Published online: 2020-03-10 Reviews Tormentillae rhizoma – Review for an Underestimated European Herbal Drug# Authors Matthias F. Melzig, Stefan Böttger Affiliation Correspondence Institute of Pharmacy, Freie Universität Berlin, Germany Prof.Dr.Dr.h.c.MatthiasF.Melzig Pharmaceutical Biology, Institute of Pharmacy, Key words Freie Universität Berlin Potentilla erecta, Tormentil, Rosaceae, phytochemistry, Königin-Luise-Str. 2 + 4, 14195 Berlin, Germany pharmacology, traditional use Phone: + 493083851451, Fax: + 4930838451451 [email protected] received January 14, 2020 accepted after revision February 25, 2020 ABSTRACT published online March 10, 2020 Potentilla erecta is a medicinal plant described under its tradi- Bibliography tional name Tormentil in medieval herbal books and used until Planta Med 2020; 86: 1050–1057 today in many European countries. Today monographs for DOI 10.1055/a-1129-7214 Tormentillae rhizoma in the European pharmacopeia, as well ISSN 0032‑0943 as a monograph of the Herbal Medicinal Product Commission © 2020. Thieme. All rights reserved. as a drug for traditional use, exist. The present review summa- Georg Thieme Verlag KG, Rüdigerstraße 14, rizes published investigations in phytochemistry and pharma- 70469 Stuttgart, Germany cology, together with new findings reflecting the mechanisms of action of ellagitannins as one of the main ingredients of this herbal drug. Taken together all in vitro and in vivo investiga- tions’ data support the traditional use for treatment of diar- rhea and mucosal inflammation despite a lack of suffcient clinical studies. Introduction Botanical Description Plant-based therapeutics and botanical supplements are increas- Potentilla erecta is widely distributed throughout Eurasia in a variety ingly offered and used all over the world. At present, there is a of environments including bogs, heaths, moors, grasslands, open need for scientific evaluation and standardization of all these woods, and alpine slopes. It is an herbaceous perennial with a stout, products. This development also concerns the use of herbal drugs hard rootstock. Procumbent and erect stems (10–25 cm) are non- This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. with a long therapeutic tradition. With the elaboration of mono- rooting, and the height is greater where the land is damp and not graphs by the Herbal Medicinal Product Commission (HMPC), a grazed by sheep. The alternate leaves are unstalked, toothed at the decision has been made that supports further therapeutic admin- apex, and hairy underneath. The leaves occur in groups of 3 with istration based on scientific evidence. One of these herbal drugs 2 stipules that resemble small leaflets, so it appears to have 5 leaf- with long tradition is Tormentil derived from Potentilla erecta L., lets. The yellow flowers occur in summer in cymes and have 4 pet- Rosaceae [1]. Although there is no approved herbal drug available als and many yellow stamens. There are 4 sepals and a 4-sectioned in European community, the drug is traditionally used and attracts epicalyx. All other Potentilla species have 5 petals. The seed is an attention in complementary medicine [2]. achene [3]. The accepted botanical name of this plant is Potentilla The following review focuses mainly on the biological and erecta L., but in many European countries, the traditional name is pharmacological effects of drug preparations with respect to their Tormentil (Engl.), Tormentille (Fr.) or Tormentilla (Ital.) coming therapeutic use. # Dedicated to Professor Dr. Wolfgang Kubelka on the occasion of his 85th birthday. 1050 Melzig MF, Böttger S. Tormentillae rhizoma – Review for … Planta Med 2020; 86: 1050–1057 | © 2020. Thieme. All rights reserved. ▶ Fig. 1 Structure of agrimoniin. from the synonyms Potentilla tormentilla Neck. or Tormentilla erecta Up to 3.5% hydrolyzable tannins form another important L.Thenameofgenus“Potentilla” refers to the Latin word “poten- group of compounds [13]. Apart from pentadigalloylglucose, tial” meaning power and is related to the powerful pharmacologi- 1 monomeric and 3 dimeric ellagitannins were isolated [8,9,14]. cal activity of the plant, which has been used for several indications Within the ellagitannins group, agrimoniin (▶ Fig. 1) is one of the in the past. In the medieval age, the traditional name “Tormentil” most representative and most complex compounds, and it is also referred to the Latin word “tormentina”, which means intesti- found in many plant materials belonging to the Rosaceae family. nal colic and also points to the specific use of the herbal drug to Agrimoniin (C82H54O52) is a dimeric ellagitannin with a molecular cure enteritis and spasmodic colics. In the German-speaking re- weight