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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 29  |  Issue : 3  |  Page : 415-421

Comparative pre- and post-treatment effects of Nigella sativa oil on lipid profile and antioxidant enzymes in a rat model of diabetes mellitus


1 Department of Pharmacology, Therapeutics and Toxicology, College of Medicine of the University of Lagos, Lagos, Nigeria
2 Department of Physiology, College of Medicine of the University of Lagos, Lagos, Nigeria
3 Department of Pharmacology and Therapeutics, Usmanu Danfodiyo University, Sokoto, Nigeria
4 Department of Internal Medicine, Federal Medical Centre, Lagos, Nigeria

Date of Submission29-Apr-2020
Date of Decision02-Jul-2020
Date of Acceptance08-Jul-2020
Date of Web Publication18-Sep-2020

Correspondence Address:
Dr. Abdullahi A. Adejare
Department of Physiology, College of Medicine of the University of Lagos, Lagos
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/NJM.NJM_42_20

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  Abstract 


Background: Lipid profile dysregulation and oxidative stress are important risk factors for cardiovascular disease in diabetic individuals. Nigella Sativa (NS) oil has been reported to have a favorable effect on triglycerides (TG) in rat models of diabetes mellitus. There is a dearth of information available about preventive or corrective use to manage and ameliorate diabetes. Aim: This study sought to ascertain the comparative pre and post-treatment effects of the oil on TG, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, and key antioxidant enzymes levels in diabetic rats. Methods: Thirty (30) Wistar rats were divided into 6 groups of 5 rats each as follows: Group I rats took normal chow ad libitum and served as Control. Group II rats were induced with diabetes using streptozocin (50 mg/Kg BW). Group III and IV rats were pre-administered with 0.5 and 1 ml of the oil, respectively, before induction, whereas Group V and VI rats were treated with 0.5 and 1 ml of the oil after induction. The listed parameters were assessed in the plasma at the end of the study. Results: Diabetes induction caused a significant increase in the TG level. There was no significant change in the oxidative stress parameters. Only post-administration caused a significant reduction in TG level, whereas both pre and post-administrations caused a significant improvement in HDL levels. Both pre- and post-administrations caused an increase in superoxide dismutase and catalase levels when causing a significant reduction in malondialdehyde level. Conclusion: Post-induction treatment may be more effective in the correction of lipid dysregulation and oxidative stress in diabetes.

Keywords: Antioxidant enzymes, atherogenic index, diabetes, lipid profile, Nigella sativa


How to cite this article:
Busari AA, Adejare AA, Kelani SO, Imam KO, Awesu AA, Adefila-Sanni I. Comparative pre- and post-treatment effects of Nigella sativa oil on lipid profile and antioxidant enzymes in a rat model of diabetes mellitus. Niger J Med 2020;29:415-21

How to cite this URL:
Busari AA, Adejare AA, Kelani SO, Imam KO, Awesu AA, Adefila-Sanni I. Comparative pre- and post-treatment effects of Nigella sativa oil on lipid profile and antioxidant enzymes in a rat model of diabetes mellitus. Niger J Med [serial online] 2020 [cited 2020 Oct 24];29:415-21. Available from: http://www.njmonline.org/text.asp?2020/29/3/415/295296




  Introduction Top


Diabetes mellitus (DM) remains the most common metabolic disorder worldwide.[1] The hallmark of this disorder includes the abnormally high level of triglycerides (TGs), reduced high-density lipoprotein (HDL), and reduced low-density lipoprotein (LDL) level.[1] Apart from these, hyperglycemia is known to play a contributory role in the development of oxidative stress in diabetes.[2] The oxidative stress if unchecked has been shown to continuously lead to damage to the biological system which eventually leads to increased production of markers of lipid peroxidation like malondialdehyde (MDA)[3] contributing to the development of diabetic complications.[4] The abnormalities in circulating lipids and lipoproteins are thus considered to be important risk factors for cardiovascular disease in diabetic individuals.[5] Reversal of these abnormalities in lipid profile may reduce accelerated atherosclerosis and the related macrovascular complications in patients with DM.[6]

