AGRIMONY -- Agrimonia eupatoria L. (Rosaceae) ++

HERBAL

MEDICINAL

PLANT

 

 

 

 

 

 

 

 

 

 

 

                                                                             

   

   

 

AGRIMONY  

Agrimonia eupatoria  L. (Rosaceae) ++

 

 BY

 

RETTODWIKART THENU

AGRIMONY  

 (a’gruh-mow-nee)

 

Agrimonia eupatoria  L. (Rosaceae) ++

 

SUMMARY AND PHARMACEUTICAL COMMENT

Limited information is available on the chemistry and pharmacological properties of agrimony. Clinical investigation of agrimony is extremely limited and rigorous studies are needed to establish the efficacy of agrimony. The tannin constituents may justify the astringent activity attributed to the herb. In view of the lack of toxicity data, excessive use of agrimony and use during pregnancy and breastfeeding should be avoided. The potential for preparations of agrimony to interfere with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered.

 

OTHER COMMON NAMES

Stickwort, Cocklebur, Liverwort, Common Agrimony, Philanthropos, Church Steeples, Sticklewort

Ackerkraut, Agronmonia, Funffing, Funffinger Kraut, Langyacao, Longyacao, Potter’s Piletabs.

 

DESCRIPTION

MEDICINAL PARTS: The drug consists of the flowering plant, which is cut a few fingers width above the ground and dried.

FLOWER AND FRUIT: The flowers are yellow, arranged along small, spike-like racemes. They have an epicalyx and 5 sepals, 5 ovate petals. 5 to 20 stamens and 2 ovaries. The calyx is rough-haired with deep furrows. The fruit is obconical and thorny (burdocks).

LEAVES, STEM AND ROOT: The plant is fifty to 100 cm high, with a villous, erect stem. The leaves are alternate and irregularly pinnate. The leaflets are deeply serrate and downy beneath.

CHARACTERISTICS: Agrimony has a slight pleasant fragrance and a tangy, bitter taste.

HABITAT: The plant is indigenous to middle and northern Europe, temperate Asia and North America.

PRODUCTION: Agrimony herb consists of the dried, aboveground parts of Agrimonia eupatoria and/or Agrimonia procera gathered just before or during flowering, as well as its preparations in effective dosage.

 

SPECIES (FAMILY)

Agrimonia eupatoria L. (Rosaceae)

Agrimonia eupatoria, Agrimonia pilosa var., Agrimonia Japonica

 

SYNONYM(S)

Agrimonia

 

ORIGIN

Agrimony is grown in Asia, Europe, and the United States.

 

PHARMACOPODIAL AND OTHER MONOGRAPHS

BHP 1996 (G9)

BP 2007(G84)

Complete German Commission E(G3)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

 

LEGAL CATEGORY (LICENSED PRODUCTS)

GSL (G37)

 

CONSTITUENTS

The following is compiled from several sources, including References 1 and 2, and General Reference G2.

Acids Palmitic acid, salicylic acid, silicic acid and stearic acid.

Flavonoids Apigenin, luteolin, luteolin-7-glucoside, quercetin, quercitrin, kaempferol and glycosides.(3)

Tannins 3–21%. Condensed tannins in herb; hydrolysable tannins (e.g. ellagitannin).

Vitamins Ascorbic acid (vitamin C), nicotinamide complex (about 100–300 mg/g leaf), thiamine (about 2 mg/g leaf) and vitamin K.

Other Constituents Bitter principle, triterpenes (e.g. a-amyrin, ursolic acid, euscapic acid), phytosterols and volatile oil 0.2%.

 

USES

USES

Agrimony in the form of tea or gargle is used to treat a sore throat. Agrimony may be used topically as an astringent, to help stop bleeding, and to treat cuts and abrasions. Little research exists on its use in humans. Some herbalists report that agrimony has antiasthmatic, sedative, antiinfl ammation, decongestant, and diuretic properties, although no scientific studies support these claims. Diuretic and uricosuric use have been reported (Giachetti et al, 1986). Most other uses are based solely on anecdotal reports. However, agrimony has been used for decades as a hemostatic to promote blood coagulation. It has been used to decrease vaginal bleeding and discharge and for urinary tract infections. Ointments made from agrimony may shrink hemorrhoids and soothe sores, insect bites, and athlete’s foot. It may be used for its antibacterial action to treat vaginal trichomoniasis.

