Isolation, Characterisation and In Silico Toxicity Evaluations of Thiocarbamates, Isothiocyanates, Nitrile, Glucosinolate and Lipids from Moringa oleifera Lam. Seed

Abstract

The phytochemical composition of medicinal plants is responsible for the ethnopharmacological applications. These phytochemicals vary in plants of same species planted in various geographical locations. The seed of Moringa oleifera Lam., a widely consumed multi-medicinal plant was examined for the bioactive phytochemicals. With the aid of Nuclear Magnetic Resonance (1H-NMR/13C-NMR) spectrometer, Electrospray Ionisation Mass Spectrometry (ESI-MS) and Fourier Transform Infrared (FT-IR) spectroscopy, the phytochemical investigation of the seed of M. oleifera afforded nine compounds which included niazimicin 1, niazidin 2, glucomoringin isothiocyanate 3, niazinin acetate 4, niazinin triacetate 5, niazirinin 6, glucotropaeolin 7, triolein 8, trivaccenin 9. The Gas Chromatography-Mass Spectrometry (GC-MS) analysis of a major oily fraction revealed the presence of additional ten compounds which include oleic acid (major), 13-docosenoic acid, stearic acid, p-hydroxybenzyl cyanide, α -l-rhamnopyranose and other fatty acids/esters.  This is the first account of a fully acetylated niazinin (a 4-(2’,3',4’-O-triacetyl-α-L-rhamnosyloxy)benzyl isothiocyanate) 5 from Moringa oleifera seed. The in silico toxicity evaluation indicated that most of the isolated compounds are either immunotoxic, carcinogenic or mutagenic. The result thus obtained could serve a basis for the pharmacological and toxicological evaluation and profiling of the seed. The result further implied the need for dosage regulation of the consumption of the seed.

Keywords

• Moringa oleifera
• niazimicin
• niazidin
• isothiocyanate
• glucosinolate
• nitrile

References

1. 1. Sastari BN. The Wealth of lndia, Council of Scientific and Industrial Research, New Delhi, 1962; p. 425.
2. 2. Liu Y, Wang X, Wei X, Gao Z, Han J. Values, properties and utility of different parts of Moringa oleifera: an overview. Chinese Herbal Medicines. 2018; 10 (4): 371-378.
3. 3. Ravani A, Prasad RV, Gajera RR, Joshi DC. Potentiality of Moringa oleifera for food and nutritional security - a review, Agric. Rev. 2017; 38: 228–232.
4. 4. Tiloke C, Anand K, Gengan, RM, & Chuturgoon AA. Moringa oleifera and their phytonanoparticles: Potential antiproliferative agents against cancer. Biomedicine & Pharmacotherapy. 2018; 108, 457–466. 
5. 5. Falowo AB, Mukumbo FE, Idamokoro EM, Lorenzo JM, Afolayan AJ, Muchenje V. Multi-functional application of Moringa oleifera Lam. in nutrition and animal food products: A review. Food Research International. 2018; 106, 317-334.
6. 6. Atolani O, Olabiyi ET, Issa AA, Azeez HT, Onoja EG, Ibrahim SO, Zubair MF, Oguntoye OS, Olatunji GA. Green synthesis and characterization of natural antiseptic soaps from the oils of underutilized tropical seed. Sustainable Chemistry and Pharmacy. 2016; 4: 32–39.
7. 7. Faizi S, Siddiqui BS., Saleem R, Siddiqui S, Aftab K, Gilani A. Isolation and Structure Elucidation of New Nitrile and Mustard Oil Glycosides from Moringa oleifera and Their Effect on Blood Pressure. J. Nat. Prod., 1994, 57 (9), 1256–126.
8. 8. Faizi S, Siddiqui BS, Saleem R, Noor F, Husnain S. Isolation and Structure Elucidation of a Novel Glycoside Niazidin from the Pods of Moringa oleifera J. Nat. Prod. 1997, 60, 1317-1321.

