IMR. J Pediatr. 1999;134(3):384-385.

4 Jones TK, Lawson BM. J Pediatr. 1998;132:550-552.

5 Rao RB, et al. J Toxicol Clin Toxicol. 1998;36(5):455.

6 Eichelbaum M, et al. Eur J Clin Pharmacol. 1979;16:183-187.

7 Vinks A, et al. Clin Pharmacol Ther. 1982;31(1):23-29.

8 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.

9 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983

10 Vogel VJ. American Indian medicine. Norman, Okla: University of Oklahoma Press, 1970.

11 Kennelly EJ, et al. J Nat Prod. 1999;62(10):1385-1389.

12 Chandler F, editor. Herbs: everyday reference for health professionals. Ottawa: Canadian Pharmacists Association, 2000.

13 Pilcher JD, Delzell WR, Burman GE. JAMA. 1916;67:490-492.

14 Ferguson HC, Edwards LD. J Am Pharm Assoc. 1954;43(1):16-21.

15 Allaire AD, Moos MK, Wells SR. Obstet Gynecol. 2000;95(1):19-23.

16 McFarlin BL, et al. J Nurse Midwifery. 1999;44(3):205-216.

BLUE FLAG

*Botanical Names:*	Iris versicolor, Iris caroliniana⁺
*Family:*	Iridaceae
*Plant Part Used:*	Rhizome

+ Medicinally interchangeable species.

PRESCRIBING INFORMATION

Actions	Depurative, laxative, cholagogue, lymphatic, diuretic
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing blue flag in formulations in the context of: • Skin, liver, and gallbladder disorders, particularly when chronic in nature (5) • Constipation, headache, or digestive problems related to poor liver function (5) • Enlarged lymph nodes, enlarged thyroid, enlarged spleen, enlarged ovaries (5) • Obesity (7)

Contraindications None known. Warnings and Precautions None required. Interactions None known. Use in Pregnancy and Lactation No adverse effects expected. Side Effects None expected if taken within the recommended dose range. Dosage Dose per day^* Dose per week^* 3–6 ml of 1:2 liquid extract 20–40 ml of 1:2 liquid extract

* This dose range is extrapolated from the British Herbal Pharmacopoeia 1983, the British Herbal Compendium 1992, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Skin diseases ^1,² • Biliousness with constipation and liver dysfunction,¹ jaundice, poor gallbladder function, chronic liver disorders, including hepatitis; constipation; nausea, vomiting, headache, or digestive problems related to poor liver function² • Reflex muscular pains resulting from gastric irritation ² • Enlarged lymph nodes, enlarged thyroid, enlarged spleen; chronic pancreatic, splenic, or renal disorders ² • Syphilis, scrofula (tuberculous infection of the cervical lymph nodes)² • Enlarged uterus or ovary; leukorrhea, dysmenorrhea; prostatic discharges, nocturnal emissions ² • Vomiting with pregnancy; regarded as an emetic, but with antiemetic activity in small doses ³
Traditional Prescribing	Blue flag was held in high regard by Native Americans and was one of the most widely used native medicines. Blue flag was used as a powerful cathartic and employed internally to treat the common cold and lung problems. Externally, blue flag was used as a poultice and wash for sores, bruises, and burns. The steamed root was taken internally to keep disease away because of its importance as a physic and panacea. The steeped root was a specific for cholera. Blue flag was official in the USP from 1820 to 1895 and in the NF from 1916 to 1942, with uses listed as cathartic, emetic, and diuretic.⁴
Pharmacologic Research	Blue flag root significantly increased plasma levels of free fatty acids and glycerol after oral administration (20 mg/kg) in an experimental model, demonstrating mobilization of fat tissue.⁵
Clinical Studies	No clinical studies using blue flag have been found.

REFERENCES

1 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.

2 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983

3 British Herbal Medicine Association. British herbal compendium. Bournemouth: BHMA, 1992.

4 Vogel VJ. American Indian medicine. Norman, Okla: University of Oklahoma Press, 1970.

5 Bambhole VD. Ancient Sci Life. 1988;8:117.

BUCHU

*Botanical Names:*	Agathosma betulina, Barosma betulina^#
*Family:*	Rutaceae
*Plant Part Used:*	Leaf

# Alternative name.

PRESCRIBING INFORMATION

Actions	Urinary antiseptic, mild diuretic
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing buchu in formulations in the context of urinary tract infection, dysuria, cystitis, urethritis, and prostatitis. (5)
Contraindications	None known.
Warnings and Precautions	None required.
Interactions	None known.
Use in Pregnancy and Lactation	Some writers suggest that buchu is contraindicated in pregnancy. However, this precaution would only be the case for buchu substitutions (e.g., Agathosma crenulata), which contain much higher levels of pulegone in their essential oil.
Side Effects	Occasional gastrointestinal irritation may occur if taken on an empty stomach.
Dosage	*Dose per day^	*Dose per week^
	2.0–4.5 ml of 1:2 liquid extract	15–30 ml of 1:2 liquid extract

