Download PDF
Planta Med 2013; 79(06): 499-505
DOI: 10.1055/s-0032-1328301
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Diarylheptanoids from Alnus glutinosa Bark and Their Chemoprotective Effect on Human Lymphocytes DNA

Miroslav Novaković
1   Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
,
Miroslava Stanković
1   Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
,
Ivan Vučković
2   Faculty of Chemistry, University of Belgrade, Belgrade, Serbia
,
Nina Todorović
1   Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
,
Snežana Trifunović
2   Faculty of Chemistry, University of Belgrade, Belgrade, Serbia
,
Vele Tešević
2   Faculty of Chemistry, University of Belgrade, Belgrade, Serbia
,
Vlatka Vajs
1   Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
,
Slobodan Milosavljević
2   Faculty of Chemistry, University of Belgrade, Belgrade, Serbia
› Author Affiliations
Further Information

Publication History

received 08 November 2012
revised 01 February 2013

accepted 07 February 2013

Publication Date:
19 March 2013 (online)

    Permissions and Reprints

Abstract

A study of secondary metabolites from the bark of Alnus glutinosa led to the isolation of fourteen diarylheptanoids: oregonin (1), platyphylloside (2), rubranoside A (3), rubranoside B (4), hirsutanonol (5), hirsutenone (6), hirsutanonol-5-O-β-D-glucopyranoside (7), platyphyllonol-5-O-β-D-xylopyranoside (8), aceroside VII (9), alnuside A (10), alnuside B (11), 1,7-bis-(3,4-dihydoxyphenyl)-5-hydroxy-heptane-3-O-β-D-xylopyranoside (12), (5S)-1-(4-hydroxyphenyl)-7-(3,4-dihydroxyphenyl)-5-O-β-D-glucopyranosyl-heptan-3-one (13), and (5S)-1,7-bis-(3,4-dihydroxyphenyl)-5-O-β-D-[6-(3,4-dimethoxycinnamoylglucopyranosyl)]-heptan-3-one (14). All of the diarylheptanoids, except 1 and 5, were found in A. glutinosa for the first time, while 13 and 14 were new compounds. The structures were determined by spectroscopic techniques: 1D and 2D NMR, HR-ESI-MS, FTIR, UV, and CD. All isolated compounds were analyzed for an in vitro protective effect on chromosome aberrations in peripheral human lymphocytes using the cytokinesis-block micronucleus assay. The majority of them, including the new compounds 13 and 14, exerted a pronounced effect in decreasing DNA damage in human lymphocytes. Diarylheptanoids 1, 2, 5, 13, and 14 at a concentration of 1 µg/mL decreased the frequency of micronuclei by 52.8 %, 43.8 %, 63.6 %, 44.4 %, and 56.0 %, respectively, exerting a much stronger effect than the synthetic protector amifostine (17.2 %, c = 1 µg/mL).

Key words

Alnus glutinosa - Betulaceae - diarylheptanoids - HPLC-DAD - NMR analysis - protective effect - CBMN assay

Supporting Information

 

