Phytochemistry and Antioxidant Activity of Aerial Parts of Phagnalon sordidum L.^[1]

Abstract

One new natural monoterpene, 5-O-β-d-glucopyranosyl-2-hydroxy-p-cymene (1), and 11 known compounds were isolated through a biologically oriented approach from the aerial parts of Phagnalon sordidum L. The most active extract and fractions were selected using 3 complementary antioxidant activity assays. Results and the different methods were compared by relative antioxidant capacity index. In addition, the most active extract of P. sordidum was subjected to liquid chromatography coupled with electrospray ionization hybrid linear ion trap quadrupole Orbitrap mass spectrometry to quantify secondary metabolites. Antioxidant activities of ethyl acetate extract, and purified 3,4-dihydroxyacetophenone (3) and nebrodenside A (7) were demonstrated by in vitro cell free model assays, and their protective effect against H₂O₂-induced oxidative stress in a HepG2 (human hepatocellular carcinoma) cell line was established.

Key words

Phagnalon sordidum - Asteraceae - phenolic derivatives - antioxidant activity - mass spectrometry

¹ Dedicated to Professor Dr. Cosimo Pizza on his 70th birthday in recognition of his outstanding contribution to natural product research.

• References

• 1 Sulaiman M, Tijani HI, Abubakar BM, Haruna S, Hindatu Y, Mohammed JN, Idris A. An overview of natural plant antioxidants: analysis and evaluation. Adv Biochem 2013; 1: 64-72
• 2 Pratheeshkumar P, Son YO, Korangath P, Manu KA, Siveen KS. Phytochemicals in cancer prevention and therapy. Biomed Res Int 2015; 2015: 324021
• 3 Kaur C, Kapoor HC. Antioxidants in fruits and vegetables – the millenniumʼs health. Int J Food Sci Tech 2001; 36: 703-725
• 4 Mangoni O, Imperatore C, Tomas CR, Costantino V, Saggiomo V, Mangoni A. The new carotenoid pigment moraxanthin is associated with toxic microalgae. Mar Drugs 2011; 9: 242-255
• 5 Safer AM, al-Nughamish AJ. Hepatotoxicity induced by the anti-oxidant food additive, butylated hydroxytoluene (BHT), in rats: an electron microscopical study. Histol Histopathol 1999; 14: 391-406
• 6 Zheng X, Wang W, Piao H, Xu W, Shi H, Zhao C. The genus Gnaphalium L. (Compositae): phytochemical and pharmacological characteristics. Molecules 2013; 18: 8298-8318
• 7 Funk VA, Susanna A, Steussy TF, Robinson HE. Classification of Compositae. In: Funk VA, Susanna A, Stuessy TF, Bayer RJ. eds. Systematics, Evolution, and Biogeography of Compositae. Vienna: International Association for Plant Taxonomy (IAPT); 2009: 171-189
• 8 Guan PC, Liu HC, Luo GY. The classification and utilization of wild vegetables resources in Guangdong. J South China Agric Univ 2000; 21: 7-11
• 9 Li GP, Liu JQ. The exploration and utilization of wild vegetable resources in Fujian province. J Southwest Agric Univ 1999; 21: 433-437
• 10 Kirschnerová L, Kirschner J. A nomenclatural and taxonomic account of Willemetia (Compositae, Lactuceae, Crepidinae). Taxon 1996; 45: 627-630
• 11 Brunel M, Vitrac C, Costa J, Vitrac X, Muselli A. Subcritical water extraction of antioxidant compounds from Phagnalon sordidum (L.). 14th European Meeting on Supercritical Fluids. Marseille, France: 2014
• 12 Epifano F, Marcotullio MC, Menghini L. Constituents of Phagnalon sordidum . Chem Nat Compd 2002; 38: 204-205
• 13 Dekdouk N, Malafronte N, Russo D, Faraone I, De Tommasi N, Ameddah S, Severino L, Milella L. Phenolic compounds from Olea europaea L. possess antioxidant activity and inhibit carbohydrate metabolizing enzymes in vitro . Evid Based Complement Alternat Med 2015; 2015: 684925