The use of natural oil and herbal products for disease control is the new order, especially in the management of diabetic complications and correcting the associated metabolic abnormalities.[7]Nigella sativa (NS) (black cumin or black seed) is among the natural sources described to have therapeutic effects in the management of many diseases.[8] The oil has been widely reported to have anti-inflammatory, immunomodulatory, anticancer, antiparasitic, antiasthmatic, and antihypertensive effects.[9],[10] It has also been reported to have antidiabetic, analgesic, antimicrobial, spasmolytic, bronchodilator, hepatoprotective, renal protective, gastroprotective, and antioxidant properties.[11] Moreover, the seeds of NS are commonly used in the management of various diseases such as bronchitis, diarrhoea, rheumatism, and skin disorders.[10] Recently, our team was able to establish the therapeutic but non-synergistic effect it has when used with Vitamin E (α-tocopherol) in the management of cisplatin-induced renal toxicities.[12] Interestingly, thymoquinone which had earlier been identified as the active component in the oil is not only an effective superoxide radical scavenger but also protects the liver from toxins.[13]

The hypolipidemic and antioxidative effects of NS oil have been demonstrated in experimental animals where it was reported to have a favourable effect on TG and lipoprotein the pattern in normal rats.[14] Similar findings were encountered by the administration of thymoquinone, the active ingredient of NS, to rabbits fed on cholesterol-enriched diet[15] and to hypercholesterolemic rats.[16] Even though the majority of authors are of the opinion that NS oil administration improves hyperglycemia,[17] oxidative stress, and lipid peroxidation,[18] there is a paucity of information on whether this oil should be given before the development of diabetes or after, especially in individuals with a family history of diabetes. This study, therefore, sought to determine the comparative therapeutic effects of pre- and post-supplementation of the oil on lipid profile and antioxidant levels in a rat model of diabetes.


  Animals and Methods Top


Ethical approval

Ethical approval for this study was granted by the College of Medicine of the University of Lagos Animal Care and Use Research Ethics Committee with reference number (CMUL/HREC/02/20/715).

Animals

The study was carried out in adult male Wistar rats weighing 140–160 g. For acclimatization, the animals were kept in the faculty animal house for 2 weeks before the start of the experiment. The Wistar rats were kept in wire mesh cages under room conditions. The animals were allowed free access to water and food pellets at a room temperature of about 29°C ± 2°C throughout the period of this experiment. They had a 12-hour light and 12-hour dark cycle. Experimental protocols complied with the Guide for the Care and Use of Laboratory Animals.[19]

Grouping and treatments per group

A total of thirty (30) Wistar rats were divided into 6 groups of 5 rats each as follows: Group I rats were fed normal rat chow ad libitum without any induction and served as Control. Group II rats were induced with diabetes without treatment (DB group). Group III rats were pretreated with 0.5 ml/kg NS oil before diabetes induction (NS0.5 + DB group) intraperitoneally. Group IV rats were pretreated with 1 ml/kg NS oil before diabetes induction (NS1 + DB group). Group V rats were treated with 0.5 ml/kg NS oil intraperitoneally after diabetes induction (DB + NS0.5) and finally Group VI rats were treated with 1 ml/kg NS oil after diabetes induction (DB + NS1) intraperitoneally. Group III and IV rats were sacrificed 72 h after induction, whereas Groups V and VI rats were sacrificed after completion of treatment.

This arrangement is illustrated in [Table 1].
Table 1: Animal groups

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Induction of diabetes

Diabetes was induced in Groups II, III, IV, V, and VI by a single intraperitoneal injection of a freshly buffered (0.1 M citrate, pH 4.5) solution of streptozotocin (STZ) at a dosage of 50 mg/kg body weight. After 72 h of STZ administration, the tail vein blood was collected to determine blood glucose level with the aid of a very sensitive glucometer. Only rats with blood glucose over 250 mg/dl were considered diabetic and included in the experiments.[20]

Administration of Nigella sativa oil

Groups III and IV rats were preadministered with 0.5 and 1 ml of the pure oil, respectively, for 2 weeks intraperitoneally before the induction of diabetes. Groups V and VI rats were administered with 0.5 and 1 ml of the pure oil, respectively, for 2 weeks intraperitoneally after the induction of diabetes.

