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Chemical diversity and pharmacological significance of the secondary metabolites of nutmeg (Myristica fragrans Houtt.)

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Abstract

Nutmeg is a valued kitchen spice that has been used for centuries all over the world. In addition to its use in flavoring foods and beverages, nutmeg has been used in traditional remedies for stomach and kidney disorders. The antioxidant, antimicrobial and central nervous system effects of nutmeg have also been reported in literature. Nutmeg is a rich source of fixed and essential oil, triterpenes, and various types of phenolic compounds. Many of the secondary metabolites of nutmeg exhibit biological activities that may support its use in traditional medicine. This article provides an overview of the chemistry of secondary metabolites isolated from nutmeg kernel and mace including common methods for analysis of extracts and pure compounds as well as recent approaches towards total synthesis of some of the major constituents. A summary of the most significant pharmacological investigations of potential drug leads isolated from nutmeg and reported in the last decade is also included.

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References

  • Abourashed EA, Khan IA (2010) Nutmeg. In: Khan IA, Abourashed EA (eds) Leung’s encyclopedia of common natural ingredients used in food, drugs and cosmetics, 3rd edn. Wiley, Hoboken, pp 467–470

    Google Scholar 

  • Aiba CJ, Gottlieb OR, Pagliosa FM, Yoshida M, Magalhaes MT (1977) Neolignans from Nectandra miranda. Phytochemsitry 16:745–748

    Article  CAS  Google Scholar 

  • Akinboro A, Mohamed KB, Asmawi MZ, Sulaiman SF, Sofiman OA (2011) Antioxidants in aqueous extract of Myristica fragrans (Houtt.) suppress mitosis and cyclophosphamide-induced chromosomal aberrations in Allium cepa L. cells. J Zhejiang Univ Sci B 12:915–922

    Article  PubMed  PubMed Central  Google Scholar 

  • Antonio RL, Kozasa EH, Galduroz JC, Dawa Dorjee Y, Kalsang T, Norbu T, Tenzin T, Rodrigues E (2013) Formulas used by Tibetan doctors at Men-Tsee-Khang in India for the treatment of neuropsychiatric disorders and their correlation with pharmacological data. Phytother Res 27:552–563

    Article  PubMed  Google Scholar 

  • Asgarpanah J, Kazemivash N (2012) Phytochemistry and pharmacologic properties of Myristica fragrans Houtt.: a review. Afr J Biotechnol 11:12787–12793

    Google Scholar 

  • Assa JR, Widjanarko SB, Kusnadi J, Berhimpon S (2014) Antioxidant potential of flesh, seed, and mace of nutmeg (Myristica fragrans Houtt). Int J Chem Tech Res 6:2460–2468

    CAS  Google Scholar 

  • Banerjee D, Bauri AK, Guha RK, Bandyopadhyay SK, Chattopadhyay S (2008a) Healing properties of malabaricone B and malabaricone C, against indomethacin-induced gastric ulceration and mechanism of action. Eur J Pharmacol 578:300–312

    Article  CAS  PubMed  Google Scholar 

  • Banerjee D, Maity B, Bandivdeker AH, Bandyopadhyay SK, Chattopadhyay S (2008b) Angiogenic and cell proliferating action of the natural diarylnonanoids, malabaricone B and malabaricone C during healing of indomethacin-induced gastric ulceration. Pharm Res 25:1601–1609

    Article  CAS  PubMed  Google Scholar 

  • Beyer J, Ehlers D, Maurer HH (2006) Abuse of nutmeg (Myristica fragrans Houtt.): studies on the metabolism and the toxicologic detection of its ingredients elemicin, myristicin, and safrole in rat and human urine using gas chromatography/mass spectrometry. Ther Drug Monit 28:568–575

    Article  CAS  PubMed  Google Scholar 

  • Boldizsár I, Füzfai Z, Tóth F, Sedlák É, Borsodi L, Molnár-Perl I (2010a) Mass fragmentation study of the trimethylsilyl derivatives of arctiin, matairesinoside, arctigenin, phylligenin, matairesinol, pinoresinol and methylarctigenin: their gas and liquid chromatographic analysis in plant extracts. J Chromatogr A 1217:1674–1682

    Article  PubMed  CAS  Google Scholar 

  • Boldizsár I, Kraszni M, Tóth F, Noszál B, Molnár-Perl I (2010b) Complementary fragmentation pattern analysis by gas chromatography-mass spectrometry and liquid chromatography tandem mass spectrometry confirmed the precious lignan content of Cirsium weeds. J Chromatogr A 1217:6281–6289

