Filipendula ulmaria (L.) Maxim. (Meadowsweet): a Review of Traditional Uses, Phytochemistry and Pharmacology

Document Type : Review

Authors

1 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

2 Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Filipendula ulmaria (L.) Maxim. commonly known as "meadowsweet", is a perennial herb native to Iran, Europe, and Western Asia. Several medicinal properties of the plant have been reported in Persian medicine. Filipendula ulmaria is traditionally used for fever, pain, inflammatory diseases (arthrosis, rheumatism, and arthritis), gastric disorders, liver dysfunction, and gout. The phytochemical studies indicate the presence of several active compounds, mainly phenolic acids, flavonoids, tannins, and terpenoids. Salicylic acid and its derivatives are the most important compounds found in essential oil and extracts of different parts of the plant. Pharmacological evaluations have shown the anti-arthritis, analgesic, anti-inflammatory, anti-oxidant, anti-cancer, anti-coagulant, anti-microbial, immunomodulatory, gastro-protective, and hepato-protective activity of F. ulmaria. Despite pharmacological activities, traditional uses and herbal supplements, there is no complete review article on this herb's properties. In this paper, we have provided a review on traditional uses, phytochemicals, pharmacological properties and medical information of this valuable medicinal plant.

Keywords


  • United States Department of Agriculture. Filipendula ulmaria. [Accessed 2021]. Available from http: //plants.usda.gov/ home/ plantProfile? symbol= FIUL.
  • Prior RC. On the popular names of British plants, being an explanation of the origin and meaning of the names of our indigenous and most commonly cultivated species. 2nd London: Williams and Norgate, 1870.
  • Van der Kooi CJ, Pen I, Staal M, Stavenga DG, Elzenga JTM. Competition for pollinators and intra‐communal spectral dissimilarity of flowers. Plant Biol. 2016; 18(1): 56–62.
  • Hadjiakhoondi A, Baligh N. Practical guide to medicinal plants. 1st Tehran: Scientific Publishing Center, 2002.
  • Piwowarski JP, Granica S, Zwierzynska M, Stefanska J, Schopohl P, Melzig MF. Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials. J Ethnopharmacol. 2014; 155(1): 801–809.
  • Katanic J, Matic S, Pferschy-Wenzig EM, Kretschmer N, Boroja T, Mihailovic V. Filipendula ulmaria extracts attenuate cisplatin-induced liver and kidney oxidative stress in rats: In vivo investigation and LC-MS analysis. Food Chem Toxicol. 2017; 99(1): 86–102.
  • Šarić-Kundalić B, Dobeš C, Klatte-Asselmeyer V, Saukel J. Ethnobotanical survey of traditionally used plants in human therapy of east, north and north-east Bosnia and Herzegovina. J Ethnopharmacol. 2011; 133(3): 1051–1076.
  • McCormack J, Power I. Nonsteroidal anti-inflammatory drugs and acetaminophen: pharmacology for the future. In: Raymond S, Ed. Acute pain management. New York: Cambridge University Press, 2009.
  • Mitra SP. Pharmacology and biochemistry behind the use of natural herbs to control arthritis, a review. Indian J Nat Prod Resour. 2017; 8(3): 204–223.
  • Katanic J, Boroja T, Stankovic N, Mihailovic V, Mladenovic M, Kreft S. Bioactivity, stability and phenolic characterization of Filipendula ulmaria (L.) Maxim. Food Funct. 2015; 6(4): 1164–1175.
  • Voicu SN, Hermenean A, Olah NK, Badulescu L, Stan MS, Dinischiotu A. Designing new mother tinctures for increased antioxidant efficiency on inflammatory intestinal diseases. 2019; 67(2): 290–295.
  • Popowski D, Pawłowska KA, Piwowarski JP, Granica S. Gut microbiota-assisted isolation of flavonoids with a galloyl moiety from flowers of meadowsweet, Filipendula ulmaria (L.) Maxim. Phytochem Lett. 2019; 30(4): 220–223.
  • Sile I, Romane E, Reinsone S, Maurina B, Tirzite D, Dambrova M. Medicinal plants and their uses recorded in the archives of Latvian folklore from the 19th J Ethnopharmacol. 2020; 249(3): 1–15.
  • Garcia-Oliveira P, Fraga-Corral M, Pereira A, Lourenço-Lopes C, Jimenez-Lopez C, Prieto M. Scientific basis for the industrialization of traditionally used plants of the Rosaceae family. Food Chem. 2020; 330(11): 1–16.
  • Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide. 4th Melbourne: Elsevier Health Sciences, 2015.
  • Parnell J, Curtis T, Cullen E. Webb's an Irish Flora. 8th Cork: Cork University Press, 2012.
  • Clapham AR, Tutin TG, Warburg EF. Excursion flora of the British Isles. 3rd Lincoln: Cambridge University Press, 1981.
  • Brunke EJ, Hammerschmidt FJ, Schmaus G. Flower scent of some traditional medicinal plants. In: teranishi R, Ed. bioactive volatile compounds from plants. Washington: American Chemical Society,
  • Halkes SBA, Beukelman CJ, Kroes BH, Van den Berg AJ, Labadie RP, Van Dijk H. In vitro immunomodulatory activity of Filipendula ulmaria. Phytoter Res. 1997; 11(7): 518–520.
  • Jackson B, Wichtl M. Herbal drugs and phytopharmaceuticals: a handbook for practice on a scientific basis. 2nd Stuttgart: Medpharm Scientific Publishers, 1994.
  • Van Hellemont J. Fytotherapeutisch compendium. 2nd Utrecht: Bohn Scheltema and Holkema, 1988.
  • Zeylstra H. Filipendula ulmaria. Br J Phytoter. 1998; 5(3): 8–12.
  • Mclntyre M. British herbal compendium. A handbook of scientific information on widely used plant drugs. Dorset: British Herbal Medicine Association, 1993.
  • Bassi P, Kumar V, Kumar S, Kaur S, Gat Y, Majid I. Importance and prior considerations for development and utilization of tea bags: a critical review. J Food Process Eng. 2020; 43(1): 1–10.
  • Bradely P. British herbal pharmacopoeia. Bournemouth: British Herbal Medicine Association, 1990.
  • House L. British herbal pharmacopoeia. Cowling: British Herbal Medicine association, 1983.
  • Madaus G. Lehrbuch der biologischen Heilmittel. Leipzig: Georg Thieme Verlag, 1938.

