Combination of Honey and Nigella sativa Oil Reduce Oxidative Stress and Inflammation in Unilateral Ureteral Obstruction in Rats


  • Qorry Amanda Department of Histology, Medical Faculty, Universitas Islam Sultan Agung, Semarang50198, Indonesia
  • Ulfah D. Indrayani Department of Histology, Medical Faculty, Universitas Islam Sultan Agung, Semarang50198, Indonesia
  • Kamilia D. Utami Department of Histology, Medical Faculty, Universitas Islam Sultan Agung, Semarang50198, Indonesia
  • Hadi Sarosa Departement of Physiology, Medical Faculty, Universitas Islam Sultan Agung, Semarang50112, Indonesia
  • Gita A. Faidiansyah Student of Medical Faculty, Universitas Islam Sultan Agung, Semarang50112, Indonesia



Antioxidant, Anti-inflammatory, Nigella sativa, Honey, Unilateral Ureteral Obstruction


Renal fibrosis plays a significant role in the development of chronic kidney disease (CKD). Therefore, treatment of renal fibrosis is essential in reducing the incidence of CKD-related problems. Due to their function as anti-inflammatory and antioxidant agents, honey and Nigella sativa may have therapeutic promise in renal fibrosis. This study aim to investigate the effects of the combination of honey and Nigella sativa oil as anti-inflammatory and antioxidant agents in a rat model of unilateral ureteral obstruction (UUO)-induced kidney injury. In this study, thirty male Wistar rats were divided randomly into five groups. One sham group, one UUO group, and three UUO groups that received varied doses of the combination of honey and Nigella sativa oil (HoNi). HoNi was administered to the rats orally, once daily for 21 days starting from the 14th day post-UUO induction. After treatment, blood samples were collected, and the levels of antioxidant enzymes; Superoxide Dismutase (SOD), Glutathione (GSH), and Catalase (CAT) were measured. The inflammatory marker; C-reactive protein (CRP) activity, and haemoglobin (Hb) levels were also measured. The results showed that the administration of the combination of honey and Nigella sativa for 21 days in UUO rat model significantly reduced CRP, while increasing the activities of SOD, GSH, and CAT, and also enhanced haemoglobin levels in a dose-dependent manner.These findings suggest that the renoprotective effect of the combination of honey and Nigella sativa oil maybe associated with its anti-inflammatory and antioxidant properties.


Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl. 2022;12(1):7-11.

Hustrini NM, Susalit E, Rotmans J. Prevalence and risk factors for chronic kidney disease in Indonesia: An analysis of the National Basic Health Survey 2018. J Glob Health. 2022;12:04071.

Jiang Z, Wang Y, Zhao X, Cui H, Han M, Ren X, Gang X, Guixia Wang G. Obesity and chronic kidney disease. Am J PhysiolEndocrinolMetab. 2023;324(1):E24-E41.

Huang R, Fu P, Ma L. Kidney fibrosis: from mechanisms to therapeutic medicines. Signal Transduct Target Ther. 2023;8(1):129.

Humphreys BD. Mechanisms of Renal Fibrosis. Annu Rev Physiol. 2018;80:309-326.

Martínez-Klimova E, Aparicio-Trejo OE, Tapia E, Pedraza-Chaverri J. Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments. Biomol. 2019;9:141.

Portolés J, Martín L, Broseta JJ, Cases A. Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments to Future Agents. Front Med. 2021;8:642296.

Ahmed S, Sulaiman SA, Baig AA, Ibrahim M, Liaqat S, Fatima S, Jabeen S, Shamim N, Othman NH. Honey as a Potential Natural Antioxidant Medicine: An Insight into Its Molecular Mechanisms of Action. Oxid Med Cell Longev. 2018;2018:8367846.

Hamad R, Jayakumar C, Ranganathan P, Mohamed R, El-Hamamy MM, Dessouki AA, Ibrahim A, Ramesh G. Honey feeding protects kidney against cisplatin nephrotoxicity through suppression of inflammation. Clin Exp Pharmacol Physiol. 2015;42(8):843-848.

Moghimipour E, Ghorbani A, Malayeri A, Siahpoosh A, Khodadoost M, Rajaeipour M, 10.Ahmadi Angali K, ZaheriAbdehvand L. Evaluation of Nigella sativa and Honey Combination for Treatment of kidney Stone: a Randomized, Placebo Controlled Clinical Trial. J Contemp Med Sci. 2019;5(1):24-27.

Hosseinian S, EbrahimzadehBideskan A, Shafei MN, Sadeghnia HR, Soukhtanloo M, Shahraki S, SamadiNoshahr Z, Khajavi Rad A. Nigella sativaextract is a potent therapeutic agent for renal inflammation, apoptosis, and oxidative stress in a rat model of unilateral ureteral obstruction. Phytother Res. 2018;32(11):2290-2298.