    Article  PubMed  CAS  Google Scholar 

  • Braun UKD (1973) Evidence for the biogenic formation of amphetamine derivatives from components of nutmeg. Pharmacology 9:312–316

    Article  CAS  PubMed  Google Scholar 

  • Calliste CA, Kozlowski D, Duroux JL, Champavier Y, Chulia AJ, Trouillas P (2010) A new antioxidant from wild nutmeg. Food Chem 118:489–496

    Article  CAS  Google Scholar 

  • Cao GY, Xu W, Yang XW, Gonzalez FJ, Li F (2015) New neolignans from the seeds of Myristica fragrans that inhibit nitric oxide production. Food Chem 173:231–237

    Article  CAS  PubMed  Google Scholar 

  • Checker R, Chatterjee S, Sharma D, Gupta S, Variyar P, Sharma A, Poduval TB (2008) Immunomodulatory and radioprotective effects of lignans derived from fresh nutmeg mace (Myristica fragrans) in mammalian splenocytes. Int Immunopharmacol 8:661–669

    Article  CAS  PubMed  Google Scholar 

  • Chiu S, Wang T, Belski M, Abourashed EA (2016) HPLC-guided isolation, purification and characterization of phenylpropanoid and phenolic constituents of nutmeg kernel (Myristica fragrans). Nat Prod Commun (accepted for publication)

  • Cho JY, Choi GJ, Son SW, Jang KS, Lim HK, Lee SO, Sung ND, Cho KY, Kim JC (2007) Isolation and antifungal activity of lignans from Myristica fragrans against various plant pathogenic fungi. Pest Manag Sci 63:935–940

    Article  CAS  PubMed  Google Scholar 

  • Choi EJ, Kang YG, Kim J, Hwang JK (2011) Macelignan inhibits melanosome transfer mediated by protease-activated receptor-2 in keratinocytes. Biol Pharm Bull 34:748–754

    Article  CAS  PubMed  Google Scholar 

  • Chong YM, Yin WF, Ho CY, Mustafa MR, Hadi AH, Awang K, Narrima P, Koh CL, Appleton DR, Chan KG (2011) Malabaricone C from Myristica cinnamomea exhibits anti-quorum sensing activity. J Nat Prod 74:2261–2264

    Article  CAS  PubMed  Google Scholar 

  • Cui CA, Jin DQ, Hwang YK, Lee IS, Hwang JK, Ha I, Han JS (2008) Macelignan attenuates LPS-induced inflammation and reduces LPS-induced spatial learning impairments in rats. Neurosci Lett 448:110–114

    Article  CAS  PubMed  Google Scholar 

  • Cuong TD, Hung TM, Na M, Hado T, Kim JC, Lee D, Ryoo S, Lee JH, Choi JS, Min BS (2011) Inhibitory effect on NO production of phenolic compounds from Myristica fragrans. Bioorg Med Chem Lett 21:6884–6887

    Article  CAS  PubMed  Google Scholar 

  • Daniel D (1994) Nutmeg processing and marketing in Grenada. Food and Agriculture Organization of the United Nations Report 6–10

  • Dawidowicz AL, Dybowski MP (2012) Determination of myristicin in commonly spices applying SPE/GC. Food Chem Toxicol 50:2362–2367

    Article  CAS  PubMed  Google Scholar 

  • Dawidowicz AL, Dybowski MP (2013) Simple and rapid determination of myristicin in human serum. Forensic Toxicol 31:119–123

    Article  CAS  PubMed  Google Scholar 

  • Dewick PM (1997) The shikimate pathway. In: Dewick PM (ed) Medicinal natural products-A biosynthetic approach. Wiley, New York, pp 109–151

    Google Scholar 

  • Dhingra D, Parle M, Kulkarni SK (2006) Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice. J Med Food 9:281–283

    Article  CAS  PubMed  Google Scholar 

  • Du SS, Yang K, Wang CF, You CX, Geng ZF, Guo SS, Deng ZW, Liu ZL (2014) Chemical constituents and activities of the essential oil from Myristica fragrans against cigarette beetle Lasioderma serricorne. Chem Biodivers 11:1449–1456

    Article  CAS  PubMed  Google Scholar 

  • Duan L, Tao HW, Hao XJ, Gu QQ, Zhu WM (2009) Cytotoxic and antioxidative phenolic compounds from the traditional Chinese medicinal plant, Myristica fragrans. Planta Med 75:1241–1245

    Article  CAS  PubMed  Google Scholar 

  • Ehlers D, Kirchhoff J, Gerard D, Quirin K- (1998) High-performance liquid chromatography analysis of nutmeg and mace oils produced by supercritical CO2 extraction—comparison with steam-distilled oils—comparison of East Indian, West Indian and Papuan oils. Int J Food Sci Tech 33:215–223

