{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:40:11Z","timestamp":1793256011466,"version":"4.5.0"},"reference-count":229,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Oradea, Oradea, Romania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Nigella sativa L. is a species of the Ranunculaceae family and belongs to the genus Nigella, which comprises 14 species native to the regions of the Eastern Mediterranean, North Africa, and subcontinental India. Several significant groups of bioactive compounds, with pharmacological activities, have been isolated from the Nigella sativa L. species. Numerous beneficial effects have been demonstrated for these compounds. This review provides a comprehensive summary of the chemical constituents, bioactive compounds, modern administration methods, studies on the antidiabetic potential, evidence in commonly associated type 2 diabetes mellitus (T2DM) conditions, and evidence of T2DM complications. Research shows that Nigella sativa L. can be successfully included in complementary and alternative therapy for T2DM pathology, having multiple benefits both in diseases associated with and in complications of T2DM.<\/jats:p>","DOI":"10.3390\/life15111681","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:38:22Z","timestamp":1761759502000},"page":"1681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of Pharmacological Properties of Nigella sativa L. Bioactive Compounds and Their Therapeutic Relevance in the Management of Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"15","author":[{"given":"Monica Tabita","family":"Morar (Romocea)","sequence":"first","affiliation":[{"name":"Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Pallag","sequence":"additional","affiliation":[{"name":"Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania"},{"name":"Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6563-5929","authenticated-orcid":false,"given":"Cristina","family":"Burlou-Nagy (Fati)","sequence":"additional","affiliation":[{"name":"Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania"},{"name":"Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-333X","authenticated-orcid":false,"given":"Laura Gra\u021biela","family":"Vica\u0219","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana Lavinia","family":"Dejeu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00fcnde","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Bei","sequence":"additional","affiliation":[{"name":"Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosmin","family":"Vesa","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Salmer\u00f3n-Manzano, E., Garrido-Cardenas, J.A., and Manzano-Agugliaro, F. (2020). Worldwide Research Trends on Medicinal Plants. Int. J. Environ. Res. Public. Health, 17.","DOI":"10.3390\/ijerph17103376"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e002122","DOI":"10.1136\/bmjdrc-2021-002122","article-title":"Quantifying the Underestimation of Projected Global Diabetes Prevalence by the International Diabetes Federation (IDF) Diabetes Atlas","volume":"9","author":"Rathmann","year":"2021","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kundnani, N.R., Lolescu, B., Dinu, A.-R., Berceanu-Vaduva, D.M., Dumitrescu, P., Tama\u0219, T.-P., Sharma, A., and Popa, M.-D. (2024). Biotechnology Revolution Shaping the Future of Diabetes Management. Biomolecules, 14.","DOI":"10.3390\/biom14121563"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Burlou-Nagy, C., B\u0103nic\u0103, F., Jurca, T., Vica\u0219, L.G., Marian, E., Muresan, M.E., B\u00e1cskay, I., Kiss, R., Feh\u00e9r, P., and Pallag, A. (2022). Echinacea purpurea (L.) Moench: Biological and Pharmacological Properties. A Review. Plants, 11.","DOI":"10.3390\/plants11091244"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ansari, P., Akther, S., Hannan, J.M.A., Seidel, V., Nujat, N.J., and Abdel-Wahab, Y.H.A. (2022). Pharmacologically Active Phytomolecules Isolated from Traditional Antidiabetic Plants and Their Therapeutic Role for the Management of Diabetes Mellitus. Molecules, 27.","DOI":"10.3390\/molecules27134278"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Duarte, A.M., Guarino, M.P., Barroso, S., and Gil, M.M. (2020). Phytopharmacological Strategies in the Management of Type 2 Diabetes Mellitus. Foods, 9.","DOI":"10.3390\/foods9030271"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tran, N., Pham, B., and Le, L. (2020). Bioactive Compounds in Anti-Diabetic Plants: From Herbal Medicine to Modern Drug Discovery. Biology, 9.","DOI":"10.3390\/biology9090252"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108819","DOI":"10.1016\/j.diabres.2021.108819","article-title":"The History of the Nobel Prize for the Discovery of Insulin","volume":"175","author":"Lindsten","year":"2021","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e35285","DOI":"10.1097\/MD.0000000000035285","article-title":"Vascular Complications of Diabetes: A Narrative Review","volume":"102","author":"Lu","year":"2023","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Balbaa, M., El-Zeftawy, M., and Abdulmalek, S.A. (2021). Therapeutic Screening of Herbal Remedies for the Management of Diabetes. Molecules, 26.","DOI":"10.3390\/molecules26226836"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Behl, T., Gupta, A., Albratty, M., Najmi, A., Meraya, A.M., Alhazmi, H.A., Anwer, M.K., Bhatia, S., and Bungau, S.G. (2022). Alkaloidal Phytoconstituents for Diabetes Management: Exploring the Unrevealed Potential. Molecules, 27.","DOI":"10.3390\/molecules27185851"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Adam, S.H., Abu, I.F., Kamal, D.A.M., Febriza, A., Kashim, M.I.A.M., and Mokhtar, M.H. (2023). A Review of the Potential Health Benefits of Nigella sativa on Obesity and Its Associated Complications. Plants, 12.","DOI":"10.3390\/plants12183210"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Derosa, G., D\u2019Angelo, A., Maffioli, P., Cucinella, L., and Nappi, R.E. (2024). The Use of Nigella sativa in Cardiometabolic Diseases. Biomedicines, 12.","DOI":"10.3390\/biomedicines12020405"},{"key":"ref_14","first-page":"55","article-title":"Anti-diabetic Effect of a Combination of Black Seed (Nigella sativa) and Cumin (Cuminum cyminum), a Two-step Study from Bench to Bed","volume":"4","author":"Ghods","year":"2024","journal-title":"Funct. Food Sci. Online"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100268","DOI":"10.1016\/j.obmed.2020.100268","article-title":"Evaluation of renoprotective potential of Ficus religiosa in attenuation of diabetic nephropathy in rats","volume":"19","author":"Singh","year":"2020","journal-title":"Obes. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s11892-024-01537-3","article-title":"Diabetes, SGLT-2 Inhibitors, and Urinary Tract Infection: A Review","volume":"24","author":"Pishdad","year":"2024","journal-title":"Curr. Diab. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1080\/13813455.2021.1886117","article-title":"Effects of resistance training and Nigella sativa on type 2 diabetes: Implications for metabolic markers, low-grade inflammation and liver enzyme production","volume":"129","author":"Dastgheib","year":"2023","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2691525","DOI":"10.1155\/2021\/2691525","article-title":"Roles of Alkaloids from Medicinal Plants in the Management of Diabetes Mellitus","volume":"2021","author":"Adhikari","year":"2021","journal-title":"J. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"851","DOI":"10.2174\/1568026621666210305102500","article-title":"Antidiabetic Potential of Naturally Occurring Sesquiterpenes: A Review","volume":"21","author":"Maurya","year":"2021","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106114","DOI":"10.1016\/j.phrs.2022.106114","article-title":"Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications","volume":"177","author":"Feng","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.2147\/DMSO.S490585","article-title":"Insulin Resistance-Nutritional Index: A Simple Index and Potential Predictor of Mortality Risk in Patients with Chronic Heart Failure and Type 2 Diabetes","volume":"17","author":"Zhou","year":"2024","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Alam, S., Sarker, M.M.R., Sultana, T.N., Chowdhury, M.N.R., Rashid, M.A., Chaity, N.I., Zhao, C., Xiao, J., Hafez, E.E., and Khan, S.A. (2022). Antidiabetic Phytochemicals From Medicinal Plants: Prospective Candidates for New Drug Discovery and Development. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.800714"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"775","DOI":"10.2174\/1381612826666201222154159","article-title":"Novel Phytochemical Constituents and their Potential to Manage Diabetes","volume":"27","author":"Khalivulla","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.2174\/18756417MTExfMTQ1z","article-title":"Herbal Medicines for Diabetes Management and its Secondary Complications","volume":"17","author":"Kumar","year":"2021","journal-title":"Curr. Diabetes Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Simon-Szab\u00f3, L., Liz\u00e1k, B., Sturm, G., Somogyi, A., Tak\u00e1cs, I., and N\u00e9meth, Z. (2024). Molecular Aspects in the Development of Type 2 Diabetes and Possible Preventive and Complementary Therapies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25169113"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Salehi, B., Ata, A., V. Anil Kumar, N., Sharopov, F., Ram\u00edrez-Alarc\u00f3n, K., Ruiz-Ortega, A., Abdulmajid Ayatollahi, S., Valere Tsouh Fokou, P., Kobarfard, F., and Amiruddin Zakaria, Z. (2019). Antidiabetic Potential of Medicinal Plants and Their Active Components. Biomolecules, 9.","DOI":"10.3390\/biom9100551"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104723","DOI":"10.1016\/j.phrs.2020.104723","article-title":"Anti-diabetic potential of plant alkaloids: Revisiting current findings and future perspectives","volume":"155","author":"Rasouli","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100404","DOI":"10.1016\/j.hermed.2020.100404","article-title":"An updated knowledge of Black seed (Nigella sativa Linn.): Review of phytochemical constituents and pharmacological properties","volume":"25","author":"Ahmad","year":"2021","journal-title":"J. Herb. Med."},{"key":"ref_29","first-page":"923","article-title":"Comprehensive and updated review on anti-oxidant effects of Nigella sativa and its constituent, thymoquinone, in various disorders","volume":"27","author":"Aslani","year":"2024","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Salehi, B., Quispe, C., Imran, M., Ul-Haq, I., \u017divkovi\u0107, J., Abu-Reidah, I.M., Sen, S., Taheri, Y., Acharya, K., and Azadi, H. (2021). Nigella Plants\u2013Traditional Uses, Bioactive Phytoconstituents, Preclinical and Clinical Studies. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.625386"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1007\/s10787-022-01035-6","article-title":"Black Seed (Nigella sativa): A Favourable Alternative Therapy for Inflammatory and Immune System Disorders","volume":"30","author":"Ojueromi","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Adam, S.H., Mohd Nasri, N., Kashim, M.I.A.M., Abd Latib, E.H., Ahmad Juhari, M.A.A., and Mokhtar, M.H. (2022). Potential health benefits of Nigella sativa on diabetes mellitus and its complications: A review from laboratory studies to clinical trials. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.1057825"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Alberts, A., Moldoveanu, E.-T., Niculescu, A.-G., and Grumezescu, A.M. (2024). Nigella sativa: A Comprehensive Review of Its Therapeutic Potential, Pharmacological Properties, and Clinical Applications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413410"},{"key":"ref_34","first-page":"12","article-title":"Antioxidant and Antimalarial Properties of Nigella sativa","volume":"15","author":"Sam","year":"2024","journal-title":"Int. J. Chem. Eng. Appl."},{"key":"ref_35","first-page":"102769","article-title":"Effects of Nigella sativa as a Treatment of Patients With Upper Respiratory Tract Infection Caused by SARS-coronavirus-2: A Prospective, Randomized, Open-label, Controlled Clinical Study","volume":"61","author":"Koshak","year":"2021","journal-title":"Clin. Gov."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nyulas, K.-I., Simon-Szab\u00f3, Z., P\u00e1l, S., Fodor, M.-A., D\u00e9nes, L., Cseh, M.J., Barab\u00e1s-Hajdu, E., Csipor, B., Szak\u00e1cs, J., and Preg, Z. (2024). Cardiovascular Effects of Herbal Products and Their Interaction with Antihypertensive Drugs\u2014Comprehensive Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126388"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"23","DOI":"10.21608\/ejdr.2023.198316.1130","article-title":"Impact of Different Planting Locations on Nigella sativa L. Yield in Egypt","volume":"73","author":"Hamed","year":"2023","journal-title":"Egypt. J. Desert Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.15835\/nbha48311957","article-title":"Variation in Nigella sativa quality and its standardization via instrumental analysis: A study based on geographical origin","volume":"48","author":"Ahmad","year":"2020","journal-title":"Not. Bot. Horti Agrobot. Cluj-Napoca"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.14260\/jemds\/2020\/469","article-title":"The Many Therapeutic Applications of Nigella sativa\u2013A Review of Literature","volume":"9","author":"Belgaumi","year":"2020","journal-title":"J. Evol. Med. Dent. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4103\/jpbs.jpbs_364_22","article-title":"Black Seeds (Nigella sativa) Medical Application and Pharmaceutical Perspectives","volume":"15","author":"Ferizi","year":"2023","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jclinepi.2021.02.003","article-title":"Updating guidance for reporting systematic reviews: Development of the PRISMA 2020 statement","volume":"134","author":"Page","year":"2021","journal-title":"J. Clin. Epidemiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1080\/15569543.2018.1514637","article-title":"An overview of in vivo toxicological profile of thymoquinone","volume":"39","author":"Rezaee","year":"2020","journal-title":"Toxin Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"112585","DOI":"10.1016\/j.jep.2020.112585","article-title":"Effects of Nigella sativa on endothelial dysfunction in diabetes mellitus: A review","volume":"252","author":"Mohebbati","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_44","first-page":"372","article-title":"Systematic Review of Randomized Controlled Trials in Uses of Nigella sativa (Black Seed) in Metabolic Syndrome","volume":"41","author":"Elhariri","year":"2024","journal-title":"W. Afr. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.jsps.2020.01.022","article-title":"Gender effect on the pharmacokinetics of thymoquinone: Preclinical investigation and in silico modeling in male and female rats","volume":"28","author":"Ahmad","year":"2020","journal-title":"Saudi Pharm. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"22","DOI":"10.15171\/apb.2019.004","article-title":"Nigella sativa and its Derivatives as Food Toxicity Protectant Agents","volume":"9","author":"Karimi","year":"2019","journal-title":"Adv. Pharm. Bull."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s10787-023-01213-0","article-title":"The effect of Nigella sativa (black seed) on biomarkers of inflammation and oxidative stress: An updated systematic review and meta-analysis of randomized controlled trials","volume":"31","author":"Kavyani","year":"2023","journal-title":"Inflammopharmacology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102769","DOI":"10.1016\/j.ctim.2021.102769","article-title":"Nigella sativa for the treatment of COVID-19: An open-label randomized controlled clinical trial","volume":"61","author":"Koshak","year":"2021","journal-title":"Complement. Ther. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Shaukat, A., Zaidi, A., Anwar, H., and Kizilbash, N. (2023). Mechanism of the antidiabetic action of Nigella sativa and Thymoquinone: A review. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1126272"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Mahomoodally, M.F., Aumeeruddy, M.Z., Legoabe, L.J., Montesano, D., and Zengin, G. (2022). Nigella sativa L. and Its Active Compound Thymoquinone in the Clinical Management of Diabetes: A Systematic Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012111"},{"key":"ref_51","first-page":"1214","article-title":"Thymoquinone: A comprehensive review of its potential role as a monotherapy for metabolic syndrome","volume":"27","author":"Ibrahim","year":"2024","journal-title":"Iran. J. Basic. Med. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bashir, K.M.I., Kim, J.W., Kim, J.-K., Chun, Y.-S., Choi, J.-S., and Ku, S.-K. (2023). Efficacy Confirmation Test of Black Cumin (Nigella sativa L.) Seeds Extract Using a High-Fat Diet Mouse Model. Metabolites, 13.","DOI":"10.3390\/metabo13040501"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"169","DOI":"10.4068\/cmj.2021.57.3.169","article-title":"Antidiabetic Activity of Nigella sativa (Black Seeds) and Its Active Constituent (Thymoquinone): A Review of Human and Experimental Animal Studies","volume":"57","author":"Maideen","year":"2021","journal-title":"Chonnam Med. J."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Alqahtani, A.S., Hidayathulla, S., Rehman, M.T., ElGamal, A.A., Al-Massarani, S., Razmovski-Naumovski, V., Alqahtani, M.S., El Dib, R.A., and AlAjmi, M.F. (2019). Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia oppositifolia. Biomolecules, 10.","DOI":"10.3390\/biom10010061"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tiji, S., Bouhrim, M., Addi, M., Drouet, S., Lorenzo, J.M., Hano, C., Bnouham, M., and Mimouni, M. (2021). Linking the Phytochemicals and the \u03b1-Glucosidase and \u03b1-Amylase Enzyme Inhibitory Effects of Nigella sativa Seed Extracts. Foods, 10.","DOI":"10.3390\/foods10081818"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.procbio.2021.01.004","article-title":"Nigella sativa flavonoids surface coated gold NPs (Au-NPs) enhancing antioxidant and anti-diabetic activity","volume":"114","author":"Veeramani","year":"2022","journal-title":"Process Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1007\/s10904-020-01713-4","article-title":"Biological Compound Capping of Silver Nanoparticle with the Seed Extracts of Blackcumin (Nigella sativa): A Potential Antibacterial, Antidiabetic, Anti-inflammatory, and Antioxidant","volume":"31","author":"Vijayakumar","year":"2021","journal-title":"J. Inorg. Organomet. Polym. Mater."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Dalli, M., Daoudi, N.E., Azizi, S.-E., Benouda, H., Bnouham, M., and Gseyra, N. (2021). Chemical Composition Analysis Using HPLC-UV\/GC-MS and Inhibitory Activity of Different Nigella sativa Fractions on Pancreatic \u03b1-Amylase and Intestinal Glucose Absorption. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/9979419"},{"key":"ref_59","first-page":"107","article-title":"\u03b1-Amylase inhibitory activity of microencapsulated Nigella sativa L. and herb- drug interaction: An in vitro analysis","volume":"9","author":"Varghese","year":"2020","journal-title":"Ann. Phytomed. Int. J."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Alkis, H., Demir, E., Taysi, M.R., Sagir, S., and Taysi, S. (2021). Effects of Nigella sativa oil and thymoquinone on radiation-induced oxidative stress in kidney tissue of rats. Biomed. Pharmacother., 139.","DOI":"10.1016\/j.biopha.2021.111540"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ali, M.Y., Akter, Z., Mei, Z., Zheng, M., Tania, M., and Khan, M.A. (2021). Thymoquinone in autoimmune diseases: Therapeutic potential and molecular mechanisms. Biomed. Pharmacother., 134.","DOI":"10.1016\/j.biopha.2020.111157"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Mahmud, N.M., Paraoan, L., Khaliddin, N., and Kamalden, T.A. (2022). Thymoquinone in Ocular Neurodegeneration: Modulation of Pathological Mechanisms via Multiple Pathways. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.786926"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Liu, Y., Huang, L., Kim, M.-Y., and Cho, J.Y. (2022). The Role of Thymoquinone in Inflammatory Response in Chronic Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810246"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/01902148.2020.1726529","article-title":"Thymoquinone treatment modulates the Nrf2\/HO-1 signaling pathway and abrogates the inflammatory response in an animal model of lung fibrosis","volume":"46","author":"Ahmad","year":"2020","journal-title":"Exp. Lung Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ate\u015f, \u015e., \u00dclger, H., U\u00e7ar, S., Okan, A., Ocak, M., G\u00fcvenilir, E., \u015e\u00fckranl\u0131, Z.Y., Kaymak, E., Do\u011fanyi\u011fit, Z., and Taheri, S. (2025). Evaluation of the Effects of Thymoquinone on RAGE\/NOX4 Expressions and Brain Tissue Morphometry in Experimental Alzheimer\u2019s Disease Induced by Amyloid Beta 1-42 Peptide. Biomolecules, 15.","DOI":"10.3390\/biom15040543"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hossen, M.J., Yang, W.S., Kim, D., Aravinthan, A., Kim, J.-H., and Cho, J.Y. (2017). Thymoquinone: An IRAK1 inhibitor with in vivo and in vitro anti-inflammatory activities. Sci. Rep., 7.","DOI":"10.1038\/srep42995"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.31557\/APJCP.2023.24.11.3739","article-title":"Regulation of NF-\u03baB Expression by Thymoquinone; A Role in Regulating Pro-Inflammatory Cytokines and Programmed Cell Death in Hepatic Cancer Cells","volume":"24","author":"Salah","year":"2023","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1002\/ptr.6905","article-title":"Biological and therapeutic activities of thymoquinone: Focus on the Nrf2 signaling pathway","volume":"35","author":"Talebi","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1089\/jmf.2024.k.0149","article-title":"A Comprehensive Review of the Antioxidant, Antimicrobial, and Therapeutic Efficacies of Black Cumin (Nigella sativa L.) Seed Oil and Its Thymoquinone","volume":"28","author":"Chatterjee","year":"2025","journal-title":"J. Med. Food"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1016\/j.drudis.2021.07.013","article-title":"Thymoquinone: A small molecule from nature with high therapeutic potential","volume":"26","author":"Malik","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.jsps.2019.09.008","article-title":"Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive\/anticancer agent: Chemistry and biological effects","volume":"27","author":"Ahmad","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"100382","DOI":"10.1016\/j.hermed.2020.100382","article-title":"Potential benefits of combination of Nigella sativa and Zn supplements to treat COVID-19","volume":"23","author":"Rahman","year":"2020","journal-title":"J. Herb. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"283","DOI":"10.4314\/tjpr.v19i2.10","article-title":"Antidiabetic potential of Nigella sativa L seed oil in alloxaninduced diabetic rabbits","volume":"19","author":"Akhtar","year":"2020","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1007\/s10787-024-01528-6","article-title":"Nigella sativa L. and its bioactive and nutraceutical components in the management of diabetic peripheral neuropathy","volume":"32","author":"Khodaie","year":"2024","journal-title":"Inflammopharmacology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"136","DOI":"10.15430\/JCP.2020.25.3.136","article-title":"Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets","volume":"25","author":"Gomathinayagam","year":"2020","journal-title":"J. Cancer Prev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2174\/0929867326666191011143642","article-title":"Targeting Inflammatory Mediators: An Anticancer Mechanism of Thymoquinone Action","volume":"28","author":"Akter","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Pop, R.M., Sabin, O., Suciu, \u0218., Vesa, S.C., Socaci, S.A., Chedea, V.S., Bocsan, I.C., and Buzoianu, A.D. (2020). Nigella sativa\u2019s Anti-Inflammatory and Antioxidative Effects in Experimental Inflammation. Antioxidants, 9.","DOI":"10.3390\/antiox9100921"},{"key":"ref_78","first-page":"90","article-title":"Potential Cytotoxic, Antifungal, and Antioxidant Activity of Dithymoquinone and Thymoquinone","volume":"48","author":"Elsharkawy","year":"2021","journal-title":"J. Hunan Univ. Nat. Sci."},{"key":"ref_79","unstructured":"(2025, July 11). PubChem, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Sakib, R., Caruso, F., Aktar, S., Belli, S., Kaur, S., Hernandez, M., and Rossi, M. (2023). Antioxidant Properties of Thymoquinone, Thymohydroquinone and Black Cumin (Nigella sativa L.) Seed Oil: Scavenging of Superoxide Radical Studied Using Cyclic Voltammetry, DFT and Single Crystal X-ray Diffraction. Antioxidants, 12.","DOI":"10.3390\/antiox12030607"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Esharkawy, E.R., Almalki, F., and Hadda, T.B. (2022). In vitro potential antiviral SARS-CoV-19- activity of natural product thymohydroquinone and dithymoquinone from Nigella sativa. Bioorganic Chem., 120.","DOI":"10.1016\/j.bioorg.2021.105587"},{"key":"ref_82","first-page":"213","article-title":"Determination of oxygen radical absorbance capacity of black cumin (Nigella sativa) seed quinone compounds","volume":"6","author":"Tesarova","year":"2011","journal-title":"Nat. Prod. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1021\/acsmacrolett.3c00208","article-title":"Thymol-Functionalized Hyaluronic Acid as Promising Preservative Biomaterial for the Inhibition of Candida albicans Biofilm Formation","volume":"12","author":"Sturabotti","year":"2023","journal-title":"ACS Macro Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"243","DOI":"10.29252\/ibj.24.4.243","article-title":"Carvacrol and Thymol Attenuate Cytotoxicity Induced by Amyloid \u03b225-35 Via Activating Protein Kinase C and Inhibiting Oxidative Stress in PC12 Cells","volume":"24","author":"Azizi","year":"2020","journal-title":"Iran. Biomed. J."},{"key":"ref_85","first-page":"863","article-title":"Effects of thymol supplementation against type 2 diabetes in streptozotocin-induced rat model","volume":"20","author":"Agarwal","year":"2020","journal-title":"Plant Arch."},{"key":"ref_86","first-page":"879","article-title":"Monoterpenes as Medicinal Agents: Exploring the Pharmaceutical Potential of p-Cymene, p-Cymenene, and \u03b3-Terpinene","volume":"80","author":"Golonko","year":"2024","journal-title":"Acta Pol. Pharm."