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CC BY-NC-ND 4.0 · Planta Med 2024; 90(07/08): 641-650
DOI: 10.1055/a-2225-8314
Natural Product Chemistry and Analytical Studies
Original Papers

Structural Characterization, and Antioxidative and Anti-inflammatory Activities of Phylloxanthobilins in Tropaeolum majus, a Plant with Relevance in Phytomedicine[ # ]

Patricia Frei
1   Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilian University of Munich, Germany
,
Christian Nadegger
2   Institute of Organic Chemistry, University of Innsbruck, Austria
,
Angelika M. Vollmar
1   Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilian University of Munich, Germany
,
Thomas Müller
2   Institute of Organic Chemistry, University of Innsbruck, Austria
,
Simone Moser 
1   Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilian University of Munich, Germany
3   Institute of Pharmacy, Department of Pharmacognosy, University of Innsbruck, Austria
› InstitutsangabenS. M. gratefully acknowledges funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation; Project-ID 448289381).
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Abstract

Tropaeolum majus (garden nasturtium) is a plant with relevance in phytomedicine, appreciated not only for its pharmaceutical activities, but also for its beautiful leaves and flowers. Here, we investigated the phytochemical composition of senescent nasturtium leaves. Indeed, we identified yellow chlorophyll catabolites, also termed phylloxanthobilins, which we show to contribute to the bright yellow color of the leaves in the autumn season. Moreover, we isolated and characterized the phylloxanthobilins from T. majus, and report the identification of a pyro-phylloxanthobilin, so far only accessible by chemical synthesis. We show that the phylloxanthobilins contribute to bioactivities of T. majus by displaying strong anti-oxidative effects in vitro and in cellulo, and anti-inflammatory effects as assessed by COX-1 and COX-2 enzyme inhibition, similar to other bioactive ingredients of T. majus, isoquercitrin, and chlorogenic acid. Hence, phylloxanthobilins could play a role in the efficacy of T. majus in the treatment of urinary tract infections, an established indication of T. majus. With the results shown in this study, we aid in the completion of the phytochemical profile of T. majus by identifying additional bioactive natural products as relevant components of this medicinal plant.

Key words

Tropaeolum majus - Tropaeolaceae - antioxidant - anti-inflammatory properties - phylloxanthobilins - pyro-phyllobilin - phytochemicals

# This work is dedicated to Professors Rudolf Bauer, Chlodwig Franz, Brigitte Kopp, and Hermann Stuppner for their invaluable contributions and commitment to Austrian Pharmacognosy.


Supporting Information

    UV/Vis data and MS2 fragmentations of all PxBs as well as NMR spectra of Tm-PxB-1,-2,-4 are available as Supporting Information.