9. 9. Dayrit FM, Alcantar AD, Villasenor IM. Studies on Moringa oleifera seeds, the antibiotic compound and its deactivation in aqueous solution. Philippine Journal of Science. 1990; 119: 23.
10. 10. Atolani O, Olorundare OE, Anoka AN, Osin AO, Biliaminu SA. Antioxidant, Proteinase Inhibitory and Membrane Stabilization Potentials of Moringa oleifera Seed Oil. FABAD Journal of Pharmaceutical Sciences. 2018; 43 (2), 1-13.
11. 11. Fahey JS. Moringa oleifera: A review of the medical evidence for its nutritional, therapeutic, and prophylactic properties. Trees for Life Journal. 2005; 1: 5.
12. 12. Kambizi L, MT Bakare-Odunola AT, Oladiji AT, Kola-Mustapha TO, Amusa O, Atolani NS, Njinga, A.L. Quadri. Proteinease inhibition, membrane stabilization, antioxidant and phytochemical evaluations of leaves, seeds and calyces of four selected edible medicinal plants. Cogent Chemistry. 2017: 3: 1314064.
13. 13. Şanli A, Tahsin KT. Geographical impact on essential oil composition of endemic Kundmannia anatolica Hub.-Mor. (Apiaceae). African Journal of Traditional, Complementary and Alternative Medicines. 14; (1): 131-137.
14. 14. Njan AA, Atolani O, Olorundare OE, Afolabi SO, Ejimkonye BC, Crucifix PG, Salami B, Olajide JO, Oyewopo AO. Oyeleke SA. Chronic toxicological evaluation and reversibility studies of Moringa oleifera ethanolic seed extract in Wistar rats. Tropical Journal of Health Sciences. 2018; 25 (1), 59-71.
15. 15. Olorundare OE, Bello MK, Billiaminu SA, Babatunde SA, Ibrahim OK, Njan AA. Acute and Subacute Toxicity of Defatted Ethanolic Extract of Moringa oleifera Seed in Albino Rats   West. Afr. J. Pharmacol. Drug Res.  2015; 30:46-51.
16. 16. Njan AA, Atolani O, Olorundare OE, Afolabi SO, Ejimkonye BC, Crucifix PG, Salami B, Olajide JO, Oyewopo AO. Assessment of developmental toxicity of Moringa oleifera (seed) in pregnant wistar rats. Centrepoint Journal (Science Edition), 2017; 23 (1): 1-18.
17. 17. Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 2018; 46, 257–263. 
18. 18. Faizi S, Siddiqui BS, Saleem R, Siddiqui S, Aftab K, Gilani A. Isolation and structure elucidation of novel hypotensive agents, Niazinin A, Niazinin B, Niazimicin and Niaziminin A + B from Moringa oleifera: The first naturally occurring thiocarbamate. Journal of the Chemical Society Perkin Transactions. 1992; 1: 3237- 3241.
19. 19. Faizi S, Siddiqui BS, Saleem R, Siddiqui S, Aftab K. Gilani AUH. Fully acetylated carbamate and hypotensive thiocarbamate glycosides from Moringa oleifera. Phytochemistry. 1995; 38(4), 957–963.
20. 20. Ragasa CY, Levida RM, Don MJ, Shen CC. Cytotoxic isothiocyanates from Moringa oleifera Lam. Philippine Science Letters. 2012; 5(1):46-52.
21. 21. de Graaf R.M., Krosse S, Swolfs AEM., Brinke E, Prill N, Leimu R, Galen PM, Wang Y., Aarts MGM. and Dam NM. Isolation and identification of 4-a-rhamnosyloxy benzyl glucosinolate in Noccaea caerulescens showing intraspecific variation. Phytochemistry. 2014; 110: 166-171.
22. 22. Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry. 2001: 56(1), 5–51.
23. 23. Kjær A, Malver O, El-Menshaw B, Reisch J,. Isothiocyanates in myrosinase-treated seed extracts of Moringa peregina. Phytochemistry. 1979; 18, 1485–1487.