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"112259","DOI":"10.1016\/j.fct.2021.112259","article-title":"Health beneficial and pharmacological properties of p-cymene","volume":"153","author":"Balahbib","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"M\u0105czka, W., Twardawska, M., Grabarczyk, M., and Wi\u0144ska, K. (2023). Carvacrol\u2014A Natural Phenolic Compound with Antimicrobial Properties. Antibiotics, 12.","DOI":"10.3390\/antibiotics12050824"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e2110092118","DOI":"10.1073\/pnas.2110092118","article-title":"The biosynthesis of thymol, carvacrol, and thymohydroquinone in Lamiaceae proceeds via cytochrome P450s and a short-chain dehydrogenase","volume":"118","author":"Krause","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"112126","DOI":"10.1016\/j.phytochem.2019.112126","article-title":"Sequencing and variation of terpene synthase gene (TPS2) as the major gene in biosynthesis of thymol in different Thymus species","volume":"169","author":"Tohidi","year":"2020","journal-title":"Phytochemistry"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.7150\/jca.57049","article-title":"P-cymene prevent high-fat diet-associated colorectal cancer by improving the structure of intestinal flora","volume":"12","author":"Jin","year":"2021","journal-title":"J. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Formiga, R.d.O., Alves J\u00fanior, E.B., Vasconcelos, R.C., Guerra, G.C.B., Antunes de Ara\u00fajo, A., Carvalho, T.G.D., Garcia, V.B., de Ara\u00fajo Junior, R.F., Gadelha, F.A.A.F., and Vieira, G.C. (2020). p-Cymene and Rosmarinic Acid Ameliorate TNBS-Induced Intestinal Inflammation Upkeeping ZO-1 and MUC-2: Role of Antioxidant System and Immunomodulation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165870"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Pyo, Y., and Jung, Y.J. (2024). Microbial Fermentation and Therapeutic Potential of p-Cymene: Insights into Biosynthesis and Antimicrobial Bioactivity. Fermentation, 10.","DOI":"10.3390\/fermentation10090488"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Ciesielska-Figlon, K., Daca, A., Kokotkiewicz, A., \u0141uczkiewicz, M., Zabiega\u0142a, B., Witkowski, J.M., and Lisowska, K.A. (2022). The influence of Nigella sativa essential oil on proliferation, activation, and apoptosis of human T lymphocytes in vitro. Biomed. Pharmacother., 153.","DOI":"10.1016\/j.biopha.2022.113349"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Olufunmilayo, E.O., Gerke-Duncan, M.B., and Holsinger, R.M.D. (2023). Oxidative Stress and Antioxidants in Neurodegenerative Disorders. Antioxidants, 12.","DOI":"10.3390\/antiox12020517"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Wojtunik-Kulesza, K., Rudkowska, M., Kasprzak-Drozd, K., Oniszczuk, A., and Borowicz-Reutt, K. (2021). Activity of Selected Group of Monoterpenes in Alzheimer\u2019s Disease Symptoms in Experimental Model Studies-A Non-Systematic Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147366"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Yang, J., Zhong, C., and Yu, J. (2023). Natural Monoterpenes as Potential Therapeutic Agents against Atherosclerosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032429"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1007\/s43440-025-00709-6","article-title":"Carvacrol in asthma management: A comprehensive review of its therapeutic potential and mechanisms of action","volume":"77","author":"Neopane","year":"2025","journal-title":"Pharmacol. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Marconi, G.D., Della Rocca, Y., Fonticoli, L., Guarnieri, S., Carradori, S., Rajan, T.S., Pizzicannella, J., and Diomede, F. (2022). The Beneficial Effect of Carvacrol in HL-1 Cardiomyocytes Treated with LPS-G: Anti-Inflammatory Pathway Investigations. Antioxidants, 11.","DOI":"10.3390\/antiox11020386"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1080\/13813455.2023.2288537","article-title":"Carvacrol is potential molecule for diabetes treatment","volume":"130","author":"Hoca","year":"2024","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Cical\u0103u, G.I.P., Babes, P.A., Calniceanu, H., Popa, A., Ciavoi, G., Iova, G.M., Ganea, M., and Scrobot\u0103, I. (2021). Anti-Inflammatory and Antioxidant Properties of Carvacrol and Magnolol, in Periodontal Disease and Diabetes Mellitus. Molecules, 26.","DOI":"10.3390\/molecules26226899"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Dong, J., Zhang, X., Wang, S., Xu, C., Gao, M., Liu, S., Li, X., Cheng, N., Han, Y., and Wang, X. (2021). Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2\/ARE Pathway. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.615598"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1134\/S0006297920020042","article-title":"Thymoquinone as a Potential Neuroprotector in Acute and Chronic Forms of Cerebral Pathology","volume":"85","author":"Isaev","year":"2020","journal-title":"Biochem. Biokhimiia"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.msec.2017.03.088","article-title":"Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by self-nanoemulsifying drug delivery system","volume":"76","author":"Kalam","year":"2017","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"934","DOI":"10.2174\/1389201019666181113122009","article-title":"Thymoquinone Shows the Diverse Therapeutic Actions by Modulating Multiple Cell Signaling Pathways: Single Drug for Multiple Targets","volume":"19","author":"Khan","year":"2018","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Isaev, N.K., Genrikhs, E.E., and Stelmashook, E.V. (2023). Antioxidant Thymoquinone and Its Potential in the Treatment of Neurological Diseases. Antioxidants, 12.","DOI":"10.3390\/antiox12020433"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Modarresi Chahardehi, A., Ojaghi, H.R., Motedayyen, H., and Arefnezhad, R. (2024). Nano-based formulations of thymoquinone are new approaches for psoriasis treatment: A literature review. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1416842"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1080\/10408398.2016.1277971","article-title":"Anti-cancer properties and mechanisms of action of thymoquinone, the major active ingredient of Nigella sativa","volume":"57","author":"Majdalawieh","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/1872211311666171129121128","article-title":"Thymoquinone a Potential Therapeutic Molecule from the Plant Nigella sativa: Role of Colloidal Carriers in its Effective Delivery","volume":"12","author":"Negi","year":"2018","journal-title":"Recent. Pat. Drug Deliv. Formul."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Nassar, W.M., El-Kholy, W.M., El-Sawi, M.R., El-Shafai, N.M., Alotaibi, B.S., Ghamry, H.I., and Shukry, M. (2023). Ameliorative Effect of Thymoquinone and Thymoquinone Nanoparticles against Diazinon-Induced Hepatic Injury in Rats: A Possible Protection Mechanism. Toxics, 11.","DOI":"10.3390\/toxics11090783"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5439","DOI":"10.1007\/s11033-023-08363-y","article-title":"Molecular mechanisms and signaling pathways of black cumin (Nigella sativa) and its active constituent, thymoquinone: A review","volume":"50","author":"Sadeghi","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1007\/s11011-021-00789-2","article-title":"Reserpine-induced altered neuro-behavioral, biochemical and histopathological assessments prevent by enhanced antioxidant defence system of thymoquinone in mice","volume":"36","author":"Samad","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"412","DOI":"10.2174\/1871527317666180702101455","article-title":"A Review on Possible Therapeutic Effect of Nigella sativa and Thymoquinone in Neurodegenerative Diseases","volume":"17","author":"Samarghandian","year":"2018","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"6167","DOI":"10.1039\/D1FO00401H","article-title":"Therapeutic perspectives of the black cumin component thymoquinone: A review","volume":"12","author":"Sarkar","year":"2021","journal-title":"Food Funct."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Imam, A.L., Okesina, A.A., Sulaimon, F.A., Imam, A., Ibiyeye, R.Y., Oyewole, L.A., Biliaminu, S.A., Shehu, M., Alli, A.O., and Omoola, O.O. (2024). Thymoquinone ameliorate oxidative stress, GABAergic neuronal depletion and memory impairment through Nrf2\/ARE signaling pathway in the dentate gyrus following cypermethrin administration. BMC Neurosci., 25.","DOI":"10.1186\/s12868-024-00896-7"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"113972","DOI":"10.1016\/j.bbr.2022.113972","article-title":"Effects of thymoquinone on scopolamine-induced spatial and echoic memory changes through regulation of lipid peroxidation and cholinergic impairment","volume":"431","author":"Kantar","year":"2022","journal-title":"Behav. Brain Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2174\/2589977515666230811092410","article-title":"Therapeutic and Phytochemical Properties of Thymoquinone Derived from Nigella sativa","volume":"16","author":"Tiwari","year":"2024","journal-title":"Curr. Drug Res. Rev."