    Article  CAS  Google Scholar 

  • El-Alfy AT, Wilson L, ElSohly MA, Abourashed EA (2009) Towards a better understanding of the psychopharmacology of nutmeg: activities in the mouse tetrad assay. J Ethnopharmacol 126:280–286

    Article  PubMed  PubMed Central  Google Scholar 

  • Engler TA, Chai W (1996) Synthesis of (±)licarin B and eupomatenoids-1 and-12: a general approach to 2-aryl-7-alkoxy-benzofuranoid neolignans. Tetrahedron Lett 37:6969–6970

    Article  CAS  Google Scholar 

  • Forrest JE, Heacock RA, Forrest TP (1974) Diarylpropanoids from nutmeg and mace (Myristica fragrans Houtt.). J Chem Soc Perkin 1(2):205–209

    Article  Google Scholar 

  • Francis KS, Suresh E, Nair MS (2014) Chemical constituents from Myristica fragrans fruit. Nat Prod Res 28:1664–1668

    Article  CAS  PubMed  Google Scholar 

  • Giang PM, Son PT, Matsunami K, Otsuka H (2006) New neolignans and lignans from Vietnamese medicinal plant Machilus odoratissima Nees. Chem Pharm Bull 54:380–383

    Article  CAS  Google Scholar 

  • Grover JK, Khandkar S, Vats V, Dhunnoo Y, Das D (2002) Pharmacological studies on Myristica fragrans–antidiarrheal, hypnotic, analgesic and hemodynamic (blood pressure) parameters. Methods Find Exp Clin Pharmacol 24:675–680

    Article  CAS  PubMed  Google Scholar 

  • Han YS, Kim MS, Hwang JK (2012) Macelignan inhibits histamine release and inflammatory mediator production in activated rat basophilic leukemia mast cells. Inflammation 35:1723–1731

    Article  CAS  PubMed  Google Scholar 

  • Hayfaa AA, Sahar AM, Awatif MA (2013) Evaluation of analgesic activity and toxicity of alkaloids in Myristica fragrans seeds in mice. J Pain Res 6:611–615

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hirano T, Wakasugi A, Oohara M, Oka K, Sashida Y (1991) Suppression of mitogen-induced proliferation of human peripheral blood lymphocytes by plant lignans. Planta Med 57:331–334

    Article  CAS  PubMed  Google Scholar 

  • Hirano T, Gotoh M, Oka K (1994) Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells. Life Sci 55:1061–1069

    Article  CAS  PubMed  Google Scholar 

  • Hosoi S, Kiuchi F, Nakamura N, Imasho M, Ali MA, Sasaki Y, Tanaka E, Tsumamoto Y, Kondo K, Tsuda Y (1999) Synthesis and nematocidal activity of diarylnonanoids related to malabaricones. Chem Pharm Bull (Tokyo) 47:37–43

    Article  CAS  Google Scholar 

  • Hou JP, Wu H, Wang Y, Weng XC (2012) Isolation of some compounds from nutmeg and their antioxidant activities. Czech J Food Sci 30:164–170

    CAS  Google Scholar 

  • Isogai A, Murakoshi S, Suzuki A, Tamura S (1973) Isolation from nutmeg of growth inhibitory substances to silkworm larvae. Agr Biol Chem 37:889–895

    Article  CAS  Google Scholar 

  • Jellin JM, Gregory PJ, Batz F, Hitchens K (2003) Pharmacist’s letter/prescriber’s letter natural medicines comprehensive database, 5th edn. Therapeutic Research Faculty, Stockton 2071

    Google Scholar 

  • Juhasz L, Kurti L, Antus S (2000) Simple synthesis of benzofuranoid neolignans from Myristica fragrans. J Nat Prod 63:866–870

    Article  CAS  PubMed  Google Scholar 

  • Kang JW, Min BS, Lee JH (2013) Anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3′,5′-tetramethoxy-8-O-4′-neolignan from Myristica fragrans. Phytother Res 27:1694–1699

    Article  CAS  PubMed  Google Scholar 

  • Kareem MA, Krushna GS, Hussain SA, Devi KL (2009) Effect of aqueous extract of nutmeg on hyperglycemia, hyperlipidemia and cardiac histology associated with isoproterenol-induced myocardial infarction in rats. Tropical J Pharmaceut Res 8:337–344

