CALENDULA

*Other Common Name:*	Marigold
*Botanical Name:*	Calendula officinalis
*Family:*	Compositae
*Plant Part Used:*	Flower

PRESCRIBING INFORMATION

Actions	Vulnerary, antiinflammatory, lymphatic, styptic (hemostatic), antimicrobial, antiviral (topically), antifungal (topically)
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing Calendula in formulations in the context of: • Internal and topical treatment for inflammation of the oral and pharyngeal mucosa (4) • Internal treatment for gastric and duodenal ulcers; enlarged or inflamed lymph nodes, acne, sebaceous cysts (5) • Internal treatment for spasmodic conditions, including dysmenorrhea (5) • Topical treatment for burns (2) • Topical treatment for inflammation of the skin and mucosa, wounds, especially poorly healing wounds (4,5) • Topical treatment for leg ulcers, venous circulatory problems, scalds; to help control bleeding (4) • Topical treatment for eczema, varicose veins, hemorrhoids, acne, vaginal discharges (5)
Contraindications	Known allergy.¹
Warnings and Precautions	The likelihood of Calendula preparations causing a contact allergy is low. However, people with known sensitivity to other members of the Compositae family (e.g., ragweed, daisies, chrysanthemums) should avoid topical application of Calendula or Calendula products.¹ Sensitization to Calendula and allergic contact reactions have been reported.^2,³ Anaphylactic shock after gargling with an infusion of Calendula has also been reported.⁴
Interactions	None known.
Use in Pregnancy and Lactation	No adverse effects expected.
Side Effects	Allergic reaction occurs rarely following topical application.¹
Dosage	*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 1934, the British Herbal Pharmacopoeia 1983, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Enlarged or inflamed lymph nodes, sebaceous cysts, gastric or duodenal ulcer, acute or chronic inflammatory skin lesions ⁵ • Amenorrhea, dysmenorrhea; nosebleed ⁵ • Spasmodic conditions, fever, chronic suppuration, capillary enlargement, varicose veins, chronic ulcers, stubborn acne, splenic and hepatic enlargement ⁶ • Topically for wounds, acne, chaffed skin in infants, cracked nipples, eczema, leg ulcers, varicose veins, hemorrhoids, anal eczema and inflammation, vaginal discharges, lymphadenoma, inflamed skin lesions, conjunctivitis ^5,⁶
Pharmacologic Research	• Various Calendula extracts and Calendula essential oil have demonstrated antibacterial, antifungal, and trichomonacidal activity in vitro.⁷ • Calendula extract enhanced the proliferation of lymphocytes in vitro.⁸ Polysaccharides from Calendula stimulated phagocytosis of human granulocytes in vitro.⁹ This finding may be relevant to topical application. • Calendula flavonoids inhibited the activity of lipoxygenase in vitro.¹⁰ Calendula extract suppressed the inflammatory process and leukocyte infiltration caused by carrageenan and prostaglandin E₁ (route unknown).¹¹ Oral dose of aqueous ethanolic extract of Calendula produced antiinflammatory activity in carrageenan-induced rat paw edema. The activity was much milder than that with indomethacin.¹² • Using the croton oil dermatitis mouse ear model, both the total extract of Calendula and the extract obtained after supercritical carbon dioxide extraction (which contains the lipophilic phytochemicals) demonstrated antiinflammatory activity after topical application. Fractionation and testing revealed that the triterpene alcohols caused the antiinflammatory activity, with the carotenoids and sterols almost inactive.¹³ The most active topical antiinflammatory constituent is the triterpenoid compound faradiol monoester.