Optimizing Thymoquinone Content of Iranian Nigella sativa Essen-tial Oil and Challenges in Commercializing it as an Active Pharma-ceutical Ingredient

Document Type : Research Paper

Authors

1 Department of Biochemistry, Payame Noor University, Tehran, Iran,

2 Department of Chemistry Payame Noor University, Tehran, Iran

3 Chemical and Bimolecular Engineering Georgia institute of Technology: Atlanta, GA, US

Abstract

The objective of this study was to produce the essential oil of Nigella sativa L. (N. sativa) with the highest thymoquinone (TQ) content and explore the challenges associated with its commercialization as an active pharmaceutical ingredient. Commercially sourced seeds of N. sativa were obtained from reputable vendors. Ground seeds underwent extraction using a variety of polar and non-polar solvents. The resulting essential oil samples were subjected to analysis via reverse-phase high-performance Liquid Chromatography (RP-HPLC) to quantify TQ content, employing a method of quantification following the validation of the method. Major components of hexane extract were analyzed by GC-MS. Non-polar solvents at ambient temperature produced the essential oil with the highest TQ content. Extraction at higher temperatures has an adverse effect on TQ and is not recommended. The Cold pressed oil showed very low TQ content. However, treatment of this oil with hexane for an extended period of times released TQ from the matrix of the oil. Moreover, we refined the extraction methodology to produce essential oil with the highest TQ content. n-heptane which has a better toxicity profile than n-hexane is the best solvent for producing the essential oil with the highest TQ content. Optimization of powder/solvent ratio, temperature, and time of extraction would provide the most economically viable option. Cold press produces an oil with a different composition in which TQ is bonded to the matrix of the oil. Comparing the therapeutic effectiveness of the two oils is recommended for future studies. The challenges associated with the commercialization of N. sativa oil as a pharmaceutical product are also discussed.