24. 24. Waterman C, Cheng DM, Rojas-Silva P, Poulev A, Dreifus J, Lila MA, Raskin I. Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro. Phytochem 2014; 103:114–122.
25. 25. Ragasa CY, Ng VAS, Shen CC. Chemical Constituents of Moringa oleifera Lam. Seeds. International Journal of Pharmacognosy and Phytochemical Research. 2016; 8(3); 495-498.
26. 26. Lamar S. and Rollin P. Synthesis of an Artificial Phosphate Bio-isostere of Glucotropaeolin. Tetrahedron Letters, 1994; 35, 14: 2173-2174.
27. 27. Aucagne V, Gueyrard D, Tatibouet A, Cottaz S, Driguez H, Lafosse M and Rollin P. The first synthesis of C-glucotropaeolin. Tetrahedron Letters 1999; 40: 7319-7321.
28. 28. Montaut S, Zhang W, Nuzillard, J., De Nicola G.R., Rollin P. Glucosinolate Diversity in Bretschneidera sinensis of Chinese Origin. Journal of Natural Products. 2015; 78 (8): 2001–2006.
29. 29. Ishida M, Hara M. Fukino, N; Kakizaki, T; Morimitsu, Y. "Glucosinolate metabolism, functionality and breeding for the improvement of Brassicaceae vegetables". Breeding Science. 2014; 64 (1): 48–59.
30. 30. Agerbirk N, Olsen CE. "Glucosinolate structures in evolution". Phytochemistry. 77: 16–45.
31. 31. Samuni BM, Arad Z, Dearing MD, Gerchman Y, Karasov WH, Izhaki I. "Friend or foe? Disparate plant–animal interactions of two congeneric rodents". Evolutionary Ecology. 27 (6): 1069–1080.
32. 32. Fuentes F, Paredes-Gonzalez X, Kong AN. Dietary Glucosinolates Sulforaphane, Phenethyl Isothiocyanate, Indole-3-Carbinol/3,3′-Diindolylmethane: Anti-Oxidative Stress/Inflammation, Nrf2, Epigenetics/Epigenomics and in Vivo Cancer Chemopreventive Efficacy". Current Pharmacology Reports. 1 (3): 179–196. 
33. 33. Singh B, Agrawal PK, Thakur RS. (1989). Long chain esters of Aesculus indica. Journal of Natural Products. 2015; 52 (1): 180-183.
34. 34. Vlahov G, Chepkwony PK, Ndalut PK. 13C NMR Characterization of Triacylglycerols of Moringa oleifera Seed Oil: An Oleic-Vaccenic Acid Oil. J. Agric. Food Chem. 2002; 50 (5): 970–975.
35. 35. Díaz M, Gavín JA, Andrade JB. Structural characterization by Nuclear Magnetic Resonance of ozonized triolein. Grasas Aceites. 2008; 59: 274-281.
36. 36. Vessby B, Uusitupa M, Hermansen K, Riccardi G, Rivellese AA, Tapsell LC, Nälsén C, Berglund L, Louheranta A, Rasmussen BM, Calvert GD, Maffetone A, Pedersen E, Gustafsson IB, Storlien LH. "Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study". Diabetologia. 2001; 44 (3): 312–319.
37. 37. Kavitha C, Ramesh M, Kumaran S. S., and Lakshmi SA. Toxicity of Moringa oleifera seed extract on some hematological and biochemical profiles in a freshwater fish, Cyprinus carpio. Experimental and Toxicologic Pathology. 2012; 64(7-8), 681–687. 
38. 38. Ayotunde EO, Fagbenro OA, Adebayo OT, Amoo AI. Toxicity of aqueous extracts of drumstick Moringa oleifera seeds to Nile tilapia Oreochromis niloticus, fingerlings and adults. In: Proceedings of 6th international symposium on tilapia; 2004.
39. 39. Kim Y, Jaja-Chimedza A, Merrill D, Mendes O, Raskin I. A 14-day repeated-dose oral toxicological evaluation of an isothiocyanate-enriched hydro-alcoholic extract from Moringa oleifera Lam. seeds in rats. Toxicology Reports. 2018: 5, 418–426.