Planta Med 2013; 79(14): 1370-1379
DOI: 10.1055/s-0033-1350618
Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Targeted and Untargeted Phytochemistry of Ligusticum canbyi: Indoleamines, Phthalides, Antioxidant Potential, and Use of Metabolomics as a Hypothesis-Generating Technique for Compound Discovery

Christina E. Turi
1   Department of Biology, University of British Columbia, Okanagan Campus, Kelowna, British Columbia, Canada
,
Susan J. Murch
2   Department of Chemistry, University of British Columbia, Okanagan Campus, Kelowna, British Columbia, Canada
› Author Affiliations
Further Information

Publication History

received 10 February 2013
revised 24 April 2013

accepted 25 June 2013

Publication Date:
22 July 2013 (online)

Abstract

Ligusticum canbyi (J.M. Coult & Rose) is a medicinal understory forest species used in traditional rituals and ceremonies for spiritual enlightenment and improved mental health. Very little is known about the phytochemical complexity or diversity of L. canbyi tissues or extracts. The current study was undertaken to determine whether Ligusticum tissues and extracts contain specifically targeted biologically active phytochemicals such as: melatonin, serotonin, Z-ligustilide, E-3-butylidenephthalide, and ferulic acid and to investigate the untargeted phytochemical complexity of the entire L. canbyi metabolome. The results of these studies identified melatonin and serotonin in roots and shoots of L. canbyi and L. porteri. Z-ligustilide, E-butylidenephthalide, and ferulic acid were quantified in roots and shoots of L. canbyi. Metabolomic analysis detected approximately 34,000 compounds in each L. canbyi extract, and predictive analysis suggests the presence of more than 70 putative phthalide metabolites. The relative contribution of the known metabolites and the unknown markers to the antioxidant potential of root and shoot tissues were compared, and it was determined that the majority of the antioxidant capacity could be attributed to ferulic acid in the tissues. These data provide new understandings of the phytomedicinal composition and potential mechanisms of activity of L. canbyi extracts and tissues.