• 14 Castillo UF, Wilkins AL, Lauren DR, McNaughton DE, Smith BL. Structure elucidation of 1, 4-dihydroxy-2-iso-propyl-5-methylphenyl-1-O-β-glucopyranoside, a constituent of Pteridium aquilinum var. caudatum . J Nat Prod 1995; 58: 1889-1891
• 15 Dal Piaz F, Vera Saltos MB, Franceschelli S, Forte G, Marzocco S, Tuccinardi T, Poli G, Nejad Ebrahimi S, Hamburger M, De Tommasi N, Braca A. Drug affinity responsive target stability (DARTS) identifies laurifolioside as a new clathrin heavy chain modulator. J Nat Prod 2016; 79: 2681-2692
• 16 Spreng S, Hofmann T. Activity-guided identification of in vitro antioxidants in beer. J Agric Food Chem 2018; 66: 720-731
• 17 Trimpin S, Lu IC, Rauschenbach S, Hoang K, Wang B, Chubatyi ND, Zhang WJ, Inutan ED, Pophristic M, Sidorenko A, McEwen CN. Spontaneous charge separation and sublimation processes are ubiquitous in nature and in ionization processes in mass spectrometry. J Am Soc Mass Spectrom 2018; 29: 304-315
• 18 Galani JHY, Patel JS, Patel NJ, Talati JG. Storage of fruits and vegetables in refrigerator increases their phenolic acids but decreases the total phenolics, anthocyanins and vitamin C with subsequent loss of their antioxidant capacity. Antioxidants 2017; 6: 59
• 19 Aquino R, Peluso G, De Tommasi N, De Simone F, Pizza C. New polyoxypregnane ester derivatives from Leptadenia hastata . J Nat Prod 1996; 59: 555-564
• 20 Sahakitpichan P, Disadee W, Ruchirawat S, Kanchanapoom T. 3-Hydroxydihydrobenzofuran glucosides from Gnaphalium polycaulon . Chem Pharm Bull 2011; 59: 1160-1162
• 21 Muhammad A, Tel-Çayan G, Öztürk M, Duru ME, Nadeem S, Anis I, Ng SW, Shah MR. Phytochemicals from Dodonaea viscosa and their antioxidant and anticholinesterase activities with structure-activity relationships. Pharm Biol 2016; 54: 1649-1655
• 22 Muhammad A, Anis I, Ali Z, Awadelkarim S, Khan A, Khalid A, Shah MR, Galal M, Khan IA, Choudhary MI. Methylenebissantin: a rare methylene-bridged bisflavonoid from Dodonaea viscosa which inhibits Plasmodium falciparum enoyl-ACP reductase. Bioorg Med Chem Lett 2012; 22: 610-612
• 23 Góngora L, Giner RM, Máñez S, del Carmen Recio M, Ríos JL. New prenylhydroquinone glycosides from Phagnalon rupestre . J Nat Prod 2001; 64: 1111-1113
• 24 Dommisse RA, Van Hoof L, Vlietinck AJ. Structural analysis of phenolic glucosides from Salicaceae by NMR spectroscopy. Phytochemistry 1986; 25: 1201-1204
• 25 Milella L, Milazzo S, De Leo M, Vera Saltos MB, Faraone I, Tuccinardi T, Lapillo M, De Tommasi N, Braca A. α-Glucosidase and α-amylase inhibitors from Arcytophyllum thymifolium . J Nat Prod 2016; 79: 2104-2112
• 26 Aversano R, Contaldi F, Adelfi MG, DʼAmelia V, Diretto G, De Tommasi N, Vaccaro C, Vassallo A, Carputo D. Comparative metabolite and genome analysis of tuber-bearing potato species. Phytochemistry 2017; 137: 42-51
• 27 Horai H, Arita M, Kanaya S, Nihei Y, Ikeda T, Suwa K, Ojima Y, Tanaka K, Tanaka S, Aoshima K, Oda Y, Kakazu Y, Kusano M, Tohge T, Matsuda F, Sawada Y, Hirai MY, Nakanishi H, Ikeda K, Akimoto N, Maoka T, Takahashi H, Ara T, Sakurai N, Suzuki H, Shibata D, Neumann S, Iida T, Tanaka K, Funatsu K, Matsuura F, Soga T, Taguchi R, Saito K, Nishioka T. MassBank: a public repository for sharing mass spectral data for life sciences. J Mass Spectrom 2010; 45: 703-714
• 28 Tuberoso CIG, Serreli G, Montoro P, DʼUrso G, Congiu F, Kowalczyk A. Biogenic amines and other polar compounds in long aged oxidized Vernaccia di Oristano white wines. Food Res Int 2018; 111: 97-103