Agrimony is used in combination with licorice root, fennel seed, and eyebright as an eyewash (Mills, Bone 2005).

 

INVESTIGATIONAL USES

Agrimonia pilosa is currently used in China to treat cancer (Sugi, 1997). One study (Min et al, 2001) showed an inhibitory effect against HIV-1. Another study (Venskutonis, 2007; Correia, 2007) showed activity of agrimony as a radical scav enger and antioxidant.

 

FOOD USE

Agrimony is listed by the Council of Europe as a natural source of food flavouring (category N2). This category indicates that  agrimony can be added to foodstuffs in small quantities, with a possible limitation of an active principle (as yet unspecified) in the final product.(G16)

 

HERBAL USE

Agrimony is stated to possess mild astringent and diuretic properties.(1) It has been used for diarrhoea in children, mucous colitis, grumbling appendicitis, urinary incontinence, cystitis, and as a gargle for acute sore throat and chronic nasopharyngeal catarrh.(G2, G7)

 

Figure 1. Agrimony (Agrimonia eupatoria).

 

 

Figure 2. Agrimony – dried drug substance (herb).

 

ACTIONS

Most of the research on agrimony was done in the 1950s and 1960s. Very little research has been done in recent years.

Hemostatic Action

Some early studies reported that agrimony promotes blood coagulation. In one study, when Agrimonia was given to rabbits intravenously, platelets and calcium increased and clotting time decreased (Yao et al, 1957). However, other early studies reported that A. pilosa does not promote coagulation but instead increases clotting time. Even at high doses (15 mg/kg), agrimony given intravenously to rabbits had this result (Qu et al, 1957). Frogs treated with agrimony experienced elevated blood pressure and respiration, as well as increased heart rate and cardiac contractility (Wu et al, 1941). Mice treated with agrimony experienced prolonged tail bleeding time and, as a result of antiplatelet action, acute pulmonary thromboembolism (Hsu et al, 1987). This conflicting research indicates that strict controls need to be in place in order to replicate these studies.

Antiinflammatory Action

The antiinfl ammatory action of agrimony has been demonstrated on rabbits. In one study, when the irritated conjunctivas of rabbits were treated with agrimony, a defi nite decrease in infl ammation occurred. This effect may have resulted from high levels of the tannin phlobaphere, a potent astringent in the herb (Eda, 1972).

Antibacterial Action

A study of 40 women with vaginal trichomoniasis showed that a decoction of agrimony extract inhibited the growth of gram-positive bacteria (Wang et al, 1953). When a 200% concentrated extract was applied over the vaginal wall and a cotton ball treated with the herb was inserted into the vagina for 3 to 4 hours, 37 of the women were cured with one treatment. In another study using a decoction of Agrimonia eupatoria, agrimony inhibited the growth of Mycobacterium tuberculosis (Peter-Horvath, 1965) and even destroyed streptomycin- and paraaminosalicylic- acid–resistant strains. The only strains not affected were those resistant to isoniazid.

Other Actions

One study showed that A. pilosa inhibited carcinoma in laboratory animals, but not in human fi broblasts (Kampo Kenkyu,1979). Another study demonstrated the antitumor activity of agrimonii, one of the tannins in agrimony, on test mice (Miyamoto et al, 1985, 1988). A single dose of 10-30 mg/kg resulted in almost complete resolution of the tumor. Yet another study (Min et al, 2001) evaluated several Korean plants for anti-HIV-1 activity. Agrimonia pilosa showed anti-HIV-1 activity. Still another study identifi ed antihyperglycemic insulin-releasing and insulin-like activity of agrimony (Gray, Flatt, 1998).