Supporting Information

 
  • References

  • 1 Ben shu G, Fading P, Watson M. Ligusticum Linnaeus, Sp. Pl. 1: 250. 1753. Flora of China 2005; 14: 140-150
  • 2 Mabberly DJ. The plant book. 2nd. edition. New York: Cambridge University Press; 1997: 409
  • 3 United States Department of Agriculture (USDA), Natural Resource Conservation Service (NRCS). The PLANTS Database. Available at http://plants.usda.gov Accessed 15 November 2012.
  • 4 Turi CE, Murch SJ. The genus Ligusticum in North America: An ethnobotanical review with special emphasis upon species commercially known as ‘Osha . Herbal Gram 2011; 89: 40-51
  • 5 The Scientific Authority of the United States of America. Species proposal for the 12th meeting of the conference of the parties: Ligusticum porteri. DOC. PC. 10.9.3. Convention on International Trade in Endangered Species of Wild Fauna and Flora. Nairobi: CITES; 2000
  • 6 Moore M. Medicinal plants of the mountain West. Sante Fe: Museum of New Mexico Press; 2003: 184-185
  • 7 Cech R. Growing at-risk medicinal herbs: Cultivation, conservation and ecology. Williams: Horizon Herbs; 2002: 155-167
  • 8 Linares E, Bye RA. A study of 4 medicinal plant-complexes of Mexico and adjacent United-States. J Ethnopharmacol 1987; 19: 153-183
  • 9 Turner NJ, Bouchard R, Kennedy D. Ethnobotany of the Okanagan-Colville Indians of British Columbia and Washington. Victoria, BC: British Columbia Provincial Museum; 1980: 64
  • 10 Hart J. Montana native plants and early peoples. Helena: Montana Historical Society Press; 1992
  • 11 Ran X, Ma L, Peng C, Zhang H, Qin LP. Ligusticum chuanxiong Hort: A review of chemistry and pharmacology. Pharm Biol 2011; 49: 1180-1189
  • 12 Beck JJ, Chou SC. The structural diversity of phthalides from the Apiaceae. J Nat Prod 2007; 70: 891-900
  • 13 Brindis F, Rodríguez R, Bye R, Gonzalez-Andrade M, Mata R. (Z)-3-butylidenephthalide from Ligusticum porteri, an alpha-glucosidase inhibitor. J Nat Prod 2010; 314-320
  • 14 Chou SC, Everngam MC, Sturtz G, Beck JJ. Antibacterial activity of components from Lomatium californicum . Phytother Res 2006; 20: 153-156
  • 15 Wang YH, Liang S, Xu DS, Lin X, He CY, Feng Y, Hong YL. Effect and mechanism of senkyunolide I as an anti-migraine compound from Ligusticum chuanxiong . J Pharm Pharmacol 2011; 63: 261-266
  • 16 Srinivasan M, Sudheer AR, Menon VP. Ferulic acid: Therapeutic potential through its antioxidant property. J Clin Biochem Nutr 2007; 40: 92-100
  • 17 Murch SJ, Simmons CB, Saxena PK. Melatonin in feverfew and other medicinal plants. Lancet 1997; 350: 1598-1599
  • 18 Murch SJ, Alan AR, Cao J, Saxena PK. Melatonin and serotonin in flowers and fruits of Datura metel L. J Pineal Res 2009; 47: 277-283
  • 19 Paredes SD, Korkmaz A, Manchester LC, Tan DX, Reiter RJ. Phytomelatonin: a review RID E-3610-2010. J Exp Bot 2009; 60: 57-69
  • 20 Reiter RJ, Manchester LC, Tan DX. Melatonin in walnuts: Influence on levels of melatonin and total antioxidant capacity of blood. Nutrition 2005; 21: 920-924
  • 21 Murch SJ, Saxena PK. Mammalian neurohormones: potential significance in reproductive physiology of St. Johnʼs wort (Hypericum perforatum L.)?. Naturwissenschaften 2002; 89: 555-560
  • 22 Jones MPA, Cao J, OʼBrien R, Murch SJ, Saxena PK. The mode of action of thidiazuron: auxins, indoleamines, and ion channels in the regeneration of Echinacea purpurea L. Plant Cell Rep 2007; 26: 1481-1490
  • 23 Cao J, Cole IB, Murch SJ. Neurotransmitters, neuroregulators and neurotoxins in the life of plants. Can J Plant Sci 2006; 86: 1183-1188
  • 24 Brown PN, Turi CE, Shipley PR, Murch SJ. Comparisons of large (Vaccinium macrocarpon Ait.) and Small (Vaccinium oxycoccos L., Vaccinium vitis-idaea L.) cranberry in British Columbia by phytochemical determination, antioxidant potential, and metabolomic profiling with chemometric analysis. Planta Med 2012; 78: 630-640
  • 25 Verpoorte R, Choi YH, Kim HK. Metabolomics: Will it stay?. Phytochem Anal 2010; 21: 2-3
  • 26 Murch SJ, Rupasinghe HP, Goodenowe D, Saxena PK. A metabolomic analysis of medicinal diversity in Huang-qin (Scutellaria baicalensis Georgi) genotypes: discovery of novel compounds. Plant Cell Rep 2004; 23: 419-425
  • 27 University of Maryland Program in Sustainable Development and Conservation Biology. Review of four species for potential listing on the Convention on International Trade. Medicinal plants working group-Paper, Reports, & Articles. Available at http://www.nps.gov/plants/medicinal/pubs/cites-a.htm%23ligtop Accessed November 18, 2011.
  • 28 Blokhina O, Virolainen E, Fagerstedt KV. Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann Bot 2003; 91: 179-194
  • 29 Gulcin I. Antioxidant activity of food constituents: an overview. Arch Toxicol 2012; 86: 345-391
  • 30 Iriti M, Varoni EM, Vitalini S. Melatonin in traditional Mediterranean diets. J Pineal Res 2010; 49: 101-105
  • 31 Chanda S, Dave R. In vitro models for antioxidant activity evaluation and some medicinal plants possessing antioxidant properties: An overview. Afr J Microbiol Res 2009; 3: 981-996
  • 32 Krishnaiah D, Sarbatly R, Nithyanandam R. A review of the antioxidant potential of medicinal plant species. Food Bioprod Process 2011; 89: 217-233
  • 33 Rosales-Corral SA, Acuna-Castroviejo D, Coto-Montes A, Boga JA, Manchester LC, Fuentes-Broto L, Korkmaz A, Ma S, Tan DX, Reiter RJ. Alzheimerʼs disease: pathological mechanisms and the beneficial role of melatonin. J Pineal Res 2012; 52: 167-202
