The Effect of Black Seed Oil as Adjuvant Therapy on Nuclear Factor Erythroid 2-Related Factor 2 Levels in Patients with Metabolic Syndrome Risk Effect of Black Seed Oil as Adjuvant Therapy on Nuclear Factor Erythroid 2-Related Factor 2
Iranian Journal of Pharmaceutical Sciences,
Vol. 16 No. 1 (2020),
15 January 2020
,
Page 9-18
https://doi.org/10.22037/ijps.v16.40441
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the transcription factors involved in providing endogenous antioxidants. Black seed oil (BSO), suspected have antioxidant effects that can be used to modulate the expression and levels of Nrf2. The study aims to determine the effect of BSO as adjuvant therapy on levels of Nrf2 to the patients with metabolic syndrome risk.The research used analytical observational with cohort design. Samples study consisted of 62 patients at risk with metabolic syndrome risk at Jetis I Public Health Center, Bantul District, from September to December 2016. Eligible subjects were divided into two groups, (1) BSO group, patients get BSO with a dose of 3 mL/day and standard therapy for 20 days. (2) Control group, patients got placebo and standard therapy during the intervention for 20 days. Levels of Nrf2 were estimates using enzyme-linked immunosorbent assay (ELISA) method. The mean values ± SD between groups were tested with independent t-test with significance of p=<0.05 (95%). The results showed that Nrf2 in group 1 was 0,866 ± 0,11 ng/ml and the group 2 was 0,864 ± 0,15 ng/mL (p=0,94). There were no significant difference in the both groups (p>0.05).In conclusion, adjuvant therapy of BSO doses 3 mL/day for 20 days could not increase levels of Nrf2 in the patients with metabolic syndrome risk based on type treatment and demographic characteristic at Jetis I Public Health Center, Bantul District.
Keywords:
- Antioxidant
- Black seed oil (BSO)
- ELISA
- Indonesia Public Health Center
- Metabolic syndrome
- Nrf2
How to Cite
A Hi, W. R. ., & Endang, D. . (2020). The Effect of Black Seed Oil as Adjuvant Therapy on Nuclear Factor Erythroid 2-Related Factor 2 Levels in Patients with Metabolic Syndrome Risk: Effect of Black Seed Oil as Adjuvant Therapy on Nuclear Factor Erythroid 2-Related Factor 2. Iranian Journal of Pharmaceutical Sciences, 16(1), 9–18. https://doi.org/10.22037/ijps.v16.40441
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[24] Darmawan, E. Imunax Development as an Immunomodulatory Antioxidant in Complementary Therapies for Metabolic Syndrome. Report on Grant Research Implementation. Faculty of Pharmacy.Universitas Ahmad Dahlan:. Yogyakarta (2016).
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(2013) 3 (2): 71-78.
[28] Khader M., Eckl PM. Thymoquinone: An Emerging Natural Drug with A Wide Range of Medical Applications. Iran. J. Basic Med. Sci. (2014):950-957.
[29] Hao, Y.F., Long, C., Hui, Y.C., Hong, X.S.Effects of Thymoquinone on Oxidative stress and Cytokine Expression in Brain of Type 2 Diebetics Rats, Fudan Univ. J. Medical Sci. (2017) 44 (4): 483-488.
[30] Bhakkiyalakshmi, E., Sireesh, D., Rajaguru, P.,Paulmurugan, R., & Ramkumar, K. M. The Emerging Role of Redox-Sensitive Nrf2–Keap1 Pathway in Diabetes. Pharmacol. Res. (2015) 91: 104-114.
[31] Li, B., Liu, S., Miao, L., & Cai, L. Prevention of Diabetic Complications by Activation of Nrf2: Diabetic Cardiomyopathy and Nephropathy. Exp.Diabetes Res. (2012) 2012: 216512.
[32] Jiang, T., Huang, Z., Lin, Y., Zhang, Z., Fang, D., & Zhang, D. D. The Protective Role of Nrf2 in Streptozotocin-Induced Diabetic Nephropathy.Diabetes (2010) 59 (4): 850-860.
[33] David, J. A., Rifkin, W. J., Rabbani, P. S., & Ceradini, D. J. The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus. J. Diabetes Res. (2017) 2017:4826724.