• 29 Wishart DS, Feunang YD, Marcu A, Guo AC, Liang K, Vázquez-Fresno R, Sajed T, Johnson D, Li C, Karu N, Sayeeda Z, Lo E, Assempour N, Berjanskii M, Singhal S, Arndt D, Liang Y, Badran H, Grant J, Serra-Cayuela A, Liu Y, Mandal R, Neveu V, Pon A, Knox C, Wilson M, Manach C, Scalbert A. HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res 2018; 46: D608-D617
• 30 Walker J, Reichelt KV, Obst K, Widder S, Hans J, Krammer GE, Ley JP, Somoza V. Identification of an anti-inflammatory potential of Eriodictyon angustifolium compounds in human gingival fibroblasts. Food Funct 2016; 7: 3046-3055
• 31 Hong S, Joo T, Jhoo JW. Antioxidant and anti-inflammatory activities of 3, 5-dicaffeoylquinic acid isolated from Ligularia fischeri leaves. Food Sci Biotechnol 2015; 24: 257-263
• 32 Joo TW, Hong SH, Park SY, Kim GY, Jhoo JW. Antioxidant effects of eriodictyol on hydrogen peroxide-induced oxidative stress in HepG2 cells. J Korean Soc Food Sci Nutr 2016; 45: 510-517
• 33 Mokdad-Bzeouich I, Mustapha N, Sassi A, Bedoui A, Ghoul M, Ghedira K, Chekir-Ghedira L. Investigation of immunomodulatory and anti-inflammatory effects of eriodictyol through its cellular anti-oxidant activity. Cell Stress Chaperones 2016; 21: 773-781
• 34 Taguchi N, Hata T, Kamiya E, Kobayashi A, Aoki H, Kunisada T. Reduction in human hair graying by sterubin, an active flavonoid of Eriodictyon angustifolium . J Dermatol Sci 2018; 92: 286-289
• 35 Baeza G, Amigo-Benavent M, Sarriá B, Goya L, Mateos R, Bravo L. Green coffee hydroxycinnamic acids but not caffeine protect human HepG2 cells against oxidative stress. Food Res Int 2014; 62: 1038-1046
• 36 Góngora L, Giner RM, Máñez S, del Carmen Recio M, Schinella G, Ríos JL. Effects of caffeoyl conjugates of isoprenyl-hydroquinone glucoside and quinic acid on leukocyte function. Life Sci 2002; 71: 2995-3004
• 37 Peluso G, De Feo V, De Simone F, Bresciano E, Vuotto ML. Studies on the inhibitory effects of caffeoylquinic acids on monocyte migration and superoxide ion production. J Natural Prod 1995; 58: 639-646
• 38 Nakajima Y, Tsuruma K, Shimazawa M, Mishima S, Hara H. Comparison of bee products based on assays of antioxidant capacities. BMC Complement Altern Med 2009; 9: 4
• 39 Granado-Serrano AB, Angeles Martín M, Izquierdo-Pulido M, Goya L, Bravo L, Ramos S. Molecular mechanisms of (−)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. J Agric Food Chem 2007; 55: 2020-2027
• 40 De Leo M, Peruzzi L, Granchi C, Tuccinardi T, Minutolo F, De Tommasi N, Braca A. Constituents of Polygala flavescens ssp. flavescens and their activity as inhibitors of human lactate dehydrogenase. J Nat Prod 2017; 80: 2077-2087
• 41 Cottiglia F, Bonsignore L, Casu L, Deidda D, Pompei R, Casu M, Floris C. Phenolic constituents from Ephedra nebrodensis . Nat Prod Res 2005; 19: 117-123
• 42 Faraone I, Rai DK, Chiummiento L, Fernandez E, Choudhary A, Prinzo F, Milella L. Antioxidant activity and phytochemical characterization of Senecio clivicolus Wedd. Molecules 2018; 23: 2497
• 43 Russo D, Miglionico R, Carmosino M, Bisaccia F, Andrade PB, Valentão P, Milella L, Armentano MF. A comparative study on phytochemical profiles and biological activities of Sclerocarya birrea (A. Rich.) Hochst leaf and bark extracts. Int J Mol Sci 2018; 19: 186
• 44 Miglionico R, Ostuni A, Armentano MF, Milella L, Crescenzi E, Carmosino M, Bisaccia F. ABCC6 knockdown in HepG2 cells induces a senescent-like cell phenotype. Cell Mol Biol Lett 2017; 22: 7