Blood sample collection

Each group of animals was sacrificed on different days after completion of the expected exposure and treatment periods. After overnight fasting, rats were sacrificed following euthanization by cervical dislocation.[21] Blood was collected via cardiac puncture into EDTA bottles and centrifuged immediately at 3000 rpm for 10 min to obtain serum for estimation of lipid profile and antioxidant enzymes.

Assessment of lipid profile

TG, total cholesterol, HDL, and LDL in the serum were analyzed using a kit meant for animals obtained from Randox Laboratories Limited, Crumlin, UK. This was carried out using the method of Morakinyo et al.[21] with some minor modifications. To 5 μL of serum, 0.5 mL of enzyme reagent was added and kept at 37°C for 5 min. Then, 5 μL of cholesterol standard and distilled water (blank) were also processed similarly. The absorbance was measured at 510 nm. To 5 μL of serum, 0.5 mL of enzyme reagent was added, mixed well, and incubated at room temperature for 10 min. Then, 5 μL of TG standard and distilled water (blank) were also processed similarly. The absorbance was measured at 510 nm. LDLs, very LDL, and chylomicron fractions were precipitated quantitatively in 0.5 mL of serum by the addition of 50 μL of HDL precipitant (phosphotungstic acid in the presence of magnesium ions). After centrifugation, the cholesterol concentration in the HDL (supernatant) fraction was also determined. HDL and VLDL fractions were eliminated by cholesterol esterase, cholesterol oxidase, and, subsequently, catalase (CAT). Thereafter, the specific measurement of LDL cholesterol marked by the intensity of the quinine imine dye produced was measured at 600 nm.

Assessment of antioxidant enzymes level and lipid peroxidation

The previously described standard methods[21] were used to carry out oxidative analyses. Briefly, the method described by Sun and Zigman[22] was used to determine the activity of superoxide dismutase (SOD) enzyme. The reduced glutathione (GSH) content of the serum was measured using the method previously described by van Doorn et al.[23] CAT activity was determined by measuring the exponential disappearance of H2O2 at 240 nm and expressed in units per milligram of protein as previously described by Aebi.[24] Lipid peroxidation was estimated with the method of Mihara and Uchiyama[25] by measuring the level of MDA. Absorbance was recorded using a Shimadzu recording spectrophotometer (UV 160, Kyoto, Japan) in all measurements.

Statistical analysis

The data were expressed as mean ± standard error of the mean and analyzed using one-way analysis of variance followed by Neumann–Keul post hoc test. P < 0.05 was considered statistically significant. Data analysis was carried out using the GraphPad Version 5.05 for Windows Vista (GraphPad Software, San Diego, CA, USA).


  Results Top


Effect of pre- and post-administration of Nigella sativa oil on cholesterol level

Induction of diabetes did not cause a significant (P > 0.05) change in the cholesterol level in the DB group compared to control. Both pre- and post-administration of the oil did not show any significant change (P > 0.05) in the level of cholesterol across all the groups. This is illustrated in [Figure 1].
Figure 1: Cholesterol level across the groups. Values are represented as mean ± standard error of the mean. Group I: Control (CTRL), Group II: Diabetic (DB), Group III: Nigella sativa group pretreated with 0.5 ml (NS0.5 + DB), Group IV: Nigella sativa group pretreated with 1ml (NS1 + DB), Group V: Nigella sativa group post-treated with 0.5 ml (DB + NS0.5), Group VI: Nigella sativa group post-treated with 1 ml (DB + NS1)

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Effect of pre- and post-administration of Nigella sativa oil on triglyceride level