(2006) 23: 469-480.
[2] Kassi, E., Pervanidou, P., Kaltsas, G., & Chrousos, G. Metabolic Syndrome: Definitions and Controversies. BMC. Medicine (2011) 9: 1-48.
[3] International Diabetes Federation. The IDF Consensus Worldwide Definition of The Metabolic Syndrome: Belgium (2006).
[4] Cameron AJ, Shaw JE, Zimmet PZ. The Metabolic Syndrome Prevalence in Worldwide Populations. Endocrinol. Metab. Clin. North Am. (2004) 33: 351-375.
[5] Ministry of Health Republic of Indonesia. Basic Health Research (Riskesdas): Jakarta (2014).
[6] Akrom, Akrom; Darmawan, Endang; Maulida,Nuril. Factors Relate to The Hypercreatininemia Event of Patients at The Risk of Metabolic Syndrome in Jetis I Public Health Center. Pharmaciana (2017) 7(2): 205-216.
[7] Zhang, Z., Zhou, S., Jiang, X., Wang, Y. H., Li,F., Wang, Y. G., & Cai, L., 2014. The Role of the Nrf2/Keap1 Pathway in Obesity and Metabolic Syndrome. Rev Endocr Metab Disord (2015) 16(1):35-45.
[8] Najmi A, Nasiruddin M, Khan, R.A, Shahzad F.H.Indigenous Herbal Product Nigella Sativa Proved Effective as an Antihypertensive in Metabolic Syndrome. Asian J. Pharm. Clin. Res. (2013) 6(1):61-64.
[9] Fajar, D.R., Akrom, Darmawan, E. The Influence of Black Cumin Seed Oil Therapy with Dosage of 1.5 mL/Day and 3 mL/Day to Interleukin-21 (IL-21) Expression of the Patients with Metabolic Syndrome
Risk. IOP Conf. Series: Mater. Sci. Eng. (2017) 259:p.012012.
[10] Kaatabi, H., et al. Nigella sativa Improves Glycemic Control and Ameliorates Oxidative Stress in Patients with Type 2 Diabetes Mellitus: Placebo Controlled Participant Blinded Clinical Trial. PLOS.One. (2015) 10 (2) e0113486.
[11] Usta, A., and S. Dede. The Effect of Thymoquinone on Nuclear Factor Kappa B Levels and Oxidative DNA Damage on Experimental Diabetic Rats. Pharmacogn. Mag. (2017) 13(3):S458-S461.
[12] Rachman, P.N.R., Akrom, Darmawan, E., 2017. The Efficacy of Black Cumin Seed (Nigella Sativa) Oil and Hypoglycemic Drug Combination to Reduce HbA1c Level in Patients with Metabolic Syndrome
Risk. IOP Conf Series: Mater. Sci. Eng. (2017) 259:p.012018.
[13] Al-Naqeep, G., et al. Antiatherogenic Potential of Nigella sativa Seeds and Oil in Diet-Induced Hypercholesterolemia in Rabbits. eCAM. (2011):213628-213628.
[14] Hidayati, T., Akrom, A., Indrayanti, I., & Sagiran, S. Evaluation of the Black Cumin Seed Oil Role (BCSO) on a Decline in eNOS Expression and Plasma NO Levels: Initial Studies Kemopreventive BCSO for Lung Cancer. IJBB. (2017) 7(2): 162-168.
[15] Entok, Emre, et al. Anti-Inflammatuar and Anti-Oxidative Effects of Nigella Sativa L.: 18 FDG-PET Imaging of Inflammation. Mol. Biol. Rep. (2014) 41 (5): 2827-2834.
[16] Hajhashemi, Valiollah, Alireza Ghannadi, and Hadi Jafarabadi. Black Cumin Seed Essential Oil, as a Potent Analgesic and Antiinflammatory Drug. Phytother. Res (2004) 18: 195-199.
[17] Ashraf SS, Rao MV, Kaneez FS, Qadri S, Al-Marzouqi AH, Chandranath IS, et al. Nigella Sativa Extract as A Potent Antioxidant for Petrochemical-Induced Oxidative Stress. J Chromatogr Sci (2011) 49: 321–326.
