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Planta Med 2021; 87(12/13): 1080-1088
DOI: 10.1055/a-1551-6337
Natural Product Chemistry and Analytical Studies
Original Papers

Identification and Quantification of Polymethoxylated Flavonoids in Different Citrus Species Using UPLC-QTOF-MS/MS and HPLC-DAD[ # ]

Maxime Brits 
1   Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
,
Tania Naessens
1   Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
,
Mart Theunis
1   Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
,
Olfa Taktak
2   Laboratory of Organic Chemistry (Natural Substances Team) LR17ES08, Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia
,
Noureddine Allouche
2   Laboratory of Organic Chemistry (Natural Substances Team) LR17ES08, Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia
,
Luc Pieters 
1   Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
,
Kenn Foubert
1   Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
› InstitutsangabenGefördert durch: Special Fund for Research (BOF) from the University of Antwerp: Concerted Research Action (GOA) Project no.: 30732
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Abstract

Many species from the genus Citrus are used in traditional medicine and contain polymethoxylated flavonoids. These compounds show anti-inflammatory and chemopreventive activities, among others, and therefore have a big potential to be developed as therapeutic agents or dietary supplements. Citrus species are different in their profile and yield of polymethoxylated flavonoids. Therefore, polymethoxylated flavonoids were identified and quantified in seven different Citrus species, including wild-type and commercially available species. All species were profiled using UPLC-QTOF-MS/MS analysis combined with mass spectral molecular networking. A total of 38 polymethoxylated flavonoids were detected and 8 of them were present in every species. As the yield of polymethoxylated flavonoids was different for each species, a generally applicable HPLC-diode array detection method was developed and validated according to the ICH guidelines to quantify the amount of nobiletin and the total amount of polymethoxylated flavonoids expressed as nobiletin. Analysis of the seven samples showed evidence that wild-type Citrus species (e.g., Citrus depressa) contain higher yields of polymethoxylated flavonoids compared to commercially available species (e.g., Citrus limon). Qualitative analysis revealed the broadest variety of different PMFs in C. depressa, Citrus reticulata, and Citrus reticulata × Citrus sinensis, which makes them interesting sources of polymethoxylated flavonoids for future development as therapeutic agents or dietary supplements.

Key words

Citrus - Rutaceae - PMFs - identification - molecular networking - quantification

# Dedicated to Arnold Vlietinck on the occasion of his 80th birthday.


Supporting Information

    An overview of all the PMFs detected in the seven studied Citrus species using UPLC-UV-QTOF-MS/MS and mass spectral molecular networking, including their main fragments, is available as Supporting Information.