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s11064-019-02741-4","article-title":"Neuroprotective Effects of Thymoquinone in Acrylamide-Induced Peripheral Nervous System Toxicity Through MAPKinase and Apoptosis Pathways in Rat","volume":"44","author":"Tabeshpour","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s10735-025-10399-2","article-title":"In vivo and in silico analysis of anti inflammatory, antipyretic and analgesic activity of methanolic extract of Nigella sativa","volume":"56","author":"Zahra","year":"2025","journal-title":"J. Mol. Histol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Glamo\u010dlija, U., Padhye, S., \u0160pirtovi\u0107-Halilovi\u0107, S., Osmanovi\u0107, A., Veljovi\u0107, E., Roca, S., Novakovi\u0107, I., Mandi\u0107, B., Turel, I., and Kljun, J. (2018). Synthesis, Biological Evaluation and Docking Studies of Benzoxazoles Derived from Thymoquinone. Molecules, 23.","DOI":"10.3390\/molecules23123297"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1111\/1440-1681.13553","article-title":"The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases","volume":"48","author":"Soubra","year":"2021","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"8041","DOI":"10.2147\/IJN.S509158","article-title":"The Effects of Novel Thymoquinone-Loaded Nanovesicles as a Promising Avenue to Modulate Autism Associated Dysregulation by Restoring Oxidative Stress in Autism in Mice","volume":"20","author":"Eissa","year":"2025","journal-title":"Int. J. Nanomedicine"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Dahmash, E.Z., Ali, D.K., Alyami, H.S., AbdulKarim, H., Alyami, M.H., and Aodah, A.H. (2022). Novel Thymoquinone Nanoparticles Using Poly(ester amide) Based on L-Arginine-Targeting Pulmonary Drug Delivery. Polymers, 14.","DOI":"10.3390\/polym14061082"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jneuroim.2018.04.018","article-title":"Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NF\u03baB pathway signaling targets in LPS\/IFN\u03b3 -activated BV-2 microglia cells","volume":"320","author":"Taka","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Ceylan, T., Akin, A.T., Karabulut, D., Tan, F.C., Ta\u015fkiran, M., and Yakan, B. (2023). Therapeutic effect of thymoquinone on brain damage caused by nonylphenol exposure in rats. J. Biochem. Mol. Toxicol., 37.","DOI":"10.1002\/jbt.23471"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Bin Abdulrahman, K., Bamosa, A., Bukhari, A., Siddiqui, I., Arafa, M., Mohsin, A., Althageel, M., Aljuaeed, M., Aldeailej, I., and Alrajeh, A. (2022). The Effect of Short Treatment with Nigella sativa on Symptoms, the Cluster of Differentiation (CD) Profile, and Inflammatory Markers in Mild COVID-19 Patients: A Randomized, Double-Blind Controlled Trial. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph191811798"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.2147\/DDDT.S308863","article-title":"Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure","volume":"15","author":"Badary","year":"2021","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Shoaib, A., Javed, S., Wahab, S., Azmi, L., Tabish, M., Sultan, M.H., Abdelsalam, K., Alqahtani, S.S., and Ahmad, M.F. (2023). Cellular, Molecular, Pharmacological, and Nano-Formulation Aspects of Thymoquinone-A Potent Natural Antiviral Agent. Molecules, 28.","DOI":"10.3390\/molecules28145435"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Wahab, S., and Alsayari, A. (2023). Potential Pharmacological Applications of Nigella Seeds with a Focus on Nigella sativa and Its Constituents against Chronic Inflammatory Diseases: Progress and Future Opportunities. Plants, 12.","DOI":"10.3390\/plants12223829"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.5958\/0974-360X.2019.00526.2","article-title":"Nigella sativa: Phytochemistry, Pharmacology and its Therapeutic Potential","volume":"12","author":"Tiwari","year":"2019","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.tifs.2021.08.023","article-title":"Biological activity of plant-based carvacrol and thymol and their impact on human health and food quality","volume":"116","author":"Rathod","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Hossain, M.S., Sharfaraz, A., Dutta, A., Ahsan, A., Masud, M.A., Ahmed, I.A., Goh, B.H., Urbi, Z., Sarker, M.M.R., and Ming, L.C. (2021). A review of ethnobotany, phytochemistry, antimicrobial pharmacology and toxicology of Nigella sativa L.. Biomed. Pharmacother. Biomedecine Pharmacother., 143.","DOI":"10.1016\/j.biopha.2021.112182"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Abbas, M., Gururani, M.A., Ali, A., Bajwa, S., Hassan, R., Batool, S.W., Imam, M., and Wei, D. (2024). Antimicrobial Properties and Therapeutic Potential of Bioactive Compounds in Nigella sativa: A Review. Molecules, 29.","DOI":"10.3390\/molecules29204914"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Ouattar, H., Zouirech, O., Kara, M., Assouguem, A., Almutairi, S.M., Al-Hemaid, F.M., Rasheed, R.A., Ullah, R., Abbasi, A.M., and Aouane, M. (2022). In Vitro Study of the Phytochemical Composition and Antioxidant, Immunostimulant, and Hemolytic Activities of Nigella sativa (Ranunculaceae) and Lepidium sativum Seeds. Molecules, 27.","DOI":"10.3390\/molecules27185946"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Sampaio, L.A., Pina, L.T.S., Serafini, M.R., Tavares, D.D.S., and Guimar\u00e3es, A.G. (2021). Antitumor Effects of Carvacrol and Thymol: A Systematic Review. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.702487"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Gheorghita, D., Robu, A., Antoniac, A., Antoniac, I., Ditu, L.M., Raiciu, A.-D., Tomescu, J., Grosu, E., and Saceleanu, A. (2022). In Vitro Antibacterial Activity of Some Plant Essential Oils against Four Different Microbial Strains. Appl. Sci., 12.","DOI":"10.3390\/app12199482"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Sousa, L.G.V., Castro, J., Cavaleiro, C., Salgueiro, L., Tom\u00e1s, M., Palmeira-Oliveira, R., Martinez-Oliveira, J., and Cerca, N. (2022). Synergistic effects of carvacrol, \u03b1-terpinene, \u03b3-terpinene, \u03c1-cymene and linalool against Gardnerella species. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-08217-w"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Shafodino, F.S., Lusilao, J.M., and Mwapagha, L.M. (2022). Phytochemical characterization and antimicrobial activity of Nigella sativa seeds. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0272457"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Caputo, L., Amato, G., De Martino, L., De Feo, V., and Nazzaro, F. (2023). Anti-Cholinesterase and Anti-\u03b1-Amylase Activities and Neuroprotective Effects of Carvacrol and p-Cymene and Their Effects on Hydrogen Peroxide Induced Stress in SH-SY5Y Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076073"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"152836","DOI":"10.1016\/j.phymed.2019.152836","article-title":"p-Cymene attenuates cancer pain via inhibitory pathways and modulation of calcium currents","volume":"61","author":"Santos","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Satira, A., Espro, C., Paone, E., Calabr\u00f2, P.S., Pagliaro, M., Ciriminna, R., and Mauriello, F. (2021). The Limonene Biorefinery: From Extractive Technologies to Its Catalytic Upgrading into p-Cymene. Catalysts, 11.","DOI":"10.20944\/preprints202102.0377.v1"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1007\/s40200-020-00658-2","article-title":"Cymene consumption and physical activity effect in Alzheimer\u2019s disease model: An in vivo and in vitro study","volume":"19","author":"Yaghmaei","year":"2020","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Shareef, S.H., Al-Medhtiy, M.H., Ibrahim, I.A.A., Alzahrani, A.R., Jabbar, A.A., Galali, Y., Agha, N.F.S., Aziz, P.Y., Thabit, M.A., and Agha, D.N.F. (2022). Gastroprophylactic Effects of p-Cymene in Ethanol-Induced Gastric Ulcer in Rats. Processes, 10.","DOI":"10.3390\/pr10071314"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.21873\/anticanres.14878","article-title":"The Anti-oxidant Monoterpene p-Cymene Reduced the Occurrence of Colorectal Cancer in a Hyperlipidemia Rat Model by Reducing Oxidative Stress and Expression of Inflammatory Cytokines","volume":"41","author":"Wang","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"104046","DOI":"10.1016\/j.micpath.2020.104046","article-title":"Antimicrobial potential of the food-grade additive carvacrol against uropathogenic E. coli based on membrane depolarization, reactive oxygen species generation, and molecular docking analysis","volume":"142","author":"Khan","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Anaeigoudari, A. (2022). Hepato- and reno-protective effects of thymoquinone, crocin, and carvacrol: A comprehensive review. Asian Pac. J. Trop. Biomed., 12.","DOI":"10.4103\/2221-1691.343386"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1002\/fsn3.2994","article-title":"Therapeutic application of carvacrol: A comprehensive review","volume":"10","author":"Imran","year":"2022","journal-title":"Food Sci. Nutr."