  • References

  • 1 Jovanović B. Genus Alnus Hill. In: Josifović VM, editor Flora of Serbia II. Belgrade: Serbian Academy of Sciences and Arts; 1970: 102-105
    Google Scholar
  • 2 Kuroyanagi M, Shimomae M, Nagashima Y, Muto N, Okuda T, Kawahara N, Nakane T, Sano T. New diarylheptanoids from Alnus japonica . Chem Pharm Bull 2005; 53: 1519-1523
    CrossrefPubMedGoogle Scholar
  • 3 Chung MY, Rho MC, Lee SW, Park HR, Kim K, Lee IA, Kim D, Jeune KH, Lee HS, Kim YK. Inhibition of diacylglycerol acyltransferase by betulinic acid from Alnus hirsuta . Planta Med 2006; 72: 267-269
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Jin WY, Cai XF, Na MK, Lee JJ, Bae KH. Diarylheptanoids from Alnus hirsuta inhibit the NF-kB activation and NO and TNF-α production. Biol Pharm Bull 2007; 30: 810-813
    CrossrefPubMedGoogle Scholar
  • 5 Stević T, Šavikin K, Zdunić G, Stanojković T, Juranić Z, Janković T, Menković N. Antioxidant, cytotoxic, antimicrobial activity of Alnus incana (L.) ssp. incana Moench, and A. viridis (Chaix) Dc ssp. viridis extracts. J Med Food 2010; 13: 700-704
    CrossrefPubMedGoogle Scholar
  • 6 Sati SC, Sati N, Sati OP. Bioactive constituents and medicinal importance of genus Alnus . Pharmacognosy Rev 2011; 5: 174-183
    PubMedGoogle Scholar
  • 7 Tung NH, Kwon HJ, Kim JH, Ra JC, Ding Y, Kim JA, Kim YH. Anti-influenza diarylheptanoids from the bark of Alnus japonica . Bioorg Med Chem Lett 2010; 20: 1000-1003
    CrossrefPubMedGoogle Scholar
  • 8 Matsuda H, Ishikado A, Nishida N, Ninomiya N, Fujiwara H, Kobayasi Y, Yoshikawa M. Hepatoprotective, superoxide scavenging, and antioxidative activities of aromatic constituents from the bark of Betula platyphylla var. japonica . Bioorg Med Chem Lett 1998; 8: 2939-2944
    CrossrefPubMedGoogle Scholar
  • 9 Tung NH, Kim SK, Ra JC, Zhao YZ, Sohn DH, Kim YH. Antioxidative and hepatoprotective diarylheptanoids from the bark of Alnus japonica . Planta Med 2010; 76: 626-629
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Park D, Kim HJ, Jung SY, Yook CS, Yin C, Lee YS. A new diarylheotanoid glycoside from the stem bark of Alnus hirsuta and protective effects of diarylheptanoid derivatives in human HepG2 cells. Chem Pharm Bull 2010; 58: 238-241
    CrossrefPubMedGoogle Scholar
  • 11 Mshvildadze V, Legault J, Lavoie S, Gauthier C, Pichette A. Anticancer diarylheptanoid glycosides from the inner bark of Betula papyrifera . Phytochemystry 2007; 68: 2531-2536
    PubMedGoogle Scholar
  • 12 Choi SE, Kim KH, Kwon JH, Kim SB, Kim HW, Lee MW. Cytotoxic activities of diarylheptanoids from Alnus japonica . Arch Pharm Res 2008; 31: 1287-1289
    CrossrefPubMedGoogle Scholar
  • 13 Sun Y, Tabata K, Matsubara H, Kitanaka S, Suzuki T, Yasukawa K. New cytotoxic diarylheptanoids from the rhizomes of Alpinia officinarum . Planta Med 2008; 74: 427-431
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Liu JX, Di DL, Wei XN, Han Y. Cytotoxic diarylheptanoids from the pericarps of walnuts (Juglans regia). Planta Med 2008; 74: 745-759
    PubMedGoogle Scholar
  • 15 Wolmuth H, Deseo MA, Brushett DJ, Thompson DR, MacFarlane G, Stevenson LM, Leach DN. Diarylheptanoids from Pleuranthodium racemigerum with in vitro prostaglandin E2 inhibitory and cytotoxic activity. J Nat Prod 2010; 73: 743-746
    CrossrefPubMedGoogle Scholar
  • 16 Lee HB, Lee HK, Kim JR, Ahn YJ. Anti-Helicobacter pylori diarylheptanoid identified in the rhizome of Alpinia officinarum . J Korean Soc Appl Biol Chem 2009; 52: 367-370
    CrossrefPubMedGoogle Scholar
  • 17 OʼRourke C, Byres M, Delazar A, Kumarasamy Y, Nahar L, Stewart F, Sarker SD. Hirsutanonol, oregonin and genkwanin from the seeds of Alnus glutinosa (Betulaceae). Biochem Syst Ecol 2005; 33: 749-752
    CrossrefPubMedGoogle Scholar
  • 18 Kumarasamy Y, Cox PJ, Jaspars M, Nahar L, Sarker SD. Bioactivity of hirsutanolol, oregonin and genkwanin, isolated from the seeds of Alnus glutinosa (Betulaceae). Nat Prod Commun 2006; 1: 641-644
    PubMedGoogle Scholar
