Abstract
Objective
This study was conducted to assess the effect of Nigella sativa (N. sativa) supplementation on inflammatory and oxidative markers among the adult population.
Methods
We carried out a comprehensive, systematic search of Scopus, Embase, Cochrane Library, Web of Science, PubMed, and Google Scholar till December 2022. A random-effects model was used to estimate the overall effect size.
Results
In total, twenty trials consisting of 1086 participants were included in the meta-analysis. Findings from 20 RCTs included in the meta-analysis suggest that N. sativa supplementation could significantly reduce serum C-reactive protein (CRP) (SMD = − 2.28; 95% CI − 3.20, − 1.37, p < 0.001), tumour necrosis factor α (TNFα) (SMD = − 1.21; 95% CI − 2.15, − 0.26; p = 0.013), and malondialdehyde (MDA) (SMD = − 2.15; 95% CI − 3.37, − 0.93, p < 0.001) levels, and significantly improves total antioxidant capacity (TAC) (SMD = 2.28; 95% CI 1.29, 3.27, p < 0.001), glutathione peroxidase (GPx) (SMD = 1.23, 95% CI 0.25, 2.22; p = 0.014) and superoxide dismutase (SOD) (SMD = 2.05; 95% CI 1.22, 2.88, p < 0.001) levels. However, no significant reduction was found in interleukin 6 (IL-6) levels (SMD = − 1.13; 95% CI − 2.72, 0.46, p = 0.162).
Conclusion
N. sativa supplementation had beneficial effects on CRP, TNF-α, MDA, SOD, GPx, and TAC. Thus, Nigella sativa can be recommended as an adjuvant anti-oxidant agent and anti-inflammatory.
Similar content being viewed by others
Data availability
Not applicable.
Code availability
Not applicable.
References
Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ (2010) Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic β-cells of streptozotocin-induced diabetic rats. J Diabetes 2(4):256–266
Abdollahi N, Nadjarzadeh A, Salehi-Abargouei A, Fallahzadeh H, Razmpoosh E, Lorzaedeh E, Safi S (2022) The effect of Nigella sativa on TAC and MDA in obese and overweight women: secondary analysis of a crossover, double blind, randomized clinical trial. J Diabetes Metab Disord. https://doi.org/10.1007/s40200-021-00954-5
Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA et al (2013) A review on therapeutic potential of Nigella sativa: a miracle herb. Asian Pac J Trop Biomed 3(5):337–352
Ahmad A, Mishra RK, Vyawahare A, Kumar A, Rehman MU, Qamar W et al (2019) Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: chemistry and biological effects. Saudi Pharmac J 27(8):1113–1126
Ahmad MF, Ahmad FA, Ashraf SA, Saad HH, Wahab S, Khan MI et al (2021) An updated knowledge of Black seed (Nigella sativa Linn.): review of phytochemical constituents and pharmacological properties. J Herb Med 25:100404
Alizadeh-naini M, Yousefnejad H, Hejazi N (2020) The beneficial health effects of Nigella sativa on Helicobacter pylori eradication, dyspepsia symptoms, and quality of life in infected patients: a pilot study. Phytother Res 34(6):1367–1376
Alkharfy KM, Ahmad A, Jan BL, Raish M (2018) Thymoquinone reduces mortality and suppresses early acute inflammatory markers of sepsis in a mouse model. Biomed Pharmacother 98:801–805
Amin F, Islam N, Anila N, Gilani A (2015) Clinical efficacy of the co-administration of Turmeric and Black seeds (Kalongi) in metabolic syndrome—a double blind randomized controlled trial–TAK-MetS trial. Complement Ther Med 23(2):165–174
Azami R, Farshbaf-Khalili A, Mahdipour M, Firozsalar FG, Shahnazi M (2022) Effect of Nigella sativa oil on early menopausal symptoms and serum levels of oxidative markers in menopausal women: a randomized, triple-blind clinical trial. Nurs Midw Stud 11(2):103
Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101
Darand M, Darabi Z, Yari Z, Saadati S, Hedayati M, Khoncheh A et al (2019) Nigella sativa and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: results from a randomized, double-blind, placebo-controlled, clinical trial. Complement Ther Med 44:204–209
Datau E, Surachmanto EE, Pandelaki K, Langi J (2010) Efficacy of Nigella sativa on serum free testosterone and metabolic disturbances in central obese male. Acta Med Indones 42(3):130–134
Di Meo S, Venditti P (2020) Evolution of the knowledge of free radicals and other oxidants. Oxid Med Cell Longev 2020:9829176
Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634
El-Mahmoudy A, Matsuyama H, Borgan M, Shimizu Y, El-Sayed M, Minamoto N, Takewaki T (2002) Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages. Int Immunopharmacol 2(11):1603–1611
Engwa GA (2018) Free radicals and the role of plant phytochemicals as antioxidants against oxidative stress-related diseases. In: Phytochemicals: source of antioxidants and role in disease prevention, vol 7. BoD–Books on Demand, pp 49–74