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Hajiaghaalizadeh, M., Sheikharabi, M., Jazi, M.S., Alhashem, R., and Hosseini, S.S. (2025). Anti-biofilm activity of carvacrol-thymoquinone nanocarriers on vulvovaginal candidiasis isolates. Diagn. Microbiol. Infect. Dis., 111.","DOI":"10.1016\/j.diagmicrobio.2024.116606"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"109339","DOI":"10.1016\/j.foodcont.2022.109339","article-title":"Unraveling the mechanism of the synergistic antimicrobial effect of cineole and carvacrol on Escherichia coli O157:H7 inhibition and its application on fresh-cut cucumbers","volume":"144","author":"Addo","year":"2023","journal-title":"Food Control"},{"key":"ref_150","first-page":"371","article-title":"Neuroprotective effects of carvacrol against Alzheimer\u2019s disease and other neurodegenerative diseases: A review","volume":"12","author":"Azizi","year":"2022","journal-title":"Avicenna J. Phytomedicine"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Asadi, S., Nayeri-Fasaei, B., Zahraei-Salehi, T., Yahya-Rayat, R., Shams, N., and Sharifi, A. (2023). Antibacterial and anti-biofilm properties of carvacrol alone and in combination with cefixime against Escherichia coli. BMC Microbiol., 23.","DOI":"10.1186\/s12866-023-02797-x"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/01480545.2018.1538233","article-title":"Safety and tolerability of carvacrol in healthy subjects: A phase I clinical study","volume":"44","author":"Ghorani","year":"2021","journal-title":"Drug Chem. Toxicol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1002\/biof.1843","article-title":"Experimental and clinical evidence on the effect of carvacrol on respiratory, allergic, and immunologic disorders: A comprehensive review","volume":"48","author":"Khazdair","year":"2022","journal-title":"BioFactors"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Qu, C., Li, Z., and Wang, X. (2021). UHPLC-HRMS-Based Untargeted Lipidomics Reveal Mechanism of Antifungal Activity of Carvacrol against Aspergillus flavus. Foods, 11.","DOI":"10.3390\/foods11010093"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Souza, G.H.d.A.d., Radai, J.A.d.S., Vaz, M.S.M., Silva, K.E.d., Fraga, T.L., Barbosa, L.S., and Simionatto, S. (2021). In vitro and in vivo antibacterial activity assays of carvacrol: A candidate for development of innovative treatments against KPC-producing Klebsiella pneumoniae. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0246003"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1002\/fsn3.4014","article-title":"Protective effects of carvacrol on lipid profiles, oxidative stress, hypertension, and cardiac dysfunction\u2013A comprehensive review","volume":"12","author":"Khazdair","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Wang, J., Qin, T., Chen, K., Pan, L., Xie, J., and Xi, B. (2022). Antimicrobial and Antivirulence Activities of Carvacrol against Pathogenic Aeromonas hydrophila. Microorganisms, 10.","DOI":"10.3390\/microorganisms10112170"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1055\/a-1388-5415","article-title":"Thymoquinone with Metformin Decreases Fasting, Post Prandial Glucose, and HbA1c in Type 2 Diabetic Patients","volume":"71","author":"Ali","year":"2021","journal-title":"Drug Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2174\/1871525721666221221161742","article-title":"Protective Effect of Nigella sativa Seed Extract and its BioactiveCompound Thymoquinone on Streptozotocin-induced Diabetic Rats","volume":"22","author":"Khan","year":"2024","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/ptr.6944","article-title":"Effects of Nigella sativa oil and thymoquinone against bisphenol A-induced metabolic disorder in rats","volume":"35","author":"Fadishei","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"361","DOI":"10.18203\/2319-2003.ijbcp20211016","article-title":"Antidiabetic effect of Nigella sativa compared with metformin on blood glucose levels in streptozotocin induced diabetic albino wistar rats","volume":"10","author":"Sadiq","year":"2021","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Faisal Lutfi, M., Abdel-Moneim, A.-M.H., Alsharidah, A.S., Mobark, M.A., Abdellatif, A.A.H., Saleem, I.Y., Al Rugaie, O., Mohany, K.M., and Alsharidah, M. (2021). Thymoquinone Lowers Blood Glucose and Reduces Oxidative Stress in a Rat Model of Diabetes. Molecules, 26.","DOI":"10.3390\/molecules26082348"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.ijbiomac.2020.05.042","article-title":"Effects of Nigella sativa seed polysaccharides on type 2 diabetic mice and gut microbiota","volume":"159","author":"Dong","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"775","DOI":"10.4103\/1319-2442.292311","article-title":"The Effect of Nigella sativa on Renal Oxidative Injury in Diabetic Rats","volume":"31","author":"Mohebbati","year":"2020","journal-title":"Saudi J. Kidney Dis. Transplant."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Mostafa, M.D., Amer, M.E., ElKomy, M.A., Othman, A.I., and El--Missiry, M.A. (2025). Thymoquinone controlled obesity and invigorated cognitive and memory performance in rats consuming a high-fat diet via modulating oxidative stress, inflammation and apoptosis. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-05716-4"},{"key":"ref_166","first-page":"395","article-title":"Comparison of the anti-diabetic and nephroprotective activities of vitamin E, metformin, and Nigella sativa oil on kidney in experimental diabetic rats","volume":"26","author":"Ayaz","year":"2023","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Almatroodi, S.A., Alnuqaydan, A.M., Alsahli, M.A., Khan, A.A., and Rahmani, A.H. (2021). Thymoquinone, the Most Prominent Constituent of Nigella sativa, Attenuates Liver Damage in Streptozotocin-Induced Diabetic Rats via Regulation of Oxidative Stress, Inflammation and Cyclooxygenase-2 Protein Expression. Appl. Sci., 11.","DOI":"10.3390\/app11073223"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2753294","DOI":"10.1155\/2022\/2753294","article-title":"Effect of Nigella sativa Oil on Oxidative Stress, Inflammatory, and Glycemic Control Indices in Diabetic Hemodialysis Patients: A Randomized Double-Blind, Controlled Trial","volume":"2022","author":"Rahmani","year":"2022","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1002\/ptr.6707","article-title":"Effect of Nigella sativa oil supplement on risk factors for cardiovascular diseases in patients with type 2 diabetes mellitus","volume":"34","author":"Kooshki","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1002\/ptr.6990","article-title":"Effect of Nigella sativa oil extract on cardiometabolic risk factors in type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial","volume":"35","author":"Hadi","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s40272-025-00687-5","article-title":"Cardioprotective Effect of Nigella sativa in Pediatric Patients with Type 1 Diabetes Mellitus: A Randomized Controlled Study","volume":"27","year":"2025","journal-title":"Pediatr. Drugs"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1089\/jmf.2020.0075","article-title":"Nigella sativa and Trigonella foenum-graecum Supplemented Chapatis Safely Improve HbA1c, Body Weight, Waist Circumference, Blood Lipids, and Fatty Liver in Overweight and Diabetic Subjects: A Twelve-Week Safety and Efficacy Study","volume":"23","author":"Rao","year":"2020","journal-title":"J. Med. Food"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13048-025-01634-1","article-title":"Effect of Nigella sativa-L supplementation on glycemia in adolescent polycystic ovarian syndrome: Secondary analysis of a randomized controlled trial study","volume":"18","author":"Mahmoudian","year":"2025","journal-title":"J. Ovarian Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s43043-021-00076-1","article-title":"Amelioration of polycystic ovary syndrome-related disorders by supplementation of thymoquinone and metformin","volume":"26","author":"Ammar","year":"2021","journal-title":"Middle East. Fertil. Soc. J."