 

PHARMACOLOGICAL ACTIONS

IN VITRO AND ANIMAL STUDIES

Significant uricolytic activity has been documented for agrimony infusions and decoctions (15% w/v), following their oral administration to male rats at a dose of 20 mL/kg body weight (equivalent to 3 g dry drug).(4) Diuretic activity was stated to be minimal and elimination of urea unchanged. A hypotensive effect in anaesthetised cats has been documented for an agrimony extract given by intravenous injection; blood pressure was lowered by more than 40%.(5) Marked antibacterial activity against Staphylococcus aureus and a-haemolytic streptococci has been reported for agrimony.(6) An aqueous ethanol extract of the herb was tested for immunomodulative activity in the peritoneal cavities of mice.(7) Immunostimulant activity resulted in an increase in phagocytic activity and increases in the activities of lysozyme and peroxidase. Agrimonia eupatoria given in the diet of mice for 12 days prior to intraperitoneal administration of streptozotocin resulted in a reduction in hyperglycaemia.(8) Further investigation revealed stimulation of 2-deoxyglucose transport, glucose oxidation and incorporation of glucose into glycogen in mouse abdominal muscle. An aqueous extract (0.25–1 mg/mL) stimulated insulin secretion from a BRIN-BD11 pancreatic B cell line.(9) These findings demonstrate that A. eupatoria aqueous extract given orally to mice has antihyperglycaemic, insulin-releasing and insulin-like activity.(9)

A related species, A. pilosa, has also been investigated. In vivo antitumour activity in mice has been attributed to the tannin agrimoniin(10) which has not been reported as a constituent of A. eupatoria. Agrimoniin was administered intraperitoneally into ascites-type and solid tumours in rodents.(11) At doses of greater than 10 mg/kg, given before or after intraperitoneal inoculation with MM2 cells, it completely rejected tumour growth in mice.(11)

Solid tumours of MH134 and Meth-A were inhibited by agrimoniin, and the number of peripheral blood cells was increased, indicating that agrimoniin has antitumour activity and that it exerts its effect by enhancing the immune response. In vitro studies have reported that agrimoniin induces the cytotoxicity of murine peritoneal exudate cells,(12) and that it induces interleukin 1 in human peripheral blood mononuclear cells and in mouse adherent peritoneal exudate cells in vivo.(13) Several phloroglucinols isolated from A. pilosa have demonstrated activity against Staphylococcus aureus,(14) and a methanol extract of the herb inhibited HIV-1 protease activity.(15) An aqueous suspension of A. pilosa herb (1 mg/kg and 5 mg/kg) given orally or intraperitoneally significantly reduced blood glucose concentrations in streptozotocin-induced diabetic rats.(16) An aqueous extract of the aerial parts of A. eupatoria inhibited the secretion of hepatitis surface antigen in an in vitro system using HepG2.2.15 cells, which produce complete virion particles and viral proteins.(17)

 

CLINICAL STUDIES

Clinical investigation of the effects of agrimony is extremely limited and rigorous randomised controlled clinical trials are needed. The use of agrimony infusions to treat cutaneous porphyria in a group of 20 patients has been described. Improvements in skin eruptions, and a decrease in serum iron concentrations and urinary porphyrins were observed,(18) although the methodological limitations of this small, uncontrolled study do not allow any conclusions to be made on the effects of agrimony.

A combination herbal preparation containing agrimony has been used in 35 patients suffering from chronic gastroduodenitis.(19) After 25 days of therapy, 75% of patients claimed to be free from pain, 95% from dyspeptic symptoms and 76% from palpitation pains. Gastroscopy was said to indicate that previous erosion and haemorrhagic mucous changes had healed. However, the methodological limitations of this small, uncontrolled study do not allow any conclusions to be made on the effects of agrimony.

 

ACTIVITIES

Aggregant (1; CRC; PH2; ZUL); Antibacterial (1; FNF); Antidiabetic (1; APA); Antiinflammatory (1; BIS); Antipyretic (1; CRC); Antiseptic (1; APA); Astringent (2; APA; KOM); Antiviral (1; APA; PNC); Candidicide (1; APA); Cholagogue (1; PNC); Depurative (f; CRC); Diuretic (1; PNC); Emmenagogue (f; CRC); Fungicide (1; APA); Hemostat (1; PH2); Hypoglycemic (1; APA); Litholytic (f; CRC); Sedative (f; CRC); Stomachic (f; WBB); Tonic (1; APA; CRC; PNC); Uricolytic (1; CAN); Vermifuge (1; CRC; WBB; ZUL); Vulnerary (f; CRC).