As illustrated in [Figure 2], the induction of diabetes caused a significant (P < 0.05) increase in the TG level in the DB group compared to control. Pre-administration of the oil in the NS0.5 + DB and NS1 + DB groups did not cause a significant (P > 0.05) change in the level of TG. There was, however, a slight reduction in the level. Post-administration of the oil caused a significant (P < 0.01) reduction in the level of TG in the DB + NS1 group compared to the DB group. Post-administration in the DB + NS1 group was also more effective to cause reduction than the DB + NS0.5 group (P < 0.01). Post-administration of NS oil, however, did not significantly (P > 0.05) change the level of TG in the DB + NS0.5 group compared to the DB group.
Figure 2: Triglyceride level across the groups. Values are represented as mean ± standard error of the mean. *: Significant increase (p < 0.05) versus Control group. μ: Significant reduction (P < 0.01) versus DB group, β: Significant reduction (P < 0.01) versus DB + NS0.5 group. Group I: Control (CTRL), Group II: Diabetic (DB), Group III: Nigella sativa group pretreated with 0.5 ml (NS0.5 + DB), Group IV: Nigella sativa group pretreated with 1 ml (NS1 + DB), Group V: Nigella sativa group post-treated with 0.5 ml (DB + NS0.5), Group VI: Nigella sativa group post-treated with 1 ml (DB + NS1)

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Effect of pre- and post-administration of Nigella sativa oil on high-density lipoprotein level

There was a slight reduction in the level of HDL, but this reduction was statistically not significant (P > 0.05) in the DB group compared to the control group. Pre-administration with NS oil in the NS0.5 + DB group caused a significant increase (P < 0.05) in the HDL level compared to the DB group. Post-administration with NS oil in the DB + NS0.5 and DB + NS1 groups also caused a significant increase (P < 0.05) in the HDL level compared to the DB group. This is illustrated in [Figure 3].
Figure 3: High-density lipoprotein level across the groups. Values are represented as mean ± standard error of the mean. *: Significant increase (P < 0.05) versus DB group. μ: Significant increase (P < 0.01) versus Control group. Group I: Control (CTRL), Group II: Diabetic (DB), Group III: Nigella sativa group pretreated with 0.5ml (NS0.5 + DB), Group IV: Nigella sativa group pretreated with 1 ml (NS1 + DB), Group V: Nigella sativa group post-treated with 0.5 ml (DB + NS0.5), Group VI: Nigella sativa group post-treated with 1 ml (DB + NS1)

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Effect of pre- and post-administration of Nigella sativa oil on low-density lipoprotein level

Induction of diabetes did not cause a significant (P > 0.05) change in the LDL level in the DB group compared to control. Both pre- and post-administration of NS oil did not show any significant change (P > 0.05) in the level of LDL across all the groups even though there appears to be a general reduction in the pre- and post-treatment groups. This is illustrated in [Figure 4].
Figure 4: Low-density lipoprotein level across the groups. Values are represented as mean ± standard error of the mean. Group I: Control (CTRL), Group II: Diabetic (DB), Group III: Nigella sativa group pretreated with 0.5ml (NS0.5+DB), Group IV: Nigella sativa group pretreated with 1ml (NS1+DB), Group V: Nigella sativa group post-treated with 0.5 ml (DB+NS0.5), Group VI: Nigella sativa group post-treated with 1 ml (DB+NS1)

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Effect of pre- and post-administration of Nigella sativa oil on atherogenic index

Induction of diabetes did not cause a significant (P > 0.05) change in the atherogenic index in the DB group compared to control. Both pre-and post-administration of the oil did not show any significant change (P > 0.05) in the atherogenic index across all the groups. This is illustrated in [Figure 5].
Figure 5: Atherogenic index across the groups. Values are represented as mean ± standard error of the mean. Group I: Control (CTRL), Group II: Diabetic (DB), Group III: Nigella sativa group pretreated with 0.5 ml (NS0.5+DB), Group IV: Nigella sativa group pretreated with 1ml (NS1+DB), Group V: Nigella sativa group post-treated with 0.5 ml (DB+NS0.5), Group VI: Nigella sativa group post-treated with 1 ml (DB+NS1)

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Effect of pre- and post-administration of Nigella sativa oil on reduced glutathione level