[28] Gessner O, Orzechowski G. Poisonous and                            medicinal plants from Central Europe. Heidelberg: Carl Winter Universitatverlag, 1974.

[29] Dorsch PM, Swanson SR, Kelley SW. The role of relationship quality in the stratification of vendors as perceived by customers. J Acad Mark Sci. 1998; 26(2): 128–142.

[30] Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW. The complete German commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council, 1998.

[31] Schulz V, Hansel R, Tyler VE. Rational phytotherapy: a physician′s guide to herbal medicine. 3rd ed. Berlin: Springer-Verlag, 1998.

[32] Chrubasik S. The scientific foundation for herbal medicinal products. 2nd ed. New York: Thieme, 2009.

[33] Barnes J, Anderson L, Phillipson D. Herbal medicines. 3rd ed. London: Pharmaceutical Press, 2007.

[34] Rasouli H, Farzaei MH, Khodarahmi R. Polyphenols and their benefits: a review. Int J Food Prop. 2017; 20(12): 1700–1741.

[35] Bahramsoltani R, Kalkhorani M, Zaidi SMA, Farzaei MH, Rahimi R. The genus Tamarix: traditional uses, phytochemistry, and pharmacology. J Ethnopharmacol. 2019; 246(1): 1–24.

[36] Khanavi M, Hajimahmoodi M, Cheraghi-Niroomand M, Kargar Z, Ajani Y, Hadjiakhoondi A. Comparison of the antioxidant activity and total phenolic contents in some Stachys species. Afr J Biotechnol. 2009; 8(6): 1143–1147.

[37] Baranenko D, Bespalov V, Nadtochii L, Shestopalova I, Chechetkina A, Lepeshkin A. Development of encapsulated extracts on the basis of meadowsweet (Filipendula ulmaria) in the composition of functional foods with oncoprotective properties. Agron Res. 2019; 17(5): 1829–1838.

[38] Bijttebier S, Peeters L, Foubert K, Hermans N, Pieters L. An integrated strategy to characterize new anti-inflammatory lead compounds derived from Filipendula ulmaria (meadowsweet). Planta Med. 2019; 85(18): 240.

[39] Farzaei MH, Khanavi M, Moghaddam G, Dolatshahi F, Rahimi R, Shams-Ardekani MR, Amin G, Hajimahmoodi M. Standardization of Tragopogon graminifolius DC. extract based on phenolic compounds and antioxidant activity. J Chem. 2014; Article ID 425965. 