  • 34 Cuzzola VF, Ciurleo R, Giacoppo S, Marino S, Bramanti P. Role of Resveratrol and its analogues in the treatment of neurodegenerative diseases: Focus on recent discoveries. CNS Neurol Disord Drug Targets 2011; 10: 849-862
  • 35 Darvesh AS, Carroll RT, Bishayee A, Novotny NA, Geldenhuys WJ, Van der Schyf CJ. Curcumin and neurodegenerative diseases: a perspective. Expert Opin Investig Drugs 2012; 21: 1123-1140
  • 36 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
  • 37 Ho CC, Kumaran A, Hwang LS. Bio-assay guided isolation and identification of anti-Alzheimer active compounds from the root of Angelica sinensis . Food Chem 2009; 114: 246-252
  • 38 Hura T, Hura K, Grzesiak S. Contents of total phenolics and ferulic acid, and PAL activity during water potential changes in leaves of maize single-cross hybrids of different drought tolerance. J Agronom Crop Sci 2008; 194: 104-112
  • 39 Hura T, Hura K, Grzesiak S. Possible contribution of cell-wall-bound ferulic acid in drought resistance and recovery in triticale seedlings. J Plant Physiol 2009; 166: 1720-1733
  • 40 Hura T, Hura K, Grzesiak M. Early stage de-etiolation increases the ferulic acid content in winter triticale seedlings under full sunlight conditions. J Photochem Photobiol B 2010; 101: 279-285
  • 41 Liu L, Gitz DC, McClure JW. Effects of Uv-B on flavonoids, ferulic acid, growth and photosynthesis in barley primary leaves. Physiol Plant 1995; 93: 725-733
  • 42 Posmyk MM, Janas KM. Melatonin in plants. Acta Physiol Plant 2009; 31: 1-11
  • 43 Tan DX, Manchester LC, Di Mascio P, Martinez GR, Prado FM, Reiter RJ. Novel rhythms of N-1-acetyl-N-2-formyl-5-methoxykynuramine and its precursor melatonin in water hyacinth: importance for phytoremediation RID E-3610-2010. Faseb J 2007; 21: 1724-1729
  • 44 Zhao Y, Qi LW, Wang WM, Saxena PK, Liu CZ. Melatonin improves the survival of cryopreserved callus of Rhodiola crenulata . J Pineal Res 2011; 50: 83-88
  • 45 Manchester LC, Tan DX, Reiter RJ, Park W, Monis K, Qi WB. High levels of melatonin in the seeds of edible plants – Possible function in germ tissue protection RID E-3610-2010. Life Sci 2000; 67: 3023-3029
  • 46 Murch SJ, Hall BA, Le CH, Saxena PK. Changes in the levels of indoleamine phytochemicals during veraison and ripening of wine grapes. J Pineal Res 2010; 49: 95-100
  • 47 Galano A, Tan DX, Reiter RJ. Melatonin as a natural ally against oxidative stress: a physicochemical examination RID B-9809-2009. J Pineal Res 2011; 51: 1-16
  • 48 Reiter RJ, Tan DX, Terron MP, Flores LJ, Czarnocki Z. Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions. Acta Biochim Pol 2007; 54: 1-9
  • 49 Yuliana ND, Khatib A, Choi YH, Verpoorte R. Metabolomics for Bioactivity Assessment of Natural Products. Phytother Res 2011; 25: 157-169
  • 50 Urich-Merzenich G, Panek D, Zeitler H, Wagner H, Vetter H. New perspectives for synergy research with the “omic”-technologies. Phytomedicine 2009; 16: 495-508
  • 51 Tianniam S, Bamba T, Fukusaki E. Non-targeted metabolite fingerprinting of oriental folk medicine Angelica acutiloba roots by ultra performance liquid chromatography time-of-flight mass spectrometry. J Sep Sci 2009; 32: 2233-2244
  • 52 Lee SM, Kim H, Jang YP. Chemometric Classification of Morphologically Similar Umbelliferae Medicinal Herbs by DART-TOF-MS Fingerprint. Phytochem Anal 2012; 23: 508-512
  • 53 Brown PN, Murch SJ. Applications of metabolomics to medicinal plants for scientific study and drug discovery. Planta Med 2012; 78: 1056-1056
  • 54 Kobayashi M, Mitsuhashi H. Studies on the constituents of Umbelliferae Plants. 17. Structures of 3 new ligustilide derivatives from Ligusticum wallichii . Chem Pharm Bull 1987; 35: 4789-4792
  • 55 Mitsuhasi H, Nomura M. Studies on constituents of Umbelliferae Plants. 12. Biogenesis of 3-butylphthalide. Chem Pharm Bull 1966; 14: 777-778
  • 56 Gold HJ, Wilson CW. Alkylidene phthalides and dihydrophthalides from celery. J Org Chem 1963; 28: 985
  • 57 Gijbels MJM, Scheffer JJC, Svendsen AB. Phthalides in the essential oil from roots of Levisticum officinale . Planta Med 1982; 44: 207-211
  • 58 Deng SX, Chen SN, Yao P, Nikolic D, Van Breemen RB, Bolton JL, Fong HHS, Farnsworth NR, Pauli GF. Serotonergic activity-guided phytochemical investigation of the roots of Angelica sinensis. J Nat Prod 2006; 69: 536-541
  • 59 Tsuchida T, Kobayashi M, Kaneko K, Mitsuhashi H. Studies on the constituents of Umbelliferae plants. 16. Isolation and structures of 3 new ligustilide derivatives from Angelica acutiloba . Chem Pharm Bull 1987; 35: 4460-4464
  • 60 Betz JM, Brown PN, Roman MC. Accuracy, precision, and reliability of chemical measurements in natural products research. Fitoterapia 2011; 82: 44-52
  • 61 Yi T, Leung KSY, Lu GH, Chan K, Zhang H. Simultaneous qualitative and quantitative analyses of the major constituents in the rhizome of Ligusticum chuanxiong using HPLC-DAD-MS. Chem Pharm Bull 2006; 54: 255-259
  • 62 Takahata Y, Ohnishi-Kameyama M, Furuta S, Takahashi M, Suda I. Highly polymerized procyanidins in brown soybean seed coat with a high radical-scavenging activity. J Agric Food Chem 2001; 49: 5843-5847
  • 63 Brown PN, Murch SJ, Shipley PR. Phytochemical diversity of cranberry (Vaccinium macrocarpon Aiton) cultivars by anthocyanin determination and metabolomic profiling with chemometric analysis. J Agric Food Chem 2012; 60: 261-271