  • Supporting Information


Publikationsverlauf

Eingereicht: 28. Dezember 2020

Angenommen nach Revision: 05. Juli 2021

Artikel online veröffentlicht:
19. August 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Augustyn A, Zeidan A, Zelazko A, Eldridge A, McKenna A, Tikkanen A, Gadzikowski A, Schreiber BA, Duignan B, Lozada C, Levin C, Mahajan D, Promeet D, Goldstein E, Rodriguez E, Gregersen E, Munez E, Shukla G, Liesangthem G, Lotha G, Young G, Bolzon H, Luebering JE, Wallenfeldt J, Hibler J, Rafferty JP, Gupta K, Rogers K, Chmielewski K, Manchanda K, Heintz K, Chaveriat L, Dixon L, Matthias M, Petruzzello M, Ray M, Metych M, Bauer P, Riley P, Bhathya P, Vasich S, Hollar S, Singh S, Gupta S, Seddon S. The Information Architects of Encyclopaedia Britannica, Veenu Setia, Wonyoung Jang, Editors. World Data. List of plants in the family Rutaceae. Encyclopædia Britannica. Accessed November 21, 2021 at: https://www.britannica.com/topic/list-of-plants-in-the-family-Rutaceae-2038278
  • 2 PlantNET. Family Rutaceae. PlantNET (The NSW Plant Information Network System). Royal Botanic Gardens and Domain Trust, Sydney. Accessed November 21, 2021 at: http://plantnet.rbgsyd.nsw.gov.au/cgi-bin/NSWfl.pl?page=nswfl&lvl=fm&name=RUTACEAE
  • 3 Nair SA, Sr RK, Nair AS, Baby S. Citrus peels prevent cancer. Phytomedicine 2018; 50: 231-237
    CrossrefPubMedSuche in Google Scholar
  • 4 Abo KA, Fred-Jaiyesimi AA, Jaiyesimi AEA. Ethnobotanical studies of medicinal plants used in the management of diabetes mellitus in South Western Nigeria. J Ethnopharmacol 2008; 115: 67-71
    CrossrefPubMedSuche in Google Scholar
  • 5 Cano JH, Volpato G. Herbal mixtures in the traditional medicine of Eastern Cuba. J Ethnopharmacol 2004; 90: 293-316
    CrossrefPubMedSuche in Google Scholar
  • 6 Heinrich M, Ankli A, Frei B, Weimann C, Sticher O. Medicinal plants in Mexico: Healersʼ consensus and cultural importance. Soc Sci Med 1998; 47: 1859-1871
    CrossrefPubMedSuche in Google Scholar
  • 7 Guarrera PM. Traditional antihelmintic, antiparasitic and repellent uses of plants in Central Italy. J Ethnopharmacol 1999; 68: 183-192
    CrossrefPubMedSuche in Google Scholar
  • 8 Ju HM, Yu KW, Cho SD, Cheong SH, Kwon KH. Anti-cancer effects of traditional Korean wild vegetables in complementary and alternative medicine. Complement Ther Med 2016; 24: 47-54
    CrossrefPubMedSuche in Google Scholar
  • 9 Jiang J, Shan L, Chen Z, Xu H, Wang J, Liu Y, Xiong Y. Evaluation of antioxidant-associated efficacy of flavonoid extracts from a traditional Chinese medicine Hua Ju Hong (peels of Citrus grandis (L.) Osbeck). J Ethnopharmacol 2014; 158 Pt A: 325-330
    CrossrefPubMedSuche in Google Scholar
  • 10 Zarshenas MM, Jamshidi S, Zargaran A. Cardiovascular aspects of geriatric medicines in traditional Persian medicine; a review of phytochemistry and pharmacology. Phytomedicine 2016; 23: 1182-1189
    CrossrefPubMedSuche in Google Scholar
  • 11 Gao Z, Gao W, Zeng SL, Li P, Liu EH. Chemical structures, bioactivities and molecular mechanisms of Citrus polymethoxyflavones. J Funct Foods 2018; 40: 498-509
    CrossrefPubMedSuche in Google Scholar
  • 12 Lee YS, Cha BY, Saito K, Choi SS, Wang XX, Choi BK, Yonezawa T, Teruya T, Nagai K, Woo JT. Effects of a Citrus depressa Hayata (shiikuwasa) extract on obesity in high-fat diet-induced obese mice. Phytomedicine 2011; 18: 648-654
    CrossrefPubMedSuche in Google Scholar
  • 13 Akachi T, Shiina Y, Ohishi Y, Kawaguchi T, Kawagishi H, Morita T, Mori M, Sugiyama K. Hepatoprotective effects of flavonoids from Shekwasha (Citrus depressa) against D-galactosamine-induced liver injury in rats. J Nutr Sci Vitaminol (Tokyo) 2010; 56: 60-67
    CrossrefPubMedSuche in Google Scholar
  • 14 Yanagihara N, Zhang H, Toyohira Y, Takahashi K, Ueno S, Tsutsui M, Takahashi K. New insights into the pharmacological potential of plant flavonoids in the catecholamine system. J Pharmacol Sci 2014; 124: 123-128
    CrossrefPubMedSuche in Google Scholar
  • 15 Nakajima A, Aoyama Y, Nguyen TT, Shin EJ, Kim HC, Yamada S, Nakai T, Nagai T, Yokosuka A, Mimaki Y, Ohizumi Y, Yamada K. Nobiletin, a Citrus flavonoid, ameliorates cognitive impairment, oxidative burden, and hyperphosphorylation of tau in senescence-accelerated mouse. Behav Brain Res 2013; 250: 351-360
    CrossrefPubMedSuche in Google Scholar
  • 16 Nakajima A, Ohizumi Y, Yamada K. Anti-dementia activity of nobiletin, a Citrus flavonoid: a review of animal studies. Clin Psychopharmacol Neurosci 2014; 12: 75-82
    CrossrefPubMedSuche in Google Scholar
