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Leonurus Cardiaca L. As a Source of Bioactive Compounds: an Update of the European Medicines Agency Assessment Report (2010)

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Leonurus Cardiaca L. As a Source of Bioactive Compounds: an Update of the European Medicines Agency Assessment Report (2010) Hindawi BioMed Research International Volume 2019, Article ID 4303215, 13 pages https://doi.org/10.1155/2019/4303215 Review Article Leonurus cardiaca L. as a Source of Bioactive Compounds: An Update of the European Medicines Agency Assessment Report (2010) Radu Claudiu Fierascu,1,2 Irina Fierascu ,1,2 Alina Ortan,1 Ioana Catalina Fierascu,3 Valentina Anuta,3 Bruno Stefan Velescu,3 Silviu Mirel Pituru,3 and Cristina Elena Dinu-Pirvu1,3 1 University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 Mar˘ as˘,ti Blvd., 011464, Bucharest, Romania 2National Institute for Research & Development in Chemistry and Petrochemistry – ICECHIM Bucharest, 202 Spl. Independentei, 060021, Bucharest, Romania 3University of Medicine and Pharmacy “Carol Davila”, 37 Dionisie Lupu Str., 030167, Bucharest, Romania Correspondence should be addressed to Irina Fierascu; [email protected] Received 25 February 2019; Revised 22 March 2019; Accepted 31 March 2019; Published 17 April 2019 Academic Editor: Francesca Mancianti Copyright © 2019 Radu Claudiu Fierascu et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Leonurus cardiaca L. (motherwort) is a perennial herb, native to Asia and southeastern Europe, with widespread global occurrence in present days. Te plant was historically used as cardiotonic and for treating gynaecological afictions (such as amenorrhea, dysmenorrhea, menopausal anxiety, or postpartum depression). Although its use in oriental and occidental medicine is relatively well documented, the recent progress registered raises the need for an update of the Medicines Agency assessment report on Leonurus cardiaca L., herba (2010). Te current study presents the progress made within the 2010-2018 timeframe regarding the potential applications and scientifc evidences supporting the traditional use of motherwort, in the same time suggesting future research opportunities. 1. Introduction ones, or for favoring of beer and tea [6], thus increasing the potential intake of the medicinal plant by the general public. Leonurus cardiaca L. (common names – motherwort in Eng- Te current review intends to present the main fndings lish, Echte Herzgespann –Deutsch,agripaume –French, regarding the composition and main biological activities of etc) represents a perennial herb belonging to the Lamiaceae L. cardiaca, as emerging from the scientifc studies pub- family. Te plants grow up to 1 m, with the hollow aerial lished within the 2010-2018 timeframe. Te time period stalks growing from the rhizomes. Te leaves are palmately was selected in order to complete the very comprehensive lobed, being covered with stif hairs. Flowers, grouped in “Assessment report on Leonurus cardiaca L., herba” pub- 10-20 clusters in the leaf’s axils of the last 10-15 knots, are lished by the European Medicine Agency [5] with the latest pink and about 1 cm long [1]. Te plant, original to Asia fndings. Te search methodology involved accessing and and southeastern Europe is now world-spread, due to its evaluating the papers found in the PubMed, ScienceDirect, medicinal use [2–4]. Te potential application in treating Wiley Online Library, ACS Publications, and SpringerLink several cardiac disorders, as well as female-specifc afictions, databases (search term “Leonurus cardiaca”, 27.12.2018). Afer made L. cardiaca a very good candidate for development the removal of duplicate entries, 283 studies were taken of alternative treatments, in both traditional eastern and into consideration. Figure 1 describes the distribution of the modern medicine [2, 5]. Besides the traditional medical use, reviewed works by publication year and type of paper. Most of motherwort is used in some cuisines as condiment in various the information presented in the present work was collected vegetable soup recipes, particularly the lentil or split peas from the “Article” type papers (176 works). 2 BioMed Research International 45 40 35 30 25 20 Reviewed works Reviewed 15 10 5 0 2010 2011 2012 2013 2014 2015 2016 2017 2018 Publication year Articles Book chapters Others (Review, Editorial, Meeting Abstract, Reference work) Figure 1: Works published in the time period 2010-2018 including L. cardiaca. 2. Composition of L. cardiaca leonurine in the L. cardiaca extracts is presented by some authors, including the previously cited report [5, 14], others Te composition of L. cardiaca was previously presented support the contrary, not identifying the compound in the L. by the EMA report [5], consisting of furanic diterpenes cardiaca extract [15]. (labdanes), alkaloids (of special interest being stachydrine), sterols, iridoids, favonoids, ursolic acid, minerals, and others. 