LC-MS N-alkylamide Profiling of an Ethanolic Anacyclus pyrethrum Root Extract

Abstract

An N-alkylamide profiling from an ethanolic Anacyclus pyrethrum DC. root extract was performed using a gradient reversed phase high performance liquid chromatography/UV/electrospray-ionization ion-trap mass spectrometry (HPLC/UV/ESI-MS) method on an embedded polar column. MS¹ and MS² fragmentation data were used for identification purposes while UV was used for quantification. Thirteen N-alkylamides (five N-isobutylamides, three N-methyl isobutylamides, four tyramides and one 2-phenylethylamide) were detected. Six of them, identified as undeca-2E,4E-diene-8,10-diynoic acid isobutylamide, undeca-2E,4E-diene-8,10-diynoic acid N-methyl isobutylamide, tetradeca-2E,4E-diene-8,10-diynoic acid tyramide, deca-2E,4E-dienoic acid N-methyl isobutylamide, tetradeca-2E,4E,XE/Z-trienoic acid tyramide and tetradeca-2E,4E,XE/Z,YE/Z-tetraenoic isobutylamide, are novel compounds which have never been reported before from Anacyclus pyrethrum.

Key words

Anacyclus pyrethrum - Asteraceae - LC-MS plant profiling - N-alkylamides - pellitorine - anacycline