  • 19 Tian Y, Ishikama H, Piao FY, Yamamoto H, Yamauchi T, Duan ZW, Zhang YM, Ma MY, Cui JS. Micronucleus assay of human lymphocytes: a comparison of cytokinesis-block and human capillary blood lymphocytes methods. J Occup Health 2003; 45: 408-409
    CrossrefPubMedGoogle Scholar
  • 20 Peace BE, Succop P. Spontaneous micronucleus frequency and age: what are normal values?. Mutat Res 1999; 425: 225-230
    PubMedGoogle Scholar
  • 21 Parliament of the Republic of Serbia. Law on Health Care. Official Gazette of the Republic of Serbia 2005; 107: 112-161
    PubMedGoogle Scholar
  • 22 Fenech M, Morley AA. The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations. Mutat Res 1993; 285: 35-44
    CrossrefPubMedGoogle Scholar
  • 23 Stanković M, Tešević V, Vajs V, Todorović N, Milosavljević S, Gođevac D. Antioxidant properties of grape seed extract on human lymphocyte oxidative defence. Planta Med 2008; 74: 730-735
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Surralles J, Xamena N, Creus A, Catalan J, Norppa H, Marcos R. Induction of micronuclei by five pyrethroid insecticides in whole-blood and isolated human lymphocyte cultures. Mutat Res 1995; 341: 169-184
    CrossrefPubMedGoogle Scholar
  • 25 Smite E, Lundgren LN, Andersson R. Arylbutanoid and diarylheptanoid glycosides from inner bark of Betula pendula . Phytochemistry 1993; 32: 365-369
    CrossrefPubMedGoogle Scholar
  • 26 Lee MW, Park MS, Jeong DW, Kim KH, Kim HH, Toh SH. Diarylheptanoids from the leaves of Alnus hirsuta Turcz. Arch Pharm Res 2000; 23: 50-53
    CrossrefPubMedGoogle Scholar
  • 27 Gonzalez-Laredo RF, Helm RF, Chen J, Karchesy JJ. Two acylated diarylheptanoid glycosides from red alder bark. Nat Prod Lett 1998; 61: 1292-1294
    CrossrefPubMedGoogle Scholar
  • 28 Ohta S, Aoki T, Hirata T, Suga T. The structures of four diarylheptanoid glycosides from the female flowers of Alnus serrulatoides . J Chem Soc [Perkin I] 1984; 1: 1635-1642
    PubMedGoogle Scholar
  • 29 Chen J, Gonzalez-Laredo RF, Karchesy JJ. Minor diarylheptanoid glycosides of Alnus rubra bark. Phytochemistry 2000; 53: 971-973
    CrossrefPubMedGoogle Scholar
  • 30 Ohta S, Koyama M, Aoki T, Suga T. Absolute configuration of platyphylloside and (−)-centrolobol. Bull Chem Soc Jpn 1985; 58: 2423-2424
    CrossrefPubMedGoogle Scholar
  • 31 Nomura M, Tokoroyama T, Kubota T. Biarylheptanoids and other constituents from wood of Alnus japonica . Phytochemistry 1981; 20: 1097-1104
    CrossrefPubMedGoogle Scholar
  • 32 Seo S, Tomita Y, Tori K, Yoshimura Y. Determination of the absolute configuration of a secondary hydroxy group in a chiral secondary alcohol using glycosidation shifts in carbon-13 nuclear magnetic resonance spectroscopy. J Am Chem Soc 1978; 100: 3331-3339
    CrossrefPubMedGoogle Scholar
  • 33 Suga T, Ohta S, Hivata T, Aoki T. Absolute configuration of diarylheptanoid xyloside, oregonine, isolated from the female flowers of Alnus serrulatoides . Chem Lett 1982; 895-898
    PubMedGoogle Scholar
  • 34 Grochová D, Šmardová J. The antimutagenic and cytoprotective effects of amifostine: the role of p 53. J Appl Biomed 2007; 5: 171-178
    PubMedGoogle Scholar
  • 35 Ortiz R, Cortes L, Gonzalez C, Lopez L, Perez P, Cortes E, Betancourt M. Analysis of mitomycin c- induced micronuclei in lymphocytes from malnourished infected children. Environ Mol Mutagen 1997; 30: 363-370
    CrossrefPubMedGoogle Scholar
  • 36 Roncada T, Vicentini VEP, Mantovani MS. Possible modulating actions of plant extracts on the chromosome breaking activity of MMC and Ara-C in human lymphocytes in vitro . Toxicol In Vitro 2004; 18: 617-622
    CrossrefPubMedGoogle Scholar
  • 37 Pfuhler S, Wolf HU. Detection of DNA-crosslinking agents with the alkaline comet assay. Environ Mol Mutagen 1996; 27: 196-201
    CrossrefPubMedGoogle Scholar
  • 38 Vučković I, Vajs V, Stanković M, Tesević V, Milosavljević S. A new prenylated flavanonol from Seseli annuum roots showing protective effect on human lymphocytes DNA. Chem Biodivers 2010; 7: 698-704
    CrossrefPubMedGoogle Scholar
  • 39 Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem 2002; 13: 572-584
    CrossrefPubMedGoogle Scholar