Download PDF
CC BY-NC-ND 4.0 · Planta Medica International Open 2018; 5(02): e68-e78
DOI: 10.1055/a-0754-5916
Original Papers
Eigentümer und Copyright ©Georg Thieme Verlag KG 2018

Targeted and Untargeted Metabolite Profiling of the Ethnobotanical Martynia annua L. Identifies Bioactive Compounds with Medicinal Properties

Saba Muazzam
1   Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan
2   Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom
,
Joe Harvey
2   Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom
,
Thibaut Deviese
3   Research Laboratory for Archaeology and the History of Art, University of Oxford, Oxford, United Kingdom
,
Muhammad Farman
1   Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan
,
James McCullagh
2   Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom
› Author Affiliations
Further Information

Publication History

received 09 July 2018
revised 28 August 2018

accepted 23 September 2018

Publication Date:
22 November 2018 (online)

   Permissions and Reprints

Abstract

Martynia annua is an indigenous plant found endemic in the Indian subcontinent where it is commonly used for self-treatment of a variety of ailments and diseases. Previous studies have shown that preparations from the plant have antiseptic, anti-inflammatory, and antiepileptic effects in vitro, but the biochemical composition and active compounds responsible for health benefits remain unknown. The aim of this study was to take extracts from different parts of the M. annua plant and, using targeted and untargeted metabolite profiling and quantitation, provide a comprehensive secondary metabolite profile to identify potential biotherapeutic metabolites.

Ultrahigh-performance liquid chromatography, coupled directly to a Thermo Q-Exactive Orbitrap mass spectrometer, was used for high-resolution targeted and untargeted analysis. 89 metabolites were identified and their relative and selected absolute abundances measured across 5 different parts of the plant (leaf, flower, fruit, stem, and root). A number of the compounds identified are known to have bioactive and therapeutic properties; these include trans-ferulic acid, homovanillic acid, syringic acid, isorhamnetin, apigenin, luteolin, and hispidulin. We report their concentrations in different parts of the plant.

Our findings significantly extend the plant metabolite profile of M. annua and amongst the compounds identified, we have highlight those with known biotherapeutic properties. These results provide a foundation for future studies addressing specific compounds that may be responsible for the bioactivity and therapeutic use of M. annua.

Key words

Martynia annua - Martyniaceae - LC-MS/MS - plant secondary metabolites - polyphenols - metabolic profiling - ethnomedicine

Supporting Information

 