  • 17 Upadhyay A, Tuenter E, Amin A, Exarchou V, Hermans N, Apers S, Pieters L. 5-O-Demethylnobiletin, a polymethoxylated flavonoid, from Citrus depressa Hayata peel prevents protein glycation. J Funct Foods 2014; 11: 243-249
    CrossrefPubMedSuche in Google Scholar
  • 18 Du Q, Chen H. The methoxyflavones in Citrus reticulata Blanco cv. ponkan and their antiproliferative activity against cancer cells. Food Chem 2010; 119: 567-572
    CrossrefPubMedSuche in Google Scholar
  • 19 Mahato N, Sharma K, Sinha M, Cho MH. Citrus waste derived nutra-/pharmaceuticals for health benefits: current trends and future perspectives. J Funct Foods 2018; 40: 307-316
    CrossrefPubMedSuche in Google Scholar
  • 20 Marín FR, Soler-Rivas C, Benavente-García O, Castillo J, Pérez-Alvarez JA. By-products from different Citrus processes as a source of customized functional fibres. Food Chem 2007; 100: 736-741
    CrossrefPubMedSuche in Google Scholar
  • 21 Quinn RA, Nothias LF, Vining O, Meehan M, Esquenazi E, Dorrestein PC. Molecular networking as a drug discovery, drug metabolism, and precision medicine strategy. Trends Pharmacol Sci 2017; 38: 143-154
    CrossrefPubMedSuche in Google Scholar
  • 22 Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y, Nguyen DD, Watrous J, Kapono CA, Luzzatto-Knaan T, Porto C, Bouslimani A, Melnik AV, Meehan MJ, Liu WT, Crüsemann M, Boudreau PD, Esquenazi E, Sandoval-Calderón M, Kersten RD, Pace LA, Quinn RA, Duncan KR, Hsu CC, Floros DJ, Gavilan RG, Kleigrewe K, Northen T, Dutton RJ, Parrot D, Carlson EE, Aigle B, Michelsen CF, Jelsbak L, Sohlenkamp C, Pevzner P, Edlund A, McLean J, Piel J, Murphy BT, Gerwick L, Liaw CC, Yang YL, Humpf HU, Maansson M, Keyzers RA, Sims AC, Johnson AR, Sidebottom AM, Sedio BE, Klitgaard A, Larson CB, Boya P CA, Torres-Mendoza D, Gonzalez DJ, Silva DB, Marques LM, Demarque DP, Pociute E, OʼNeill EC, Briand E, Helfrich EJN, Granatosky EA, Glukhov E, Ryffel F, Houson H, Mohimani H, Kharbush JJ, Zeng Y, Vorholt JA, Kurita KL, Charusanti P, McPhail KL, Nielsen KF, Vuong L, Elfeki M, Traxler MF, Engene N, Koyama N, Vining OB, Baric R, Silva RR, Mascuch SJ, Tomasi S, Jenkins S, Macherla V, Hoffman T, Agarwal V, Williams PG, Dai J, Neupane R, Gurr J, Rodríguez AMC, Lamsa A, Zhang C, Dorrestein K, Duggan BM, Almaliti J, Allard PM, Phapale P, Nothias LF, Alexandrov T, Litaudon M, Wolfender JL, Kyle JE, Metz TO, Peryea T, Nguyen DT, VanLeer D, Shinn P, Jadhav A, Müller R, Waters KM, Shi W, Liu X, Zhang L, Knight R, Jensen PR, Palsson BO, Pogliano K, Linington RG, Gutiérrez M, Lopes NP, Gerwick WH, Moore BS, Dorrestein PC, Bandeira N. Sharing and community curation of mass spectrometry data with global natural products social molecular networking. Nat Biotechnol 2016; 34: 828-837
    CrossrefPubMedSuche in Google Scholar
  • 23 ICH. Validation of analytical procedures: text and methodology Q2 (R1). Amsterdam: European Medicines Agency; 2005: 1-13
    Suche in Google Scholar
  • 24 Xing TT, Zhao XJ, Zhang YD, Li YF. Fast separation and sensitive quantitation of polymethoxylated flavonoids in the peels of Citrus using UPLC-Q-TOF-MS. J Agric Food Chem 2017; 65: 2615-2627
    CrossrefPubMedSuche in Google Scholar
  • 25 Canan İ, Gündoğdu M, Seday U, Oluk CA, Karaşahin Z, Eroğlu EÇ, Yazici E, Ünlü M. Determination of antioxidant, total phenolic, total carotenoid, lycopene, ascorbic acid, and sugar contents of Citrus species and mandarin hybrids. Turk J Agric For 2016; 40: 894-899
    CrossrefPubMedSuche in Google Scholar
  • 26 Goulas V, Manganaris GA. Exploring the phytochemical content and the antioxidant potential of Citrus fruits grown in Cyprus. Food Chem 2012; 131: 39-47
    CrossrefPubMedSuche in Google Scholar
  • 27 Green CO, Wheatley AO, Osagie AU, St A Morrison EY, Asemota HN. Determination of polymethoxylated flavones in peels of selected Jamaican and Mexican citrus (Citrus spp.) cultivars by high-performance liquid chromatography. Biomed Chromatogr 2007; 21: 48-54
    CrossrefPubMedSuche in Google Scholar
  • 28 Manthey JA, Grohmann K. Phenols in Citrus peel byproducts. Concentrations of hydroxycinnamates and polymethoxylated flavones in Citrus peel molasses. J Agric Food Chem 2001; 49: 3268-3273
    CrossrefPubMedSuche in Google Scholar
  • 29 Asikin Y, Taira I, Inafuku-Teramoto S, Sumi H, Ohta H, Takara K, Wada K. The composition of volatile aroma components, flavanones, and polymethoxylated flavones in Shiikuwasha (Citrus depressa Hayata) peels of different cultivation lines. J Agric Food Chem 2012; 60: 7973-7980
    CrossrefPubMedSuche in Google Scholar
  • 30 Tomás-Berberán FA, Espín JC. Phenolic compounds and related enzymes as determinants of quality in fruits and vegetables. J Sci Food Agric 2001; 81: 853-876
    CrossrefPubMedSuche in Google Scholar