[40] Jafari S, Moradi A, Salaritabar A, Hadjiakhoondi A, Khanavi M. Determination of total phenolic and flavonoid contents of Leonurus cardiaca L. in compare with antioxidant activity. Res J Biol Sci. 2010; 5(7): 484–487.

[41] Katanić J, Pferschy-Wenzig EM, Mihailović V, Boroja T, Pan SP, Nikles S. Phytochemical analysis and anti-inflammatory effects of Filipendula vulgaris Moench extracts. Food Chem Toxicol. 2018; 122(12): 151–162.

[42] Pukalskienė M, Venskutonis P, Pukalskas A. Phytochemical composition and antioxidant properties of Filipendula vulgaris as a source of healthy functional ingredients. J Funct Foods. 2015; 15(5): 233–242.

[43] Kumar N, Goel N. Phenolic acids: natural versatile molecules with promising therapeutic applications. Biotechnol Rep. 2019; 24(12): 1–10.

[44] Olennikov DN, Kruglova MY. A new quercetin glycoside and other phenolic compounds from the genus Filipendula. Chem Nat Compd. 2013; 49(4): 610–616.

[45] Adamczak A, Ożarowski M, Karpiński TM. Antibacterial activity of some flavonoids and organic acids widely distributed in plants. J Clin Med. 2020; 9(1): 1–17.

[46] Sharma A, Sidhu GPS, Araniti F, Bali AS, Shahzad B, Tripathi DK. The role of salicylic acid in plants exposed to heavy metals. Molecules. 2020; 25(3): 1–22.

[47] Papp I, Simándi B, Blazics B, Alberti Á, Héthelyi É, Szoke É. Monitoring volatile and non-volatile salicylates in Filipendula ulmaria by different chromatographic techniques. Chromatographia. 2008; 68: 125–129.

[48] Blazics B, Papp I, Kéry A. LC-MS qualitative analysis and simultaneous determination of six Filipendula salicylates with two standards. Chromatographia. 2010; 71: 61–67.

[49] Kikuchi H, Yuan B, Hu X, Okazaki M. Chemopreventive and anticancer activity of flavonoids and its possibility for clinical use by combining with conventional chemotherapeutic agents. Am J Cancer Res. 2019; 9(8): 1517–1535.

[50] Kalkhorani M, Hadjiakhoondi A, Yassa N, Amin M, Damankash S, Moradkhani F. Bioguided fractionation of Centaurea bruguierana subsp. belangeriana extract based on anti-Helicobacter pylori. Res J Pharmacogn. 2020; 7(1): 61–67.

[51] Almasian A, Najafi F, Eftekhari M, Ardekani MRS, Sharifzadeh M, Khanavi M. Polyurethane/ carboxymethylcellulose nano fibers containing Malva sylvestris extract for healing diabetic wounds: preparation, characterization, in vitro and in vivo studies. Mater Sci Eng C Mater Biol Appl. 2020; 114(9): 1–14.

[52] Rathee P, Chaudhary H, Rathee S, Rathee D, Kumar V, Kohli K. Mechanism of action of flavonoids as anti-inflammatory agents: a review. Inflamm Allergy Drug Targets. 2009; 8(3): 229–235.

[53] Uritu CM, Mihai CT, Stanciu GD, Dodi G, Alexa-Stratulat T, Luca A. Medicinal plants of the family Lamiaceae in pain therapy: a review. Pain Res Manag. 2018; Article ID 7801543. 

[54] Faggio C, Sureda A, Morabito S, Sanches-Silva A, Mocan A, Nabavi SF. Flavonoids and platelet aggregation: a brief review. Eur J Pharmacol. 2017; 807(7): 91–101.

[55] Asgarpanah J, Motamed SM, Farzaneh A, Ghanizadeh B, Tomraee S. Antioxidant activity and total phenolic and flavonoid content of Astragalus squarrosus Bunge. Afr J Biotechnol. 2011; 10(82): 19176–19180.

[56] Goodarzi S, Hadjiakhoondi A, Yassa N, Khanavi M, Tofighi Z. Essential oils chemical composition, antioxidant activities and total phenols of Astrodaucus persicus. Iran J Basic Med Sci. 2016; 19(2): 159–165.

[57] Wang X, Zhang F, Yang L, Mei Y, Long H, Zhang X. Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in vitro and in vivo. Biomed Res Int. 2011; Article ID 419343.