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"107947","DOI":"10.1016\/j.jdiacomp.2021.107947","article-title":"Nigella sativa as a promising intervention for metabolic and inflammatory disorders in obese prediabetic subjects: A comparative study of Nigella sativa versus both lifestyle modification and metformin","volume":"35","author":"Mostafa","year":"2021","journal-title":"J. Diabetes Complicat."},{"key":"ref_176","first-page":"9","article-title":"The Potential of Nigella sativa oil on Clinical output improvement of diabetic neuropathy","volume":"13","author":"Syuhada","year":"2023","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s10787-023-01338-2","article-title":"Topical Nigella sativa L. product: A new candidate for the management of diabetic peripheral neuropathy","volume":"32","author":"Khodaie","year":"2024","journal-title":"Inflammopharmacology"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1016\/j.sjbs.2020.05.005","article-title":"Sinteza verde a nanoparticulelor de argint cu extract de Nigella sativa atenueaz\u0103 neuropatia diabetic\u0103 prin efecte antiinflamatorii \u0219i antioxidante","volume":"27","author":"Alkhalaf","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Alrafiah, A. (2021). Thymoquinone Protects Neurons in the Cerebellum of Rats through Mitigating Oxidative Stress and Inflammation Following High-Fat Diet Supplementation. Biomolecules, 11.","DOI":"10.3390\/biom11020165"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1089\/jmf.2023.0228","article-title":"Thymoquinone Abrogates Acrylamide-Induced Cerebellar Toxicity via Modulation of Nuclear Factor Erythroid 2-Related Factor 2\/Nuclear Factor Kappa B Signaling, Oxidative Neuroinflammation, and Neuroapoptosis in Rats","volume":"27","author":"Famurewa","year":"2024","journal-title":"J. Med. Food"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"117162","DOI":"10.1016\/j.taap.2024.117162","article-title":"Thymoquinone inhibits Neuroinflammatory mediators and vasoconstriction injury via NF-\u03baB dependent NeuN\/GFAP\/Ki-67 in hypertensive Dams and F1 male pups on exposure to a mixture of Bisphenol-A analogues","volume":"494","author":"Okoh","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Abo Mansour, H.E., Elberri, A.I., Ghoneim, M.E.-S., Samman, W.A., Alhaddad, A.A., Abdallah, M.S., El-Berri, E.I., Salem, M.A., and Mosalam, E.M. (2023). The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer\u2019s Disease-like Condition: Mechanistic Insights. Molecules, 28.","DOI":"10.3390\/molecules28186566"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1007\/s10792-023-02799-8","article-title":"Low-dose rosmarinic acid and thymoquinone accelerate wound healing in retinal pigment epithelial cells","volume":"43","author":"Sen","year":"2023","journal-title":"Int. Ophthalmol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s42535-021-00201-5","article-title":"Evaluation of genoprotective and antioxidative potentiality of ethanolic extract of N. sativa seed in streptozotocin induced diabetic albino rats","volume":"34","author":"Nehar","year":"2021","journal-title":"Vegetos"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.1002\/ptr.7140","article-title":"A randomized, double-blind, placebo-controlled, clinical trial to evaluate the benefits of Nigella sativa seeds oil in reducing cardiovascular risks in hypertensive patients","volume":"35","author":"Najafi","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s12020-020-02265-w","article-title":"The effects of Nigella sativa on anthropometric and biochemical indices in postmenopausal women with metabolic syndrome","volume":"69","author":"Shirazi","year":"2020","journal-title":"Endocrine"},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Pop, R.M., Vassilopoulou, E., Jianu, M.-E., Ro\u0219ian, \u0218.H., Taulescu, M., Negru, M., Bercian, C., Boarescu, P.-M., Bocsan, I.C., and Feketea, G. (2024). Nigella sativa oil attenuates inflammation and oxidative stress in experimental myocardial infarction. BMC Complement Med. Ther., 24.","DOI":"10.1186\/s12906-024-04648-2"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/1440-1681.13614","article-title":"Thymoquinone attenuates isoproterenol-induced myocardial infarction by inhibiting cytochrome C and matrix metalloproteinase-9 expression","volume":"49","author":"Medhet","year":"2022","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Bocsan, I.C., Pop, R.M., Sabin, O., Sarkandy, E., Boarescu, P.-M., Ro\u015fian, \u015e.H., Leru, P.M., Chedea, V.S., Socaci, S.A., and Buzoianu, A.D. (2021). Comparative Protective Effect of Nigella sativa Oil and Vitis vinifera Seed Oil in an Experimental Model of Isoproterenol-Induced Acute Myocardial Ischemia in Rats. Molecules, 26.","DOI":"10.3390\/molecules26113221"},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Rathod, S., Agrawal, Y., Sherikar, A., Nakhate, K.T., Patil, C.R., Nagoor Meeran, M.F., Ojha, S., and Goyal, S.N. (2022). Thymoquinone Produces Cardioprotective Effect in \u03b2-Receptor Stimulated Myocardial Infarcted Rats via Subsiding Oxidative Stress and Inflammation. Nutrients, 14.","DOI":"10.3390\/nu14132742"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.repc.2020.12.015","article-title":"Prevention of doxorubicin-induced experimental cardiotoxicity by Nigella sativa in rats","volume":"41","author":"Karahan","year":"2022","journal-title":"Rev. Port. Cardiol."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Hafez, M.H., Ez Elarab, S.M., Tohamy, H.G., and El-Far, A.H. (2024). Thymoquinone attenuates diabetes-induced hepatic damage in rat via regulation of oxidative\/nitrosative stress, apoptosis, and inflammatory cascade with molecular docking approach. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-62780-y"},{"key":"ref_193","first-page":"1179","article-title":"Thymoquinone modulates oxidative stress and inflammation, correcting mercury-induced HO-1\/NRF\/Trx pathway disruption in experimental rat hepatorenal system: An in vivo and in silico study","volume":"38","author":"Owumi","year":"2025","journal-title":"Biometals Int. J. Role Met. Ions Biol. Biochem. Med."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Esmail, M., Anwar, S., Kandeil, M., El-Zanaty, A.M., and Abdel-Gabbar, M. (2021). Effect of Nigella sativa, atorvastatin, or L-Carnitine on high fat diet-induced obesity in adult male Albino rats. Biomed. Pharmacother., 141.","DOI":"10.1016\/j.biopha.2021.111818"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Ramineedu, K., Sankaran, K.R., Mallepogu, V., Rendedula, D.P., Gunturu, R., Gandham, S., Md, S.I., and Meriga, B. (2024). Thymoquinone mitigates obesity and diabetic parameters through regulation of major adipokines, key lipid metabolizing enzymes and AMPK\/p-AMPK in diet-induced obese rats. 3 Biotech, 14.","DOI":"10.1007\/s13205-023-03847-x"},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Razmpoosh, E., Safi, S., Mazaheri, M., Khalesi, S., Nazari, M., Mirmiran, P., and Nadjarzadeh, A. (2024). A crossover randomized controlled trial examining the effects of black seed (Nigella sativa) supplementation on IL-1\u03b2, IL-6 and leptin, and insulin parameters in overweight and obese women. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-023-04226-y"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1080\/1028415X.2020.1831261","article-title":"High fat diet-induced obesity causes a reduction in brain tyrosine hydroxylase levels and non-motor features in rats through metabolic dysfunction, neuroinflammation and oxidative stress","volume":"25","author":"Bittencourt","year":"2022","journal-title":"Nutr. Neurosci."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Kao, Y.-C., Wei, W.-Y., Tsai, K.-J., and Wang, L.-C. (2019). High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010207"},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Schmitt, L.O., and Gaspar, J.M. (2023). Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes. Metabolites, 13.","DOI":"10.3390\/metabo13010086"},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Neto, A., Fernandes, A., and Barateiro, A. (2023). The complex relationship between obesity and neurodegenerative diseases: An updated review. Front. Cell. Neurosci., 17.","DOI":"10.3389\/fncel.2023.1294420"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1210\/clinem\/dgad450","article-title":"New Horizons: Epidemiology of Obesity, Diabetes Mellitus, and Cancer Prognosis","volume":"109","author":"Harborg","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.semcancer.2024.01.003","article-title":"The obesity-autophagy-cancer axis: Mechanistic insights and therapeutic perspectives","volume":"99","author":"Behrooz","year":"2024","journal-title":"Semin. Cancer Biol."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Ravi, Y., Vethamoni, P.I., Saxena, S.N., Kaviyapriya, M., Santhanakrishnan, V.P., Raveendran, M., Ashoka, N.N., Choudhary, S., Verma, A.K., and Harisha, C.B. (2025). Anticancer potential of Thymoquinone from Nigella sativa L.: An in-silico and cytotoxicity study. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0323804"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"102068","DOI":"10.1016\/j.eti.2021.102068","article-title":"Removal of microbial pathogens and anticancer activity of synthesized nano-thymoquinone from Nigella sativa seeds","volume":"24","author":"Gnanasekaran","year":"2021","journal-title":"Environ. Technol. Innov."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Alsanosi, S., Sheikh, R.A., Sonbul, S., Altayb, H.N., Batubara, A.S., Hosawi, S., Al-Sakkaf, K., Abdullah, O., Omran, Z., and Alhosin, M. (2022). The Potential Role of Nigella sativa Seed Oil as Epigenetic Therapy of Cancer. Molecules, 27.","DOI":"10.3390\/molecules27092779"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"103174","DOI":"10.1016\/j.ctim.2025.103174","article-title":"Effects of black seed (Nigella sativa L.) on cardiometabolic indices in type 2 diabetic patients: A systematic review and meta-analysis of RCTs","volume":"90","author":"Karimi","year":"2025","journal-title":"Complement. Ther. Med."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Saadati, S., Naseri, K., Asbaghi, O., Abhari, K., Zhang, P., Li, H.-B., and Gan, R.-Y. (2022). Nigella sativa supplementation improves cardiometabolic indicators in population with prediabetes and type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.977756"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/ehf2.14224","article-title":"Diabetic cardiomyopathy: A brief summary on lipid toxicity","volume":"10","author":"Ke","year":"2023","journal-title":"ESC Heart Fail."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Tekba\u015f, A., Bremer-Streck, S., Wissenbach, D.K., Peters, F.T., von Lilienfeld-Toal, M., Soonawalla, Z., Rauchfu\u00df, F., Settmacher, U., and Dahmen, U. (2023). Gas Chromatography\u2013Mass Spectrometry Detection of Thymoquinone in Oil and Serum for Clinical Pharmacokinetic Studies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216431"},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Shehata, T.M., Almostafa, M.M., and Elsewedy, H.S. (2022). Development and Optimization of Nigella sativa Nanoemulsion Loaded with Pioglitazone for Hypoglycemic Effect. Polymers, 14.","DOI":"10.3390\/polym14153021"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"7703","DOI":"10.2147\/IJN.S262395","article-title":"Pharmacokinetics and Biodistribution of Thymoquinone-loaded Nanostructured Lipid Carrier After Oral and Intravenous Administration into Rats","volume":"15","author":"Latifah","year":"2020","journal-title":"Int. J. Nanomedicine"},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Behzadifar, S., Barras, A., Plaisance, V., Pawlowski, V., Szunerits, S., Abderrahmani, A., and Boukherroub, R. (2023). Polymer-Based Nanostructures for Pancreatic Beta-Cell Imaging and Non-Invasive Treatment of Diabetes. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15041215"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1080\/17425247.2020.1730808","article-title":"Nanocarriers: More than tour de force for thymoquinone","volume":"17","author":"Rathore","year":"2020","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Shariare, M.H., Khan, M.A., Al-Masum, A., Khan, J.H., Uddin, J., and Kazi, M. (2022). Development of Stable Liposomal Drug Delivery System of Thymoquinone and Its In Vitro Anticancer Studies Using Breast Cancer and Cervical Cancer Cell Lines. Molecules, 27.","DOI":"10.3390\/molecules27196744"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s13346-022-01193-8","article-title":"Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: Optimization, characterization, pharmacokinetic, and hepatotoxicity studies","volume":"13","author":"Rathore","year":"2023","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Allemailem, K.S., Almatroudi, A., Alrumaihi, F., Aljaghwani, A., Alnuqaydan, A.M., Khalilullah, H., Younus, H., El-Kady, A.M., Aldakheel, F.M., and Khan, A.A. (2021). Antimicrobial, Immunomodulatory and Anti-Inflammatory Potential of Liposomal Thymoquinone: Implications in the Treatment of Bacterial Pneumonia in Immunocompromised Mice. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111673"},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Vallianou, N.G., Dalamaga, M., Pavlou, A., Rebelos, E., Karamanolis, N.N., Papachristoforou, E., Mavrothalassitis, E., Eleftheriadou, I., Tentolouris, N., and Kounatidis, D. (2025). The Transformative Role of Nanotechnology in the Management of Diabetes Mellitus: Insights from Current Research. Biomolecules, 15.","DOI":"10.3390\/biom15050653"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"103159","DOI":"10.1016\/j.dsx.2024.103159","article-title":"Nanotechnology as a potential treatment for diabetes and its complications: A review","volume":"18","author":"Manral","year":"2024","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"9990","DOI":"10.1038\/s41467-024-54265-3","article-title":"Rational strategies for improving the efficiency of design and discovery of nanomedicines","volume":"15","author":"Shan","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_220","doi-asserted-by":"crossref","unstructured":"Swingler, S., Gupta, A., Gibson, H., Kowalczuk, M., Adamus, G., Heaselgrave, W., and Radecka, I. (2022). Thymoquinone: Hydroxypropyl-\u03b2-cyclodextrin Loaded Bacterial Cellulose for the Management of Wounds. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122816"},{"key":"ref_221","first-page":"1","article-title":"Innovative Nanocomposites for Drug Delivery: A Novel Approach for Diabetic Foot Ulcer","volume":"22","author":"Parveen","year":"2024","journal-title":"Curr. Drug Deliv."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.reth.2023.12.012","article-title":"In vitro and functional investigation reveals the curative effect of thymoquinone from black cumin-loaded chitosan nanoparticles on streptozotocin induced paediatric diabetes","volume":"25","author":"Xue","year":"2024","journal-title":"Regen. Ther."},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Rahim, M.A., Shoukat, A., Khalid, W., Ejaz, A., Itrat, N., Majeed, I., Koraqi, H., Imran, M., Nisa, M.U., and Nazir, A. (2022). A Narrative Review on Various Oil Extraction Methods, Encapsulation Processes, Fatty Acid Profiles, Oxidative Stability, and Medicinal Properties of Black Seed (Nigella sativa). Foods, 11.","DOI":"10.3390\/foods11182826"},{"key":"ref_224","doi-asserted-by":"crossref","unstructured":"Hannan, M.A., Zahan, M.S., Sarker, P.P., Moni, A., Ha, H., and Uddin, M.J. (2021). Protective Effects of Black Cumin (Nigella sativa) and Its Bioactive Constituent, Thymoquinone against Kidney Injury: An Aspect on Pharmacological Insights. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22169078"},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"Hannan, M.A., Rahman, M.A., Sohag, A.A.M., Uddin, M.J., Dash, R., Sikder, M.H., Rahman, M.S., Timalsina, B., Munni, Y.A., and Sarker, P.P. (2021). Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety. Nutrients, 13.","DOI":"10.3390\/nu13061784"},{"key":"ref_226","unstructured":"(2025, July 11). Novatek Pharmaceuticals A Randomized, Double-Blind, Placebo-Controlled Study. To Evaluate the Safety and Efficacy of TQ Formula in Treating Participants Who Have Tested Positive for Novel Coronavirus 2019 (BOSS-Covid-19). Clin. Gov., Available online: https:\/\/clinicaltrials.gov\/study\/NCT04914377."},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Li, T., Tan, Q., Wei, C., Zou, H., Liu, X., Mei, Z., Zhang, P., Cheng, J., and Fu, J. (2023). Design, Synthesis, and Acute Toxicity Assays for Novel Thymoquinone Derivative TQFL12 in Mice and the Mechanism of Resistance to Toxicity. Molecules, 28.","DOI":"10.3390\/molecules28135149"},{"key":"ref_228","doi-asserted-by":"crossref","unstructured":"Allemailem, K.S., Alnuqaydan, A.M., Almatroudi, A., Alrumaihi, F., Aljaghwani, A., Khalilullah, H., Younus, H., Khan, A., and Khan, M.A. (2021). Safety and Therapeutic Efficacy of Thymoquinone-Loaded Liposomes against Drug-Sensitive and Drug-Resistant Acinetobacter baumannii. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13050677"},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Sanpinit, S., Wetchakul, P., Chonsut, P., Ngamdokmai, N., Ahmad, A.R., and Warinhomhoun, S. (2023). Repeated 28-Day Oral Toxicological Study and Gastroprotective Effects of Nigella sativa L. Oil (Shuhada) against Ethanol-Induced Gastric Mucosal Injury in Rats. Nutrients, 15.","DOI":"10.3390\/nu15061532"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1681\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:58:46Z","timestamp":1761760726000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":229,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["life15111681"],"URL":"https:\/\/doi.org\/10.3390\/life15111681","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]}}}