[18] Aycan, İ. Ö., et al. Thymoquinone Treatment Against Acetaminophen-Induced Hepatotoxicity in Rats. Int. J. Surg. (2014) 12: 213–218.
[19] Akrom & Darmawan, E. Tolerability and Safety of Black Cumin Seed Oil (BCSO) Administration for 20 Days in Healthy Subjects. Biomed. Res. (2017) 28(9): 4196-4201.
[20] Akrom, Darmawan, E., Yuhelvia, L. Black Cumin Seed Oil (Nigella Sativa L) as Hepatoprotector in decreasing SGPT and SGOT activity and increasing p53 gene expression in rats induced by Alloxan, Int.J. Pub. Health Sci. (2015) 4 (3): 159-163.
[21] Kundu J.,Kim Hee Do.,Kundu,K.J., Chun, Soo-Kyung. Thymoquinone Induces Heme Oxygenase-1 Expression in HaCaT Cells Via Nrf2/ARE Activation: Akt and AMPKα as Upstream Targets. Food Chem.Toxicol. (2014) 65: 18-26.
[22] Ariani, N., Akrom, Darmawan, E. Kadar NDA (Malondialdehi) dan Ekspresi Gen Nrf2 (Nuclear Erythroid P45-Related Factor 2) pada Relawan Sehat yang Diberi MBJH (Minyak Biji Jinten Hitam). Thesis. PFakultas Farmasi. Universitas Ahmad Dahlan: Yogyakarta (2015).
[23] Gore R.P.,Prajapati P.C.,Mahajan B.U et al.,Protective Effect to Thymoquinone against Cyclophosphamide-Induced Hemorrhagic Cystitis through Inhibiting DNA Damage and Upregulation of Nrf2 Expression. Int. J. Biol. Sci. (2016) 12: 944-953.
[24] Darmawan, E. Imunax Development as an Immunomodulatory Antioxidant in Complementary Therapies for Metabolic Syndrome. Report on Grant Research Implementation. Faculty of Pharmacy.Universitas Ahmad Dahlan:. Yogyakarta (2016).
[25] Akrom, A., Darmawan, E., et al. Phase 2 Imunax@ Clinical Trial as an Antioxidant Immunomodulator in Patients with Metabolic Syndrome (2016).
[26] Jiménez-Osorio, Angélica S., et al. Nrf2 and Redox Status in Prediabetic and Diabetic Patients. Int. J. Mol. Sci. (2014) 15 (11): 20290-20305.
[27] Siewert, Susana, et al. Downregulation of Nrf2 and HO-1 Expression Contributes to Oxidative Stress in Type 2 Diabetes Mellitus: A study in Juana Koslay City, San Luis, Argentina. Int. J. Diabetes Mellit.
(2013) 3 (2): 71-78.
[28] Khader M., Eckl PM. Thymoquinone: An Emerging Natural Drug with A Wide Range of Medical Applications. Iran. J. Basic Med. Sci. (2014):950-957.
[29] Hao, Y.F., Long, C., Hui, Y.C., Hong, X.S.Effects of Thymoquinone on Oxidative stress and Cytokine Expression in Brain of Type 2 Diebetics Rats, Fudan Univ. J. Medical Sci. (2017) 44 (4): 483-488.
[30] Bhakkiyalakshmi, E., Sireesh, D., Rajaguru, P.,Paulmurugan, R., & Ramkumar, K. M. The Emerging Role of Redox-Sensitive Nrf2–Keap1 Pathway in Diabetes. Pharmacol. Res. (2015) 91: 104-114.
[31] Li, B., Liu, S., Miao, L., & Cai, L. Prevention of Diabetic Complications by Activation of Nrf2: Diabetic Cardiomyopathy and Nephropathy. Exp.Diabetes Res. (2012) 2012: 216512.
[32] Jiang, T., Huang, Z., Lin, Y., Zhang, Z., Fang, D., & Zhang, D. D. The Protective Role of Nrf2 in Streptozotocin-Induced Diabetic Nephropathy.Diabetes (2010) 59 (4): 850-860.
[33] David, J. A., Rifkin, W. J., Rabbani, P. S., & Ceradini, D. J. The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus. J. Diabetes Res. (2017) 2017:4826724.
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