Potential Cytotoxic, Antifungal, and Antioxidant Activity of Dithymoquinone and Thymoquinone

Eman Ramadan Elsharkawy, Emad M. Abdallah, Ahmad Abo Markb

Abstract

Nigella sativa is a well-known plant with various applications in traditional medicine. The research goals of the current study were focused on discovering Nigella sativa’s active substances with antifungal, antioxidant, and anticancer properties. The major compound of the plant’s essential oil was found to be thymoquinone (TQ), which was used to synthesize dithymoquinone (DTQ) by the simple photodimerization method. Formation of the compound was confirmed by high-performance liquid chromatography (HPLC), HNMR, IR, and ESI. Both compounds (TQ and DTQ) were assayed for antifungal, antioxidant, and cytotoxic properties, and the results showed higher activity of TQ compared to DTQ. In conclusion, thymoquinone is a promising antifungal, antioxidant, and anticancer agent and is recommended for further pharmaceutical evaluation. To the best of our knowledge, this is the first study to evaluate the bioactivity potential of DTQ synthesized from thymoquinone as it is present in low quantities in the essential oil of Nigella sativa.

Keywords: cytotoxicity, antioxidant, thymoquinone, dithymoquinone.


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GHOLAMNEZHAD Z., KEYHANMANESH R., and BOSKABADY M. Anti-inflammatory, antioxidant, and immunomodulatory aspects of Nigella sativa for its preventive and bronchodilatory effects on obstructive respiratory diseases: A review of basic and clinical evidence. Journal of Functional Foods, 2015, 17: 910-927. https://doi.org/10.1016/j.jff.2015.06.032

ABDALLAH E.M. Plants: An alternative source for antimicrobials. Journal of Applied Pharmaceutical Science, 2011, 1(6): 16-20. https://www.japsonline.com/admin/php/uploads/118_pdf.pdf

GULSHAN K., & MOYE-ROWLEY W. S. Multidrug Resistance in Fungi. Eukaryotic Cell, 2020, 6(11), 1933-1942. https://doi.org/10.1128/EC.00254-07

COWAN M. M. Plant products as antimicrobial agents. Clinical Microbiology Reviews, 1999, 12(4): 564-582. https://doi.org/10.1128/CMR.12.4.564

HASSANIEN M. F., ASSIRI A. M., ALZOHAIRY A. M., and ORABY H. F. Health-promoting value and food applications of black cumin essential oil: an overview. Journal of Food Science and Technology, 2015, 52(10): 6136-6142. https://doi.org/10.1007/s13197-015-1785-4

CASCELLA M., PALMA G., BARBIERI A., BIMONTE S., AMRUTHRAJ N. J., and MUZIO M. R. Role of Nigella sativa and its constituent thymoquinone on chemotherapy-induced nephrotoxicity: evidence from experimental animal studies. Nutrients, 2017, 9(6): 625. https://doi.org/10.3390/nu9060625

OZER E. K., GOKTAS M. T., TOKER A., PEHLIVAN S., BARISKANER H., and UGURLUOGLU C. Thymoquinone protects against the sepsis induced mortality, mesenteric hypoperfusion, aortic dys-function and multiple organ damage in rats. Pharmacological Reports, 2017, 69(32): 683–690. https://doi.org/10.1016/j.pharep.2017.02.021

FAISAL R., SHINWARI L., and JEHANGIR T. Comparison of the therapeutic effects of thymoquinone and methotrexate on renal injury in pristane induced arthritis in rats. Journal of the College of Physicians and Surgeons Pakistan, 2015, 25(8): 597-601. https://applications.emro.who.int/imemrf/J_Coll_Physicians_Surg_Pak/J_Coll_Physicians_Surg_Pak_2015_25_8_597_601.pdf

GALI-MUHTASIB H., ROESSNER A., and SCHNEIDER-STOCK R. Thymoquinone: A promising anti-cancer drug from natural sources. The International Journal of Biochemistry & Cell Biology, 2006, 38(8): 1249-1253. https://doi.org/10.1016/j.biocel.2005.10.009

RAMADAN M. F. Nutritional value, functional properties and nutraceutical applications of black cumin (Nigella sativa L.): an overview. International Journal of Food Science & Technology, 2007, 42(10): 1208–1218. https://doi.org/10.1111/j.1365-2621.2006.01417.x

SHATERZADEH-YAZDI H., NOORBAKHSH M.-F., SAMARGHANDIAN S., and FARKHONDEH T. An Overview on Renoprotective Effects of Thymoquinone. Kidney Diseases, 2018, 4(2): 74-82. https://doi.org/10.1159/000486829

GHOSHEH O. A., HOUDI A. A., and CROOKS P. A. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). Journal of Pharmaceutical and Biomedical Analysis, 1999, 19(5): 757–762. https://doi.org/10.1016/S0731-7085(98)00300-8

PATHAN S. A., JAIN G. K., ZAIDI S. M. A., AKHTER S., VOHORA D., CHANDER P., KOLE P. L., AHMAD F. J., and KHAR R. K. Stability-indicating ultra-performance liquid chromatography method for the estimation of thymoquinone and its application in biopharmaceutical studies. Biomedical Chromatography, 2011, 25(5): 613–620. https://doi.org/10.1002/bmc.1492

ABDEL GAWWAD M. R., MAHMOOD A., AL FARRAJ D. A., EL-ABEDEIN A. I. Z., MAHMOUD A. H., and BUKHARI S. M. In-vitro antimicrobial activities of Solanum villosum (L.) lam; crude extract solvent comparison. Journal of King Saud University – Science, 2020, 32: 2129–2133. https://doi.org/10.1016/j.jksus.2020.01.035