Keywords

Main Subjects

References

  1. Ahmad M.F., Ahmad F.A., Ashraf S.A., Saad H.H., Wahab S., Khan M.I., Ali M., Mohan S., Hakeem K.R., Athar M.T., An updated knowledge of Black seed (Nigella sativa Linn.): Review of phyto-chemical constituents and pharmacological properties. J Herb Med. 2021; 25:100404.
  2. Rahmani R., Khalesro S., Heidari G., Mokhatssi-Bidgoli A., Vermicompost and zeolite improve yield, nutrient uptake, essential and fixed oil production, and composition of Nigella sativa L. Front Sustain Food Syst. 2023; 7:1214691.
  3. Rezaei-Chiyaneh E., Seyyedi S.M., Ebrahimian E., Moghaddam S.S., Damalas C.A., Exogenous applica-tion of gamma-aminobutyric acid (GABA) alleviates the effect of water deficit stress in black cumin (Nigel-la sativa L.). Ind Crops Prod. 2018;112: 741-748.
  4. Safaei Z., Azizi M., Davarynejad G., Aroiee H., The Effect of Planting Seasons on Quantitative and Quali-tative Characteristics of Black cumin (Nigella sativa L.). J Med Plants By-Prod, 2017. 6(1): p. 27-33.
  5. Haj Seyed Hadi M.R., Darzi M.T., Riazi G., Black cumin (Nigella sativa L.) yield affected by irrigation and plant growth promoting bacteria. J Med Plants By-Prod. 2016; 5(2): 125-133.
  6. Salehi S.,Kiran R., Integrated experimental and analytical wellbore strengthening solutions by mud plastering effects. J Energy Resour Technol. 2016; 138(3): 032904.
  7. Kokoska L., Havlik J., Valterova I., Sovova H., Sajfr-tova M., Jankovska I., Comparison of chemical com-position and antibacterial activity of Nigella sativa seed essential oils obtained by different extraction methods. J Food Prot. 2008; 71(12): 2475-2480.
  8. Burits M., Bucar F., Antioxidant activity of Nigella sativa essential oil. Phytother Res. 2000; 14(5): 323-328.
  9. Ghahramanloo K.H., Kamalidehghan B., Akbari Javar H., Teguh Widodo R., Majidzadeh K., Noordin M.I., Comparative analysis of essential oil composition of Iranian and Indian Nigella sativa L. extracted using supercritical fluid extraction and solvent extraction. Drug Des Devel Ther. 2017; 2221-2226.
  10. Salea R., Widjojokusumo E., Hartanti A.W., Verian-syah B., Tjandrawinata R.R., Supercritical fluid carbon dioxide extraction of Nigella sativa (black cumin) seeds using taguchi method and full factorial design. Optimization. 2013; 13(14): 16-17.
  11. Benazzouz-Smail L., Achat S., Brahmi F., Bachir-Bey M., Arab R., Lorenzo J.M., Benbouriche A., Boudiab K., Hauchard D., Boulekbache L., Biological proper-ties, phenolic profile, and botanical aspect of Nigella sativa L. and Nigella damascena L. seeds: A compara-tive study. Molecules. 2023; 28(2): 571.
  12. Salmani J.M.M., Asghar S., Lv H., Zhou J., Aqueous solubility and degradation kinetics of the phytochemi-cal anticancer thymoquinone; probing the effects of solvents, pH and light. Molecules. 2014; 19(5): 5925-5939.
  13. Iqbal M.S., Ahmad A., Pandey B., Solvent based optimization for extraction and stability of thymoqui-none from Nigella sativa Linn. and its quantification using RP-HPLC. Physiol Mol Biol Plants. 2018; 24: 1209-1219.
  14. Mohammed N.K., Abd Manap M.Y., Tan C.P., Mu-hialdin B.J., Alhelli A.M., Hussin A.S.M., The effects of different extraction methods on antioxidant proper-ties, chemical composition, and thermal behavior of black seed (Nigella sativa L.) oil. Evid Based Com-plement Alternat Med. 2016;2016.
  15. Tiruppur Venkatachallam S.K., Pattekhan H., Divakar S., Kadimi U.S., Chemical composition of Nigella sati-va L. seed extracts obtained by supercritical carbon dioxide. J Food Sci Technol. 2010; 47: 598-605.
  16. Shahidi F., Ambigaipalan P., Phenolics and polyphe-nolics in foods, beverages and spices: Antioxidant activity and health effects–A review. J Funct Foods. 2015; 18: 820-897.
  17. Gad A., El–Dakhakhny M., Hassan M., Studies on the chemical constitution of Egyptian Nigella sativa L. oil. Planta Medica. 1963; 11(02): 134-138.
  18. Gali-Muhtasib H., Roessner A., Schneider-Stock R., Thymoquinone: a promising anti-cancer drug from natural sources. Int J Biochem Cell Biol. 2006; 38(8): 1249-1253.
  19. Tabassum S., Rosli N., Ichwan S.J.A., Mishra P., Thymoquinone and its pharmacological perspective: A review. Pharmacol Res - Mod Chin Med. 2021; 1: 100020.
  20. Alam M., Hasan G.M., Ansari M.M., Sharma R., Yadav D.K., Hassan M.I., Therapeutic implications and clini-cal manifestations of thymoquinone. Phytochemistry. 2022; 200: 113213.
  21. Khalife K., Lupidi G., Nonenzymatic reduction of thymoquinone in physiological conditions. Free Radic Res. 2007; 41(2): 153-161.
  22. Armutcu F., Akyol S., Akyol O., The interaction of glutathione and thymoquinone and their antioxidant properties. Electron J Gen Med. 2018; 15(4).
  23. Erdoğan Ü., Yılmazer M., Erbaş S., Hydrodistillation of Nigella sativa seed and analysis of Thymoquinone with HPLC and GC-MS. Bilgesci. 2020; 4(1):27-30.
  24. International Council for Harmonization of Technical Requirements for Pahramaceuticals for Human Use (ICH). Available from: https://www.ich.org/.
  25. Available from: https://www.ema.europa.eu/en/partners-networks/international-activities/multilateral-coalitions-initiatives/international-council-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich.
  26. Q3C (R8) Impurities: Guidance for Residual Solvents Guidance for Industry. 2021.
  27. Jiménez-González C., Constable D.J., Ponder C.S., Evaluating the “Greenness” of chemical processes and products in the pharmaceutical industry—a green met-rics primer. Chem Soc Rev. 2012; 41(4): 1485-1498.
  28. Jiménez-González C., Curzons A.D., Constable D.J., Cunningham V.L., Cradle-to-gate life cycle inventory and assessment of pharmaceutical compounds. Int J Life Cycle Assess. 2004;9: 114-121.
  29. Jiménez-González C., Kim S., Overcash M.R., Meth-odology for developing gate-to-gate life cycle inven-tory information. Int J Life Cycle Assess. 2000; 5: 153-159.
  30. Jiménez-González C.n., Ollech C., Pyrz W., Hughes D., Broxterman Q.B., Bhathela N., Expanding the bounda-ries: developing a streamlined tool for eco-footprinting of pharmaceuticals. Org Process Res Dev. 2013; 17(2): 239-246.
  31. Reichmanis E., Sabahi M., Life cycle inventory assessment as a sustainable chemistry and engineering education tool. ACS Publications. 2017.
  32. ISO 14044:2006(en) Environmental Management-Life Cycle Assessment-Requirements and guidelines. https://www.iso.org/Standard/38498.html.
Journal of Medicinal plants and By-Products
Volume 13, Issue 4
December 2024
Pages 1149-1158

Files

Share

How to cite

Statistics