* This dose is extrapolated from the British Herbal Pharmacopoeia 1983, the British Herbal Compendium 1992, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Diseases of the genitourinary tract, especially inflammation of the mucous membranes of the lower urinary system and prostate (e.g., cystitis, urethritis, prostatitis);urinary discharges, urinary gravel ^1,² • Incontinence associated with a diseased prostate, desire to urinate with little relief from micturition ² • Improving appetite, relieving nausea and flatulence ²
Traditional Prescribing	Traditional South African medicinal uses include stomach complaints, kidney and urinary tract diseases, and rheumatism.³
Pharmacologic Research	An alcoholic extract of buchu demonstrated activity against microflora typical of urinary tract infections in vitro. Only the essential oil showed considerable activity against all the test organisms.
Clinical Studies	No clinical studies using buchu have been found.

REFERENCES

The following book was referred to in the compilation of the pharmacologic and clinical information that has not been referenced hereMills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Edinburgh: Churchill Livingstone, 2000.

1 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.

2 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983

3 van Wyk B-E, van Oudtshoorn B, Gericke N. Medicinal plants of South Africa. Arcadia, South Africa: Briza Publications, 1997.

BUGLEWEED

*Botanical Names:*	Lycopus virginicus, Lycopus europaeus⁺
*Family:*	Labiatae
*Plant Part Used:*	Aerial parts

+ Medicinally interchangeable species.

PRESCRIBING INFORMATION

Actions	Thyroid-stimulating hormone (TSH) antagonist, antithyroid, reduces heart rate, mild sedative
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing bugleweed in formulations in the context of hyperthyroidism, especially Graves’ disease and associated symptoms, such as tachycardia, rapid pulse, and exophthalmia. (4,5)
Contraindications	Thyroid hypofunction, enlargement of the thyroid without functional disorder;¹ pregnancy and lactation.²
Warnings and Precautions	None required.
Interactions	Bugleweed should not be administered concurrently with preparations containing thyroid hormone and may interfere with administration of thyroid diagnostic procedures that use radioactive isotopes.¹
Use in Pregnancy and Lactation	Contraindicated in pregnancy and lactation because of potential antigonadotropic activity.
Side Effects	In rare cases, extended therapy and high (undefined) doses of bugle-weed preparations have resulted in an enlargement of the thyroid. Sudden discontinuation of bugleweed preparations can cause increased symptoms of the disease.¹ The following side effects have been reported in the literature from clinical use of bugleweed preparations published between 1941 to 1968:headache, increase in size of thyroid, and occasionally an increase in hyperthyroid symptoms, including nervousness, tachycardia, and loss of weight. The increase in thyroid size was observed in patients with goiter not linked to thyroid malfunction.²
Dosage	*Dose per day^	*Dose per week^
	2–6 ml of 1:2 liquid extract	15–40 ml of 1:2 liquid extract