[58] Davis EM, Croteau R. Cyclization enzymes in the biosynthesis of monoterpenes, sesquiterpenes and diterpenes. Biosynthesis. 2000; 209(11): 53–95.

[59] Neto CC, Vaisberg AJ, Zhou BN, Kingston DG, Hammond GB. Cytotoxic triterpene acids from the Peruvian medicinal plant Polylepis racemosa. Planta Med. 2000; 66(5): 483–484.

[60] Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2012; 64(12): 128–137.

[61] Nitta Y, Kikuzaki H, Azuma T, Ye Y, Sakaue M, Higuchi Y, Komori H, Ueno H. Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylase. Food Chem. 2013; 138(2-3): 1551–1556.

[62] Sroka Z, Cisowski W, Seredynska M, Luczkiewicz M. Phenolic extracts from meadowsweet and hawthorn flowers have antioxidative properties. Z Naturforsch. 2001; 56(9-10): 739–744.

[63] Proestos C, Boziaris IS, Kapsokefalou M, Komaitis M. Natural antioxidant constituents from selected aromatic plants and their antimicrobial activity against selected pathogenic microorganisms. Food Technol Biotechnol. 2008; 46(2): 151–156.

[64] Denev P, Kratchanova M, Ciz M, Lojek A, Vasicek O, Blazheva D. Antioxidant, antimicrobial and neutrophil-modulating activities of herb extracts. Acta Biochim Pol. 2014; 61(2): 359–367.

[65] Bijttebier S, Voorspoels S, Apers S, Pieters L. A first step in the quest for the active constituents in Filipendula ulmaria (meadowsweet): comprehensive secondary metabolite identification by liquid chromatography-quadrupole orbitrap mass spectrometry. Planta Med. 2015; 81(16): 1545–1546.

[66] Krasnov EA, Raldugin VA, Shilova IV, Avdeeva EY. Phenolic compounds from Filipendula ulmaria. Chem Nat Compd. 2006; 42(2): 148–151.

[67] Bespalov VG, Alexandrov VA, Vysochina GI, Kostikova Vcapital AC, Baranenko DA. The inhibiting activity of meadowsweet extract on neurocarcinogenesis induced transplacentally in rats by ethylnitrosourea. J Neurooncol. 2017; 131(3): 459–467.

[68] Gniewosz M, Synowiec A, Kraśniewska K, Przybył JL, Baczek K, Weglarz Z. The antimicrobial activity of pullulan film incorporated with meadowsweet flower extracts (Filipendulae ulmariae flos) on post-harvest quality of apples. Food Control. 2014; 37(1): 351–361.

[69] Olennikov DN, Kashchenko NI, Chirikova NK. Meadowsweet teas as new functional beverages: comparative analysis of nutrients, phytochemicals and biological effects of four Filipendula species. Molecules. 2016; 22(1): 16–38.

[70] Fecka I. Qualitative and quantitative determination of hydrolysable tannins and other polyphenols in herbal products from meadowsweet and dog rose. Phytochem Anal. 2009; 20(3): 177–190.

[71] Papp I, Apati P, Andrasek V, Blazovics A, Balazs A, Kursinszki L. LC-MS analysis of antioxidant plant phenoloids. Chromatographia. 2004; 60: 93–100.

[72] Pukalskienė M, Venskutonis PR, Pukalskas A. Phytochemical characterization of Filipendula ulmaria by UPLC/Q-TOF-MS and evaluation of antioxidant activity. Rec Nat Prod. 2015; 9(3): 451–455.

[73] Pemp E, Reznicek G, Krenn L. Fast quantification of flavonoids in Filipendulae ulmaria flos by HPLC/ESI-MS using a nonporous stationary phase. Chem Nat. 2007; 62(7): 669–673.

[74] Bukreeva TV, Shukhobodskii BA. Structure of the main flavonoid glycoside from the flowers of Filipendula ulmaria. Chem Nat Compd. 1987; 23(5): 631–632.

[75] Krasnov EA, Raldugin VA, Avdeeva EY. Filimarin, a new flavanol glycoside from Filipendula ulmaria and its antioxidant activity. Pharm Chem J. 2009; 43(11): 613–614.

[76] Sofic E, Copra-Janicijevic A, Salihovic M, Tahirovic I, Kroyer G. Screening of medicinal plant extracts for quercetin-3-rutinoside (rutin) in Bosnia and Herzegovina. Med Plants Int J Phytomed Relat Ind. 2010; 2(2): 97–102.