of 1871.282, having 2D‑glucopyranose cores with α-glu- gions in Europe, the name is “Blutwurz” and refers to the red color cosidic linkages in both units. The absolute configuration of all of the broken roots, which is the result of the formation of red-col- 4 atropoisomeric biaryl hexahydroxydiphenoyl (HHDP) groups is ored tannins and also indicates the therapeutic use for stopping S-configuration [15]. Yields of about 2% (w/w) can be found in bleedings in former times [4]. the underground parts of P. erecta [16]. Laevitagin B and Laevita- gin F (Tormentillin) are also dimeric ellagitannins and quite rare Phytochemistry of the Underground Parts derivatives of Agrimoniin [17]. Pedunculagin, a monomeric ellagi- tannin, can yield about 0.4% (w/w) in the underground parts of About 55 compounds have been described for the underground P. erecta [16]. The biaryl HHDP groups can also be seen as dimers parts of P. erecta. With a total of 15–20%, condensed tannins of hexahydroxydiphenic acid and precursors of ellagic acid. Ellagic (syn. proanthocyanidins, nonhydrolyzable tannins) are the most acid is the dilactone of hexahydroxydiphenic acid, and yields of abundant group of compounds. Monomeric, dimeric, and trimeric about 0.4% can be found [16,18]. As a structural element, it is re- proanthocyanidins of type B were isolated and their structures lated to the ellagitannins. This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. elucidated. They are usually transconfigurated and connected via Nine triterpenoid compounds were isolated and elucidated, 4,8‑,4,6‑,6,6‑ or 6,8-bonds, like the [4,6]-all-trans-bi-(+)‑cate- generally based on an Ursan- or an Olean skeleton, and present chin (Procyanidin B6) and the [4, 8]-all-trans-bi-(+)‑catechin (Pro- as aglycones and/or C-28-O-β-D-glucosyl esters. None of the tri- cyanidin B3). The [4,8]-2,3-trans-3,4-cis-bi-(+)‑catechin is a rare terpens bared a sugar moiety at a C-3-OH-Group, if present [5]. example of a cis-configurated dimeric proanthocyanidin. The Pro- Best investigated are Tormentoside (Rosamultin), a glucopyrano- cyanidins B1, B2, and B5 were only detected in traces. Tetra-, pen- sylester, and its aglycon, Tormentic acid. Overall, the fraction of ta-, and hexamers have been also detected, but their structures triterpens yields between 0.6–1.7% [19,20]. were not completely elucidated [5–10]. The fraction of the con- Further ingredients include a series of organic acids and phenol densed tannins consists of 49–62% monomers, dimers, and carboxylic acids like caffeic acid, gallic acid, or salicylic acid. Some trimers, 24–37% of tetramers, and 10–15% of pentamers and of these compounds are only present after hydrolysis of more com- hexamers, depending on the author [9–11]. Several precursors plex structures [21,22]. Some flavonoids like a cyanidinglucoside, for condensed tannins were identified like (+)‑catechin, (−)‑epi- kaempferol, and leucoanthocyanidin are also present but are more catechin, (+)‑gallocatechin, (−)‑epigallocatechin, and (−)‑epigal- abundant in the aerial parts of P. erecta [8,12,23]. ▶ Table 1 sum- locatechingallate [8, 9, 12]. marizes the phytochemical findings for the tannins and triterpens. Melzig MF, Böttger S. Tormentillae rhizoma – Review for … Planta Med 2020; 86: 1050–1057 | © 2020. Thieme. All rights reserved. 1051 Reviews Traditional Use ▶ Table 1 Compounds of the underground parts of Potentilla erecta L. (modified from [8]). Presumably, the plant was not used in the ancient world, but ther- apeutic reports from medieval herbal books are known [4]. In the Compound Compound Refer- Contrafayt Kreüterbuch by Otto Brunfels (1532). Tormentilla was class ences used for the treatment of hemorrhaging, excessive menstruation, Hydrolysable tannins diarrhea, or cholera [29]. Some of these indications have impor- ▪ Mono- Pedunculagin [24] tance until today. The use of an infusion or alcoholic extract of mers Pentadigalloylglucose [14] the drug (tincture) for the treatment of diarrhea with and without ▪ vomiting, enteritis, intestinal bleedings, and dysentery were re- Dimers Agrimoniin [25] ported as standard medicinal therapy until the middle of the Laevigatin B [26] 20th century. The use as gargle in case of oropharyngeal inflam- Laevigatin F (= Tormentillin) [17] mations or as a compress/ointment for wound healing in exuda- Condensed tannins (proanthocyanidins) tive eczema, as well as for contusions and hematomas, has also ▪ Dimers [4, 6]-all-trans-bi-(+)-Catechin [7] been reported and is still used today for self-medication. The dos- (= Procyanidin B6) age ranged from 2–4 g of the powdered drug or 15–20 g of a de- [4, 8]-2,3-trans-3,4-cis-bi-(+)-Catechin [7] coction of the dried rhizome. The drug has