 

INDICATIONS

Acne (f; CRC); Anthrax (f; WBB; ZUL); Asthma (f; CRC); Bacteria (1; FNF; ZUL); Bile (f; ZUL); Bleeding (1; CRC; PH2; ZUL); Bronchosis (f; CRC); Cancer (f; JLH); Cancer, bladder (f; JLH); Cancer, breast (f; JLH); Cancer, face (f; JLH); Cancer, ganglion (f; JLH); Cancer, groin (f; JLH); Cancer, joint (f; JLH); Cancer, kidney (f; JLH); Cancer, liver (f; JLH); Cancer, sinew (f; JLH); Cancer, spleen (f; JLH); Cancer, stomach (f; JLH); Cancer, uterus (f; JLH); Candida (1; APA); Carcinoma (f; JLH); Cholecystosis (f; APA); Cholelithiasis (f; ZUL); Cholestasis (f; PH2); Cold (f; CRC; WBB); Condyloma (f; CRC; JLH); Congestion (f; APA); Corn (f; CRC; JLH); Cystosis (f; JLH); Decubitis (f; CRC); Dermatosis (2; APA; CAN; KOM); Diabetes (1; APA); Diarrhea (2; APA; FAD; KOM); Dysentery (1; FNF); Dyspepsia (1; CAN; KOM); Eczema (f; PH2); Enterosis (f; CRC; PH2); Enuresis (f; PH2); Eruption (f; CRC); Fever (1; CRC; FAD); Fungus (1; APA); Gastrosis (f; CAN; KOM); Gastroduodenosis (f; CAN); Gastroenterosis (1; APA; BIS); Gout (f; CRC; FAD); Hemorrhoid (f; CRC; APA); Hematuria (1; CRC); Hepatosis (f; APA; FAD; JLH; WO3); Hyperglycemia (1; APA); Icterus (f; ZUL); Infection (1; APA); Inflammation (1; BIS); Insomnia (f; CRC); Jaundice (f; CRC); Kernel (f; JLH); Kidney Stone (f; APA); Metrorrhagia (1; CRC); Mucososis (1; APA; PHR; PH2); Mycosis (1; APA); Nephrosis (f; JLH; PH2); Nervousness (f; CRC); Neuralgia (f; CRC); Neurosis (f; CRC); Porphyria (f; CAN); Pharyngosis (2; FAD; KOM; PHR; PH2); Psoriasis (f; PH2); Rash (1; APA); Rheumatism (f; CRC); Scirrhus (f; JLH); Sclerosis (f; CRC); Scrotum (f; CRC); Seborrhea (f; PH2); Sinew (f; CRC); Snakebite (f; CRC); Sore (1; APA; JLH); Sore Throat (1; APA; CRC); Splenosis (f; CRC; JLH); Stomatosis (2; KOM; PHR); Stone (f; CRC); Tuberculosis (f; CRC; ZUL); Tumor (f; CRC); Ulcer (1; APA); Uterosis (f; JLH); Varicosis (1; APA); Virus (1; APA; PNC); Wart (f; CRC; JLH); Water Retention (1; PNC); Worm (1; CRC; FAD; PH2; WBB; ZUL); Wound (1; APA; JLH; PH2); Yeast (1; APA).

INDICATIONS AND USAGE

Approved by Commission E:

• Diarrhea

• Inflammation of the skin

• Inflammation of the mouth and pharynx

UNPROVEN USES: Agrimony is used internally for mild, nonspecific, acute diarrhea, cholestasis, inflammation of oral and pharyngeal mucosa, inflammation of kidney and bladder, diabetes and childhood bedwetting; externally for poorly healing wounds, chronic pharyngitis, psoriasis, seborrhoeic eczema as well in hip-baths for lower abdominal conditions.

CHINESE MEDICINE: Agrimony is used as a hemostyptic. It is also used for certain forms of cancer and as an anthelmintic.