  • References

  • 1 Flora G, Josephine MM, Chandra M, Nanthini M, Shalini K, Shantha P, Sivam AR, Valli S. Study on antioxidant potential of different parts of Martynia annua Linn. – a road side weed. Int J Dev Res 2013; 3: 051-054
    PubMedGoogle Scholar
  • 2 Nagda D, Saluja A, Nagda C. Antioxidant activities of methanolic and aqueous extract from leaves of Martynia annua Linn. Pharmacogn J 2009; 1: 288-297
    PubMedGoogle Scholar
  • 3 Dhingra AK, Chopra B, Mittal SK. Martynia annua L.: A review on its ethnobotany, phytochemical and pharmacological profile. J Pharmacogn Phytochem 2013; 1: 135-140
    PubMedGoogle Scholar
  • 4 Babu HB, Mohana LS, Saravana AK. Studies on phytochemical and anticonvulsant property of Martynia annua Linn. Int J Phytopharmacol 2010; 1: 82-86
    PubMedGoogle Scholar
  • 5 Satyavati GV, Gupta AK, Tandon N. Medicinal plants of India. Vol. II. Indian Council of Medical Research; New Delhi: 1987: 223-229
    Google Scholar
  • 6 Watt G. Dictionary of the economic products of India. Vol. V, Cosmo Publications; New Delhi: 1972: 676
    Google Scholar
  • 7 Pillai TSK, Thampi PP, Verma KC. Preliminary pharmacognostioc study of Martynia diandiae Glox. Madhya Bharti J 1964 29: 11-13
    PubMedGoogle Scholar
  • 8 Parvati A, Narayana IL. Chemotaxonomy of a few taxa of Pedaliaceae. Curr Sci 1978; 47: 282
    PubMedGoogle Scholar
  • 9 Frei B, Higdon JV. Antioxidant activity of tea polyphenols in vivo: Evidence from animal studies. J Nutr 2003; 133: 3275S-3284S
    CrossrefPubMedGoogle Scholar
  • 10 French K, Harvey J, McCullagh JSO. Targeted and untargeted metabolic profiling of wild grassland plants identifies antibiotic and anthelmintic compounds targeting pathogen physiology, metabolism and reproduction. Sci Rep 2018; 8: 1695
    CrossrefPubMedGoogle Scholar
  • 11 Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2009; 2: 270-278
    CrossrefPubMedGoogle Scholar
  • 12 Scholz S, Williamson G. Interactions affecting the bioavailability of dietary polyphenols in vivo. Int J Vitam Nutr Res 2007; 77: 224-235
    CrossrefPubMedGoogle Scholar
  • 13 Shen Y, Zhang H, Cheng L, Wang L, Qian H, Qi X. In vitro and in vivo antioxidant activity of polyphenols extracted from black highland barley. Food Chem 2016; 194: 1003-1012
    CrossrefPubMedGoogle Scholar
  • 14 Guo Q, Zhao L, You Q, Yang Y, Gu H, Song G, Lu N, Xin J. Anti-hepatitis B virus activity of wogonin in vitro and in vivo. Antiviral Res 2007; 74: 16-24
    CrossrefPubMedGoogle Scholar
  • 15 Cãrdenas M, Marder M, Blank VC, Roguin LP. Antitumor activity of some natural flavonoids and synthetic derivatives on various human and murine cancer cell lines. Bioorg Med Chem 2006; 14: 2966-2971
    CrossrefPubMedGoogle Scholar
  • 16 Hong JW, Yang GE, Kim YB, Eom SH, Lew JH, Kang H. Anti-inflammatory activity of cinnamon water extracts in vivo and in vitro LPS-induced models. BMC Complement Altern Med 2012; 12: 237
    CrossrefPubMedGoogle Scholar
  • 17 Mondal A, Maity TK, Pal D, Sannigrahi S, Singh J. Isolation and in vivo hepatoprotective activity of Melothria heterophylla (Lour.) Cogn. against chemically induced liver injuries in rats. Asian Pac J Trop Med 2011; 4: 619-623
    CrossrefPubMedGoogle Scholar
  • 18 Tijburg LB, Mattern T, Folts JD, Weisgerber UM, Katan MB. Tea flavonoids and cardiovascular disease: a review. Crit Rev Food Sci Nutr 1997; 37: 771-785
    CrossrefPubMedGoogle Scholar
  • 19 Want EJ, Masson P, Michopoulos F, Wilson ID, Theodoridis G, Plumb RS, Shockcor J, Loftus N, Holmes E, Nicholson JK. Global metabolic profiling of animal and human tissues via UPLC-MS. Nat Protoc 2013; 8: 17-32
    CrossrefPubMedGoogle Scholar