AshagrieTafere D. Chemical composition and uses of Honey: A Review. J Food Sci NutrRes. 2021;4(3):194-201.

Khalil MI, Sulaiman SA, Boukraa L. Antioxidant Properties of Honey and Its Role in Preventing Health Disorder. Open Nutraceut J. 2010;3(1):6-16.

Osman MT, Hamza AJA, Omar E, Adnan A. The New Miracle of HabbatusSauda: Its Major Component Thymoquinone can be used in the Management of Autoimmune Diseases. Procedia - Soc Behav Sci. 2014;121:304-314.

Huang L, Ni J, Duncan T, Song Z, Johnson TS. Development of a unilateral ureteral obstruction model in cynomolgus monkeys. Anim Models Exp Med. 2021;4(4):359-368.

Chaabane W, Praddaude F, Buleon M, Jaafar A, Vallet M, Rischmann P, Galarreta CI, Chevalier RL, Tack I. Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO). Am J Physiol Renal Physiol. 2013;304(4):F432-F439.

Li J, Chen J, Lan H Yao, Tang Y. Role of C-Reactive Protein in Kidney Diseases. Kidney Dis. 2023;9(2):73-81.

Phanish MK, Wahab NA, Hendry BM, Dockrell ME. TGF-beta1-induced connective tissue growth factor (CCN2) expression in human renal proximal tubule epithelial cells requires Ras/MEK/ERK and Smadsignalling. Nephron Exp Nephrol. 2005;100(4):e156-e165.

Dong R, Yu J, Yu F, Yang S, Qian Q, Zha Y. IGF-1/IGF-1R blockade ameliorates diabetic kidney disease through normalizing Snail1 expression in a mouse model. Am J Physiol-Endocrinol Metab. 2019;317(4):E686-E698.

Li F, Rajendran P, Sethi G. Thymoquinone inhibits proliferation, induces apoptosis, and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway. Br J Pharmacol. 2010;161(3):541-554.

Hannan MA, Rahman MA, Sohag AAM, Uddin MJ, Dash R, Sikder MH, Rahman MS, Timalsina B, Munni YA, Sarker PP, Alam M, Mohibbullah M, Haque MN, Jahan I, Hossain MT, Afrin T, Rahman MM, Tahjib-Ul-Arif M, Mitra S, Oktaviani DF, Khan MK, Choi HJ, Moon IS, Kim B.Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety. Nutrients. 2021;13(6):1784.

Hayatdavoudi P, Khajavi Rad A, Rajaei Z, Hadjzadeh MAR. Renal injury, nephrolithiasis and Nigella sativa: A mini review. Avicenna J Phytomedicine. 2016;6(1):1-8.

Ranneh Y, Akim AM, Hamid HA, Khazaai H, Fadel A, Zakaria ZA, Albujja M, Bakar MFA. Honey and its nutritional and anti-inflammatory value. BMC Complement Med Ther. 2021;21(1):30.

Asrida A, Astuti A, Leli L, Saad R. Effect of Honey to Levels Hemoglobin and Levels of 8-Hydroxy-2-Deoxyguanosin (8-Ohdg) in Pregnant Women with Anemia. J Asian Multicult Res Med Health Sci Study. 2022;3(3):25-31.

Cascella M, Palma G, Barbieri A, Bimonte S, Amruthraj NJ, Muzio MR, Del Vecchio V, Rea D, Falco M, Luciano A,

Arra C, Cuomo A. Role of Nigella sativa and Its Constituent Thymoquinone on Chemotherapy-Induced Nephrotoxicity: Evidences from Experimental Animal Studies. Nutrients. 2017;9(6):625.

El-Shanshory M, Hablas NM, Aboonq MS, Fakhreldin AR, Attia M, Arafa W, Mariah RA, Baghdadi H, Ayat M, Zolaly M, Nabo MMH, Almaramhy HH, El-Sawy SA, Zidan M, Elshazley M, Alharbi R, Moustafa S, Naga MA, El Sayed SM. Nigella sativa improves anemia, enhances immunity, and relieves iron overload-induced oxidative stress as a novel promising treatment in children having beta-thalassemia major. J Herb Med. 2019;16:100245.

Alam MA, Nasiruddin M, Haque SF, Khan RA. Evaluation of Safety and Efficacy Profile of Nigella sativa Oil as an Add-On Therapy, in Addition to Alpha-Keto Analogue of Essential Amino Acids in Patients with Chronic Kidney Disease. Saudi J Kidney Dis Transplant. 2020;31(1):21.




How to Cite

Amanda, Q., Indrayani, U. D., Utami, K. D., Sarosa, H., & Faidiansyah, G. A. (2024). Combination of Honey and Nigella sativa Oil Reduce Oxidative Stress and Inflammation in Unilateral Ureteral Obstruction in Rats. Tropical Journal of Natural Product Research (TJNPR), 8(6), 7489–7493.