  • Ergänzendes Material


Publikationsverlauf

Eingereicht: 28. Juni 2023

Angenommen nach Revision: 28. November 2023

Artikel online veröffentlicht:
06. Juni 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Wang P, Karg CA, Frey N, Frädrich J, Vollmar AM, Moser S. Phyllobilins as a challenging diverse natural product class: Exploration of pharmacological activities. Arch Pharm 2021; 354: e2100061
    CrossrefPubMedSuche in Google Scholar
  • 2 Kräutler B. Phyllobilins – The abundant bilin-type tetrapyrrolic catabolites of the green plant pigment chlorophyll. Chem Soc Rev 2014; 43: 6227-6238
    CrossrefPubMedSuche in Google Scholar
  • 3 Moser S, Ulrich M, Müller T, Kräutler B. A yellow chlorophyll catabolite is a pigment of the fall colours. Photochem Photobiol Sci 2008; 7: 1577-1581
    CrossrefPubMedSuche in Google Scholar
  • 4 Vergeiner C, Ulrich M, Li C, Liu X, Müller T, Kräutler B. Stereo- and regioselective phyllobilane oxidation in leaf homogenates of the peace lily (Spathiphyllum wallisii): hypothetical endogenous path to yellow chlorophyll catabolites. Chem Eur J 2015; 21: 136-149
    CrossrefPubMedSuche in Google Scholar
  • 5 Erhart T, Vergeiner S, Kreutz C, Kräutler B, Müller T. Chlorophyll breakdown in a fern – Discovery of carbon-skeleton rearranged phyllobilin isomers. Angew Chem Int Ed 2018; 57: 14937
    CrossrefPubMedSuche in Google Scholar
  • 6 Li C, Wurst K, Berghold J, Podewitz M, Liedl KR, Kräutler B. Pyro-phyllobilins: Elusive chlorophyll catabolites lacking a critical carboxylate function of the natural chlorophylls. Chem Eur J 2018; 24: 2987-2998
    CrossrefPubMedSuche in Google Scholar
  • 7 Moser S, Erhart T, Neuhauser S, Kräutler B. Phyllobilins from senescence-associated chlorophyll breakdown in the leaves of Basil (Ocimum basilicum) show increased abundance upon herbivore attack. J Agric Food Chem 2020; 68: 7132-7142
    CrossrefPubMedSuche in Google Scholar
  • 8 Mathesius U. Flavonoid functions in plants and their interactions with other organisms. Plants (Basel) 2018; 7: 30
    PubMedSuche in Google Scholar
  • 9 Faizal A, Geelen D. Saponins and their role in biological processes in plants. Phytochem Rev 2013; 12: 877-893
    CrossrefPubMedSuche in Google Scholar
  • 10 Dixon RA. Natural products and plant disease resistance. Nature 2001; 411: 843-847
    CrossrefPubMedSuche in Google Scholar
  • 11 Hayes M, Ferruzzi MG. Update on the bioavailability and chemopreventative mechanisms of dietary chlorophyll derivatives. Nutr Res 2020; 81: 19-37
    CrossrefPubMedSuche in Google Scholar
  • 12 Vaňková K, Marková I, Jašprová J, Dvořák A, Subhanová I, Zelenka J, Novosádová I, Rasl J, Vomastek T, Sobotka R, Muchová L, Vítek L. Chlorophyll-mediated changes in the redox status of pancreatic cancer cells are associated with its anticancer effects. Oxid Med Cell Longev 2018; 2018: 4069167
    CrossrefPubMedSuche in Google Scholar
  • 13 Karg CA, Taniguchi M, Lindsey JS, Moser S. Phyllobilins – Bioactive natural products derived from chlorophyll – Plant origins, structures, absorption spectra, and biomedical properties. Planta Med 2023; 89: 637-662
    Thieme ConnectPubMedSuche in Google Scholar
  • 14 Karg CA, Wang P, Vollmar AM, Moser S. Re-opening the stage for Echinacea research – Characterization of phylloxanthobilins as a novel anti-oxidative compound class in Echinacea purpurea . Phytomedicine 2019; 60: 152969
    CrossrefPubMedSuche in Google Scholar
  • 15 Karg CA, Doppler C, Schilling C, Jakobs F, Dal Colle MCS, Frey N, Bernhard D, Vollmar AM, Moser S. A yellow chlorophyll catabolite in leaves of Urtica dioica L.: An overlooked phytochemical that contributes to health benefits of stinging nettle. Food Chem 2021; 359: 129906
    CrossrefPubMedSuche in Google Scholar
  • 16 Berg D, Youdim MB, Riederer P. Redox imbalance. Cell Tissue Res 2004; 318: 201-213
    CrossrefPubMedSuche in Google Scholar
  • 17 Stocker R, John F, Keaney J. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004; 84: 1381-1478
    CrossrefPubMedSuche in Google Scholar
  • 18 Behl T, Kaur I, Kotwani A. Implication of oxidative stress in progression of diabetic retinopathy. Surv Ophthalmol 2016; 61: 187-196
    CrossrefPubMedSuche in Google Scholar
  • 19 Toledo-Ibelles P, Mas-Oliva J. Antioxidants in the fight against atherosclerosis: Is this a dead end?. Curr Atheroscler Rep 2018; 20: 36
    CrossrefPubMedSuche in Google Scholar
  • 20 Karg CA, Parráková L, Fuchs D, Schennach H, Kräutler B, Moser S, Gostner JM. A chlorophyll-derived phylloxanthobilin is a potent antioxidant that modulates immunometabolism in human PBMC. Antioxidants (Basel) 2022; 11: 2056
    CrossrefPubMedSuche in Google Scholar
  • 21 Jakubczyk K, Janda K, Watychowicz K, Aukasiak J, Wolska J. Garden nasturtium (Tropaeolum majus L.) – a source of mineral elements and bioactive compounds. Rocz Panstw Zakl Hig 2018; 69: 119-126
    PubMedSuche in Google Scholar
  • 22 Gasparotto Junior A, Prando TB, Leme Tdos S, Gasparotto FM, Lourenço EL, Rattmann YD, Da Silva-Santos JE, Kassuya CA, Marques MC. Mechanisms underlying the diuretic effects of Tropaeolum majus L. extracts and its main component isoquercitrin. J Ethnopharmacol 2012; 141: 501-509