[77] Katanic J, Boroja T, Mihailovic V, Nikles S, Pan SP, Rosic G. Corrigendum to: in vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent. J Ethnopharmacol. 2017; 198(2): 608–609.

[78] Toiu A, Vlase L, Oniga I, Benedec D, Tamas M. HPLC analysis of salicylic acid derivatives from natural products. Farmacia. 2011; 59(1): 106–112.

[79] Barros L, Alves CT, Duenas M, Silva S, Oliveira R, Carvalho AM. Characterization of phenolic compounds in wild medicinal flowers from Portugal by HPLC-DAD-ESI/MS and evaluation of antifungal properties. Ind Crops Prod. 2013; 44(1): 104–110.

[80] Hamid KH, Azman NA, Md Shaarani S, Zain N, Ahmad N, Sulaiman AZ, Chik SS, Ishak WF, Almajano Pablos MP. Alchemilla vulgaris and Filipendula ulmaria extracts as potential natural preservatives in beef patties. Malaysian J Anal Sci M. 2017; 21(8): 986–995.

[81] Valle MG, Nano GM, Tira S. The essential oil of Filipendula ulmaria. Planta Med. 1988; 54(2): 181–182.

[82] Farré-Armengol G, Fernández-Martínez M, Filella I, Junker RR, Peñuelas J. Deciphering the biotic and climatic factors that influence floral scents: a systematic review of floral volatile emissions. Front Plant Sci. 2020; 11(7): 1–16.

[83] Hamblin L, Laird A, Parkes E, Walker AF. Improved arthritic knee health in a pilot RCT of phytotherapy. R Soc Health J. 2008; 128(5): 255–262.

[84] Matic S, Katanic J, Stanic S, Mladenovic M, Stankovic N, Mihailovic V. In vitro and in vivo assessment of the genotoxicity and antigenotoxicity of the Filipendula hexapetala and Filipendula ulmaria methanol extracts. J Ethnopharmacol. 2015; 174(11): 287–292.

[85] Harbourne N, Jacquier JC, O'Riordan D. Optimisation of the aqueous extraction conditions of phenols from meadowsweet (Filipendula ulmaria L.) for incorporation into beverages. Food Chem. 2009; 116(3): 722–727.

[86] Kudriashov B, Ammosova I, Liapina L, Osipova N, Azieva L, Liapin G, Basanova A. Heparin from the meadowsweet (Filipendula ulmaria) and its properties. Izv Akad Nauk SSSR Biol. 1991; 6: 939–943.

[87] Liapina L, Koval'chuk G. A comparative study of the action on the hemostatic system of extracts from the flowers and seeds of the meadowsweet (Filipendula ulmaria (L.) Maxim.). Izv Akad Nauk SSSR Biol. 1993; 1(4): 625–628.

[88] Kudriashov B, Liapina L, Azieva L. The content of a heparin-like anticoagulant in the flowers of the meadowsweet (Filipendula ulmaria). Farmakol Toksikol. 1990; 53(4): 39–41.

[89] Chrubasik-Hausmann S. Phytomedicines for inflammatory conditions. In: Ramzan I, Ed. Phytotherapies: efficacy, safety, and regulation. New York: John Wiley and Sons Inc, 2015.

[90] Harbourne N, Marete E, Jacquier JC, O'Riordan D. Stability of phytochemicals as sources of anti-inflammatory nutraceuticals in beverages, a review. Int Food Res J. 2013; 50(2): 480–486.

[91] Samardzic S, Tomic M, Pecikoza U, Stepanovic-Petrovic R, Maksimovic Z. Antihyperalgesic activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris Moench in a rat model of inflammation. J Ethnopharmacol. 2016; 193(12): 652–656.

[92] Drummond EM, Harbourne N, Marete E, Martyn D, Jacquier JC, O'Riordan D. Inhibition of proinflammatory biomarkers in thp1 macrophages by polyphenols derived from chamomile, meadowsweet and willow bark. Phytother Res. 2013; 27(4): 588–594.

[93] Trouillas P, Calliste CA, Allais DP, Simon A, Marfak A, Delage C, Duroux JL. Antioxidant, anti-inflammatory and antiproliferative properties of sixteen water plant extracts used in the Limousin countryside as herbal teas. Food Chem. 2003; 80(3): 399–407.

[94] Santoro D, Ahrens K, Vesny R, Navarro C, Gatto H, Marsella R. Evaluation of the in vitro effect of boldo and meadowsweet plant extracts on the expression of antimicrobial peptides and inflammatory markers in canine keratinocytes. Re Vet Sci. 2017; 115(12): 255–262.