As illustrated in [Table 2] for the antioxidant enzymes, the level of GSH appears to be reduced, but this reduction was found not to be statistically significant (P > 0.05) when the DB group is compared with control. Pre-administration of the oil in the NS0.5+DB group caused a statistically significant (P < 0.05) increase in GSH level when compared with the DB group. Pre-administration of the oil in the NS1+DB group, however, did not cause a statistically significant (P > 0.05) difference in GSH level when compared with DB group. post-administration of NS in the DB + NS0.5 and the DB + NS1 groups also did not cause a statistically significant (P > 0.05) difference in GSH level when compared with DB group.
Table 2: Antioxidant levels across the groups

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Effect of pre-and post-administration of Nigella sativa oil on superoxide dismutase level

The level of SOD was not statistically different (P > 0.05) in the DB group compared to control. Pre-administration of the oil in the NS0.5 + DB and NS1 + DB groups caused a statistically significant (P < 0.01) increase in SOD level when compared with the DB group. In a similar manner, post-administration of the oil in the DB + NS0.5 and DB + NS1 groups caused a statistically significant (P < 0.01) increase in SOD level when compared with the DB group.

Effect of pre- and post-administration of Nigella sativa oil on catalase level

It appears that CAT level was reduced in the DB group compared to control. However, this reduction was found not to be statistically significant (P > 0.05). Pre-administration in the NS0.5 + DB group and post-administration in the DB + NS0.5 and DB + NS1 groups caused a significant increase (P < 0.01, P < 0.01, and P < 0.001, respectively) in the CAT level. CAT level was also found not to be significantly different (P > 0.05) in the NS1 + DB group compared to the DB group.

Effect of pre- and post-administration of Nigella sativa oil on malondialdehyde level

The level of MDA was significantly higher (P < 0.05) in the DB group compared to control. MDA level was significantly (P < 0.05) lower in the NS0.5 + DB and NS1 + DB groups (P < 0.01) compared to DB group. MDA level was also found to be markedly reduced in the DB + NS0.5 (P < 0.01) and DB + NS1 groups when compared with the DB group.


  Discussion Top


Even with the advancement in the management of DM, exploration for innovative agents continues since the existing synthetic agents have numerous limitations.[26] Even though NS oil has been shown to have a lot of beneficial effects; it is crucial to decide whether it should be used as a protective or corrective agent. This study is, thus, the first to compare the pre- and post-treatment effects in an animal model of DM.

Cholesterol level appeared to be high in the diabetes group, while neither pre-treatment nor post-treatment with the oil had a significant effect on the level. Increased serum total cholesterol concentrations are directly associated with an increased risk of coronary heart disease.[27] Both pre- and post-treatment with the oil slightly reduced the cholesterol level, and this effect may be due to de novo cholesterol synthesis inhibition or stimulation of excretion of bile acid. It is well known that both effects would lead to a decrease in serum cholesterol.[28],[29] The slight reduction could also be due to the presence of phytosterols such as beta-sitosterol, polyunsaturated fatty acids, and their antioxidant activity.[30],[31] These results further confirmed earlier reports that NS oil could be used as an adjunct therapy for glycemic control[28] either for prevention or correction of high glucose level.

The level of TG was observed to be significantly high in the DB group in this study. Elevated TG level is no doubt a risk factor[32] for atherosclerosis and this could be due to decreased clearance rate of TG.[33] It is worthy of note that post-treatment with the oil caused a significant reduction in the TG level, while the effect appears to be minimal when given before the induction. Kocyigit et al.[14] had demonstrated the hypolipidemic potential of the oil when used in diabetic rats, and our result further confirmed this earlier result and others.[15],[16]

Our results also showed the ability of the oil to cause a marked improvement in the level of HDL when used either before or after diabetes induction. This is a pointer to the ability of the oil to either prevent or correct the HDL level in diabetes. This observation is in line with the result of Kaatabi et al.[33] HDL is a key lipoprotein that helps remove lipids from macrophage foam cells in the arterial wall and thereby offer useful protection from LDL oxidation.[34] Surprisingly, the obvious reductions observed in the LDL in pre- and post-treated rats were found not to be statistically significant. In essence, there is no obvious mechanism to explain the antiatherogenic pattern of lipoprotein profile found in the present study following oil pre- or post-treatment. This could, however, mean the non-preference of pre-treatment over post-treatment and vice-versa. Our study also showed the ability of post-treatment to ameliorate the atherogenic index compared to the pre-treatment slightly. Based on the results of this study, neither pre-treatment nor post-treatment of the oil can, thus, be guaranteed as a treatment option usable to correct this cardiovascular risk factor.

