Tormentil: Herbal Medicines

Printed from: Herbal Medicines. [online] London: Pharmaceutical Press. www.medicinescomplete.com [Accessed on 14 Mar 2012 (GMT)].

Tormentil
Summary and Pharmaceutical Comment
The chemistry of tormentil is well studied and its reported pharmacological actions are generally attributed to its high tannin content. There is little clinical evidence to support the traditional herbal uses of tormentil, although one study described a reduction in the duration of diarrhoea in children. Tormentil may cause gastrointestinal adverse effects such as abdominal discomfort, nausea and heartburn.

Species (Family)
Potentilla erecta (L.) Raeusch. (Rosaceae)

Synonym(s)
Common Tormentil, Erect Cinquefoil, P. tormentilla Stokes., Potentilla, Tormentilla, Tormentilla erecta.

Part(s) Used
Rhizome

Pharmacopoeial and Other Monographs
In BHP 1983 (Potentilla); BP 2011 (Tormentil, Tormentil Tincture). Ph.Eur. 7.2 Tormentil The whole or cut, dried rhizome, freed from the roots, of Potentilla erecta (L.) Raeusch. (P. tormentilla Stokes). Tormentil Tincture is also listed. Tormentil is also included in the Complete German Commission E, HMPC monographs and Martindale 37th edition.

Legal Category (Licensed Products)
Tormentil is included in the GSL.1

Constituents
Tannins 15-20% condensed tannins (proanthocyanidins) and their precursors including different catechins.2, 3, 4 Pharmacopoeial standard, minimum 7% of tannins, expressed as pyrogallol.5 During storage, the catechin tannins may convert to phlobaphenes (tormentilla red).2 Also, 3.5% hydrolysable tannins including agrimoniin (1%) and pentadigalloylglucose.3, 4 Pedunculagin, laevigatin B and laevigatin F (tormentillin) are also present.2, 3, 4
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Tormentil: Herbal Medicines

Triterpenoids Aglycones and their glycosides such as tormentoside (rosamultin).2, 3 Flavonoids Kaempferol, cyanidinglucoside, leucoanthocyanidin.3, 4 Other constituents Phenol carboxylic acids2, 3, 4 and fatty acids.3, 4

Food Use
Tormentil root is listed by the Council of Europe as a natural source of food flavouring (category 5), see Appendix 3.6 Tormentil root is used in alcoholic beverages (200 mg/kg).6

Herbal Use
Tormentil has astringent properties and has traditionally been used for the treatment of unspecified diarrhoeal disorders,7 as an oral rinse for inflammation of the throat and mouth,7, 8 and topically for haemorrhoids8 and wounds such as pressure sores and ulcers.9 The European Medicines Agency Committee on Herbal Medicinal Products (HMPC) has adopted a Community Herbal monograph for tormentil. Under traditional use, the monograph specifies the indications of oral use for ‘symptomatic treatment of mild diarrhoea' and topical use for 'symptomatic treatment of minor inflammations of the oral mucosa'.10

Dosage
Dosages for oral administration (adults) for traditional uses recommended in standard herbal reference texts are given below. Dried rhizome 2-4 g (or by infusion), 3 times a day,8 or 4-6 g daily.7 Liquid extract 2-4 ml (1 : 1 in 25% alcohol), 3 times a day.8 Tincture 2-4 ml (1 : 5 in 45% alcohol), 3 times a day.8

Pharmacological Actions
In vitro and animal studies The non-clinical pharmacological data of tormentil has been reviewed,3 and the following properties noted: Antidiarrhoeal activity Application of 200-800 μg/ml lyophilised hot water tormentil extracts to isolated rabbit colon mucosa increased the prostaglandin E2 stimulated Cl- secretion, in a dose-dependent manner, by 4 to 32%.3
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Tormentil: Herbal Medicines

Anti-ulcerogenic activity Tormentil extracts scavenged superoxide and peroxyl radicals in a dose-dependent manner in cell-freeoxidant-generating systems and reduced oxygen radical release from inflamed human colorectal biopsies.3 Antimicrobial and antiviral activity A number of early in vitro studies have reported antiviral properties of the tannin constituents of tormentil against herpes virus types I and II, influenza virus type A2 and cowpox. Also, in a more recent study, aqueous extracts of nine Potentilla species including P. erecta had high activity against Helicobacter pylori; moderate activity against gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis); and no significant activity against other gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia). The extracts also showed moderate antifungal activity against Candida albicans.3 Anticariogenic activity In addition to a mild antibacterial effect, an aqueous extract of tormentil inhibited insoluble glucan synthesis and mutans streptococci biofilm formation in an in vitro study of anticariogenic activity.3, 11 Anti-inflammatory activity A water extract of tormentil inhibited cyclooxygenase and resulting prostaglandin synthesis and platelet activity factor induced exocytosis.3 Antineoplastic activity Crude ethanolic extracts (40%) of tormentil at concentrations of 10 and 50 μg/ml suppressed cell growth of lymphoma cells in vitro.3 Antioxidant activity Procyanidin oligomers and dimers isolated from tormentil had antioxidative activity and monomers showed less activity. Pentamer and hexamers were reported to have anti-elastase activity. In a study in rats, 0.05 and 0.1 ml per 100 g doses of tormentil tincture (TPTR; 1 : 5) administered intragastrically for 14 days decreased malonaldehyde and endogenic lipids after 3 doses.3 Clinical studies Diarrhoea caused by rotavirus In a double-blind placebo-controlled study in 40 children hospitalised with rotavirus diarrhoea, a tormentil extract reduced the volume of stool output by the second day (26 ml/kg versus 31.5 ml/kg) and shortened the duration of diarrhoea (3 versus 5 days) compared to placebo. All children received oral and/or parenteral rehydration, and those given tormentil required less parenteral fluids. In this study, the tormentil root extract was prepared as an alcohol extract using 1 part of dried root to 10 parts of 40% ethanol. The extract was given at a dose of 3 drops per year of the child's life, which was equivalent to about 1.5 mg/kg of solids, given three times daily.12 Ulcerative colitis In an open, dose-finding, pilot study in 15 patients with active ulcerative colitis, a tormentil extract decreased the disease activity index (activity index based on laboratory findings and symptoms), and reduced stool frequency and the frequency of bloody stools. The best effect was seen at a dose of 2.4 g daily (decreased from active ulcerative colitis into remission); lower doses of 1.2 and 1.8 g daily were less
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Tormentil: Herbal Medicines