Farhangi MA, Tajmiri S (2020) The effects of powdered black cumin seeds on markers of oxidative stress, intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in patients with Hashimoto’s thyroiditis. Clin Nutr ESPEN 37:207–212
Hadi V, Kheirouri S, Alizadeh M, Khabbazi A, Hosseini H (2016) Effects of Nigella sativa oil extract on inflammatory cytokine response and oxidative stress status in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial. Avicenna J Phytomed 6(1):34
Hadi S, Mirmiran P, Daryabeygikhotbehsara R, Hadi V (2018) Effect of Nigella sativa oil extract on inflammatory cytokine response and oxidative stress among people with type 2 diabetes mellitus: a randomized, double-blind, placebo controlled trial. Avicenna J Phytomed. 6:34–43
Hannan MA, Rahman MA, Sohag AAM, Uddin MJ, Dash R, Sikder MH et al (2021) Black cumin (Nigella sativa L.): a comprehensive review on phytochemistry, health benefits, molecular pharmacology, and safety. Nutrients 13(6):1784
Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (2019) Cochrane handbook for systematic reviews of interventions. Wiley, Hoboken
Higgins JP (2008) Cochrane handbook for systematic reviews of interventions version 5.0. 1. The Cochrane Collaboration. http://www.cochrane-handbook.org
Islam M, Guha B, Hosen S, Riaz T, Shahadat S, Da Rocha Sousa L et al (2017) Nigellalogy: a review on Nigella sativa. MOJ Bioequiv Availab 3(6):00056
Kaatabi H, Bamosa AO, Badar A, Al-Elq A, Abou-Hozaifa B, Lebda F et al (2015) Nigella sativa improves glycemic control and ameliorates oxidative stress in patients with type 2 diabetes mellitus: placebo controlled participant blinded clinical trial. PLoS ONE 10(2):e0113486
Kheirouri S, Hadi V, Alizadeh M (2016) Immunomodulatory effect of Nigella sativa oil on T lymphocytes in patients with rheumatoid arthritis. Immunol Invest 45(4):271–283
Kooshki A, Taghizadeh M, Akbarzadeh R (2022) The effects of Nigella sativa oil on serum levels inflammatory markers, oxidative stress markers, and lipid profile in dialysis patients: a double-blind clinical trail. J Nutr Food Secur 7(3):272–281
Leong X-F, Rais Mustafa M, Jaarin K (2013) Nigella sativa and its protective role in oxidative stress and hypertension. Evid Based Complement Altern Med. https://doi.org/10.1155/2013/120732
Mahboubi M, Kashani LMT, Mahboubi M (2018) Nigella sativa fixed oil as alternative treatment in management of pain in arthritis rheumatoid. Phytomedicine 46:69–77
Mahdavi R, Namazi N, Alizadeh M, Farajnia S (2016) Nigella sativa oil with a calorie-restricted diet can improve biomarkers of systemic inflammation in obese women: a randomized double-blind, placebo-controlled clinical trial. J Clin Lipidol 10(5):1203–1211
Majeed A, Muhammad Z, Ahmad H, Hayat SSS, Inayat N, Siyyar S (2021) Nigella sativa L.: uses in traditional and contemporary medicines–an overview. Acta Ecol Sin 41(4):253–258
Malekian S, Ghassab-Abdollahi N, Mirghafourvand M, Farshbaf-Khalili A (2021) The effect of Nigella sativa on oxidative stress and inflammatory biomarkers: a systematic review and meta-analysis. J Complement Integr Med 18(2):235–259
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4(1):1–9
Mohit M, Farrokhzad A, Faraji SN, Heidarzadeh-Esfahani N, Kafeshani M (2020) Effect of Nigella sativa L. supplementation on inflammatory and oxidative stress indicators: a systematic review and meta-analysis of controlled clinical trials. Complement Ther Med 54:102535
Mohtashami A, Mahaki B, Azadbakht L, Entezari MH (2016) Effects of bread with Nigella sativa on lipid profiles, apolipoproteins and inflammatory factor in metabolic syndrome patients. Clin Nutr Res 5(2):89–95
Montazeri RS, Fatahi S, Sohouli MH, Abu-Zaid A, Santos HO, Găman MA, Shidfar F (2021) The effect of Nigella sativa on biomarkers of inflammation and oxidative stress: a systematic review and meta-analysis of randomized controlled trials. J Food Biochem 45(4):e13625
Moustafa HAM, El Wakeel LM, Halawa MR, Sabri NA, El-Bahy AZ, Singab AN (2019) Effect of Nigella sativa oil versus metformin on glycemic control and biochemical parameters of newly diagnosed type 2 diabetes mellitus patients. Endocrine 65(2):286–294
Namazi N, Mahdavi R, Alizadeh M, Farajnia S (2015) Oxidative stress responses to Nigella sativa oil concurrent with a low-calorie diet in obese women: a randomized, double-blind controlled clinical trial. Phytother Res 29(11):1722–1728
Nikkhah-Bodaghi M, Darabi Z, Agah S, Hekmatdoost A (2019) The effects of Nigella sativa on quality of life, disease activity index, and some of inflammatory and oxidative stress factors in patients with ulcerative colitis. Phytother Res 33(4):1027–1032
Pipalia PR, Annigeri RG, Mehta R (2016) Clinicobiochemical evaluation of turmeric with black pepper and Nigella sativa in management of oral submucous fibrosis—a double-blind, randomized preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol 122(6):705–712