    Google Scholar 

  • Kasture SB, Gujar KN (2005) Depressant effect of trimyristin and its inhibition by some antidepressants in mice. In: Bernath J, Nemeth E, Cracker LE, Gardner ZE (eds) Proceedings WOCMAO III 2005,vol 1. Bioprospecting and Ethnopharmacology. Acta Hort 675, ISHS, pp 147–152

  • Kawaguchi Y, Yamauchi S, Masuda K, Nishiwaki H, Akiyama K, Maruyama M, Sugahara T, Kishida T, Koba Y (2009) Antimicrobial activity of stereoisomers of butane-type lignans. Biosci Biotechnol Biochem 73:1806–1810

    Article  CAS  PubMed  Google Scholar 

  • Ki SH, Lee JW, Lim SC, Hien TT, Im JH, Oh WK, Lee MY, Ji YH, Kim YG, Kang KW (2013) Protective effect of nectandrin B, a potent AMPK activator on neointima formation: inhibition of Pin1 expression through AMPK activation. Br J Pharmacol 168:932–945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kishimoto T, Takahashi N, Hamada M, Nakajima N (2015) Biomimetic oxidative coupling of sinapyl acetate by silver oxide: preferential formation of beta-O-4 type structures. J Agric Food Chem 63:2277–2283

    Article  CAS  PubMed  Google Scholar 

  • Kiyofuji K, Kurauchi Y, Hisatsune A, Seki T, Mishima S, Katsuki H (2015) A natural compound maceligna protects midbrain dopaminergic neurons from inflammatory degeneration via microglial arginase-1 expression. Eur J Pharmcol 760:129–135

    Article  CAS  Google Scholar 

  • Kong WJ, Liu SY, Qiu F, Xiao XH, Yang MH (2013) Simultaneous multi-mycotoxin determination in nutmeg by ultrasound-assisted solid-liquid extraction and immunoaffinity column clean-up coupled with liquid chromatography and on-line post-column photochemical derivatization-fluorescence detection. Analyst 138:2729–2739

    Article  CAS  PubMed  Google Scholar 

  • Kuo YH, Kao ST, Lin YT (1976) Extractive components from the nutmeg of Myristica simarum A.DC.: the structure of lignan-ketone: otobanone. Experientia 32:828–829

    Article  CAS  PubMed  Google Scholar 

  • Kwon YY, Kim D, Kim J, Hwang JK (2011) Effects of licarin E on expression of matrix metalloproteinase-1 and type-1 procollagen in UVB-irradiated human skin fibroblasts. Phytother Res 25:1891–1894

    Article  CAS  PubMed  Google Scholar 

  • Latha PG, Sidhu PG, Suja SR, Geetha BS, Pushpangadan P, Rajasekharan S (2005) Pharmacology and chemistry of Myristica fragrans Houtt.—a review. J Spices Aromatic Crop 14:94–101

    Google Scholar 

  • Lee SU, Shim KS, Ryu SY, Min YK, Kim SH (2009) Machilin A isolated from Myristica fragrans stimulates osteoblast differentiation. Planta Med 75:152–157

    Article  CAS  PubMed  Google Scholar 

  • Lee KE, Mun S, Pyun HB, Kim MS, Hwang JK (2012a) Effects of macelignan isolated from Myristica fragrans (Nutmeg) on expression of matrix metalloproteinase-1 and type I procollagen in UVB-irradiated human skin fibroblasts. Biol Pharm Bull 35:1669–1675

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Seo J, Ryoo S, Cuong TD, Min BS, Lee JH (2012b) Malabaricone C inhibits PDGF-induced proliferation and migration of aortic smooth muscle cells through induction of heme oxygenase-1. J Cell Biochem 113:2866–2876

    Article  CAS  PubMed  Google Scholar 

  • Leiter E, Hitchcock G, Godwin S, Johnson M, Sedgwick W, Jones W, McCall S, Ceremuga TE (2011) Evaluation of the anxiolytic properties of myristicin, a component of nutmeg, in the male Sprague-Dawley rat. AANA J 79:109–114

    PubMed  Google Scholar 

  • Leon-Diaz R, Meckes M, Said-Fernandez S, Molina-Salinas GM, Vargas-Villarreal J, Torres J, Luna-Herrera J, Jimenez-Arellanes A (2010) Antimycobacterial neolignans isolated from Aristolochia taliscana. Mem Inst Oswaldo Cruz, Rio de Janeiro 105:45–51

    Article  CAS  Google Scholar 

  • Leon-Diaz R, Meckes-Fischer M, Valdovinos-Martinez L, Campos MG, Hernandez-Pando R, Jimenez-Arellanes MA (2013) Antitubercular activity and the subacute toxicity of (—)-Licarin A in BALB/c mice: a neolignan isolated from Aristolochia taliscana. Arch Med Res 44:99–104