• References

• 1 Christensen LP, Lam J. Acetylenes and related compounds in Heliantheae. Phytochemistry 1991; 30: 11-49
• 2 Christensen LP, Lam J. Acetylenes and related compounds in Asteraceae (= Compositae). Phytochemistry 1991; 30: 2453-2476
• 3 Xiong QB, Shi DW, Yamamoto H, Mizuno M. Alkylamides from pericarps of Zanthoxylum bungeanum . Phytochemistry 1997; 46: 1123-1126
• 4 Venkatakrishnabhatt H, Panchal GM, Patel VK. Toxicity of anacyclus pyrethrum in mice. Curr Sci 1988; 57: 912-913
• 5 Crombie L. Amides of vegetable origin .4. The nature of pellitorine and anacyclin. J Chem Soc 1955; 999-1006
• 6 Patel VK, Patel RV, Venkatakrishnabhatt H, Gopalakrishna G, Devasankariah G. A clinical appraisal of Anacyclus pyrethrum root extract in dental patients. Phytother Res 1992; 6: 158-159
• 7 Pahuja M, Mehla J, Reeta KH, Joshi S, Gupta YK. Protective effect of Anacyclus pyrethrum against seizures and seizure-induced cognitive impairment in rats. Eur Neuropsychopharmacol 2010; 20: S246-S247
• 8 Zaidi SMA, Pathan SA, Jain GK, Pathan SA, Jain GK, Ahmad FJ, Jamil S, Singh S, Khar RK. Anticonvulsant and neuropharmacological studies of Anacyclus pyrethrum root extract. Neurosci Res 2009; 65: S250
• 9 Bendjeddou D, Lalaoui K, Satta D. Immuno stimulating activity of the hot water-soluble polysaccharide extracts of Anacyclus pyrethrum, Alpinia galanga and Citrullus colocynthis . J Ethnopharmacol 2003; 88: 155-160
• 10 Sharma V, Thakur M, Chauhan NS, Dixit VK. Immunomodulatory activity of petroleum ether extract of Anacyclus pyrethrum . Pharm Biol 2010; 48: 1247-1254
• 11 Goel V, Chang C, Slama JV, Barton R, Bauer R, Gahler R, Basu TK. Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats. Int Immunopharmacol 2002; 2: 381-387
• 12 Cech NB, Kandhi V, Davis JM, Hamilton A, Eads D, Laster SM. Echinacea and its alkylamides: Effects on the influenza A-induced secretion of cytokines, chemokines, and PGE(2) from RAW 264.7 macrophage-like cells. Int Immunopharmacol 2010; 10: 1268-1278
• 13 Clifford LJ, Nair MG, Rana J, Dewitt DL. Bioactivity of alkamides isolated from Echinacea purpurea (L.) Moench. Phytomedicine 2002; 9: 249-253
• 14 Lalone CA, Hammer KDP, Wu L, Bae J, Leyva N, Liu Y, Solco KS, Kraus GA, Murphy PA, Wurtele ES, Kim OK, Seo KI, Widrlechner MP, Birt DF. Echinacea species and alkamides inhibit prostaglandin E-2 production in RAW264.7 mouse macrophage cells. J Agric Food Chem 2007; 55: 7314-7322
• 15 Raduner S, Majewska A, Chen JZ, Xie XQ, Hamon J, Faller B, Altmann KH, Gertsch J. Alkylamides from Echinacea are a new class of cannabinomimetics – Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects. J Biol Chem 2006; 281: 14192-14206
• 16 Stevenson LM, Matthias A, Banbury L, Penman KG, Bone KM, Leach D, Lehmann RP. Modulation of macrophage immune responses by Echinacea . Molecules 2005; 10: 1279-1285
• 17 Woelkart K, Xu W, Pei Y, Makriyannis A, Picone RP, Bauer R. The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots. Planta Med 2005; 71: 701-705
• 18 Wu L, Fan N, Lin M, Chu IR, Huang SJ, Hu CY, Han SY. Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-Induced inflammatory mediators. J Agric Food Chem 2008; 56: 2341-2349
• 19 Boonen J, Bronselaer A, Nielandt J, Veryser L, De Tré G, De Spiegeleer B. Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides. J Ethnopharmacol 2012; 142: 563-590
• 20 Muller-Jakic B, Breu W, Probstle A, Redl K, Greger H, Bauer R. In-vitro inhibition of cyclooxygenase and 5-lipoxygenase by alkamides from Echinacea and Achillea species. Planta Med 1994; 60: 37-40
• 21 Rimbau V, Risco E, Canigueral S, Iglesias J. Antiinflammatory activity of some extracts from plants used in the traditional medicine of North-African countries. Phytother Res 1996; 10: 421-423
• 22 Sharma V, Thakur M, Chauhan N, Dixit V. Evaluation of the anabolic, aphrodisiac and reproductive activity of Anacyclus pyrethrum DC in male rats. Sci Pharm 2009; 97-110
• 23 Sharma V, Thakur M, Chauhan N, Dixit V. Effect of ethanolic extract Anacyclus pyrethrum DC on reproductive parameter of male rats. Planta Med 2010; 76: 1214-1214