3. Biological Activities of L. cardiaca Figure 2 presents the constituents of L. cardiaca and their potential biomedical application, as presented by the pre-2010 Te main biological activities of L. cardiaca can be divided in literature sources. several main categories. Te data briefy presented in Figure 2 can be completed with the fndings from the time period covered by the present 3.1. Cardiovascular Action. Te application of L. cardiaca review.Ruschetal.[7]identifedintheL. cardiaca extract the in cardiovascular disorders represents one of the main presence of a chlorinated major iridoid glucoside (7-chloro-6- applications of motherwort products [2]. Ritter et al. [16] desoxy-harpagide), confrmed by ESI-MS and 1d/2d 1H/13C evaluated the cardiac and electrophysiological efects of NMR. Kuchta et al. [8] quantifed by RP-HPLC the presence several types of L. cardiaca extracts by epicardial potential of ferulic acid, chlorogenic acid, cafeic acid, cichoric acid, mapping and by evaluation of the efect on the cardiac ion rutoside, lavandulifolioside, verbascoside, and isoquercitrin currents using diferent types of cell models. Te obtained in L. cardiaca extract, as well as stachydrine in diferent parts results suggested that L. cardiaca extractactsasamixed of L. cardiaca, included, for the frst time in literature, in the ICa.L- (L-type calcium current), IKr- (rapid delayed rectifer fruits (0.2%) [9, 10]. current) antagonist, and If (funny current, recorded in Te leaves essential oil was found to contain caryophyl- sinoatrial node cells from guinea pigs) modulator, support- lene, 39.8%; �-humulene, 34.8%; �-pinene, 5.6%; �-pinene, ing its application as an antianginal and antiarrhythmic 0.5%; linalool, 0.7%; and limonene, 0.4%, while the ursolic agent. acid present in the leaves was quantifed to be 0.26% (dry wt.) Te cardioprotective potential of ursolic acid (the natural [11]. pentacyclic triterpenoid carboxylic acid commonly found Using HPLC-MS, Zhogova et al. [12] quantifed sev- in diferent L. cardiaca formulations) was demonstrated by eral active compounds in both medicinal plant raw mate- Liobikas et al. [17]. Teir study revealed that the ursolic acid rial and medicinal preparation (harpagide, ajugol, galirido- induced uncoupling of oxidative phosphorylation in the heart side, harpagide acetate, ajugoside, galiridoside, chlorogenic mitochondria without afecting State 3 respiration rate, in acid, lavandulifolioside, verbascoside, rutin, hyperoside, iso- thesametimesuppressingtheH2O2 production in isolated quercitrin, and apigenin-7-O-glucoside). mitochondria, in a dose-dependent manner. Te uncoupling An optimized recipe for the extraction of polysaccharides of mitochondrial oxidation from phosphorylation, partial from motherwort leaves was presented by Tahmouzi and inhibition of the mitochondrial respiratory chain, and a ∘ Ghodsi [13], obtaining a yield of 9.17 ± 0.39% for 81.4 C reduction in the generation of free radicals in mitochondria extraction temperature, 106.6 min. extraction time, and 45.2 were also observed by Bernatoniene et al. [18] in rat heart ratio of water to raw material. Although the presence of mitochondria using L. cardiaca ethanol extracts. BioMed Research International 3 Constituents O Application Furanic labdane diterpenes Anti-infammatory OH ＃（ H 3 Antiarrhythmic H O O ＃（3 O O OH Antifatulent O O O O O O O O H O O O （3C ＃（3 Antispasmodic leocardin leosibiricin hispanolone Astringent Alkaloids - O O O N ．（ O 2 Birthing aid + O ．（2 N H HO ＃（ （3C 3 O Cardiac stachydrine leonurine Glycosides Diaphoretic Iridoids OH OH HO H HO HO ＃（3 HO OH O O H Emmenagogue OH O HO O H HO OH O O O OH OH O OH O O Nervine HO H O （3C O O HO O Glucose O ＃（ Analgesic 3 OH OH ajugol reptosid Lavandulifolioside Others Stomachic HO ＃／2H Tonic H OH O H H Women’s complaints O HO O H H H OH HO OH Antibacterial H OH Antioxidant HO ursolic acid germacrene D -sitosterol chlorogenic acid Figure 2: Composition and applications of L. cardiaca as emerging from pre-2010 works (adapted from [5]). Te clinical trial conducted by Shikov et al. [19] on and inhibits the expression of nitric oxide synthase (iNOS) ffy patients treated with 1200 mg L. cardiaca oil extract and cyclooxygenase-2 (COX-2). Te suggested mechanism per day for 28 days revealed signifcant changes in systolic involves the inhibition of expression of toll-like receptor blood pressure, diastolic blood pressure, heart rate, and 4(TLR4)andnuclearfactor-kappaB(NF-�B) activation ECG for patients with stages 1 and 2 arterial hypertensions, and mitogen-activated protein kinases (p38), extracellular accompanied by an improvement of psychoemotional status signal-regulated kinase (ERK), and Jun N-terminal kinase (anxiety, emotional
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