  • 20 Sumner LW, Amberg A, Barrett D, Beale MH, Beger R, Daykin CA, Fan TWM, Fiehn O, Goodacre R, Griffin LJ, Hankemeier T, Hardy N, Harnly J, Higashi R, Kopka J, Lane AN, Lindon AC, Marriott P, Nicholls AW, Reily MD, Thaden JJ, Viant MR. Proposed minimum reporting standards for chemical analysis chemical analysis working group (CAWG) metabolomics standards initiative (MSI). Metabolomics 2007; 3: 211-221
    CrossrefPubMedGoogle Scholar
  • 21 Dunn WB, Alexander E, Ralf JM. Weber Darren J. Creek Marie B, Rainer B, Thomas H, Royston G, Steffen N, Joachim K, Mark RV. Mass appeal: Metabolite identification in mass spectrometry-focused untargeted metabolomics. Metabolomics 2013; 9: 44-66
    PubMedGoogle Scholar
  • 22 Grayer RJ, Kite GC, Abou-Zaid M, Archer LJ. The application of atmospheric pressure chemical ionisation liquid chromatography-mass spectrometry in the chemotaxonomic study of flavonoids: Characterisation of flavonoids from ocimum gratissimum var. gratissimum. Phytochem Anal 2000; 11: 257-267
    CrossrefPubMedGoogle Scholar
  • 23 Sánchez-Rabaneda F, Jáuregui O, Casals I, Andrés-Lacueva C, Izquierdo-Pulido M, Lamuela-Raventós RM. Liquid chromatographic/electrospray ionization tandem mass spectrometric study of the phenolic composition of cocoa (theobroma cacao). J Mass Spectrom 2003; 38: 35-42
    CrossrefPubMedGoogle Scholar
  • 24 March RE, Lewars EG, Stadey CG, Miao XS, Zhao X, Metcalfe CD. A comparison of flavonoid glycosides by electrospray tandem mass spectrometry. J Mass Spectrom 2006; 248: 61-85
    PubMedGoogle Scholar
  • 25 Benayad Z, Gómez-Cordovés C, Es-Safi NE. Characterization of flavonoid glycosides from fenugreek (Trigonella foenum-graecum) crude seeds by HPLC-DAD-ESI/MS analysis. Int J Mol Sci 2014; 15: 20668-20685
    CrossrefPubMedGoogle Scholar
  • 26 Iwashina T. The structure and distribution of the flavonoids in plants. J Plant Res 2000; 113: 287-299
    CrossrefPubMedGoogle Scholar
  • 27 Markham KR. Techniques of flavonoid identification. New York: Academic Press; 1982: 36-51
    Google Scholar
  • 28 Yip ECH, Chan ASL, Pang H, Tam YK, Wong YH. Protocatechuic acid induces cell death in HepG2 hepatocellular carcinoma cells through a c-Jun N-terminal kinase-dependent mechanism. Cell Biol Toxicol 2006; 22: 293-302
    CrossrefPubMedGoogle Scholar
  • 29 Yin MC, Lin CC, Wu HC, Tsao SM, Hsu CK. Apoptotic effects of protocatechuic acid in human breast, lung, liver, cervix, and prostate cancer cells: Potential mechanisms of action. J Agric Food Chem 2009; 57: 6468-6473
    CrossrefPubMedGoogle Scholar
  • 30 An LJ, Guan S, Shi GF, Bao YM, Duan YL, Jiang B. Protocatechuic acid from alpinia oxyphylla against MPP+-induced neurotoxicity in PC12 cells. Food Chem Toxicol 2006; 44: 436-443
    CrossrefPubMedGoogle Scholar
  • 31 Ashidate K, Kawamura M, Mimura D, Tohda H, Miyazaki S, Teramoto T, Yamamoto Y, Hirata Y. Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma. Eur J Pharmacol 2005; 513: 173-179
    CrossrefPubMedGoogle Scholar
  • 32 Alves MJ, Ferreira ICFR, Froufe HJC, Abreu RMV, Martins A, Pintado M. Antimicrobial activity of phenolic compounds identified in wild mushrooms, SAR analysis, and docking studies. J Appl Microbiol 2013; 115: 346-357
    CrossrefPubMedGoogle Scholar
  • 33 Hwang HJ, Park HJ, Chung HJ, Min HY, Park EJ, Hong JY, Lee SK. Inhibitory effects of caffeic acid phenethyl ester on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells. J Nutr Biochem 2006; 17: 356-362
    CrossrefPubMedGoogle Scholar
  • 34 Itoh A, Isoda K, Kondoh M, Kawase M, Watari A, Kobayashi M, Tamesada M, Yagi K. Hepatoprotective effect of syringic acid and vanillic acid on CCl4-induced liver injury. Biol Pharm Bull 2010; 33: 983-987
    CrossrefPubMedGoogle Scholar