Purwatiningsih S, Syamsuddin S, Lisal ST, Liaury K, Bahar B, Yustisia I (2022) Black seed (Nigella sativa) efficacy in improving clinical symptoms and interleukin-6 levels schizophrenic patients. Open Access Macedonian J Med Sci 10(B):374–382
Rahmani A, Niknafs B, Naseri M, Nouri M, Tarighat-Esfanjani A (2022) Effect of Nigella sativa oil on oxidative stress, inflammatory, and glycemic control indices in diabetic hemodialysis patients: a randomized double-blind, controlled trial. Evid Based Complement Altern Med. https://doi.org/10.1155/2022/2753294
Rashidmayvan M, Mohammadshahi M, Seyedian SS, Haghighizadeh MH (2019) The effect of Nigella sativa oil on serum levels of inflammatory markers, liver enzymes, lipid profile, insulin and fasting blood sugar in patients with non-alcoholic fatty liver. J Diabetes Metab Disord 18(2):453–459
Rezayian M, Niknam V, Ebrahimzadeh H (2019) Oxidative damage and antioxidative system in algae. Toxicol Rep 6:1309–1313
Ridker PM (2003) Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107(3):363–369
Sahebkar A, Beccuti G, Simental-Mendia LE, Nobili V, Bo S (2016) Nigella sativa (black seed) effects on plasma lipid concentrations in humans: a systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res 106:37–50
Sayed-Ahmed MM, Nagi MN (2007) Thymoquinone supplementation prevents the development of gentamicin-induced acute renal toxicity in rats. Clin Exp Pharmacol Physiol 34(5–6):399–405
Sharma N, Ahirwar D, Jhade D, Gupta S (2009) Medicinal and phamacological potential of Nigella sativa: a review. Ethnobotanical Leaflets 2009(7):11
Shoaei-Hagh P, Kamelan Kafi F, Najafi S, Zamanzadeh M, Heidari Bakavoli A, Ramezani J et al (2021) A randomized, double-blind, placebo-controlled, clinical trial to evaluate the benefits of Nigella sativa seeds oil in reducing cardiovascular risks in hypertensive patients. Phytother Res 35(8):4388–4400
Sultan MT, Butt MS, Karim R, Zia-Ul-Haq M, Batool R, Ahmad S et al (2014) Nigella sativa fixed and essential oil supplementation modulates hyperglycemia and allied complications in streptozotocin-induced diabetes mellitus. Evid Based Complement Altern Med. https://doi.org/10.1155/2014/826380
Tavakkoli A, Mahdian V, Razavi BM, Hosseinzadeh H (2017) Review on clinical trials of black seed (Nigella sativa) and its active constituent, thymoquinone. J Pharmacopunct 20(3):179
Tavakoli-Rouzbehani OM, Abbasnezhad M, Kheirouri S, Alizadeh M (2022) Efficacy of Nigella sativa oil on endothelial function and atherogenic indices in patients with coronary artery diseases: a randomized, double-blind, placebo-control clinical trial. Phytother Res. https://doi.org/10.1002/ptr.7568
Tavakoly R, Arab A, Vallianou N, Clark CC, Hadi A, Ghaedi E, Ghavami A (2019) The effect of Nigella sativa L. supplementation on serum C-reactive protein: a systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 45:149–155
Woo CC, Kumar AP, Sethi G, Tan KHB (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83(4):443–451
Yimer EM, Tuem KB, Karim A, Ur-Rehman N, Anwar F (2019) Nigella sativa L. (black cumin): a promising natural remedy for wide range of illnesses. Evid Based Complement Altern Med 2019:1528635
Acknowledgements
We are thankful from Student Research Committee, Isfahan University of Medical Sciences for their financial support. The present study has been performed by a grant from Student Research Committee, Isfahan University of Medical Sciences (grant number: 1401284).
Funding
The present study has been performed by a grant from Student Research Committee, Isfahan University of Medical Sciences (grant number: 1401284).
Author information
Authors and Affiliations
Contributions
VM and MV conceived the study. The literature search and screening data were done by GA. Data extraction and quality assessment was performed independently by VM and MV. VM and MV analyzed and interpreted data and wrote the manuscript. GA supervised the study. All authors read and approved the final manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Consent for publication
Not applicable.
Ethical approval
The study protocol was approved and registered by the ethics committee of Isfahan University of Medical Sciences (Identifier: IR.MUI.RESEARCH.REC.1401.356).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
10787_2023_1213_MOESM1_ESM.docx
Supplementary file1 Supplementary file.1. The results of funnel plots for biomarkers of inflammation and oxidative stress. (DOCX 4689 KB)
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Kavyani, Z., Musazadeh, V., Golpour-hamedani, S. et al. 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. Inflammopharmacol 31, 1149–1165 (2023). https://doi.org/10.1007/s10787-023-01213-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-023-01213-0