WONG J. X., & RAMLI S. Antimicrobial activity of different types of Centella asiatica extracts against foodborne pathogens and food spoilage microorganisms. LWT, 2021, 142: 111026. https://doi.org/10.1016/j.lwt.2021.111026

ELSHARKAWY E. R., & SHIBOOB M. Antioxidant Activity of Phenolic and Alkaloid Fractions Accumulated in Artemisia Judaica and Artemisia Herba Alba. Journal of Natural Remedies, 2017, 17(4): 2320-3358. https://doi.org/10.18311/jnr/2017/18731

ALAUFI O. M., NOORWALI A., ZAHRAN F., AL-ABD A. M., and AL-ATTAS S. Cytotoxicity of thymoquinone alone or in combination with cisplatin (CDDP) against oral squamous cell carcinoma in vitro. Scientific Reports, 2017, 7(1): 13131. https://doi.org/10.1038/s41598-017-13357-5

BASHA L. I. A., RASHED M. S., and ABOUL-ENEIN H. Y. TLC Assay of Thymoquinone in Black Seed Oil (Nigella Sativa Linn) and Identification of Dithymoquinone and Thymol. Journal of Liquid Chromatography & Related Technologies, 1995, 18(1): 105–115. https://doi.org/10.1080/10826079508009224

YUSUFI M., BANERJEE S., MOHAMMAD M., KHATAL S., VENKATESWARA S. K., KHAN E. M., ABOUKAMEEL A., SARKAR F. H., and PADHYE S. Synthesis, characterization and anti-tumor activity of novel thymoquinone analogs against pancreatic cancer. Bioorganic & Medicinal Chemistry Letters, 2013, 23(10): 3101-3104. https://doi.org/10.1016/j.bmcl.2013.03.003

MAHMOUDV H., SEPAHVAND A., JAHANBAKHSH S., EZATPOUR B., and MOUSAVI S. A. A. Evaluation of antifungal activities of the essential oil and various extracts of Nigella sativa and its main component, thymoquinone against pathogenic dermatophyte strains. Journal de Mycologie Medicale, 2014, 24(4): 155-161. https://doi.org/10.1016/j.mycmed.2014.06.048

SITARA U., NIAZ I., NASEEM J., and SULTANA N. Antifungal Effect of Essential Oils on In Vitro Growth of Pathogenic Fungi. Pakistan Journal of Botany, 2008, 40(1): 409-414. https://www.pakbs.org/pjbot/PDFs/40(1)/45.pdf

HARZALLAH H., NOUMI E., KARIMA B., BAKHROUF A., and MAHJOUB T. Chemical composition, antibacterial and antifungal properties of Tunisian Nigella sativa fixed oil. African Journal of Microbiology Research, 2012, 6(22): 4675-4679. https://doi.org/10.5897/AJMR11.1073

KHAN M. A. U., ASHFAQ M. K., ZUBERI H. S., MAHMOOD M. S., and GILANI A. H. The in vivo antifungal activity of the aqueous extract from Nigella sativa seeds. Phytotherapy Research, 2003, 17(2): 183-186. https://doi.org/10.1002/ptr.1146

TOMA C. C., OLAH N. K., VLASE L., MOGOŞAN C., and MOCAN A. Comparative studies on polyphenolic composition, antioxidant, and diuretic effects of nigella sativa L. (black cumin) and nigella damascena L. (Lady-in-aMist) seeds. Molecules, 2015, 20(6): 9560-9574. https://doi.org/10.3390/molecules20069560

REDDY S. H., AL-KALBANI A. S., and AL-RAWAHI A. S. Studies on Phytochemical Screening - Gc-Ms Characterization, Antimicrobial and Antioxidant Assay of Black Cumin Seeds (Nigella Sativa) and Senna Alexandria (Cassia Angustifolia) Solvent Extracts. International Journal of Pharmaceutical Sciences and Research, 2018, 9(2): 490-497. https://doi.org/10.13040/IJPSR.0975-8232.9(2).490-97

ISHTIAQ S., ASHRAF M., HAYAT M. Q., and ASRAR M. Phytochemical analysis of nigella sativa and its antibacterial activity against clinical isolates identified by ribotyping. International Journal of Agriculture and Biology, 2013, 15(6): 1151-1156. https://www.fspublishers.org/published_papers/7026_..pdf

YUSUFI M., BANERJEE S., MOHAMMAD M., KHATAL S., VENKATESWARA S. K., KHAN E. M., ABOUKAMEEL A., SARKAR F. H., and PADHYE S. Synthesis, characterization and anti-tumor activity of novel thymoquinone analogs against pancreatic cancer. Bioorganic & Medicinal Chemistry Letters, 2013, 23(10): 3101-3104. https://doi.org/10.1016/j.bmcl.2013.03.003

BUTT A. S., NISAR N., GHANI N., ALTAF I., and MUGHAL T. A. Isolation of thymoquinone from Nigella sativa L. and Thymus vulgaris L., and its anti-proliferative effect on HeLa cancer cell lines. Tropical Journal of Pharmaceutical Research, 2019, 18(1): 37-42. https://doi.org/10.4314/tjpr.v18i1.6

BAÑUELOS A., REYES E., OCADIZ R., ALVAREZ E., MORENO M., MONROY A., and GARIGLIO P. Neocarzinostatin induces an effective P53-dependent response in human papillomavirus-positive cervical cancer cells. Journal of Pharmacology and Experimental Therapeutics, 2003, 306(2): 671-680. https://doi.org/10.1124/jpet.103.051557


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