* This dose range is extrapolated from the British Herbal Pharmacopoeia 1983 and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Nervous tachycardia, Graves’ disease with cardiac involvement; thyro-toxicosis with difficult breathing, tachycardia, and tremor;³ exophthalmic goiter⁴ • Organic and functional cardiac disease; abnormally active circulation, rapid pulse with high temperature ⁴ • Chronic cough, irritating and wet cough, pneumonia, bronchitis ^3,⁴ • Restlessness, insomnia, anxiety ⁴
Traditional Prescribing	Bugleweed is considered in European herbal medicine as having antithyroid activity. Being less powerful than orthodox drugs, bugleweed is recommended for mild thyroid hyperfunction and can be used as a long-term treatment.⁵
Pharmacologic Research	• Lycopus europaeus aqueous ethanolic extract has demonstrated antithyrotropic and antigonadotropic activity in experimental models in vivo (both after injection and oral administration).⁶ The following activities have been observed: • Decreased triiodothyronine (T₃) levels, possibly resulting from reduced peripheral thyroxin (T₄) deiodination • Decreased T₄ and TSH levels • Decreased LH levels • In this series of experiments, testosterone levels were reduced, but prolactin remained unchanged after oral administration of bugleweed extracts.⁶ In an earlier study, L. virginicus aqueous ethanolic extract strongly lowered prolactin levels after intravenous injection.⁷ This activity was demonstrated at a dose much higher than was the dose that produced the previously noted antithyrotropic activity.⁸ L. virginicus extract reduced the weight of the testes, but LH-dependent testosterone synthesis was not significantly changed (route unknown).⁹ • Injection of bugleweed extract reduced serum TSH and pituitary TSH levels under normal thyroid conditions but caused an increase in pituitary TSH levels under hypothyroid conditions (also with decreased serum TSH).⁸ • An antigonadotropic activity has been demonstrated for L. virginicus and L. europaeus extracts and for some of their constituents.^7,¹⁰ The antithyrotropic activity is probably exerted by the ability of phytochemicals in bugleweed to form adducts with TSH and inhibit its ability to bind to the TSH receptor. This inhibitory interaction has also been demonstrated for the Graves’ autoantibody in vitro.^10,¹¹ An intracellular mechanism of inhibition may also be present.¹² • L. europaeus extract demonstrated antioxidant activity in vitro.¹³
Clinical Studies	• Lycopus europaeus inhibited iodine metabolism and thyroid T₄ output in human volunteers.¹⁴ • Lycopus europaeus extract has been beneficial for treating hyperthyroidism in uncontrolled trials conducted in the 1940s and 1950s.¹⁵^–¹⁸ • In Germany, the Commission E supports using bugleweed to treat mild thyroid hyperfunction with disturbances of the autonomic nervous system and mastodynia (breast pain or tenderness).¹

REFERENCES

1 Blumenthal M, et al, editors. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council, 1998.

2 de Smet PAGM, et al, editors. Adverse effects of herbal drugs. Berlin: Springer-Verlag, 1993.

3 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.

4 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983

5 Weiss RF. Herbal medicine. In Meuss AR, editor: Lehrbuch der phytotherapie, ed 6, Beaconsfield, U.K.: Beaconsfield Publishers, 1988.

6 Winterhoff H, et al. Arzneim Forsch. 1994;44(1):41-45.

7 Sourgens H, et al. Int J Crude Drug Res. 1986;24(2):53-63.

8 Sourgens H, et al. Planta Med. 1982;45:78-86.

9 Sourgens H, et al. Acta Endocrinol Suppl. 1980;234:49.

10 Auf’mkolk M, et al. Endocrinology. 1985;116(5):1687-1693.

11 Auf’mkolk M, et al. Endocrinology. 1984;115(2):527-534.

12 Kleeman S, Winterhoff H. Planta Med. 1990;56:683P.

13 Lamaison JL, Petitjean-Freytet C, Carnat A. Pharm Acta Helv. 1991;66(7):185-188.

14 Hiller E, Deglmann H. Arzneim Forsch. 1955;5:465-470.

15 Mattausch F. Hippokrates. 1943;14:168-171.

16 Leppert H. Therapiewoche. 1951;952:2. 571-572

17 Frank J. Munch Med Wschr. 1959;101:203-204.

18 Fiegel G. Med Klin. 1954;49:1221.

BUPLEURUM

*Botanical Names:*	Bupleurum falcatum, Bupleurum scorzonerifolium⁺
*Family:*	Umbelliferae
*Plant Part Used:*	Root

+ Medicinally interchangeable species.

PRESCRIBING INFORMATION

Actions	Antiinflammatory, hepatoprotective, diaphoretic, antitussive
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing Bupleurum in formulations in the context of: • Chronic inflammatory disorders (7) • Poor liver function (5) • Feverish conditions, influenza, the common cold (4,5) • Prolapse of uterus and rectum, irregular menstruation (5)

Contraindications According to TCM, Bupleurum is contraindicated in deficient yin cough (cough with debility) or liver fire ascending to the head, such as some cases of headache and hypertension. Bupleurum can occasionally cause nausea or vomiting, in which case the smallest dose possible is used. Warnings and Precautions Bupleurum has a sedative effect in some patients. Interactions None known. Use in Pregnancy and Lactation No adverse effects expected. Side Effects

Large doses may cause a sedative effect in some patients, increase bowel movements, and flatulence. Bupleurum can occasionally cause nausea and reflux in sensitive patients, a property common to most saponin-rich herbs.

A traditional Chinese herbal formula, which included Bupleurum, has induced pneumonitis in some patients and liver damage in rare cases. Whether this condition was a result of Bupleurum or one of the other herbs present is unclear.

Dosage Dose per day^* Dose per week^* 3.5–8.5 ml of 1:2 liquid extract 25–60 ml of 1:2 liquid extract

* This dose range is adapted from dried plant doses administered by decoction in TCM.¹ The author’s experience and the fact that ethanol-water is a more effective solvent than water for many phytochemicals are taken into account.