  • 35 Kong WK, Zhao YL, Shan LM, Xiao XH, Guo WY. Thermochemical studies on the quantity-antibacterial effect relationship of four organic acids from Radix isatidis on Escherichia coli growth. Biol Pharm Bull 2008; 31: 1301-1305
    CrossrefPubMedGoogle Scholar
  • 36 Zielińska D, Szawara-Nowak D, Zieliński H. Determination of the antioxidant activity of rutin and its contribution to the antioxidant capacity of diversified buckwheat origin material by updated analytical strategies. Pol J Food Nutr Sci 2010; 60: 315-321
    PubMedGoogle Scholar
  • 37 Kamalakkannan N, Prince PS. Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats. Basic Clin Pharmacol Toxicol 2006; 98: 97-103
    CrossrefPubMedGoogle Scholar
  • 38 Dixit S. Anticancer effect of rutin isolated from the methanolic extract of triticum aestivum straw in mice. Med Sci 2014; 2: 153-160
    PubMedGoogle Scholar
  • 39 Dhananjaya BL, Nataraju A, Gowda CDR, Sharath BK, D'Souza CJM. Vanillic acid as a novel specific inhibitor of snake venom 5'-nucleotidase: A pharmacological tool in evaluating the role of the enzyme in snake envenomation. Biochemistry (Mosc) 2009; 74: 1315-1319
    PubMedGoogle Scholar
  • 40 Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20: 933-956
    CrossrefPubMedGoogle Scholar
  • 41 Heleno SA, Ferreira ICFR, Calhelha RC, Esteves AP, Queiroz MJRP. Cytotoxicity of coprinopsis atramentaria extract, organic acids and their synthesized methylated and glucuronate derivatives. Food Res Int 2014; 55: 170-175
    CrossrefPubMedGoogle Scholar
  • 42 Heleno SA, Ferreira ICFR, Ćirić A, Glamočlija J, Martins A, Queiroz MJRP, Soković M. Coreopsis atramentaria extract, organic acids, 25 synthesized glucuronated and methylated derivatives as antibacterial and antifungal agents. Food Funct 2014; 5: 2521-2528
    CrossrefPubMedGoogle Scholar
  • 43 Galano A, Francisco-Marquez M, Alvarez-Idaboy JR. Mechanism and kinetics studies on the antioxidant activity of Sinapinic acid. Phys Chem Chem Phys 2011; 13: 11199-11205
    CrossrefPubMedGoogle Scholar
  • 44 Kampa M, Alexaki VI, Notas G, Nifli AP, Nistikaki A, Hatzoglou A, Bakogeorgou E, Kouimtzoglou E, Blekas G, Boskou D, Gravanis A, Castanas E. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: Potential mechanisms of action. Breast Cancer Res 2004; 6: R63-R74
    CrossrefPubMedGoogle Scholar
  • 45 Kikuzaki H, Hisamoto M, Hirose K, Akiyama K, Taniguchi H. Antioxidant properties of ferulic acid and its related compounds. J Agric Food Chem 2002; 50: 2161-2168
    CrossrefPubMedGoogle Scholar
  • 46 Lin AN, Nakatsui T. Salicylic acid revisited. Int J Dermat 1998; 37: 335-342
    CrossrefPubMedGoogle Scholar
  • 47 Brown JE, Rice-Evans CA. Luteolin-rich artichoke extract protects low density lipoprotein from oxidation in vitro. Free Radic Res 1998; 29: 247-255
    CrossrefPubMedGoogle Scholar
  • 48 Fang J, Zhou Q, Shi XL, Jiang BH. Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells. Carcinogenesis 2007; 28: 713-723
    PubMedGoogle Scholar
  • 49 Mittra B, Saha A, Chowdhury AR, Pal C, Mandal S, Mukhopadhyay S, Bandyopadhyay S, Majumder HK. Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis. Mol Med 2000; 6: 527-541
    PubMedGoogle Scholar
  • 50 Ziyan L, Yongmei Z, Nan Z, Ning T, Baolin L. Evaluation of the anti-inflammatory activity of luteolin in experimental animal models. Planta Med 2007; 73: 221-226
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Nayaka HB, Londonkar RL, Umesh MK, Tukappa A. Antibacterial attributes of apigenin, isolated from portulaca oleracea L. Int J Bacteriol 2014; 2014: 175851
    PubMedGoogle Scholar
  • 52 Budhraja A, Gao N, Zhang Z, Son YO, Cheng S, Wang X, Ding S, Hitron A, Chen G, Luo J, Shi X. Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo. Mol Cancer Ther 2012; 11: 132-142
    CrossrefPubMedGoogle Scholar