    Article  CAS  PubMed  Google Scholar 

  • Leung EM, Tang PN, Ye Y, Chan W (2013) Analysis of 2-alkylcyclobutanones in cashew nut, nutmeg, apricot kernel, and pine nut samples: re-evaluating the uniqueness of 2-alkylcyclobutanones for irradiated food identification. J Agric Food Chem 61:9950–9954

    Article  CAS  PubMed  Google Scholar 

  • Li F, Yang XW (2011) Metabolism of the lignan dehydrodiisoeugenol in rats. Planta Med 77:1712–1717

    Article  CAS  PubMed  Google Scholar 

  • Li F, Yang XW (2012) Analysis of anti-inflammatory dehydrodiisoeugenol and metabolites excreted in rat feces and urine using HPLC-UV. Biomed Chromatogr 26:703–707

    Article  CAS  PubMed  Google Scholar 

  • Li G, Lee CS, Woo MH, Lee SH, Chang HW, Son JK (2004) Lignans from the bark of Machilus thunbergii and their DNA topoisomerases I and II inhibition and cytotoxicity. Biol Pharm Bull 27:1147–1150

    Article  CAS  PubMed  Google Scholar 

  • Lindsley CW, Hopkins CR, Sulikowski GA (2011) Biomimetic synthesis of lignans. In: Poupon E, Nay B (eds) Biomimetic organic synthesis. Wiley-VCH Verlag, pp 677–693

    Chapter  Google Scholar 

  • Lipovka Y, Konhilas JP (2015) AMP-Activated protein kinase signaling in cancer and cardiac hypertrophy. Cardiovasc Pharm Open Access 4:3

    Google Scholar 

  • Liu SY, Wang GQ, Liang ZY, Wang QA (2013) Synthesis of dihydrobenzofuran neolignans licarin a and dihydrocarinatin as well as related triazolylglycosides. Chem Res Chin Univ 29:1119–1124

    Article  CAS  Google Scholar 

  • Lopez V, Gerique J, Langa E, Berzosa C, Valero MS, Gomez-Rincon C (2015) Antihelmintic effects of nutmeg (Myristica fragrans) on Anisakis simplex L3 larvae obtained from Micromesistius potassou. Res Vet Sci 100:148–152

    Article  PubMed  Google Scholar 

  • Ma CJ, Kim SR, Kim J, Kim YC (2005) Meso-dihyrdoguaiaretic acid and licarin A of Machilus thunbergii protects against glutamate-induced toxicity in primary cultures of a rat cortical cells. Brit J Pharmacol 146:752–759

    Article  CAS  Google Scholar 

  • Ma J, Hwang YK, Cho WH, Han SH, Hwang JK, Han JS (2009) Macelignan attenuates activations of mitogen-activated protein kinases and nuclear factor kappa B induced by lipopolysaccharide in microglial cells. Biol Pharm Bull 32:1085–1090

    Article  CAS  PubMed  Google Scholar 

  • Maity B, Banerjee D, Bandyopadhyay SK, Chattopadhyay S (2009) Regulation of arginase/nitric oxide synthesis axis via cytokine balance contributes to the healing action of malabaricone B against indomethacin-induced gastric ulceration in mice. Int Immunopharmacol 9:491–498

    Article  CAS  PubMed  Google Scholar 

  • Martins C, Doran C, Silva IC, Miranda C, Rueff J, Rodrigues AS (2014) Myristicin from nutmeg induces apoptosis via the mitochondrial pathway and down regulates genes of the DNA damage response pathways in human leukaemia K562 cells. Chem Biol Interact 218:1–9

    Article  CAS  PubMed  Google Scholar 

  • Matsui T, Ito C, Masubuchi S, Itoigawa M (2015) Licarin A is a candidate compound for the treatment of immediate hypersensitivity via inhibition of rat mast cell line RBL-2H3 cells. J Pharm Pharmacol 67:1723–1732

    Article  CAS  PubMed  Google Scholar 

  • Milton G (2000) Nathaniel’s Nutmeg. Hodder and Stoughton, London

    Google Scholar 

  • Min BS, Cuong TD, Hung TM, Min BK, Shin BS, Woo MH (2011) Inhibitory Effect of Lignans from Myristica fragrans on LPS-induced NO Production in RAW264.7 Cells. Bull Korean Che Soc 32:4059–4062

    Article  CAS  Google Scholar 

  • Moinuddin G, Devi K, Kumar Khajuria D (2012) Evaluation of the anti-depressant activity of Myristica fragrans (Nutmeg) in male rats. Avicenna J Phytomed 2:72–78

    PubMed  PubMed Central  Google Scholar 

  • Moss GP (2000) Nomenclature of lignans and neolignans (IUPAC recommendations 2000). Pure Appl Chem 72:1493–1523

    Article  CAS  Google Scholar 

  • Motilal S, Maharaj RG (2013) Nutmeg extracts for painful diabetic neuropathy: a randomized, double-blind, controlled study. J Altern Complement Med 19:347–352

    Article  PubMed  Google Scholar 

  • Muchtaridi Subarnas A, Apriyantono A, Mustarichie R (2010) Identification of compounds in the essential oil of nutmeg seeds (Myristica fragrans Houtt.) that inhibit locomotor activity in mice. Int J Mol Sci 11:4771–4781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naidu PURMUR, Kumar TR, Shobia JC (1997) Evaluation of the efficacy and safety of a new herbal revitalizer reviving. Ancient Sci Life 16:190–195

    Google Scholar 

  • Neris PL, Caldas JP, Rodrigues YK, Amorim FM, Leite JA, Rodrigues-Mascarenhas S, Barbosa-Filho JM, Rodrigues LC, Oliveira MR (2013) Neolignan licarin A presents effect against Leishmania (Leishmania) major associated with immunomodulation in vitro. Exp Parasitol 135:307–313

    Article  CAS  PubMed  Google Scholar 

  • Nguyen PH, Le TV, Kang HW, Chae J, Kim SK, Kwon KI, Seo DB, Lee SJ, Oh WK (2010) AMP-activated protein kinase (AMPK) activators from Myristica fragrans (nutmeg) and their anti-obesity effect. Bioorg Med Chem Lett 20:4128–4131

    Article  CAS  PubMed  Google Scholar 

  • Olaleye MT, Akinmoladun AC, Akindahunsi AA (2006) Antioxidant properties of Myristica fragrans (Houtt) and its effect on selected organs of albino rats. Afr J Biotechnol 5:1274–1278

    Google Scholar 

  • Orabi KY, Mossa JS, El-Feraly FS (1991) Isolation and characterization of two antimicrobial agents from mace (Myristica fragrans). J Nat Prod 54:856–859

    Article  CAS  PubMed  Google Scholar 

  • Pandey R, Rameshkumar KB, Kumar B (2015) Ultra high performance liquid chromatography tandem mass spectrometry method for the simultaneous determination of multiple bioactive constituents in fruit extracts of Myristica fragrans and its marketed polyherbal formulations using a polarity switching technique. J Sep Sci 38:1277–1285

    Article  CAS  PubMed  Google Scholar 

  • Parthasarathy MR, Gupta S (1985) Synthesis of malabaricone A-Confirmation of its structure. Indian J Chem Sect B 24B:965–965

    CAS  Google Scholar 

  • Patro BS, Bauri AK, Mishra S, Chattopadhyay S (2005) Antioxidant activity of Myristica malabarica extracts and their constituents. J Agric Food Chem 53:6912–6918

    Article  CAS  PubMed  Google Scholar 

  • Patro BS, Tyagi M, Saha J, Chattopadhyay S (2010) Comparative nuclease and anti-cancer properties of the naturally occurring malabaricones. Bioorg Med Chem 18:7043–7051

    Article  CAS  PubMed  Google Scholar 

  • Paul S, Hwang JK, Kim HY, Jeon WK, Chung C, Han JS (2013) Multiple biological properties of macelignan and its pharmacological implications. Arch Pharm Res 36:264–272

    Article  CAS  PubMed  Google Scholar 

  • Pereira AC, Magalhaes LG, Goncalves UO, Luz PP, Moraes AC, Rodrigues V, da Matta Guedes PM, da Silva Filho AA, Cunha WR, Bastos JK, Nanayakkara NP, e Silva ML (2011) Schistosomicidal and trypanocidal structure-activity relationships for (±)-licarin A and its (−)- and (+)-enantiomers. Phytochemistry 72:1424–1430

    Article  CAS  PubMed  Google Scholar 

  • Piaru SP, Mahmud R, Abdul Majid AM, Ismail S, Man CN (2012) Chemical composition, antioxidant and cytotoxicity activities of the essential oils of Myristica fragrans and Morinda citrifolia. J Sci Food Agric 92:593–597

    Article  CAS  PubMed  Google Scholar 

  • Piras A, Rosa A, Marongiu B, Atzeri A, Dessi MA, Falconieri D, Porcedda S (2012) Extraction and separation of volatile and fixed oils from seeds of Myristica fragrans by supercritical CO(2): chemical composition and cytotoxic activity on Caco-2 cancer cells. J Food Sci 77:C448–C453

    Article  CAS  PubMed  Google Scholar 

  • Poluzzi E, Carlo P, Raschi E, Rampa A, Recanatini M, De Ponti F (2014) Phytoestrogens in postmenopause: the state of the art from a chemical, pharmacological and regulatory perspective. Curr Med Chem 21:417–436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poornima B, Anand Kumar D, Siva B, Venkanna A, Vadaparthi PR, Kumar K, Tiwari AK, Suresh Babu K (2016) Advanced glycation end-products inhibitors isolated from Schisandra grandiflora. Nat Prod Res 30:493–496

    Article  CAS  PubMed  Google Scholar 

  • Purushothaman KK, Sarada A, Connolly JD (1977) Malabaricones A–D, novel diarylnonanoids from Myristica malabarica Lam (Myristicaceae). J Chem Soc Perkin 1(5):587–588

    Article  Google Scholar 

  • Sangalli BC, Chiang W (2000) Toxicology of nutmeg abuse. J Toxicol Clin Toxicol 38:671–678

    Article  CAS  PubMed  Google Scholar 

  • Sattaponpan C, Kondo S (2011) Antibacterial activity of crude extracts of prasaprophyai formula and its components against pathogenic bacteria. J Med Assoc Thai Suppl 7:S153–S161

    Google Scholar 

  • Schmidt TJ, Hemmati S, Klaes M, Konuklugil B, Mohagheghzadeh A, Ionkova I, Fuss E, Alfermann AW (2010) Lignans in flowering aerial parts of Linum species—chemodiversity in the light of systematics and phylogeny. Phytochemistry 71:1714–1728

    Article  CAS  PubMed  Google Scholar 

  • Sen R, Bauri AK, Chattopadhyay S, Chatterjee M (2007) Antipromastigote activity of the malabaricones of Myristica malabarica (rampatri). Phytother Res 21:592–595

    Article  CAS  PubMed  Google Scholar 

  • Shafiei Z, Shuhairi NN, Md Fazly Shah Yap N, Harry Sibungkil CA, Latip J (2012) Antibacterial activity of Myristica fragrans against oral pathogens. Evid Based Complement Alternat Med 2012:825362

    Article  PubMed  PubMed Central  Google Scholar 

  • Sharma PV (2001). In: Dravyaguna Vijnana (Vegetable Drugs), Vol. 1 edn. Varanasi, Chaukambha Bharti Academy, India, pp 151–160

  • Shin K, Chung HC, Kim DU, Hwang JK, Lee SH (2013) Macelignan attenuated allergic lung inflammation and airway hyper-responsiveness in murine experimental asthma. Life Sci 92:1093–1099

    Article  CAS  PubMed  Google Scholar 

  • Shinohara C, Mori S, Ando T, Tsuji T (1999) Arg-gingipain inhibition and anti-bacterial activity selective for Porphyromonas gingivalis by malabaricone C. Biosci Biotechnol Biochem 63:1475–1477

    Article  CAS  PubMed  Google Scholar 

  • Shulgin AT (1966) Possible implication of myristicin as a psychotropic substance. Nature 210:380–384

    Article  CAS  PubMed  Google Scholar 

  • Sólyomváry A, Tóth G, Komjáti B, Horváth P, Kraszni M, Noszál B, Molnár-Perl I, Boldizsár I (2015a) Identification and isolation of new neolignan and sesquineolignan species: their acid-catalyzed ring closure and specific accumulation in the fruit wall of Cirsium eriophorum (L.) Scop. Process Biochem 50:853–858

    Article  CAS  Google Scholar 

  • Sólyomváry A, Mervai Z, Tóth G, Ress Á, Noszál B, Molnár-Perl I, Baghy K, Kovalszky I, Boldizsár I (2015b) A simple and effective enrichment process of the antiproliferative lignan arctigenin based on the endogenous enzymatic hydrolysis of Serratula tinctoria and Arctium lappa Fruits. Process Biochem 50:2281–2288

    Article  CAS  Google Scholar 

  • Sonavane GS, Sarveiya V, Kasture V, Kastre SB (2001) Behavioral actions of Myristica fragrans seeds. Indian J Pharmacol 33:417–424

    Google Scholar 

  • Sonavane GS, Sarveiya VP, Kasture VS, Kasture SB (2002) Anxiogenic activity of Myristica fragrans seeds. Pharmacol Biochem Behav 71:239–244

    Article  CAS  PubMed  Google Scholar 

  • Szokol-Borsodi L, Sólyomváry A, Molnár-Perl I, Boldizsár I (2012) Optimum yields of dibenzylbutyrolactone-type lignans from Cynareae fruits, during their ripening, germination and enzymatic hydrolysis processes, determined by on-line chromatographic methods. Phytochem Anal 23:598–603

    Article  CAS  PubMed  Google Scholar 

  • Takahashi T (1993) Aflatoxin contamination in nutmeg: analysis of interfering TLC spots. J Food Sci 58:197–198

    Article  CAS  Google Scholar 

  • Takikawa A, Abe K, Yamamoto M, Ishimaru S, Yasui M, Okubo Y, Yokoigawa K (2002) Antimicrobial activity of nutmeg against Escherichia coli O157. J Biosci Bioeng 94:315–320

    Article  CAS  PubMed  Google Scholar 

  • Thiengsusuk A, Chaijaroenkul W, Na-Bangchang K (2013) Antimalarial activities of medicinal plants and herbal formulations used in Thai traditional medicine. Parasitol Res 112:1475–1481

    Article  PubMed  Google Scholar 

  • Tripathi IP, Dwivedi N (2015) Pharmacognostical standardization of nutmeg seeds (Myristica fragrans Houtt.)—a traditional medicine. Int J Pharm Sci Res 6:3096–3102

    CAS  Google Scholar 

  • Truitt EB, Callaway E, Braude MC, Krantz JC (1961) The pharmacology of myristicin. A contribution to the psychopharmacology of nutmeg. J Neuropsychiatr 2:205–210

    CAS  PubMed  Google Scholar 

  • Tsuda Y, Hosoi S, Goto Y (1991) Synthesis of malabaricones, diarylnonanoids occuring in Myriticaceous plants. Chem Pharm Bull 39:18–22

    Article  CAS  Google Scholar 

  • Tyagi M, Patro BS, Chattopadhyay S (2014) Mechanism of the malabaricone C-induced toxicity to the MCF-7 cell line. Free Radic Res 48:466–477

    Article  CAS  PubMed  Google Scholar 

  • Umezawa T (2003) Diversity in lignan biosynthesis. Phytochem Rev 2:371–390

    Article  CAS  Google Scholar 

  • Variyar PS, Chatterjee S, Sajilata MG, Singhal RS, Sharma A (2008) Natural existence of 2-alkylcyclobutanones. J Agric Food Chem 56:11817–11823

    Article  CAS  PubMed  Google Scholar 

  • Wahab A, Ul Haq R, Ahmed A, Khan RA, Raza M (2009) Anticonvulsant activities of nutmeg oil of Myristica fragrans. Phytother Res 23:153–158

    Article  CAS  PubMed  Google Scholar 

  • Ward RS (1982) The synthesis of lignans and neolignans. Chem Soc Rev 11:75–125

    Article  CAS  Google Scholar 

  • Ward RS (1995) Lignans, neolignans, and related compounds. Nat Prod Rep 12:183–205

    Article  CAS  PubMed  Google Scholar 

  • Weil AT (1966) The use of nutmeg as a psychotropic agent. B Narcotics 18:15–23

    Google Scholar 

  • Yadav AS, Bhatnagar D (2007) Free radical scavenging activity, metal chelation and antioxidant power of some of the Indian spices. BioFactors 31:219–227

    Article  CAS  PubMed  Google Scholar 

  • Yang XW, Huang X, Ma L, Wu Q, Xu W (2010) The intestinal permeability of neolignans from the seeds of Myristica fragrans in the Caco-2 cell monolayer model. Planta Med 76:1587–1591

    Article  CAS  PubMed  Google Scholar 

  • Zacchino SA, Badano H (1985) Stereoselective synthesis of 8.O.4′ neolignans: (±)-surinamensin and (±)-virolin. J Nat Prod 48:830–832

    Article  CAS  Google Scholar 

  • Zhang YB, Zhu LQ, Yang XW (2013) Cerebral nuclei distribution study of dehydrodiisoeugenol as an anxiogenic agent determined by RP-HPLC. Fitoterapia 84:47–53

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors are grateful to the National Institute On Drug Abuse of the National Institutes of Health (NIDA-NIH) for Award Number R24DA036410. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to Ehab A. Abourashed.

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Abourashed, E.A., El-Alfy, A.T. Chemical diversity and pharmacological significance of the secondary metabolites of nutmeg (Myristica fragrans Houtt.). Phytochem Rev 15, 1035–1056 (2016). https://doi.org/10.1007/s11101-016-9469-x

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