¹⁴ • Calendula extract has demonstrated angiogenic activity (formation of new blood vessels, such as within a wound) in an in vitro assay. Calendula-treated tissue was positive for hyaluronan, a tissue glycan associated with neovascularization, unlike the control tissue, which lacked the presence of hyaluronan.¹⁵ This finding is possibly relevant to topical use of Calendula. • Topical application of an ointment containing Calendula fractions and allantoin stimulated physiological regeneration and epithelialization in experimentally induced wounds.¹⁶ A Calendula ointment improved wound healing in experimentally induced wounds.¹⁷ Calendula facilitated the collagen maturation phase of wound healing and influenced epithelial cell proliferation and migration.¹⁸ Topical application of a Calendula glycetract had a vasoprotective activity on normal animal skin by decreasing capillary activity.¹⁹ • Antiulcer activity was demonstrated in three experimental models after administrating an isolated saponin from Calendula. Antiinflammatory and sedative activities were also observed.^20,²¹ Fractions isolated from Calendula also showed activity (route unknown).²² • Calendula demonstrated antipyretic and analgesic activities in experimental models (route unknown).²³ • The saponin fraction of Calendula normalized experimentally induced hyperlipidemia after oral administration over a 12-week period ⁷ but was without effect in normolipemia.²⁴ • Oral administration of Calendula extract exhibited antitumor activity in experimentally induced carcinoma.²⁵
Clinical Studies	• An herbal preparation containing Calendula, dandelion, St. John’s wort, lemon balm, and fennel reduced intestinal pain in an uncontrolled trial in patients with chronic colitis. Defecation was normalized in these patients with diarrhea syndrome.²⁶ • Calendula extract accelerated the healing time of an artificially induced skin abrasion in volunteers (most likely by topical application).²⁷ An evaluation of aerosol formulations designed to provide a protective film over wounds in human volunteers found that addition of Calendula tincture was satisfactory at controlling bleeding.²⁸ • In a small, uncontrolled trial, Calendula was successful in treating periodontal inflammation.²⁹ • Calendula ointment has been positively used in uncontrolled trials for treating bedsores, venous circulatory problems, and skin conditions such as leg ulcers and thrombophlebitis.⁷ Calendula demonstrated benefit as an adjuvant therapy for rendering scar tissue more supple in patients with cleft lip and palate who were undergoing dermatography.³⁰ • Calendula gel applied for 13 to 14 days provided good results for the healing of burns and scalds in 30 patients.³¹ The effects of three ointments on managing burns were investigated in a randomized, controlled, multicenter clinical study involving 156 patients. Calendula and the proteolytic ointment showed similar efficacy, both superior to Vaseline. However, the Calendula ointment was better tolerated than the proteolytic ointment.³² • Improved outcomes and faster healing of ulceration were obtained when acyclovir treatment was combined with an herbal formula containing Calendula, burdock, and Geranium robertianum in patients with herpetic keratitis (most likely by topical application).³³ • In Germany, the Commission E supports using Calendula to treat inflammation of the oral and pharyngeal mucosa internally and topically. Externally, Calendula is recommended for poorly healing wounds and leg ulcers.³⁴ • ESCOP recommends Calendula for treating inflammations of the skin and mucosa and as an aid to wound healing.¹