SUPPORTING INFORMATION

Traditional Prescribing

Uses and properties from TCM include:

• Bitter and cold, acting as a diaphoretic (in fever management), to regulate and restore gastrointestinal and liver function ²

• Alternating chills and fever (e.g., malaria), liver enlargement, prolapse of the uterus and rectum, menstrual problems, epigastric pain, nausea, indigestion ¹^–³

Pharmacologic Research

Bupleurum root contains triterpenoid saponins, including the saikosaponins.

• The antiinflammatory activity of the saikosaponins appears to be related, at least partially, to their ability to both induce secretion of endogenous corticosterone and potentiate its antiinflammatory activity. Orally, saikosaponins may be used to reduce the dose of glucocorticoid drugs and to prevent glucocorticoid-induced adrenal suppression.

• The ability of saikosaponins to raise blood glucose levels was demonstrated in several pharmacologic studies following both oral and injected doses. This result may be a direct consequence of the ability of saikosaponins to increase the levels of endogenous glucocorticoids. Because saikosaponins also increase liver glycogen stores, Bupleurum may prove to be useful in treating reactive hypoglycemia.

• In experimental models, injection of saikosaponins stimulated immune function.

• Saikosaponins have increased hepatic protein synthesis in vitro and in vivo.

• Saikosaponins (by injection) have demonstrated nephroprotective activity. This activity was partly the result of antiplatelet and corticosterone-releasing activities, as well as an inhibition of the decrease in free-radical scavengers such as glutathione peroxidase.

• Saikosaponins have reduced gastric ulcer development, lowered cholesterol, and exerted antipyretic activity.

• Injection of saikosaponins demonstrated a potent antitussive effect in an experimental model.

Clinical Studies

• In an uncontrolled clinical study of 143 patients treated with Bupleurum, fever subsided within 24 hours in 98% of influenza cases and in 88% of patients with the common cold.

• In another study involving 40 patients with pathological fever, Bupleurum produced an antipyretic effect in 97.5% of patients and achieved a reduction of 1° to 2° C (1.8° to 3.6° F) in body temperature in 77.5% of all patients.

• Intravenous injection of Bupleurum gave positive results in treating infectious hepatitis.

REFERENCES

1 Pharmacopoeia Commission of the People’s Republic of China. Pharmacopoeia of the People’s Republic of China, English ed. Beijing: Chemical Industry Press, 1997.

2 Chang HM, But PP. Pharmacology and applications of Chinese materia medica. Singapore: World Scientific, 1987.

3 Bensky D, Gambel A. Chinese herbal medicine materia medica. Seattle: Eastland Press, 1986.

BURDOCK

*Botanical Name:*	Arctium lappa
*Family:*	Compositae
*Plant Part Used:*	Root

PRESCRIBING INFORMATION

Actions	Depurative, mild diuretic, mild laxative
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing burdock in formulations in the context of: • Skin disorders, particularly eczema, psoriasis and other chronic skin disorders; boils (5) • Disorders requiring increased elimination from the body, such as gout and rheumatism (5)

Contraindications None known. Warnings and Precautions None required. Interactions None known. Use in Pregnancy and Lactation No adverse effects expected. Side Effects None expected when taken within the recommended dose range. Dosage Dose per day^* Dose per week^* 1.5–3.5 ml of 1:2 liquid extract 10–25 ml of 1:2 liquid extract

* This dose range is extrapolated from British Herbal Pharmacopoeia 1983, the British Herbal Compendium 1992, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Skin eruptions, particularly when weak circulation and impaired nutrition exist; eczema, venereal, and leprous disorders, long term use for psoriasis; boils, styes ^1,² • Rheumatism, cystitis, gout ^1,² • Anorexia nervosa, dyspepsia ^1,² • Considered one of the best depuratives ³
Traditional Prescribing	Native Americans used burdock for a wide variety of applications, including as a general tonic and blood purifier and as an ingredient in treatments for stomach pain and during labor. Burdock was official in the USP from 1831 to 1842 and 1851 to 1916 and in the NF from 1916 to 1947 and was listed as a diuretic and diaphoretic.⁴
Pharmacologic Research	• Burdock extract antagonized platelet-activating factor in vitro.⁵ • Burdock extract has demonstrated free-radical scavenging activity in vitro and inhibited carrageenan-induced edema and carbon tetrachloride–induced hepatotoxicity in vivo after injection.⁶ Isolated caffeoylquinic acid derivatives from burdock have been verified as antioxidants.⁷ • Methanol extract of burdock administered by injection demonstrated antitumor activity.⁸
Clinical Studies	No clinical studies using burdock have been found.

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