[95] Samardzic S, Arsenijevic J, Bozic D, Milenkovic M, Tesevic V, Maksimovic Z. Antioxidant, anti-inflammatory and gastroprotective activity of Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris Moench. J Ethnopharmacol. 2018; 213(3): 132–137.

[96] Cholet J, Decombat C, Vareille-Delarbre M, Gainche M, Berry A, Ogéron C. Comparison of the anti-inflammatory and immunomodulatory mechanisms of two medicinal herbs: meadowsweet (Filipendula ulmaria) and harpagophytum (Harpagophytum procumbens). Int J Plant Anim Environ Sci. 2019; 9(3): 145–163.

[97] Bespalov VG, Baranenko DA, Aleksandrov VA, Semenov AL, Kovan'ko EG, Ivanov SD. Chemoprevention of radiation-induced carcinogenesis using decoction of meadowsweet (Filipendula ulmaria) flowers. Pharm Chem J. 2019; 52(10): 860–862.

[98] Bespalov VG, Alexandrov VA, Semenov AL, Vysochina GI, Kostikova VA, Baranenko DA. The inhibitory effect of Filipendula ulmaria (L.) Maxim. on colorectal carcinogenesis induced in rats by methylnitroso urea. J Ethnopharmacol. 2018; 227(12): 1–7.

[99] Lima MJ, Sousa D, Lima RT, Carvalho AM, Ferreira ICFR, Vasconcelos MH. Flower extracts of Filipendula ulmaria (L.) Maxim. inhibit the proliferation of the NCI-H460 tumour cell line. Ind Crops Prod. 2014; 59(8): 149–153.

[100] Mazzio EA, Soliman KF. In vitro screening for the tumoricidal properties of international medicinal herbs. Phytother Res. 2009; 23(3): 385–398.

[101] Mărgăoan R, Zăhan M, Mărghitaş LA, Dezmirean DS, Erler S, Bobiş O. Antiproliferative activity and apoptotic effects of Filipendula ulmaria pollen against C26 mice colon tumour cells. J Apic Sci. 2016; 60(1): 135–144.

[102] Peresun'ko AP, Bespalov VG, Limarenko AI, Aleksandrov VA. Clinico-experimental study of using plant preparations from the flowers of Filipendula ulmaria (L.) Maxim. for the treatment of precancerous changes and prevention of uterine cervical cancer. Vopr Onkol. 1993; 39(7-12): 291–295.

[103] Amosova E, Shilova I, Zueva E, Rybalkina OY. Influence of Filipendula ulmaria (L.) Maxim. extract on Lewis lung carcinoma development and cytostatic therapy effectiveness in mice. Pharm Chem J. 2019; 53(5): 458–461.

[104] Franco JVA, Arancibia M, Szeinman DJ, Alonso IT, Vietto V. Herbal (non-Chinese) medicines for functional dyspepsia. Cochrane Database Syst Rev. 2019;  4: 1–16.

[105] Shilova IV, Zhavoronok TV, Suslov NI, Krasnov EA, Novozheeva TP, Veremeev AV. Hepatoprotective and antioxidant activity of meadowsweet extract during experimental toxic hepatitis. Bull Exp Biol Med. 2006; 142(2): 216–218.

[106] Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol. 2019; 70(1): 151–171.

[107] Akbarzadeh T, Sabourian R, Saeedi M, Rezaeizadeh H, Khanavi M, Ardekani MRS. Liver tonics: review of plants used in Iranian traditional medicine. Asian Pac J Trop Biomed. 2015; 5(3): 170–181.

[108] Katanic J, Pferschy-Wenzig EM, Bauer R, Mihailovic V. Meadowsweet (Filipendula ulmaria): LC-MS phenolic characterization and ameliorating effect on cisplatin-induced hepatotoxicity. Planta Med. 2015; 81(16): 9.

[109] Shilova IV, Zhavoronok TV, Souslov NI, Novozheeva TP, Mustafin RN, Losseva AM. Hepatoprotective properties of fractions from meadowsweet extract during experimental toxic hepatitis. Bull Exp Biol Med. 2008; 146(1): 49–51.

[110] Hansen MB, Nielsen SE, Berg K. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods. 1989; 119(2): 203–210.

[111] Kroes B, Van Ufford HQ, Boer RT, Van den Berg A, Beukelman C, Labadie R. Modulatory effects of Artemisia annua extracts on human complement, neutrophil oxidative burst and proliferation of T lymphocytes. Phytother Res. 1995; 9(8): 551–554.