effective and a higher dose of 3 g daily provided no additional benefit.13 The tormentil extract used in this study was a commercially available ethanolic drug extract containing 200 mg per capsule (Ratiogast). These promising preliminary findings require confirmation in a placebo-controlled study with endoscopy control.13,
14

Pharmacokinetics In two healthy subjects given a single dose of tormentil extract 2 g (Ratiogast), no tannins or tannin metabolites were detected in serum over an 8-hour period after administration. This suggests that tannins taken orally are not absorbed.13

Side-effects, Toxicity
There is little clinical safety and toxicity data for tormentil and further investigations of these aspects is required. Clinical data In an uncontrolled clinical trial assessing the effect of tormentil on ulcerative colitis, 6 out of 16 patients experienced mild upper abdominal discomfort (stomach discomfort and nausea/fullness), 3 had mild heartburn, and one had mild abdominal cramps. This is likely to be due to the tannin content. One patient did not complete the study because they required hospitalisation for exacerbation of ulcerative colitis, but the relation of this to the tormentil treatment is unclear.13 Preclinical data An aqueous extract of tormentil in doses of 2.5 g/kg and 6.8 g/kg administered by the intragastric route and 3.8 and 14.5 g/kg administered intraperitoneally, did not show any effect on mortality, appearance, behaviour or body weight of rats after 2 weeks and 3 days, respectively. Additionally, no pathological changes were found after macroscopic and microscopic studies of the internal organs.15

Contra-indications, Warnings
The use of tormentil has been contraindicated in patients with hypersensitivity to the active substance10 (i.e. tannins). For diarrhoea, the most important aspect of the treatment is rehydration therapy to avoid dehydration and loss of electrolytes, and is essential whether or not a herbal such as tormentil is also used. Drug interactions None found. However, the potential for preparations of tormentil to interact with other medicines administered concurrently, particularly those with similar or opposing effects should be considered. Tannins might interfere with the absorption of some substances, including iron supplements. The European Medicines Agency Committee on Herbal Medicinal Products (HMPC) recommend separating medicines by one hour to minimise the risk of delayed absorption of concurrently administered medicines.10 Pregnancy and lactation On the basis of the absence of sufficient data, the European Medicines Agency Committee on Herbal Medicinal Products (HMPC) do not recommend the use of tormentil during pregnancy or lactation.10

References
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1. The Medicines (Products other than Veterinary Drugs) (General Sales List), SI No.769: 1984, as amended SI No.1540: 1985; SI No.1129: 1990; and SI No.2410: 1994. 2. Wichtl M (ed.). Herbal Drugs and Phytopharmaceuticals. A handbook for practice on a scientific basis. 3rd edition. Stuttgart: medpharm Scientific publishers, 2004. 3. Tomczyk M, Latté KP. Potentilla – A review of its phytochemical and pharmacological profile. J Ethnopharm 2009; 122: 184–204. 4. European Medicines Agency, Committee on Herbal Medicinal Products (HMPC). Assessment report on Potentilla erecta (L.) Raeusch., rhizome. London, 25 November 2010. EMA/HMPC/5511/2010. Available at http://www.ema.europa.eu (accessed 03-11-11). 5. European Pharmacopoeia, 7th edn. Strasbourg: Council of Europe, 2011. 6. Council of Europe. Natural Sources of Flavourings, Report No.2, 4th edn, Strasbourg, 2007. 7. Blumenthal M et al., eds. The Complete German Commission E Monographs. Austin, Texas: American Botanical Council, 1998. 8. British Herbal Pharmacopoeia. Keighley: British Herbal Medicine Association, 1983. 9. Williamson EM. Potter's Herbal Cyclopaedia. Saffron Waldon: CW Daniel Co., 2003. 10. European Medicines Agency (EMEA), Committee on Herbal Medicinal Products (HMPC). Community Herbal Monograph on Potentilla erecta (L.) Raeusch., rhizoma. London, 25th November 2010. EMEA/HMPC/5513/2010. Available at http://www.ema.europa.eu/ (accessed 14/09/11). 11. Tomczyk M et al. Variation in total polyphenolics contents of aerial parts of Potentilla species and their anticariogenic activity. Molecules 2010; 15: 4639–4651. (PubMed) 12. Subbotina MD et al. Effect of oral administration of tormentil root extract (Potentilla tormentilla) on rotavirus diarrhea in children: a randomized, double blind, controlled trial. Pediatr Infect Dis J 2003; 22: 706–710. (PubMed) 13. Huber R et al. Tormentil for active ulcerative colitis: An open-label, dose-escalating study. J Clin Gastroenterol 2007; 41: 834–838. (PubMed) 14. Moss AC, Cheifetz AS. Reducing the torment of diarrhea: tormentil for active ulcerative colitis. J Clin Gastroenterol 2007; 41: 797–798. (PubMed) 15. Shushunov S et al. Determination of acute toxicity of the aqueous extract of Potentilla erecta (tormentil) rhizomes in rats and mice. J Med Food 2009; 12: 1173–1176. (PubMed)

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