REFERENCES

1 Scientific Committee of the European Scientific Cooperative on Phytotherapy (ESCOP). ESCOP monographs: Calendulae flos. Argyle House, Gandy Street, Exeter, Devon, EX4 3LS, United Kingdom: European Scientific Cooperative on Phytotherapy, ESCOP Secretariat, March 1996.

2 Wrangsjo K, Ros AM, Wahlberg JE. Contact Dermatitis. 1990;22(3):148-154.

3 Hausen BM, Oestmann G. Derm Beruf Umwelt. 1988;36(4):117-124.

4 Goldman II. Klin Med. 1974;52(4):142-143.

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

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

7 Isaac I. Die Ringelblume: Botanik, Chemie, Pharmakologie, Toxikologie, Pharmazie und therapeutische Verwendung; Handbuch für ärzte, apotheker und andere naturwissenschaftler. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 1992.

8 Amirghofran Z, Azadbakht M, Karimi MH. J Ethnopharmacol. 2000;72(1-2):167-172.

9 Varljen J, Liptak A, Wagner H. Phytochem. 1989;28(9):2379-2383.

10 Bezakova L, et al. Pharmazie. 1996;51:126-127.

11 Shipochliev T, Dimitrov A, Aleksandrova E. Vet Med Nauki. 1981;18(6):87-94.

12 Mascolo N, et al. Phytother Res. 1987;1:28-31.

13 Della Loggia R. Z Phytother. 2000;21:149-150.

14 Della Loggia R, et al. Planta Med. 1994;60(6):516-520.

15 Patrick KFM, et al. Phytomed. 1996;3(1):11-18.

16 Klouchek-Popova E, et al. Acta Physiol Pharmacol Bulg. 1982;8(4):63-67.

17 Ansari MA, et al. Indian Vet J. 1997;74(7):594-597.

18 Rao SG, et al. Fitoterapia. 1991;62(6):508-510.

19 Russo M. Riv Ital EPPOS. 1972;54:730.

20 Yatsuno AI, Belova LF, Lipkina GS. Pharmacol Toxicol SSSR. 1978;41:193-198.

21 Iatsyno AI, et al. Farmakol Toksikol. 1978;41(5):556-560.

22 Manolov P, et al. Probl Vatr Med. 1983;11:70-74.

23 Ahmad S, et al. Pak J Sci Ind Res. 2000;43(1):50-54.

24 Wojcicki J, Samochowiec L. Herba Pol. 1980;26:233-237.

25 Boucaud-Maitre Y, Algernon O, Raynaud J. Pharmazie. 1988;43:220-221.

26 Chakurski I, et al. Vutr Boles. 1981;20(6):51-54.

27 Fleischner AM. Cosmet Toiletries. 1985;100:54-55.

28 Garg S, Sharma SN. Pharmazie. 1992;47(12):924-926.

29 Gasiorowska I, et al. Czas Stomatol. 1983;36(4):307-311.

30 van der Velden EM, van der Dussen MFN. J Oral Maxillofac Surg. 1995;53(1):9-12.

31 Baranov AP. Dtsch Apoth Ztg. 1999;139:61-66.

32 Lievre M, et al. Clin Trials Meta-Analys. 1992;28:9-12.

33 Corina P, et al. Oftalmologia. 1999;46(1):55-57.

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

CALIFORNIA POPPY

*Other Common Name:*	Californian poppy
*Botanical Names:*	Eschscholzia californica, Eschscholtzia californica^#
*Family:*	Papaveraceae
*Plant Part Used:*	Aerial parts

# Alternative name.

PRESCRIBING INFORMATION

Actions	Anxiolytic, mild sedative, analgesic, hypnotic
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing California poppy in formulations in the context of: • Painful conditions involving the irritation or stimulation of pain fibers (similar to when morphine or codeine might be used) (5) • Disturbed sleep, in combination with Corydalis cava (3) • Disturbed sleep (5) • Anxiety and conditions in which anxiety plays a major role (6,7)
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. Whether California poppy will interfere with standard drug tests for opiate alkaloids is unclear. However, this interference is unlikely.
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 traditional Western herbal medicine and the author’s education and experience.¹