[112] Woods-Panzaru S, Nelson D, McCollum G, Ballard LM, Millar BC, Maeda Y. An examination of antibacterial and antifungal properties of constituents described in traditional Ulster cures and remedies. Ulster Med J. 2009; 78(1): 13–15.

[113] Bensch K, Tiralongo J, Schmidt K, Matthias A, Bone KM, Lehmann R. Investigations into the antiadhesive activity of herbal extracts against Campylobacter jejuni. Phytother Res. 2011; 25(8): 1125–1132.

[114] Rauha JP, Remes S, Heinonen M, Hopia A, Kahkonen M, Kujala T. Antimicrobial effects of Finnish plant extracts containing flavonoids and other phenolic compounds. Int J Food Microbiol. 2000; 56(S1): 3–12.

[115] Csedo K, Monea M, Sabau M, Esianu S. The antibiotic activity of Filipendula ulmaria. Planta Med. 1993; 59(S1): 675.

[116] Boziaris IS, Proestos C, Kapsokefalou M, Komaitis M. Antimicrobial effect of Filipendula ulmaria plant extract against selected foodborne pathogenic and spoilage bacteria in laboratory media, fish flesh and fish roe product. Food Technol Biotechnol. 2011; 49(2): 263–270.

[117] Boziaris IS, Proestos C, Kapsokefalou M, Komaitis M. Acid-induced injury renders Salmonella enteritidis PT4 sensitive to the antimicrobial action of Filipendula ulmaria plant extract. Int J Food Sci Technol. 2012; 47(8): 1784–1787.

[118] Shilova IV, Krasnov EA, Korotkova EI, Nagaev MG, Lukina AN. Antioxidant properties of extracts from the above-ground parts of Filipendula ulmaria. Pharm Chem J. 2006; 40(12): 660–662.

[119] Nikolova M, Dzhurmanski A. Evaluation of free radical scavenging capacity of extracts from cultivated plants. Biotechnol Equip. 2009; 23(1): 109–111.

[120] Pukalskiene M, Slapsyte G, Dedonyte V, Lazutka JR, Mierauskiene J, Venskutonis PR. Genotoxicity and antioxidant activity of five Agrimonia and Filipendula species plant extracts evaluated by comet and micronucleus assays in human lymphocytes and Ames Salmonella/microsome test. Food Chem Toxicol. 2018; 113(3): 303–313.

[121] Calliste CA, Trouillas P, Allais DP, Simon A, Duroux JL. Free radical scavenging activities measured by electron spin resonance spectroscopy and B16 cell antiproliferative behaviors of seven plants. J Agric Food Chem. 2001; 49(7): 3321–3327.

[122] Ciobotaru LGG, Pavel AZ, Poenaru R, Moaca EA, Florescu R, Danciu R. Assessment of the antioxidant effect of ethanolic extracts obtained from Agrimonia eupatoria L., Filipendula ulmaria (L.) Maxim. and Filipendula vulgaris moench collected from the estern part of Romania. Rev Chim. 2018; 69(9): 2385–2390.

[123] Neagu E, Paun G, Albu C, Radu GL. Assessment of acetylcholinesterase and tyrosinase inhibitory and antioxidant activity of Alchemilla vulgaris and Filipendula ulmaria extracts. J Taiwan Inst Chem Eng. 2015; 52(7): 1–6.

[124] Abdullin IF, Turova EN, Gaisina GK, Budnikov GK. Use of electrogenerated bromine for estimating the total antioxidant capacity of plant raw materials and plant-based medicinal preparations. J Anal Chem. 2002; 57(6): 557–560.

[125] Khanavi M, Hadjiakhoondi A. Comparison of antioxidant activity and total phenol contents of some date seed varieties from Iran. Iran J Pharm Res. 2010; 9(2): 141–146.

[126] DerMarderosian A, Liberti L Beutler JA, Grauds C, Tatro DS, Cirigliano M, DeSilva, D. Meadowsweet. Review of natural products. Facts and comparisons. St. Louis: Wolters Kluwer Health Inc, 2012.

[127] Bechtel D, Beyer L, Gurley BJ. Botanical safety handbook. 2nd ed.  Boca Raton: Taylor and Francis, 2013.