Diabetes induction in this study caused a slight reduction in GSH and CAT levels. It also caused a slight increase in MDA level. Only pre-treatment caused a significant improvement in GSH level. Both pre-treatment and post-treatment with the oil caused a marked improvement in the level of SOD and CAT. It is interesting to know that both pre-treatment and post-treatment with the oil also caused a marked reduction in the level of MDA. In agreement with some of these observations, Omidi et al.[35] reported a significant improvement in antioxidant parameters in diabetic rats following NS oil administration. Also, Pencina et al.[36] reported a reduction in MDA following NS oil administration, and this was also the observation made by El Rabey et al.[37] It does mean that both pre- and post-treatment with NS oil have the potential to improve the antioxidant system and reduce lipid peroxidation, but the post-treatment appears to be more effective. Contrary to these observations, however, the dietary black seed had been shown not to significantly affect TAS, SOD, and GPX levels in hyperlipidemic rabbits.[38] This finding could, however, be attributed to the difference in the route of administration of the oil or species-specific cum genetic differences in the animals used.

Acknowledgment

The authors wish to thank Prof. I. A. Oreagba, Head of the Department of Pharmacology, Therapeutics and Toxicology of the College of Medicine of the University of Lagos, for his unwavering support. We gratefully thank Prof. S. O. Olayemi, former Head of the Department of Pharmacology, Therapeutics and Toxicology of the College of Medicine of the University of Lagos, for his useful comment and encouragements.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Schwartz SL. Diabetes and dyslipidaemia. Diabetes Obes Metab 2006;8:355-64.  Back to cited text no. 1
    
2.
Al-Assaf AH. Antihyperglycemic and antioxidant effect of ginger extract on streptozotocin-diabetic rats. Pakistan J Nutr 2012;11:1107-12.  Back to cited text no. 2
    
3.
Al-Malki AL, Sayed AA, El Rabey HA. Proanthocyanidin attenuation of oxidative stress and NF-κB protects apolipoprotein e-deficient mice against diabetic nephropathy. Evid Based Complementary Altern Med 2013;20:76940-9.  Back to cited text no. 3
    
4.
van Eupen MG, Schram MT, Colhoun HM, Hanssen NM, Niessen HW, Tarnow L, et al. The methylglyoxal-derived AGE tetrahydropyrimidine is increased in plasma of individuals with type 1 diabetes mellitus and in atherosclerotic lesions and is associated with sVCAM-1. Diabetologia 2013;56:1845-55.  Back to cited text no. 4
    
5.
Kumar A, Singh V. Atherogenic dyslipidemia and diabetes mellitus: what's new in the management arena? Vasc Health Risk Manag 2010;6:665-9.  Back to cited text no. 5
    
6.
Betteridge DJ. Lipid control in patients with diabetes mellitus. Nat Rev Cardiol 2011;8:278-90.  Back to cited text no. 6
    
7.
Yimer EM, Tuem KB, Karim A, Ur-Rehman N, Anwar N. NS L.(Black Cumin): A promising natural remedy for wide range of Illnesses. Evid-Based Complementary Altern Med 2019;6:1-16.  Back to cited text no. 7
    
8.
Kanter M, Meral I, Yener Z, Ozbek H, Demir H. Partial regeneration/proliferation of the beta-cells in the islets of Langerhans by NS L. in streptozotocin-induced diabetic rats. Tohoku J Exp Med 2003;201:213-19.  Back to cited text no. 8
    
9.
Hmza AJA, Osman MT, Adnan A, Omar A. Immunomodulatory effect of NS oil in the disease process of type 1 diabetic rats. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2013;4:980-88.  Back to cited text no. 9
    
10.
Kaatabi H, Bamosa AO, Lebda FM, Al Elq AH, Ali I. Al-Sultan AI. Favorable impact of Nigella sativa seeds on lipid profile in type 2 diabetic patients. J Family Community Med 2012;19:155-61.  Back to cited text no. 10
    