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Reducing pain and producing calm sleep without the dangers of opiates ² • Enhancing sleep, particularly for children with whooping cough ³ • Relieving pain of colic in children ⁴ • Migraine, nervous bowel, neuralgia, anxiety, depression, stress ¹ • Topically for treating sores and ulcers ⁴
	Native Americans and native Hispanics used the aerial parts, leaves, or flowers of California poppy for sedative and analgesic activity, to promote sleep, and for relief of toothache, particularly in children.⁴
	California poppy was of interest to medical practitioners of the United States in the late nineteenth century, with the liquid extract entered into the Park-Davis catalog in 1890. California poppy was referred to in 1892 as an “excellent soporific (sleep inducing) and analgesic, above all harmless” and in 1893, reporting that,“…the effect produced by Eschscholtzia californica upon patients is the same as that of morphine, without the inconveniences of the latter drug.”⁵
Pharmacologic Research	The aerial parts of California poppy contain isoquinoline alkaloids (mainly eschscholtzine and californidine, with smaller amounts of sanguinarine and chelerythrine)⁶ and flavonol glycosides.⁷ • California poppy extract inhibits the enzymatic degradation of catecholamines and the synthesis of epinephrine (adrenaline) in vitro. Preserving high levels of catecholamines may explain the sedative and antidepressant activity of California poppy.⁸ An extract formula containing 80% California poppy and 20% Corydalis cava has demonstrated the ability to interact with opiate receptors in vitro,⁹ which indicates potential analgesic activity. • Alkaloids from California poppy enhanced gamma-aminobutyric acid (GABA) binding to rat brain synaptic membrane receptors. This finding may indicate a benzodiazepine-like activity.¹⁰ Constituents of California poppy exhibited dose-dependent binding to benzodiazepine receptors and displaced the benzodiazepine flurazepam from the receptor.¹¹ • A sedative effect was observed for California poppy extract after injection in experimental models in terms of both behavioral effects and promotion of sleep.^12,¹³ At lower doses, an anxiolytic effect was observed.¹² Sedative effects have also been observed after treatment with high oral doses.¹⁴ The sedative and anxiolytic effects of California poppy are most likely linked to benzodiazepine-receptor activation because they were antagonized by the benzodiazepine-receptor antagonist flumazenil in vivo (by injection).¹⁵ • Isoquinoline alkaloids are known to possess in vivo sedative activity.⁹ • Muscle relaxant and analgesic activities have been reported in vivo,¹¹ although no muscle relaxant activity was observed in vivo in a later study. Dose-dependent peripheral analgesic activity was demonstrated for California poppy in vivo (by injection), but central analgesic activity was not recorded.¹⁵ • California poppy tincture inhibited experimentally induced contractions of isolated smooth muscle.¹³ • Two alkaloids isolated from California poppy, chelerythrine and sanguinarine, exhibited affinity for vasopressin receptors and demonstrated competitive inhibition of vasopressin binding in vitro.¹⁶ Substances that have this activity have been used pharmacologicly as renal agents, vasoconstricting agents, and hemostatics.
Clinical Studies	• Single administration of a California poppy extract (equivalent to 6.7 g of herb) to volunteers resulted in a quantitative electroencephalographic (EEG) recording that was distinguishable from that obtained from placebo. Results from the self-rating assessment of alertness, however, did not differ from placebo.¹⁷ An acute sedative effect was not demonstrated, but analysis after ongoing administration may demonstrate a sedative effect. • In two controlled clinical trials, the combination of California poppy and Corydalis cava normalized disturbed sleeping behavior without evidence of carry-over effects or addiction. This preparation consisted of alcoholic extracts of California poppy (standardized for protopine) and Corydalis (standardized for bulbocapnine) in the ratio of 4:1. The dosage was not defined.¹⁴

REFERENCES

1 Bartram T. Encyclopedia of herbal medicine, ed 1. Dorset, England: Grace Publishers, 1995.

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

3 Cheney RH. Quart J Crude Drugs. 1963;3:413-416.

4 Brinker FJ. Eclectic dispensatory of botanical therapeutics, vol 2 . Eclectic Medical Publications, Sandy, Oregon, 1995.

5 Davis GS. The pharmacology of the newer materia medica. Davis, Detroit, 1892. Bender GA. Pharm Hist. 1980;22(2):49-59.

6 Tome F, Colombo ML, Caldiroli L. Phytochem Anal. 1999;10:264-267.

7 Beck MA, Haberlein H. Phytochem. 1999;50(2):329-332.

8 Kleber E, et al. Arzneim Forsch. 1995;45(2):127-131.

9 Reimeier C, et al. Arzneim Forsch. 1995;45(2):132-136.

10 Kardos J, Blasko G, Simonyi M. Arzneim Forsch. 1986;36(6):939-940.

11 Rolland A. Doctoral thesis, University of Metz, France, 1988. Cited in Schafer HL et al. Arzneim Forsch. 1995;45(2):124-126.

12 Rolland A, et al. Planta Med. 1991;57(3):212-216.

13 Vincieri FF, et al. Pharmacol Res Commun. 1988;20(suppl 5):41-44.

14 Schafer HL, et al. Arzneim Forsch. 1995;45(2):124-126.

15 Rolland A, et al. Phytother Res. 2001;15:377-381.

16 Granger I, et al. Planta Med. 1992;58(1):35-38.

17 Schulz H, Jobert M, Hubner WD. Phytomed. 1998;5(6):449-458.

CASCARA

*Other Common Name:*	Cascara sagrada
*Botanical Names:*	Rhamnus purshiana, Rhamnus purshianus,^# Frangula purshiana^#
*Family:*	Rhamnaceae
*Plant Part Used:*	Bark

