The effect of Nigella sativa on inflammation-induced myocardial fibrosis in male rats

Fatemeh Norouzi Norouzi, Azam Abareshi, Fereshteh Asgharzadeh, Farimah Beheshti, Mahmoud Hosseini, Mehdi Farzadnia, Majid Khazaei


Nigella sativa (NS) (Ranunculaceae) used as a protective and therapeutic traditional medicine. This study evaluates the effect of NS on inflammation-induced myocardial fibrosis, serum and tissue inflammatory markers, and oxidative stress status in male rats. Fifty male Wistar rats were divided into five groups: (1) control; (2) lipopolysaccharide (LPS), 1 mg/kg/day; (3) LPS + NS (hydroalcoholic extract), 100 mg/kg/day; (4) LPS + NS, 200 mg/kg/day; (5) LPS + NS, 400 mg/kg/day (n = 10 in each group). The duration of LPS administration was two weeks. At the end of the experiment, blood samples were taken and ventricles were homogenized and stained for histological evaluation. Serum nitrite levels were lower in LPS group than the control group (22.98 ± 1.03 vs 28.5 ± 0.93 μmol/L), in which they were significantly increased by NS treatment (P < 0.05). Higher levels of heart interlukine-6 (IL-6) and tumor necrosis factor-α (TNF-α) were observed in LPS group compared to the controls (IL-6: 6805 ± 656 vs 4733 ± 691 pg/mL; TNF-α: 6504 ± 501 vs 5309 ± 452 pg/mL), in which they were reduced by NS 400 mg/kg compared to LPS groups (P < 0.05). A significant increment of malondialdehyde and reduction in heart total thiol, superoxide dismutase and catalase concentrations were observed in LPS group (p < 0.05) which significantly restored with treatment by three doses of NS. Histopathological studies showed higher inflammatory cell infiltrates, cardiac fibrosis, and collagen deposition in LPS group, which were reduced by the administration of NS. Treatment by NS reduced myocardial fibrosis in inflammation-induced fibrosis, possibly through improving oxidative/anti-oxidative balance.


Lipopolysacchride; Heart; Collagen; Oxidative stress; Inflammation

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Shabana A, El-Menyar A, Asim M, Al-Azzeh H, Al Thani H. Cardiovascular benefits of black cumin (Nigella sativa). Cardiovasc Toxicol. 2013;13(1):9-21.

Yarnell E, Abascal K. Nigella sativa: holy herb of the Middle East. Altern Compl Therap. 2011;17:99-105.

Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol. 2005;5(13-14):1749-1770.

Majdalawieh AF, Fayyad MW. Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review. Int Immunopharmacol. 2015:28(1):295-304.

Kanter M, Demir H, Karakaya C, Ozbek H. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World J Gastroenterol. 2005;11(42):6662-6666.

Shafiq H, Ahmad A, Masud T, Kaleem M. Cardio-protective and anti-cancer therapeutic potential of Nigella sativa. Iran J Basic Med Sci. 2014;17(12):967-979.

Doi K, Leelahavanichkul A, Yuen PS, Star RA. Animal models of sepsis and sepsis-induced kidney injury. J Clin Invest. 2009;119(10):2868-2878.

Abbas AK, Lichtman AHH. Basic immunology updated edition: functions and disorders of the immune system. 3rd edition. Saunders Elsevier. 2006, pp. 11-13.

Frantz S, Kobzik L, Kim YD, Fukazawa R, Medzhitov R, Lee RT, et al. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest. 1999;104(3):271-280. 10. Thompson M, Kliewer A, Maass D, Becker L, White DJ, Bryant D, et al. Increased cardiomyocyte intracellular calcium during endotoxin-induced cardiac dysfunction in guinea pigs. Pediatr Res. 2000;47(5):669-676.

Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. ChemBiol Interact. 2012;197(1):40-46.

Mahmood MS, Gilani AH, Khwaja A, Rashid A, Ashfaq MK. The in vitro effect of aqueous extract of Nigella sativa seeds on nitric oxide production. Phytother Res. 2003;17(8):921-924.

Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR. Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death. Cell Mol Neurobiol. 2010;30(4):591-598.

Elmi S, Sallam NA, Rahman MM, Teng X, Hunter AL, Moien-Afshari F, et al. Sulfaphenazole treatment restores endothelium-dependent vasodilation in diabetic mice. Vascul Pharmacol. 2008;48(1):1-8.

Nematollahi S, Nematbakhsh M, Haghjooyjavanmard S, Khazaei M, Salehi M. Inducible nitric oxide synthase modulates angiogenesis in ischemic hindlimb of rat. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009;153(2):125-129.

Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-310.

Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci. 2005;8(3):394-399.

Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-126.

Tahergorabi Z, Khazaei M. The relationship between inflammatory markers, angiogenesis, and obesity. ARYA atheroscler. 2013;9(4):247-253.

Sturzu A, Sheikh S, Echner H, Nagele T, Deeg M, Amin B, et al. Rhodamine-marked bombesin: a novel means for prostate cancer fluorescence imaging. Invest New Drugs. 2014;32(1):37-46.

Kokku SB, Mahapatra B, Tucker S, Saggurti N, Prabhakar P. Effect of public-private partnership in treatment of sexually transmitted infections among female sex workers in Andhra Pradesh, India. Indian J Med Res. 2014;139(2):285-293.

Wilson H, Carvalho B, Granot M, Landau R. Temporal stability of conditioned pain modulation in healthy women over four menstrual cycles at the follicular and luteal phases. Pain. 2013;154(12):2633-2638.

Carvalho BM, Abdalla Saad MJ. Influence of gut microbiota on subclinical inflammation and insulin resistance. Mediators Inflamm. 2013(2013), ID 986734.

Kanter M, Coskun O, Budancamanak M. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol. 2005;11(42):6684-6688.

Khozoie C, Borland MG, Zhu B, Baek S, John S, Hager GL, et al. Analysis of the peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) cistrome reveals novel co-regulatory role of ATF4. BMC Genomics. 2012;13:665.

Gonzalez F. Adrenal dysfunction in polycystic ovary syndrome: has it been lost to follow-up? Fertil Steril. 2013;99(2):352-353.


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