 

PRODUCT AVAILABILITY

Gargle, Tablets, Tea, Ointment, Capsules, Poultices, Bath Tonics

PLANT PARTS USED: Flowers, Leaves, Stems

 

DOSAGES

 

DOSAGES

Ophthalmic

·         Adult topical eyewash: 30 g/500 mL licorice root, fennel seed, eyebright, and agrimony (dilution 1:1) (Mills, Bone, 2000)

Sore Throat

·         Adult PO gargle: 3 g in water/day

Other

·         Adult PO tablet: 3 g daily or equivalent (Blumenthal, 1998)

·         Adult PO tea: 3 tsp in 1 cup boiling water, up to 4_/day

·         Adult topical: apply as poultice as needed using 10% water extract

DOSAGES

Dosages for oral administration (adults) for traditional uses recommended in older standard herbal reference texts are given below.

·         Dried Herb   2 – 4 g by infusion three times daily.(G7)

·         Liquid Extract   1 – 3 mL (1 : 1 in 25% alcohol) three times daily.(G7)

·         Tincture   1 – 4 mL (1 : 5 in 45% alcohol) three times daily.(G7)

DOSAGES

·         3 g herb (KOM; PHR); 3–6 g herb (APA); 1–1.5 g (BIS); 2–4 g 3 ×/day (CAN); 1 tsp herb/cup water (RFW);

·         1–3 mL extract (1:1 in 25% ethanol) 3 ×/day (CAN); 2–4 mL liquid herb extract (PNC);

·         1–4 mL tincture (1:5) in 45% alcohol 3 ×/day (CAN).

DOSAGES

Daily Dosage: Internally, the average daily dose is 3 to 6 gram of herb or equivalent preparations. Externally, a poultice prepared from a decoction (10%) several times a day is applied.

 

PRECAUTIONS AND ADVERSE REACTIONS

No health hazards or side effects are known in conjunction with the proper administration of designated therapeutic dosages. Because of the constituent tannins, the intake of larger quantities could lead to digestive complaints and constipation.

CONTRAINDICATIONS, INTERACTIONS, AND SIDE EFFECTS

Class 1 (AHP). None known (Kom; PHR). “Hazards and/or side effects not known for proper therapeutic dosages” (PH2). Excessive doses may interact with anticoagulant, hypotensive, and hypertensive therapies. As with other tannin-rich herbs, “excessive use” should be avoided. In view of the lack of toxicity data, use of agrimony should be avoided during pregnancy and lactation. Reportedly affects the menstrual cycle (CAN).

CONTRA-INDICATIONS, WARNINGS

In view of the tannin constituents, excessive use of agrimony should be avoided.

Drug Interactions In view of the documented pharmacological actions of agrimony, the potential for preparations of agrimony to interfere with other medicines administered concurrently (particularly those with similar or opposing effects) should be considered.

Pregnancy And Lactation Agrimony is reputed to affect the menstrual cycle.(G22) In view of the lack of toxicity data, use of agrimony should be avoided during pregnancy and lactation.

CONTRAINDICATIONS

Until more research is available, agrimony should not be used during pregnancy and breastfeeding, and it should not be given to children. Agrimony should not be used by persons with hypersensitivity to this plant or to roses.

 

SIDE EFFECTS/ADVERSE REACTIONS

CV: Palpitations, fl ushing of the face, hypotension

GI: Upset, constipation

INTEG: Photosensitivity, photodermatitis

SYST: Hypersensitivity, rash, allergic reactions, hypoglycemia

 

INTERACTIONS A

Drug

Anticoagulants (warfarin, heparin): Agrimony may decrease clotting times when used with anticoagulants; avoid concurrent use (PO) (theoretical).

Antihypertensives: Agrimony used wih antihypertensives may increase hypotension.

Antidiabetics: Agrimony may increase hypoglycemic effect; monitor blood glucose (Jellin et al, 2008).

Lab Test

Agrimony decreases glucose test; increases PT, INR, and clotting time.

 

EFFECTS

Agrimony is an astringent.