# Alternative name.

PRESCRIBING INFORMATION

Actions	Laxative
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing cascara in formulations in the context of: • Constipation,^* flatulence, abdominal fullness, in combination with boldo (3) • Dyspepsia,^* stimulating gastric secretion, loss of appetite, asthenia, postprandial bloating, coated tongue, itching of skin, in combination with gentian, rhubarb, and boldo (3) • Headache resulting from constipation or intestinal weakness (5) • Conditions other than constipation in which easy defecation with a soft stool is desirable, such as with hemorrhoids and anal fissure (5) • Gastrointestinal conditions with hepatic involvement (5)
Contraindications	Intestinal obstruction,¹ intestinal inflammation, such as Crohn’s disease, ulcerative colitis, and appendicitis; abdominal pain of unknown origin. Children under 12 years of age should not be prescribed cascara.²
Warnings and Precautions	Although short-term use of anthraquinone glycoside–containing laxatives is generally regarded as safe, long-term use is not recommended.³ Stimulating laxatives should not be used over an extended period (more than 2 weeks) without medical advice. Using stimulating laxatives longer than is recommended can lead to intestinal sluggishness, although concurrent intake of fiber in sufficient quantities of water can counteract this condition. Cascara should be used only if no benefit can be obtained through change of diet or use of bulk-forming products.² As with all laxatives, cascara should not be prescribed when any undiagnosed acute or persistent abdominal symptoms are present.⁴ Fresh or inadequately prepared cascara bark should not be used because severe vomiting and intestinal spasm can result.²
Interactions	Anthraquinone glycoside–containing laxatives may potentially decrease the transit time of concomitantly administered oral drugs and thereby decrease their absorption.⁵ Excessive use of cascara can cause disturbance of fluid and electrolyte balance (especially potassium deficiency). Potassium deficiency potentiates the action of cardiac glycosides ⁵ and interferes with antiarrhythmic drugs.² Simultaneous application of thiazide diuretics, corticosteroids, or licorice will increase potassium loss.^2,⁴ Speculations suggest that abuse of laxatives such as senna (Cassia spp.) may potentiate the development of analgesic nephropathy (resulting from dehydration).⁵
Use in Pregnancy and Lactation	According to the British Herbal Compendium, cascara is contraindicated in pregnancy and lactation.¹ However, this caution seems excessive provided that the dosage recommendations here are observed. Doses that cause an excessively loose stool should not be used during pregnancy.
Side Effects	Cramplike discomfort of the gastrointestinal tract may occur at normal therapeutic doses. These cases require a dose reduction.² Diarrhea resulting from abuse of cascara has been reported.⁶ Long-term use or abuse may cause disturbances of electrolyte balance, including potassium deficiency, which can lead to disorders of heart function and muscular weakness. A harmless pigmentation of the intestinal mucosa (pseudomelanosis coli) may occur with chronic use and usually reverses after discontinuing cascara.² Chronic intake of anthraquinone laxatives has been associated with an increased risk of colorectal cancer,³ although this connection has been debated.^7,⁸ A case of cascara-induced intrahepatic cholestasis causing portal hyper-tension has been reported. The dosage was one capsule three times per day for 3 days. Each capsule contained 425 mg of aged cascara bark, standardized to 5% cascarosides (1.3 g bark containing 64 mg cascaro-sides per day).⁹
Dosage	*Dose per day^*	*Dose per week^*
	3–8 ml of 1:2 liquid extract	20–55 ml of 1:2 liquid extract

* Cascara has also been used in traditional herbal medicine for treating constipation and dyspepsia and is recommended by both the Commission E and ESCOP for the short-term treatment of constipation. (4,5)

** This dose range is extrapolated from the British Pharmaceutical Codex 1934, the British Pharmacopoeia 1932, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Constipation,¹⁰ particularly when habitual or chronic in nature and when a tonic for the intestines is required¹¹ • Dyspeptic conditions related to constipation and caused by intestinal weakness; headache resulting from similar causes ¹¹ • Loss of tone in the rectum ¹¹ • Conditions in which a soft stool is desirable, such as anal fissure or hemorrhoids ¹ • Rheumatism;gastric, duodenal, or biliary catarrh with jaundice; chronic diseases of the liver ^11,¹²
Traditional Prescribing	Native Americans used cascara as a cathartic. Native South Americans also used cascara.¹³
Pharmacologic Research	Key constituents of cascara bark include hydroxyanthracene derivatives in a complex mixture (approximately 8%) consisting mainly of anthrone glycosides, especially cascarosides. Other constituents include aloins, deoxyaloins, and O-glycosides of the anthraquinones aloe-emodin, emodin, and chrysophanol.^1,¹⁴ • The hydroxyanthracene derivatives are carried unabsorbed to the large bowel, where metabolism via glycosidases from intestinal flora results in the formation of the active aglycones.^3,¹⁵ (Because of this metabolism, defecation occurs several hours after ingestion.) These aglycones exert their laxative effect by local activity in the intestine by the following mechanisms:modification of intestinal motility (by stimulating intestinal muscle) and accumulation of fluid.⁸ The increase in motility is a faster response than is the effect resulting from the increase in fecal water. A number of chemical mediators are implicated in producing these effects, including release of prostaglandins,¹⁶ inhibition of intestinal tone and segmentation,⁸ and production of high concentrations of nitric oxide synthase (which evokes net intestinal fluid secretion).¹⁷ • After absorption, the anthraquinones are transformed mainly to their corresponding glucuronide and sulfate derivatives, which finally appear in urine and bile. Therapy with anthraquinone glycosides such as those found in cascara and senna is regarded as preferable to therapy with free anthraquinones because the glycosides are less readily absorbed from the gastrointestinal tract and are active at much lower doses.¹⁵ Anthraquinone glycosides hence have lower potential toxicity. • The addition of a preparation containing Curcuma aromatica rhizome, whole roots of Curcuma amara, and cascara to a high-cholesterol diet was found to lower both serum and liver cholesterol in rats.¹⁸
Clinical Studies	• A preparation containing cascara, gentian, rhubarb, and boldo was tested in 24 healthy volunteers and in 80 patients with mild gastroin-testinal disturbances. The herbal preparation induced a significant increase in salivary secretion from 1 to 30 minutes after oral administration, similar to the active control (citric acid) and unlike placebo or placebo plus alcohol. In this double-blind study, the herbal preparation was significantly better than placebo for the following symptoms: asthenia, loss of appetite, coated tongue, postprandial bloating, difficult digestion, constipation, flatulence, abdominal fullness, and itching of skin. The test preparation was more efficacious than the two pairs of its components (cascara and boldo; gentian and rhubarb).¹⁹ The following herb equivalents were probably administered for the paired preparations:cascara (200 mg/day) and boldo (100 mg/day);gentian (40 mg/day) and rhubarb (200 mg/day). • A survey of 3257 elderly patients admitted to 58 hospitals in Italy in 1991 recorded that plant anthranoid laxatives were the second most frequently prescribed laxative (1.9% in hospital, 3.3% prehospital).²⁰ • In Germany, the Commission E supports using cascara to treat constipation.² • ESCOP recommends cascara for short-term use in cases of occasional constipation.⁴ • Cascara has remained official in the USP since the first entry in early 1890 and is currently official in the USP24-NF19.

REFERENCES

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

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

3 van Gorkom BA, et al. Aliment Pharmacol Ther. 1999;13(4):443-452.

4 Scientific Committee of the European Scientific Cooperative on Phytotherapy [ESCOP]. ESCOP monographs: Rhamni purshiani cortex. Argyle House, Gandy Street, Exeter, Devon, EX4 3LS, United Kingdom: European Scientific Cooperative on Phytotherapy, ESCOP Secretariat, June 1997.

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

6 Cummings JH, et al. Br Med J. 1974;1:537-541.

7 Nusko G, et al. Gut. 2000;46(5):651-655.

8 Mascolo N, et al. Phytother Res. 1998;12(supp 1):S143-S145.

9 Nadir A, Reddy D, Van Thiel DH. Am J Gastroenterol. 2000;95(12):3634-3637.

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

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

12 Ellingwood F, Lloyd JU. American materia medicam, therapeutics and pharmacognosy, ed 11. Portland: Eclectic Medical Publications, 1983.

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

14 Wagner H, Bladt S. Plant drug analysis: a thin layer chromatography atlas, ed 2. Berlin: Springer-Verlag, 1996.

15 de Witte P, Lemli L. Hepatogastroenterol. 1990;37(6):601-605.

16 Geboes K. Verh K Acad Geneeskd Belg. 1995;57(1):51-74.

17 Izzo AA, Mascolo N, Capasso F. Dig Dis Sci. 1998;43(8):1605-1620.

18 Beynen AC. Artery. 1987;14(4):190-197.

19 Borgia M, et al. Curr Ther Res. 1981;29(3):525-536.

20 Pahor M, et al. Aging (Milano). 1995;7(2):128-135.

CAT’S CLAW

*Other Common Name:*	Uña de gato
*Botanical Name:*	Uncaria tomentosa
*Family:*	Rubiaceae
*Plant Part Used:*	Stem bark

PRESCRIBING INFORMATION

Actions	Immune enhancing, antiinflammatory, antioxidant
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing cat’s claw in formulations in the context of: • Poor immunity, tendency to infections (7) • Inflammatory conditions such as arthritis, gastritis, cystitis (6) • Convalescence, debility (6) • Adjuvant therapy for cancer (3,6) • HIV infection, AIDS (4)
	As cat’s claw has been traditionally used as a tonic (6) and may also be used to treat other health issues requiring this action, including chronic fatigue syndrome.
Contraindications	None known.
Warnings and Precautions	None required.
Interactions	None known.
Use in Pregnancy and Lactation	Cat’s claw should be used with caution in pregnancy and lactation. (The root of Uncaria tomentosa has been used traditionally as a contraceptive; pharmacologic results have demonstrated an antifertility effect in one animal model.¹ Oral use of the bark decoction is traditionally prescribed in Bolivia for irregular menstruation.²)
Side Effects	Diarrhea and indigestion have occurred in several patients taking cat’s claw. In one case, a high (undefined) dose had been consumed.³ Acute renal failure caused by “cat’s claw” was reported in a 35-year-old Peruvian female with systemic lupus erythematosus (SLE). The contents of the capsules were not analyzed, and the duration of treatment was not stated. One month after discontinuing the herbal preparation, her condition had improved. The patient in all likelihood experienced an idiosyncratic adverse reaction to the herbal preparation.⁴
Dosage	*Dose per day^	*Dose per week^
	4.5–11.0 ml of 1:2 liquid extract	30–75 ml of 1:2 liquid extract
	It is recommended that only the pentacyclic oxindole alkaloid-predominant type of cat’s claw be used in therapy.

* This dose range is extrapolated from traditional use of decoction of the bark.³

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Peruvian medicinal uses include degenerative processes (e.g., cancer), inflammatory conditions (e.g., arthritis, gastritis, inflammation of the genitourinary tract and skin), gastric ulcers, diabetes, asthma, convalescence, and debility.^3,⁵ Cat’s claw is also regarded in traditional Peruvian medicine as a tonic or restorative.³ Cat’s claw is one of the powerful plants that the Asháninka priests exclusively used to eliminate disturbance in the communication between body and spirit.⁶
Pharmacologic Research	Cat’s claw stem bark contains a number of oxindole alkaloids.⁷ Two different chemotypes of U. tomentosa that have been identified are likely to have distinctly different pharmacologic properties. One chemotype contains only, or predominantly, pentacyclic oxindole alkaloids (POA);the other contains POA and significant quantities of tetracyclic oxindole alkaloids (TOA). Intriguingly, indigenous priests are said to be able to identify the correct chemotype and harvest exclusively the chemotype containing POA, even though the two chemotypes are botanically identical.^6,⁷ • Cat’s claw extract has exhibited antioxidant activity in vitro⁸ and antiinflammatory activity in experimental models after oral administration.⁹^–¹¹ Results of an in vitro study suggested that the antiinflammatory action may be a result of immunomodulation via suppression of tumor necrosis factor-alpha synthesis.¹² • Cat’s claw extract has significantly stimulated interleukin-1 and interleukin-6 production in vitro.¹³ Cat’s claw extracts and POA stimulated phagocytosis in vitro and by injection.¹⁴^–¹⁶ POA were found to induce endothelial cells to release a factor that influences the proliferation of lymphocytes.^6,¹⁷ The TOA antagonized the effects of the POA.⁶ These studies indicate immune enhancement for the POA chemotypes. • POA demonstrated antitumor activity in vitro.¹⁸ • Cat’s claw was shown to exhibit antiestrogenic effects in vitro.¹⁹
Clinical Studies	• A double-blind, randomized study assessed the effects of a freezedried aqueous extract of U. tomentosa on the mutagenic activity of urine collected from 12 smokers and 12 nonsmokers. A progressive decrease in mutagenic activity in the smokers’ urine was observed with increasing dose.²⁰ • In an uncontrolled trial, 13 patients with HIV took 20 mg/day of an aqueous hydrochloric acid extract of U. tomentosa root (containing 12 mg total POA/g) for 2.2 to 5.0 months. Although the total white blood cell count remained unchanged within the group, results indicated that low values were raised and high values were lowered. The lymphocyte count increased significantly to an average of approximately 35%. However, no significant changes in T4/T8 cell ratios were observed.⁶ • Standardized U. tomentosa root extract was used in a long-term, open study involving 44 patients with AIDS.¹ The daily dose varied from 20 to 60 mg per day (the dried herb equivalent would be much higher), with some patients also taking azidothymidine (AZT). Patients who had CD4 lymphocyte counts of 200 to 500 × 10⁶/L demonstrated the best results for immunologic parameters: • CD4 cells increased significantly for the first year of therapy, and the increase persisted for the first 3 years. Patients continued to show stable counts for as long as 4 and 5 years after beginning treatment. • p24 antigen levels decreased. • B lymphocyte counts increased.

REFERENCES

1 Jones K. Cat’s claw: healing vine of Peru. Seattle: Sylvan Press, 1995.

2 Bourdy G, et al. J Ethnopharmacol. 2000;70(2):87.

3 Obregón Vilches, Lida E. Cat’s claw: Uncaria genus. Botanical, chemical, and pharmacological studies of Uncaria tomentosa and Uncaria guianensis. Lima: Instituto de Fitoterapia Americano, 1995.

4 Hilepo JN, Bellucci AG, Mossey RT. Nephron. 1997;77(3):361.

5 Maxwell N. Witch doctor’s apprentice, ed 3. New York: Citadel Press, 1990.

6 Keplinger K, et al. J Ethnopharmacol. 1999;64:23.

7 Laus G, Brossner D, Keplinger K. Phytochemistry. 1997;45(4):855.

8 Desmarchelier C, et al. Phytother Res. 1997;11(3):254.

9 Sandoval M, et al. Ailment Pharmacol Ther. 1998;12(12):1279-1289.

10 Miller MJS, et al. Peditr Res. 1999;45:114A.

11 Aquino R, et al. J Nat Prod. 1991;54(2):453-459.

12 Sandoval M, et al. Free Radic Biol Med. 2000;29(1):71-78.

13 LeMaire I, et al. J Ethnopharmacol. 1999;64(2):109-115.

14 Wagner H, et al. Planta Med. 1985;51(2):139.

15 Wagner H, Kreutzkamp B, Jurcic K. Planta Med. 1985;51(5):419.

16 United States Patent 5302611, April 12, 1994.

17 Wurm M, et al. Planta Med. 1998;64(8):701-704.

18 Stuppner H, et al. Planta Med. 1993;59(Suppl):A583.

19 Salazar EL, Jayme V. Proc West Pharmacol Soc. 1998;41:123-124.

20 Reinhard KH. J Altern Complement Med. 1999;5(2):143-151.

CELERY SEED

*Botanical Name:*	Apium graveolens
*Family:*	Umbelliferae
*Plant Part Used:*	Fruit (sometimes referred to as seed)

PRESCRIBING INFORMATION

Actions	Diuretic, antiinflammatory, antirheumatic
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing celery seed in formulations in the context of: • Relief of osteoarthritis and rheumatism (4,5) • Prevention of gout (5)
Contraindications	No evidence has been found that celery seed is contraindicated in pregnancy. This attribution comes from the mistaken assumption that the essential oil contains significant levels of apiol.
Warnings and Precautions	Caution is advised in kidney disorders, in particular inflammation of the kidneys, because the essential oil may increase the inflammation by causing epithelial irritation.^1,²
Interactions	None known.
Use in Pregnancy and Lactation	No adverse effects expected.
Side Effects	Allergic reaction is possible but rare.¹ The furanocoumarins in combination with ultraviolet light may cause photodermatitis.²
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