11.
Ahmad S, Beg ZH. Alleviation of plasma, erythrocyte and liver lipidemic-oxidative stress by thymoquinone and limonene in atherogenic suspension fed rats. J Funct Foods 2013;5:251-9.  Back to cited text no. 11
    
12.
Busari AA, Adejare AA, Shodipe AF, Oduniyi OA, Ismail-Badmus KB, Oreagba IA. Protective but non-synergistic effects of NS and Vitamin e against cisplatin-induced renal toxicity and oxidative stress in wistar rats. Drug Res 2018;68:1-8.  Back to cited text no. 12
    
13.
Hayes JD, Strange RC. Potential contribution of the glutathione S-transferase supergene family to resistance to oxidative stress. Free Radic Res 1995;22:193-207.  Back to cited text no. 13
    
14.
Kocyigit Y, Atamer Y, Uysal E. The effect of dietary supplementation of NS L. on serum lipid profile in rats. Saudi Med J 2009;30:893-6.  Back to cited text no. 14
    
15.
Nader MA, El-Agamy DS, Suddek GM. Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch Pharm Res 2010;33:637-43.  Back to cited text no. 15
    
16.
Ismail M, Al-Naqeep G, Chan KW. NS thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats. Free Radic Biol Med 2010;48:664-72.  Back to cited text no. 16
    
17.
Salama RH. Hypoglycemic effect of lipoic acid, carnitine and NS in Diabetic Rat Model. Int J Health Sci 2011;5:126-34.  Back to cited text no. 17
    
18.
Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ. Effects of NS and thymoquinone on biochemical and subcellular changes in pancreatic β-cells of streptozotocin-induced diabetic rats. J Diabetes 2010;2:256-66.  Back to cited text no. 18
    
19.
NIH Publication No. 85-23 guidelines (NIH, 1985).  Back to cited text no. 19
    
20.
Ibrahim SS. “Protective effect of hesperidin, a citrusbioflavonoid, on diabetes-induced brain damage in rats.” J Appl Sci Res 2008;4:84-95.  Back to cited text no. 20
    
21.
Morakinyo AO, Adekunbi DA, Dada KA, Adegoke OA. Testosterone promotes glucose intolerance, lipid disorder and oxidative stress in type 1 diabetic rats. J Basic Clin Physiol Pharmacol 2014;25:13-20.  Back to cited text no. 21
    
22.
Sun M, Zigman S. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Anal Biochem 1978;90:81-9.  Back to cited text no. 22
    
23.
van Doorn R, Leijdekkers CM, Henderson PT. Synergistic effects of phorone on the hepatotoxicity of bromobenzene and paracetamol in mice. Toxicology 1978;11:225-33.  Back to cited text no. 23
    
24.
Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121-6.  Back to cited text no. 24
    
25.
Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271-8.  Back to cited text no. 25
    
26.
Daryabeygi-Khotbehsara R, Golzarand M, Ghaffari MP, Djafarian K. “NS improves glucose homeostasis and serum lipids in type 2 diabetes: A systematic review and metaanalysis.” Complement The Med2017;35:6-3.  Back to cited text no. 26
    
27.
Navar-Boggan AM, Peterson ED, D'Agostino RB, Neely B, Sniderman AD, Pencina MJ. Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease. Circulation 2015;114:012477.  Back to cited text no. 27
    
28.
Najmi A, Nasiruddin M, Khan RA, Haque SF. Therapeutic effect of NS in patients of poor glycemic control. Asian J Pharm Clin Res 2012;5:224-8.  Back to cited text no. 28
    
29.
Beynen AC, Katan MB, Van Zutphen LF. Hypo- and hyperresponders: individual differences in the response of serum cholesterol concentration to changes in diet. Adv Lipid Res 1987;22:115-71.  Back to cited text no. 29
    
30.
De Jong A, Plat J, Mensink RP. Metabolic effects of plant sterols and stanols (Review). J Nutr Biochem 2003;14:362-369.  Back to cited text no. 30
    
31.
Sabzghabaee AM, Dianatkhah M, