Isothiocyanates: a review

Document Type: Review

Authors

1 Glocal School of Pharmacy, The Glocal University, Uttar Pradesh, India.

2 School of Pharmaceutical Sciences, IFTM University, Uttar Pradesh, India.

3 Department of Biotechnology, IFTM University, Uttar Pradesh, India.

Abstract

Isothiocyanates (ITCs) are naturally occurring molecules belonging to highly reactive organosulphur synthons, with the general structure R–N=C=S. The precursor molecule glucosinolate anions are hydrolyzed enzymatically (under the effect of myrosinase enzymes) or unenzymatically to produce nitriles or isothiocyanates depending upon conditions such as pH and temperature. Brassicaceae  Family is known to contain abundant ITCs. A significant number of isothiocyanates has been isolated from different plant sources and some of them have been synthesized. Several isothiocyanates have demonstrated significant pharmacological activities including anti-cancer, anti-inflammatory, anti-microbial activities, etc. Pharmacokinetic profiles of these sulphur containing compounds are well established. However, safety profiles of ITCs need consideration and a well-designed study with appropriate control, for their production as lead compounds. This review summarises the chemistry, sources, pharmacokinetics, pharmacological activity and toxicity profiles of the isothiocyanates.
 

Keywords


[1] Satyavan S. Sulphur reports: isothiocyanates in heterocyclic synthesis. Alexender S, Ed. Harwood: Academic Publishers GmBH United Kingdom, 1989.

[2] Wu X, Zhou QH, Xu K. Are isothiocyanates potential anti-cancer drugs? Acta Pharmacol Sin. 2009; 30(5): 501-512.

[3] Hecht SS. Chemoprotection by isothiocyanates. In: Kelloff GJ, Hawk ET, Sigman CC, Eds. Promising  cancer chemopreventive agents. Totowa: Humana Press, 2004.

[4] Redovnikovic IR, Glivetic T, Delonga K, Furac JV. Glucosinolates and their potential role in plant. Period Biol. 2008; 110(4): 297-309.

[5] Food and Health Innovation Service. The Brassicas-an undervalued nutritional and health beneficial plant family. Accessed 2012]. Available from: http://www.foodhealthinnovation.com/media/5567/brassicas_report_.pdf.

[6] Fahey JWZalcmann ATTalalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry. 2001; 56(1): 5-51.

[7] Linus pauling Institute, Oregan University. Isothiocyantes. Micronutrient information centre. [Accessed 2017]. Available from http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/isothiocyanates.

[8] Fimognari C, Turrini E, Ferruzzi L, Lenzi M, Hrelia P. Natural isothiocyanates: genotoxic potential versus chemoprotection. Mutat Res. 2012; 750(2): 107-131.

[9] Jiao D, Eklind KL, Chsoi  CI, Desai DH, Amin SG, Chung FL. Structure-activity relationships of isothiocyanates as mechanism-based inhibitors of 4-(methy initrosamino) -1-(3-pyridy1)-1-butanone-induced lung tumorigenesis in A/J Mice1.  Cancer Res. 1994; 54(16): 4327-4333.

[10] Rahman AU. Studies in natural products chemistry: bioactive natural products (Part F). 1st ed. Amsterdam: Elsevier Science Ltd, 2001. 

[11] Dufour V, Stahl M, Baysse C. The antibacterial properties of isothiocyanates. Microbiol. 2015; 161(2): 229-243.

[12] Tichy M. Quantitative structure-activity relationships. Proceedings of the chemical structure-biological activity relationships conference. 1973 June 27-29; Prague, Czechoslovakia.

[13] Johnson IT. Glucosinolates in human diet. Bioavailability and implication for health. Phytochem Rev. 2002; 1(2):183-188.

[14] Zhang Y. Allylisothiocyanate as cancer chemoprotective phytochemical. Mol Nutr Food Res. 2011; 57(1): 127-135.

[15] Elfoul L, Rabot S, Khelifa N, Quinsac A, Duguay A, Rimbault A. Formation of AITC from sinigrin in digestive tract of ratsmonoassociated with the human colonic strain bacteroids thetaiotaomicron. FEMS Microbiol Lett. 2001; 197(1): 99-103.

[16] Petri N, Tannergren C, Holst B, Mellon FA, Bao Y, Plumb GW, Bacon J, O'Leary KA, Kroon PA, Knutson L, Forsell P, Eriksson T, Lennernas H, Williamson G. Absorption/metabolism of sulforaphane and quercitin  and regulation of phase II enzymes in human jejunum in vivo. Drug metab Dispos. 2003; 31(6): 805-813.

[17]  Ye L, Dinkova-Kostova AT, Wade KL, Zhang Y, Shapiro TA,  Talalay P. Quantitative determination of dithiocarbamates in human plasma serum, erythrocytes and urine. pharmacokinetics of broclli sprout ITC in human. Clin Chim Acta. 2002; 321(1-2): 127-129.

[18]  Bricker GV, Riedl KM, Ralston RA, Tober KL, Oberyszyn TM, Schwartz SJ. ITC metabolism, distribution, interconversion in mice following consumption of thermally processed broccoli sprouts or purified sulphoraphane. Mol Nutr Food Res. 2014; 58(70): 1991-2000.

[19] Clarke JD, Hsu A, Williams DE, Dashwood RH, Stevens JF, Yamamoto M, Ho E. Metabolism and tissue distribution of sulforaphane in nrf-2 knckout and wild type mice. Pharm Res. 2011; 28(12): 3171-3179.

[20] Zhang Y. The molecular basis that unifies metabolism and cellular uptake and chenmoprevention activites of dietary ITC. Carcinogenesis. 2012; 33(1): 2-9.

[21] Telang U, Ji Y, Morris ME. ABC transporters and ITC: potential for pharmacokinetic diet-drug interaction. Biopharm Drug Dispos. 2009; 30(7): 335-344.

[22] Kolm RH, Danielson H, Zhang Y, Talalay P, Mannervik B. Isothiocyanaytes as substrate for human glutathione transferase: structure activity studies. Biochem J. 1995; 311(2): 453-459.

[23] Gasper AV, Al-Janobi A, Smith JA, Bacon JR, Fortun P, Atherton C, Taylor MA, Hawkey CJ, Barrett DA, Mithen FZ. Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr. 2005; 82(6): 1283-1291.

[24] Steck SE, Gammon MD, Hebert JR, Wall DE, Zeisel SH. GSTM1, GSTT1, GSTP1 and GSTA1 polymorphisms in urinary ITC metabolite following broccoli consumption in humans. J Nutr. 2007; 137(4): 904-909.

[25] Lee Ms. Enzyme induction and comparative oxidation desulfuration of isothiocyanates to isocyantaes. Chem Res Toxicol. 1996; 9(7): 1072-1078.

[26] Yoshigae Y, Sridar C, Kent VM, Hollenberg PF. The inactivation of human CYP2E1 by PEITC, a naturally occurring chemoprotective agaents and its oxidative bioactivation. Drug Metab Dispos. 2013; 41(4): 858-869.

[27] Vermeulen M, Katelaars IWAAK, Berg RVD, Vaes WHJ. Biovavailbility and kinectics of sulforaphane in human after consumption of cooked versus raw broccoli. J Agric Food Chem. 2008; 56(22): 10505-10509.

[28] Mennicke WH, Gorler K, Krumbiegel G, Lorenz D, Rittmann N. Studies on the metabolism and excretion of benzyl isothiocyanates in man. Xenobiotica. 1988; 18(4): 441-447.

[29] Bollard M, Stribbling S, Mitchell S, Caldwell J. The disposition of AITC in rat and mouse. Food Chem Toxicol. 1997; 35(10-11): 933-943.

[30] Borghoff J. Age related changes in metabolism and excretion of allyl isothiocyanate. A model compound for glutathione conjugation. Drug Metab Dispos. 1986; 14(4): 417-422.

[31] Seow A, Shi CY, Chung FL, Jiao D, Hankin JH, Lee HP, Coetzee GA, Yu MC. Urinary total isothiocyanate (ITC) in a population-based sample of middle-aged and older Chinese in Singapore: relationship with dietary total ITC and glutathione S-transferase M1/T1/P1 genotypes. Cancer Epidemiol Biomarkers Prev. 1988; 7(9): 775-781.

[32] Gianni ED, Turrini E, Milelli A, Maffei F, Carini M, Minarini A, Tumiatti V, Ros TD, Prato M, Fimognari C. Study of the cytotoxic effects of the new synthetic isothiocyanate CM9 and its fullerene derivative on human t-leukemia cells.  Toxins. 2015; 7(2): 535-552.

[33] Wang D, Upadhyaya B, Liu Y, Knudsen D, Dey M. Phenethyl isothiocyanate upregulates death receptors 4 and 5 and inhibits proliferation in human cancer stem-like cells. BMC Cancer. 2014; Article ID 4148558.

[34] Qazi A, Pal J, Maitah M, Fulciniti M, Pelluru D, Nanjappa P, Lee S, Batchu RB, Prasad M, Bryant CS, Rajput S, Gryaznov S, Beer DG, Weaver DW, Munshi NC, Goyal RK, Shammas MA. Anticancer activity of a broccoli derivative, sulforaphane, in barrett adenocarcinoma. Potential use in chemoprevention and as adjuvant in chemotherapy. Transl Oncol. 2010; 3(6): 389-399.

[35] Devi JR, Thangam EB. Mechanisms of anticancer activity of sulforaphane from Brassica oleracea in HEp-2 human epithelial carcinoma cell line. Asian Pac J Cancer Prev. 2012; 13(5): 2095-2100.

[36] Li Y, Karagoz GE, Seo YH, Zhang T, Jiang Y, Yu Y, Duarte AM, Schwartz SJ, Boelens R, Carroll K, Rüdiger SG, Sun D. Sulforaphane inhibits pancreatic cancer through disrupting Hsp90– p50 Cdc37 complex and direct interactions with amino acids residues of Hsp90. J Nutr Biochem. 2012; 23(12): 1617-1626.

[37] Chaudhuri D, Orsulic S, Ashok BT. Antiproliferative activity of sulforaphane in Akt-overexpressing ovarian cancer cells. Mol Cancer Ther. 2006;6(1): 334-345.

[38] Farag MA, Motaal AAA. Sulforaphane composition, cytotoxic and antioxidant activity of crucifer vegetables. J Adv Res. 2010; 1(1): 65-70.

[39] Geng F, Tang L, Li Y, Yang L, Choi KS, Kazim AL, Zhang Y. Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation. J Biol Chem. 2011; 286(37):32259-32267.

[40] Bhattacharya A, Li Y, Wade KL, Paonessa JD, Fahey JW, Zhang Y. Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion. Carcinogenesis. 2010; 31(12): 2105-2110.

[41] Tsai SC, Huang WW, Huang WC, Lu CC, Chiang JH, Peng SF, Chung JG, Lin YH, Hsu YM, Amagaya S, Yang JS. ERK-modulated intrinsic signaling and G(2)/M phase arrest contribute to the induction of apoptotic death by allyl isothiocyanate in MDA-MB-468 human breast adenocarcinoma cells. Int J Oncol. 2012; 41(6): 2065-2072.

[42] Tripathi K, Hussein UK, Anupalli R, Barnett R, Bachaboina L, Scalici J, Rocconi RP, Owen LB, Piazza GA, Palle K. Allyl isothiocyanate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation. Oncotargets. 2015; 6(7): 5237-5252.

[43] Zhang Y, Tang L. Discovery and development of sulforaphane as a cancer chemopreventive phytochemical. Acta Pharmacol Sin. 2007; 28(9): 1343-1354.

[44] Taylor M. Handbook of natural antimicrobials for food safety and quality, 1st ed. Cambridge: Woodhead Publishing, 2014.

[45] Lin CM, Preston JF, Wei CI. Antibacterial mechanism of allyl isothiocyanate. J Food Prot. 2000; 63(6): 727-734.

[46] Kim HY, Phan-a-god S, Shin IS. Antibacterial activities of isothiocyanates extracted from horseradish (Armoracia rusticana) root against antibiotic-resistant bacteria. Food Sci Biotechnol. 2015; 24(3): 1029-1034.

[47] Padla EP, Solis LT, Levida RM, Shen CC, Ragasa CY. Antimicrobial isothiocyanates from the seeds of Moringa oleissfera Lam. Z Naturforsch C. 2012; 67(11-12): 557-564.

[48] Dufour V, Stahl M, Baysse C. The antibacterial properties of isothiocyanates. Microbiol. 2015; 161(2): 229-243.

[49] Dufour V, Alazzam B, Ermel G,Thepaut M, Rossero A, Tresse O, Baysse C. Antimicrobial activities of isothiocyanates against Campylobacter jejuni isolates. Front Cell Infect Microbiol. 2012; Article ID 3417524.

[50] Dias C, Aires A, Saavedra MJ. Antimicrobial activity of isothiocyanates from cruciferous plants against methicillin-resistant Staphylococcus aureus (MRSA). Int J Mol Sci. 2014; 15(11): 19552-19561.

[51] Aires A, Mota VR, Saavedra MJ, Rosa EAS, Bennett RN. The antimicrobial effects of glucosinolates and their respective enzymatic hydrolysis products on bacteria isolated from the human intestinal tract. J Appl Microbiol. 2009; 106(6): 2086-2095.

[52] Tarozzi A, Angeloni C,Malaguti M,Morroni F,  Hrelia S, Hrelia P. Sulforaphane as a potential protective phytochemical against neurodegenerative diseases. Oxid Med Cell Longe. 2013; Article ID 415078. 
[53] Benedict AL, Mountney A, Hurtado A, Bryan KE, Schnaar RL, Dinkova-Kostova AT, Talalay P. Neuroprotective effects of sulforaphane after contusive spinal cord injury. J Neurotrauma. 2012; 29(16): 2576-2578.

[54] Tarozzi A, Morroni F, Bolondi C, Sita G, Hrelia P, Djemil A, Cantelliforti G. Neuroprotective effects of erucin against 6-hydroxydopamine-induced oxidative damage in a dopaminergic-like neuroblastoma cell line. Int J Mol Sci. 2012; 13(9): 10899-10910.

[55] Wellejus A, Elbrond-Bek H, Kelly NM, Weidner MS, Jorgensen SH. 4-iodophenyl isothiocyanate: a neuroprotective compound. Restor Neurol Neurosci. 2012; 30(1): 21-38.

[56] Tarozzi A,  Angeloni C, Malaguti M, Morroni F, Hrelia S, HreliaP. Sulforaphane as a potential protective phytochemical against neurodegenerative diseases. Oxid Med Cell Longev. 2013; Article ID 415078.

[57] Kelsey N, Wilkins HM, Linseman DA. Nutraceutical antioxidants as novel neuroprotective agents. Molecules. 2010; 15(11): 7792-7814.
[58] Morroni F,  Tarozzi A,  Sita G,  Bolondi C,  Manuel J, Moraga Z, Cantelliforti G,  Hrelia P. Neuroprotective effect of sulforaphane in 6 hydroxydopamine-lesioned mouse model of Parkinson's disease. Neurotoxicology. 2013; 36: 63-71.

[59] Angeloni C, Malaguti M, Rizzo B, Barbalace MC, Fabbri D, Hrelia S. Neuroprotective effect of sulforaphane against methylglyoxal cytotoxicity. Chem Res Toxicol. 2015; 28(6): 1234-1245.

[60] Chittezhath M, Kuttan G. Radioprotective activity of naturally occurring organosulfur compounds. Tumori. 2006; 92(2): 163-169.

[61] Soni AK, Samarth RM, Kumar M, Shukla S, Meena PD, Kumar M, Kumar A. Modulation of radiation induced alterations in Swiss albino mice by Brassica compestris (var sarason). Pharmacologyonline. 2006; 2: 190-199.

[62] Karami M, Nosrati A, Naderi M, Makhloogh M, Shahani S. Protective effects of Nasturtium officinale against gamma-irradiation-induced hepatotoxicity in C57 mice. Res J Pharmacogn. 2015; 2(2): 19-25.

[63] Bai Y, Wang X, Zhao S, Ma C, Cui J, Zheng Y. Sulforaphane protects against cardiovascular disease via Nrf2 activation. Oxid Med Cell Longe. 2015; Article ID 407580.