  • 53 Luo H, Rankin GO, Liu L, Daddysman MK, Jiang BH, Chen YC. Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells. Nutr Cancer 2009; 61: 554-563
    CrossrefPubMedGoogle Scholar
  • 54 Damianaki A, Bakogeorgou E, Kampa M, Notas G, Hatzoglou A, Panagiotou S, Gemetzi C, Kouroumalis E, Martin PM, Castanas E. Potent inhibitory action of red wine polyphenols on human breast cancer cells. J Cell Biochem 2000; 78: 429-441
    CrossrefPubMedGoogle Scholar
  • 55 Kim B, Choi YE, Kim HS. Eruca sativa and its flavonoid components, quercetin and isorhamnetin, improve skin barrier function by activation of peroxisome proliferator activated receptor (PPAR)-α and suppression of inflammatory cytokines. Phytother Res 2014; 28: 1359-1366
    CrossrefPubMedGoogle Scholar
  • 56 Shirzad M, Pezhman B, Esfandiar H. The effects of hesperetin on apoptosis induction and inhibition of cell proliferation in the prostate cancer PC3 cells. J Herbmed Pharmacol 2015; 4: 121-124
    PubMedGoogle Scholar
  • 57 Roohbakhsh A, Parhiz H, Soltani F, Rezaee R, Iranshahi M. Molecular mechanisms behind the biological effects of hesperidin and hesperetin for the prevention of cancer and cardiovascular diseases. Life Sci 2015; 124: 64-74
    CrossrefPubMedGoogle Scholar
  • 58 Cho J. Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin. Arch Pharm Res 2006; 29: 699-706
    CrossrefPubMedGoogle Scholar
  • 59 Hamalainen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-κB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm 2007; 2007: 45673
    PubMedGoogle Scholar
  • 60 Lee YS. Role of NADPH oxidase-mediated generation of reactive oxygen species in the mechanism of apoptosis induced by phenolic acids in HepG2 human hepatoma cells. Arch Pharm Res 2005; 28: 1183-1189
    CrossrefPubMedGoogle Scholar
  • 61 Kim SH, Choi KC. Anti-cancer effect and underlying mechanism(s) of kaempferol, a phytoestrogen, on the regulation of apoptosis in diverse cancer cell models. Toxocol Res 2013; 29: 229-234
    PubMedGoogle Scholar
  • 62 Antunes-Ricardo M, Gutiérrez-Uribe JA, Martínez-Vitela C, Serna-Saldívar SO. Topical anti-inflammatory effects of isorhamnetin glycosides isolated from Opuntia ficus-indica. Biomed Res Int 2015; 2015: 847320
    CrossrefPubMedGoogle Scholar
  • 63 Xu SL, Choi RC, Zhu KY, Leung KW, Guo AJ, Bi D, Xu H, Lau DT, Dong TT, Tsim KW. Isorhamnetin, a flavonol aglycone from Ginkgo biloba L., induces neuronal differentiation of cultured PC12 cells: Potentiating the effect of nerve growth facto. r. Evid Based Complement Alternat Med 2012; 2012: 278273
    PubMedGoogle Scholar
  • 64 Viola H, Wasowski C, Levi De Stein M, Wolfman C, Silveira R, Dajas F, Medina JH, Paladini AC. Apigenin a component of matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med 1995; 61: 213-216
    Article in Thieme ConnectPubMedGoogle Scholar
  • 65 Jacobson KA, Moro S, Manthey JA, West PL, Ji XD. Interactions of flavones and other phytochemicals with adenosine receptors. Adv Exp Med Biol 2002; 505: 163-171
    PubMedGoogle Scholar
  • 66 Losi G, Puia G, Garzon G, de Vuono MC, Baraldi M. Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical neurons. Eur J Pharm 2004; 502: 41-46
    CrossrefPubMedGoogle Scholar
  • 67 Katavic PL, Lamb K, Navarro H, Prisinzano TE. Flavonoids as opioid receptor ligands: Identification and preliminary structure-activity relationships. J Nat Prod 2007; 70: 1278-1282
    CrossrefPubMedGoogle Scholar
  • 68 Kavvadias D, Sand P, Youdim KA, Qaiser MZ, Rice-Evans C, Baur R, Sigel E, Rausch WD, Riederer P, Schreier P. The flavone hispidulin, a benzodiazepine receptor ligand with positive allosteric properties, traverses the blood-brain barrier and exhibits anticonvulsive effects. Brit J Pharmacol 2004; 142: 811-820
    CrossrefPubMedGoogle Scholar