    CrossrefPubMedSuche in Google Scholar
  • 23 Gasparotto Junior A, Gasparotto FM, Lourenço EL, Crestani S, Stefanello ME, Salvador MJ, da Silva-Santos JE, Marques MC, Kassuya CA. Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: evidence for the inhibition of angiotensin converting enzyme. J Ethnopharmacol 2011; 134: 363-372
    CrossrefPubMedSuche in Google Scholar
  • 24 Kleinwächter M, Schnug E, Selmar D. The glucosinolate-myrosinase system in nasturtium (Tropaeolum majus L.): variability of biochemical parameters and screening for clones feasible for pharmaceutical utilization. J Agric Food Chem 2008; 56: 11165-11170
    CrossrefPubMedSuche in Google Scholar
  • 25 Gasparotto jr. A, Boffo MA, Lourenço EL, Stefanello ME, Kassuya CA, Marques MC. Natriuretic and diuretic effects of Tropaeolum majus (Tropaeolaceae) in rats. J Ethnopharmacol 2009; 122: 517-522
    CrossrefPubMedSuche in Google Scholar
  • 26 Bazylko A, Granica S, Filipek A, Piwowarski J, Stefańska J, Osińska E, Kiss AK. Comparison of antioxidant, anti-inflammatory, antimicrobial activity and chemical composition of aqueous and hydroethanolic extracts of the herb of Tropaeolum majus L. Ind Crops Prod 2013; 50: 88-94
    CrossrefPubMedSuche in Google Scholar
  • 27 Wakana D, Kato H, Momose T, Sasaki N, Ozeki Y, Goda Y. NMR-based characterization of a novel yellow chlorophyll catabolite, Ed-YCC, isolated from Egeria densa . Tetrahedron Lett 2014; 55: 2982-2985
    CrossrefPubMedSuche in Google Scholar
  • 28 Müller T, Vergeiner S, Kräutler B. Structure elucidation of chlorophyll catabolites (phyllobilins) by ESI-mass spectrometry – pseudo-molecular ions and fragmentation analysis of a nonfluorescent chlorophyll catabolite (NCC). Int J Mass Spectrom 2014; 365 – 366: 48-55
    CrossrefPubMedSuche in Google Scholar
  • 29 Berghold J, Breuker K, Oberhuber M, Hörtensteiner S, Kräutler B. Chlorophyll breakdown in spinach: On the structure of five nonfluorescent chlorophyll catabolites. Photosynth Res 2002; 74: 109-119
    CrossrefPubMedSuche in Google Scholar
  • 30 Moser S, Müller T, Holzinger A, Lütz C, Kräutler B. Structures of chlorophyll catabolites in bananas (Musa acuminata) reveal a split path of chlorophyll breakdown in a ripening fruit. Chemistry 2012; 18: 10873-10885
    CrossrefPubMedSuche in Google Scholar
  • 31 Kuai B, Chen J, Hörtensteiner S. The biochemistry and molecular biology of chlorophyll breakdown. J Exp Bot 2017; 69: 751-767
    CrossrefPubMedSuche in Google Scholar
  • 32 Liu J, Wang H, Manicke NE, Lin JM, Cooks RG, Ouyang Z. Development, characterization, and application of paper spray ionization. Anal Chem 2010; 82: 2463-2471
    CrossrefPubMedSuche in Google Scholar
  • 33 Liu J, Wang H, Cooks RG, Ouyang Z. Leaf spray: direct chemical analysis of plant material and living plants by mass spectrometry. Anal Chem 2011; 83: 7608-7613
    CrossrefPubMedSuche in Google Scholar
  • 34 Apak R, Güçlü K, Demirata B, Özyürek M, Çelik SE, Bektaşoğlu B, Berker KI, Özyurt D. Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay. Molecules 2007; 12: 1496-1547
    CrossrefPubMedSuche in Google Scholar
  • 35 Li X, Jiang Q, Wang T, Liu J, Chen D. Comparison of the antioxidant effects of quercitrin and isoquercitrin: Understanding the role of the 6″-OH group. Molecules 2016; 21: 1246
    CrossrefPubMedSuche in Google Scholar
  • 36 Conrad A, Biehler D, Nobis T, Richter H, Engels I, Biehler K, Frank U. Broad spectrum antibacterial activity of a mixture of isothiocyanates from nasturtium (Tropaeoli majoris herba) and horseradish (Armoraciae rusticanae radix). Drug Res (Stuttg) 2013; 63: 65-68
    Thieme ConnectPubMedSuche in Google Scholar
  • 37 Lee EH, Park HJ, Jung HY, Kang IK, Kim BO, Cho YJ. Isoquercitrin isolated from newly bred Green ball apple peel in lipopolysaccharide-stimulated macrophage regulates NF-κB inflammatory pathways and cytokines. 3 Biotech 2022; 12: 100
    CrossrefPubMedSuche in Google Scholar
  • 38 Gerhäuser C. 68 – Phenolic Beer Compounds to Prevent Cancer. In: Preedy VR. editor Beer in Health and Disease Prevention. San Diego: Academic Press; 2009: 669-684
    Suche in Google Scholar
  • 39 Strohalm M, Kavan D, Novák P, Volný M, Havlícek V. mMass 3: A cross-platform software environment for precise analysis of mass spectrometric data. Anal Chem 2010; 82: 4648-4651
    CrossrefPubMedSuche in Google Scholar
  • 40 Moser S, Scherzer G, Kräutler B. On the nature of isomeric nonfluorescent chlorophyll catabolites in leaves and fruit – A study with a ubiquitous phylloleucobilin and its main isomerization product. Chem Biodivers 2017; 14: e1700368
    CrossrefPubMedSuche in Google Scholar
  • 41 Karg CA, Wang P, Kluibenschedl F, Müller T, Allmendinger L, Vollmar AM, Moser S. phylloxanthobilins are abundant linear tetrapyrroles from chlorophyll breakdown with activities against cancer cells. European J Org Chem 2020; 2020: 4499-4509
    CrossrefPubMedSuche in Google Scholar