• 24 Sharma V, Thakur M, Chauhan N, Dixit V. Effect of Petroleum ether extract of Anacyclus pyrethrum DC on sexual behavior in male rats. J Chin Integr Med 2010; 8: 613-623
• 25 Sukumaran K, Kuttan R. Inhibition of tobacco-induced mutagenesis by eugenol and plant-extracts. Mutat Res Genetic Toxicol 1995; 343: 25-30
• 26 Kalim MD, Bhattacharyya D, Banerjee A, Chattopadhyay S. Oxidative DNA damage preventive activity and antioxidant potential of plants used in Unani system of medicine. BMC Complement Altern Med 2010; 10: 77
• 27 Boonen J, Baert B, Burvenich C, Blondeel P, De Saeger S, De Spiegeleer B. LC-MS profiling of N-alkylamides in Spilanthes acmella extract and the transmucosal behaviour of its main bio-active spilanthol. J Pharm Biomed Anal 2010; 53: 243-249
• 28 He XG, Bernart MW, Lian LZ, Lin LZ. High-performance liquid chromatography electrospray mass spectrometric analysis of pungent constituents of ginger. J Chromatogr A 1998; 796: 327-334
• 29 Kartal M, Kan Y, Gulpinar AR. LC-MS analysis of alkamides in Echinacea purpurea and Echinacea pallida cultivated in Turkey. Planta Med 2007; 73: 253
• 30 Luo XB, Chen B, Yao SZ, Zeng JG. Simultaneous analysis of caffeic acid derivatives and alkamides in roots and extracts of Echinacea purpurea by high-performance liquid chromatography-photodiode array detection-electrospray mass spectrometry. J Chromatogr A 2003; 986: 73-81
• 31 Spelman K, Wetschler MH, Cech NB. Comparison of alkylamide yield in ethanolic extracts prepared from fresh versus dry Echinacea purpurea utilizing HPLC–ESI-MS. J Pharm Biomed Anal 2009; 49: 1141-1149
• 32 Nagashima M, Nakatani N. LC-MS analysis and structure determination of pungent alkamides from spilanthes-acmella flowers. Food Sci Technol 1992; 25: 417-421
• 33 Nakatani N, Nagashima M. Pungent alkamides from Spilanthes acmella L. var. oleracea Clarke. Biosci Biotechnol Biochem 1992; 56: 759-762
• 34 Hiserodt RD, Pope BM, Cossette M, Dewis ML. Proposed mechanisms for the fragmentation of doubly allylic alkenamides (tingle compounds) by low energy collisional activation in a triple quadrupole mass spectrometer. J Am Soc Mass Spectrom 2004; 15: 1462-1470
• 35 Cech NB, Eleazer MS, Shoffner LT, Crosswhite MR, Davis AC, Mortenson AM. High performance liquid chromatography/electrospray ionization mass spectrometry for simultaneous analysis of alkamides and caffeic acid derivatives from Echinacea purpurea extracts. J Chromatogr A 2006; 1103: 219-228
• 36 Crombie L. Isolation and structure of an N-isobutyldienediynamide from Pellitory (Anacyclus pyrethrum DC). Nature 1954; 174: 832-833
• 37 Jente R, Bohlmann F, Bonnet PH. Polyacetylenic compounds .206. Constituents of Anacyclus pyrethrum DC. Chemische Berichte-Recueil 1972; 105: 1694-1700
• 38 Burden RS, Crombie L. Amides of vegatible origin .12. A new series of alka-2, 4-dienoic tyramine-amides from Anacyclus pyrethrum DC (Compositae). J Chem Soc C 1969; 2477-2481
• 39 Boonen J, Baert B, Roche N, Burvenich C, De Spiegeleer B. Transdermal behaviour of the N-alkylamide spilanthol (affinin) from Spilanthes acmella (Compositae) extracts. J Ethnopharmacol 2010; 127: 77-84
• 40 Sharma V, Boonen J, Chauhan NS, Thakur M, De Spiegeleer B, Dixit VK. Spilanthes acmella ethanolic flower extract: LC-MS alkylamide profiling and its effects on sexual behavior in male rats. Pythomedicine 2011; 18: 1161-1169
• 41 Martin R, Becker H. Amides and other constituents from Acmella ciliata . Phytochemistry 1985; 24: 2295-2300
• 42 Rios-Chavez P, Ramirez-Chavez E, Armenta-Salinas C, Molina-Torres J. Acmella radicans var. radicans: In vitro culture establishment and alkamide content. In Vitro Cell Dev Biol Plant 2003; 39: 37-41
• 43 Greger H, Werner A. Comparative HPLC analyses of alkamides within the Achillea millefolium group. Planta Med 1990; 56: 482-486
• 44 Greger H, Zdero C, Bohlmann F. Pyrrolidine and piperidine amides from Achillea . Phytochemistry 1984; 23: 1503-1505
• 45 Bohlmann F, Zdero C. Polyacetylenverbindungen .119. Über zwei neue Isobutylamide aus Chrysanthemum frutescens L. Chemische Berichte-Recueil 1967; 100: 104-106
• 46 Stöhr JR, Xiao PG, Bauer R. Isobutylamides and a new methylbutylamide from Piper sarmentosum . Planta Med 1999; 65: 175-177