[128] Barnaulov OD, Boldina IG, Galushko VV, Karatygina GK, Kumkov AV, Lumarenko A, Marminson TG, Shukhobodskii BA. Pharmacological properties of galenical preparations from the flowers of Filipendula ulmaria (L.) Maxim. Rastit Resur. 1979; 15(S): 399–407.

[129] Klessig DF, Tian M, Choi HW. Multiple targets of salicylic acid and its derivatives in plants and animals. Front Immunol. 2016; 7(5): 1–10.

[130] Rezabakhsh A, Mahmoodpoor A, Soleimanpour H. Historical perspective of aspirin: a journey from discovery to clinical practice ancient and modern history. J Cardiovasc Thorac Res. 2021; 13(2): 179–180.

[131] Kulyar MF, Bhutta ZA, Ali M, Nawaz S, Asif M. Conventional medicine in the treatment of different diseases as a complementary and alternative medicine. Turkish J Agric Food Sci Technol. 2020; 8(6): 1283–1285.

[132] Filipendula ulmaria. [Accessed 2020]. Available from: https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/filipendula-ulmaria Chevallier.

[133] Li Z, Wang Z, Shen B, Chen C, Ding X, Song H. Effects of aspirin on the gastrointestinal tract: pros vs. cons. Oncol Lett. 2020; 20(3): 2567–2578.

[134] Laster J, Satoskar R. Aspirin-induced acute liver injury. ACG Case Rep J. 2014; 2(1): 48–49.

[135] Akram M, Rashid A. Anti-coagulant activity of plants: mini review. J Thromb Thrombolys. 2017; 44(3): 406–411.

[136] Yang L, Li H, Yang M, Zhang W, Li M, Xu Y, Li J, Kang J, Zhang J, Guo S. Exploration in the mechanism of kaempferol for the treatment of gastric cancer based on network pharmacology. Biomed Res Int. 2020; Article ID 5891016.

[137] Da J, Xu M, Wang Y, Li W, Lu M, Wang Z. Kaempferol promotes apoptosis while inhibiting cell proliferation via androgen-dependent pathway and suppressing vasculogenic mimicry and invasion in prostate cancer. Anal Cell Pathol. 2019; Article ID 1907698.

[138] Bian S, Wan H, Liao X, Wang W. Inhibitory effects of apigenin on tumor carcinogenesis by altering the gut microbiota. Mediators Inflamm. 2020; Article ID 7141970. 

[139] Wang J, Li T, Zang L, Pan X, Wang S, Wu Y, Wang G. Apigenin inhibits human SW620 cell growth by targeting polyamine catabolism. Evid based Complement Altern Med. 2017; Article ID 3684581.

[140] Liao Y, Xu Y, Cao M, Huan Y, Zhu L, Jiang Y, Shen W, Zhu G. Luteolin induces apoptosis and autophagy in mouse macrophage ANA-1 cells via the Bcl-2 pathway. J Immunol Res. 2018; Article ID 4623919.  

[141] Mutlu Altundağ E, Kasacı T, Yılmaz AM, Karademir B, Koçtürk S, Taga Y, Yalçın AS. Quercetin-induced cell death in human papillary thyroid cancer (B-CPAP) cells. J Thyroid Res. 2016; Article ID 9843675.

[142] Rowles JL, Erdman Jr. JW. Carotenoids and their role in cancer prevention. Biochim Biophys Acta Mol Cell Biol Lipids. 2020; 1865(11): 1–27.

[143] Martins CDA, Rocha GDG, Gattass CR, Takiya CM. Pomolic acid exhibits anticancer potential against a docetaxel‑resistant PC3 prostate cell line. Oncol Rep. 2019; 42(1): 328–338.

[144] Brindha P. Role of phytochemicals as immunomodulatory agents: a review. Int J Green Pharm. 2016; 10(1): 1–18.

[145] Tofighi Z, Eshaghi A, Asl MM, Tajic AR, Navai MS, Tavakoli S. Investigation of chemical keys for relationship between plants and their unifloral honeys by hydrodistillation and SPME and biological activities of honeys. Eur Food Res. 2014; 238(4): 665–673.

[146] Cushnie TT, Lamb AJ. Antimicrobial activity of flavonoids. Int J Antimicrob. 2005; 26(5): 343–356.

[147] Petrakou K, Iatrou G, Lamari FN. Ethnopharmacological survey of medicinal plants traded in herbal markets in the Peloponnisos, Greece. J Herb Med. 2020; 19(2): 1–79.

[148] Bayer G. Martindale: the complete drug reference. 38th ed. London: Pharmaceutical Press, 2014.