[64] Owis AI. Broccoli; the green beauty: a review. J Pharm Sci Res. 2015; 7(9): 696-703.

[65] Testai L, Marino A, Tomita K, Citi V, Martelli L, Breschi MC, Levi R, Calderone V. Carboxyphenyl isothiocyanate (4-CPI), a novel hydrogen sulfide-donor endowed with cardioprotective property. Nitric Oxide. 2015; 47(S): 14-60.

[66] Leoncini E, Malaguti MAngeloni CMotori EFabbri D, Hrelia S. Cruciferous vegetable phytochemical sulforaphane affects phase II enzyme expression and activity in rat cardiomyocytes through modulation of Akt signaling pathway. J Food Sci. 2011; 76(7): 175-181.

[67] Luo J. Investigating the potential anti-diabetic effect of sulforaphane. M.Sc. thesis. Faculty of the Virginia Polytechnic Institute and State University, Blacksburg, Virginia, 2014.

[68] Jayakumar T, Chen WFLu WJChou DSHsiao GHsu CYSheu JR, Hsieh CY. A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase: ex vivo and in vivo studies. J Nutr Biochem. 2013; 24(6): 1086-1095.

[69] Oh CH, Shin JI, Mo SJ, Yun SJ, Kim SH, Rhee YH. Antiplatelet activity of L-sulforaphane by regulation of platelet activation factors, glycoprotein IIb/IIIa and thromboxane A2. Blood Coagul Fibrinolysis. 2013; 24(5): 498-504.

[70] Lee DS, Kim TH, Jung YS. Inhibitory effect of allyl isothiocyanate on platelet aggregation. J Agric Food Chem. 2014; 62(29): 7131-7139.

[71] Masutomi N, Toyoda K, Shibutani M, Niho N, Uneyama C, Takahashi N, Hirose M. Toxic effects of BITC and AITC and benzyl ioform specific metabolites in urinary bladder after a single intravesical application to rats. Toxicol Pathol. 2001; 26(2): 617-622.

[72] Bathaie SZ, Tamanoi F. Mechanism of the anticancer effect of phytochemicals. 1st ed. Waltham: Academic Press, 2015.

[73] Lewerenz HJ. Subacute oral toxicity study of BITC in rats. Food. 1992; 36(2): 190-198.

[74] Health Canada Pest Management Regulatory Agency. Oriental mustard seed (OMS). Ottawa: Pest Management Regulatory Agency, 2011.

[75] Fofaria NM, Ranjan A, Kim S, Srivastava SK. Mechanism of anticancer effects of isothiocyanates.  Enzymes. 2015; 37:111-137.

[76] Gupta P. Molecular targets of ITC in cancer: Recent Advances. Mol Nutr Food Res. 2014; 58(8): 1685-1707.

[77] Troncoso R, Espinoza C, Estrada AS, Tiznado ME, García HS. Analysis of the isothiocyanates present in cabbage leaves extract and their potential application to control Alternaria rot in bell peppers. Food Res Int. 2005; 38(6): 701-708.

[78] Yehuda H,Khatib S,Sussan I, Musa R, Vaya J, Tamir S. Potential skin anti-inflammatory effects of 4-methylthiobutylisothiocyanate (MTBI) isolated from rocket (Eruca sativa) seeds. Biofactors. 2009; 35(3): 295-305.

[79] Hanafi EM, Hegazy EM, Riad RM. Bio-protective effect of Eruca sativa seed oil against the hazardus effect of aflatoxin b1 in male-rabbits. Int J Acad Res. 2010; 2(2): 67-74.

[80] Ganin H, Rayo J, Amara N, Levy N, Krief P, Meijler M. Sulforaphane and erucin, natural isothiocyanates from broccoli, inhibit bacterial quorum sensing. Med Chem Commun. 2013;4: 175-179.

[81] Rose P, Faulkner K, Williamson G, Mithen R. 7-Methylsulfinylheptyl and 8- methylsulfinyloctyl isothiocyanates from watercress are potent inducers of phase II enzymes. Carcinogenesis. 2000; 21(11): 1983-1988.

[82] Uto T,  Hou DX, Morinaga O, Shoyama Y. Molecular mechanisms underlying anti-inflammatory actions of 6-(methylsulfinyl)hexyl isothiocyanate derived from Wasabi (Wasabia japonica). Adv Pharmacol  Sci. 2012; Article ID 614046.

[83] Faizi S, Siddiqui BS, Saleem F, Gilani AH. Hypotensive constituents from the pods of Moringa oleifera. Planta Med. 1998; 64(3): 225-228.

[84] Nakamura Y, Iwahashi T, Tanaka A, Koutani J, Matsuo T, Okamoto S, Sato K, Ohtsuki K. 4-(methylthio)-3-butenyl isothiocyanate, a principal antimutagen in daikon (Raphanus sativus; Japanese white radish). J Agric Food Chem. 2001; 49(12): 5755-5760.

[85] Lim JH, Kim HW, Jeon JH, Lee HS. Acaricidal constituents isolated from Sinapis alba L. seeds and structure-activity relationships. J Agric Food Chem. 2008; 56(21): 9962-9966.

[86] Naser SA, Besheli BA, Mehr SS. The isolation and determination of sulforaphane from broccoli tissues by reverse phase-high performance liquid chromatography. J Chin Chem Soc. 2011; 58(7): 906-910.

[87] Hifnawy MS, Salam RMS, Rabeh MA, Aboseada MA. Glucosinolates, glycosidically bound volatiles and antimicrobial activity of Brassica oleraceae Var. botrytis, (Soultany cultivar). J Biol Agric Healthcare. 2013; 3(17): 66-80.

[88] Radonic A, Blazevic I, Mastelic J, Zekic M, Skocibusic M, Maravic A. Phytochemical analysis and antimicrobial activity of Cardaria draba (L.) Desv. volatiles. Chem Biodivers. 2011; 8(6): 1170-1181.

[89] Olivier C, Vaughn SF, Mizubuti ESG, Loria R. Variation in allyl isothiocyanate production within Brassica species and correlation with fungicidal activity. J Chem Eco. 1999; 25(12): 2687-2701.

[90] Mastelic J, Blazevic I, Kosalec I.  Chemical composition and antimicrobial activity of volatiles from Degenia velebitica, a European stenoendemic plant of the Brassicaceae family. Chem Biodivers. 2010; 7(11): 2755-2765.

[91] Sofrata A, Santangelo EM, Azeem M, Borg-karlson AK, Gustafsson A, Putsep K. Benzyl isothiocyanates, a major compound from roots of Salvadora persica is highly active against gram positive bacteria. Plos One. 2011; 6(8): 1-10

[92] Mastelic J, Jerkovic I, Blazevi I, Radoni A, Krstulovi L. Hydrodistillation–adsorption method for the isolation of water-soluble, non-soluble and high volatile compounds from plant materials. Talanta. 2008; 76(4): 885-891.

[93] Li L, Lee W, Lee WJ, Auh JH, Kim SS, Yoon J. Extraction of allyl isothiocyanate from wasabi (Wasabia japonica Matsum) using supercritical carbon dioxide. Food Sci Biotechnol. 2010; 19(2): 405-410.

[94] Sharma HK, Ingle S, Singh C, Sarkar BC, Upadhyay A. Effect of various process treatment conditions on the allyl isothiocyanate extraction rate from mustard meal. J Food Sci Technol. 2012; 49(3): 368-372.

[95] Marton MR, Lavric V. A simple method for the quantification of isothiocyanates from mustard. UPB Sci Bull Series B. 2013; 75(1): 63-72.

[96] Ivica B, Josip M. Free and bound volatiles of garlic mustard (Alliaria petiolata). Croat Chem Acta. 2008; 81(4): 607-613.

[97] Vaughn SF, Berhow MA. Allelochemicals isolated from tissues of the invasive weed garlic mustard (Alliaria petiolata). J Chem Ecol. 1999; 25(11): 2495-2504.

[98] Jiang ZT, Li R, Yu JC. Pungent components from thioglucosides in Armoracia rusticana grown in China, obtained by enzymatic hydrolysis. Food Technol Biotechnol. 2006; 44(1): 41-45.

[99] Kim YK, Kin GH. Determination of 3-butenyl isothiocyanate in different part and cultivators of Chinese cabbage. Food Sci Biotech. 2005; 14(4): 466-469.

[100] Hong E, Kim GH. GC-MS analysis of extracts from Korean cabbage. (Brassica campeteris L. ssp pekinensis) and its seed. Prev Nutr Food Sci. 2013; 18(3): 218-221.

[101] Jones G, Sander OG, Grimm C. Aromatic compounds in three varieties of turnip greens harvested at three maturity leaves. J Food Quality. 2007; 30(2): 218-227.

[102] Taveira M, Fernades F, Pinho PGD, Andrade PB, Pereira JA, Valentao P. Evaluation of Brassica rapa var rapa L. volatile composition by HS-SPME and GC/IT-MS. Microchem J. 2009; 93(2): 140-146.

[103] Sharma S, Agrawal N. Nourishing and healing power of garden cress. Indian J Nat Prod Resour. 2011; 2(3): 292-297.

[104] Lykkesfeldt J, Moller BL. Synthesis of benzylglucosinolate in Tropaeolum majus L. Plant Physiol. 1993; 102(2): 609-613.

[105] Goyal BR, Agrawal BB, Goyal RK, Mehta AA. Phytopharmacology of Moringa oleifera Lam. an overview. Nat Prod Rad. 2001; 6(4): 347-353.

[106] Santhi S, Shanthipriya S. High- performance liquid chromatography in the study of benzylisothiocyante from Raphanus sativus (white radish). SIRJ-APBBP. 2014; 1(4): 28-33.

[107] Li J, Xie B, Yan S, Li H, Wang Q. Extraction and determination of 4-methylthio-3-butenyl isothiocyanate in Chinese radish (Raphanus sativus L.) roots. LWT Food Sci Technol. 2015; 60(2): 1080-1087.

[108] Puntambekar SV. Mustard oil and mustard oil glycoside occuring in seed kernels of Putranjiva roxburghii. Banglore: Indian Academy of Sciences, 1950.

[109] Li W, Du Y, Zhang Y, Chi Y, Shi Z, Chen W, Ruan M, Zhu H. Optimized formation of benzyl isothiocyanate by endogenous enzyme and its extraction from Carica Papaya seed. Trop J Pharm Sci. 2014; 13(8): 1303-1311.

[110] Biro-Sandor Z. Assessment report on Sisymbrium officinale (L.) Scop. herba. London: European Medicine Agency, Committee on herbal medicinal product, 2014.

[111] Zheng BL, Kim CH, Wolthoff S, He K, Rogers L, Shao Y, Zheng QI, inventors;Pure World Botanicals, Inc, assignee.Extract of Lepidium meyenii roots for pharmaceutical applications. United States Patent US 6267995 B1. 2001 July 31.

[112] Rajesh P, Selvamani P, Latha S, Saraswathy A, Kannan VR. A review on chemical and medicobiological applications of capparidaceae family. Pharmacog Rev. 2009; 3(6): 378-387.  

[113] Muhaidat R, Al-Qudah MA, Al-Shayeb A, Jacob JH, Al-Jaber H, Hussein E, Al Tarawneh IN, Orabi STA. Chemical profile and antibaceterial activity of crude fractions and essential oils of Capparis ovata Desf. and Capparis spinosa L. (capparaceae). Int J Integr Biol. 2013; 14(1): 39-47.

[114] Tripodia G, Verzeraa A, Dimaa G, Condursoa C, Ragusab S. Brassica fruticulosa Cyr. and Brassica incana Ten. (Brassicaceae) as Mediterranean traditional wild vegetables: a valuable source of bioactive compounds. J Essent Oil Res. 2012; 24(6): 539-545.

[115] El-Egami AA, Burham BO, El-Kamali HH. Essential oil composition of the flowering aerial parts of Sudanese Morettia phillaeana (Del.) DC. Curr Res J Biol Sci. 2011; 3(2): 100-103.

[116] Zhang B, Wang X, Yang Y, Zhang X. Extraction and identification of isothiocyanates from broccolini seeds. Nat Prod Commun. 2011; 6(1): 65-66.

[117] Blazevic I. Glucosinolates: novel sources and biological potential. Austin J Bioorg Org Chem. 2014; 1(1): 4.