 

SIDE-EFFECTS, TOXICITY

None documented for A. eupatoria. A polar fraction containing flavonoids and triterpenes, but not tannins, produced a negative result in the Ames test.(1)

In mice, agrimoniin has been documented to cause stretching and writhing reactions when administered by intraperitoneal injection, and cyanosis and necrosis at the site of intravenous injection.(11) These reactions were considered to be inflammatory reactions. The LD50 of agrimoniin in mice has been estimated as 33 mg/kg (by intravenous injection), 101 mg/kg (by intraperitoneal injection), and greater than 1 g/kg (by mouth).(11) Cytotoxic activity has been reported for A. pilosa(10) (see Pharmacological Actions, In vitro and animal studies).

 

CLIENT CONSIDERATIONS

ASSESS

·         Assess the reason the client is using this product.

·         Assess the client for hypersensitivity reactions such as rash or breathing diffi culty. If such reactions are present, discontinue use of agrimony and administer antihistamines.

·         Assess for the use of anticoagulants, antidiabetics, and antihypertensives (see Interactions).

administer

·         Instruct the client to take agrimony PO in tea or tablet form.

·         Instruct the client to dilute the herb in warm water for use as a gargle.

·         Instruct the client to store eyewash frozen in sterile blocks, or use immediately.

·         Advise the client to boil the herb for 10 minutes using low heat and apply as a poultice several times per day.

TEACH CLIENT/FAMILY

·         Until more research is available, caution the client not to use agrimony during pregnancy and breastfeeding and not to give it to children.

·         Inform the client that agrimony may increase hypotension when taken with antihypertensives. It may decrease blood glucose levels when taken with antidiabetics, including insulin. Agrimony may increase the risk of bleeding when taken with anticoagulants.

 

EXTRACTS 

Uricolytic activity demonstrated for 15% infusions ED = 20 mL/kg orl rat (equivalent to 3 g dry drug); hypotensive (ivn cat); bactericidal against Staphylococcus and Streptococcus. The tannin constituent agrimoniin (from A. pilosa) has antitumor activity, perhaps via immunostimulant activity (CAN). Aqueous extracts inhibited Mycobacterium tuberculosis, in vitro, and ethanolic extracts show antiviral activity (PNC). Twenty cutaneous porphyria patients successfully treated with agrimony infusions. Chinese research indicates agrimony increases blood coagulability ~50% (CAN).

 

PREPARATIONS

 

PROPRIETARY SINGLE-INGREDIENT PREPARATIONS

Czech Republic: Nat Repiku Lekarskeho; Repik Lekarsky; Repikovy Caj, Repikova Nat.

 

PROPRIETARY MULTI-INGREDIENT PREPARATIONS

Austria: Amersan; Gallen- und Lebertee St Severin; Novocholin. Czech Republic: Amersan; Cynarosan; Eugastrin; Hemoral; Naturland Grosser Swedenbitter; Nontusyl; Species Cholagogae Planta; Stomaran; The Salvat; Ungolen; Zlucnikova Cajova Smes. France: Tisane Hepatique de Hoerdt. Russia: Herbion Drops for the Gallbladder (Гербион Капли Желчегонные). Spain: Natusor Astringel; Natusor Farinol. UK: Piletabs.

 

 

REFERENCE

 

Barnes, J., Anderson, L. A., and Phillipson, J. D. 2007. Herbal Medicines Third Edition. Pharmaceutical Press. Auckland and London.

 

Duke, J. A. with Mary Jo Bogenschutz-Godwin, Judi duCellier, Peggy-Ann K. Duke. 2002. Handbook of Medicinal Herbs 2nd Ed. CRC Press LLC. USA.

 

Gruenwald, J., Brendler, T., Jaenicke, Ch. 2000.  PDR for Herbal Medicines.  Medical Economics Company, Inc. at Montvale, NJ 07645-1742. USA

 

Linda S-Roth. 2010. Mosby’s Handbook Of Herbs & Natural Supplements, Fourth Edition. Mosby Elsevier. USA

 

 

 

Figure 3. Primary Chemical Components and Possible Actions

(Linda, S-R. 2010)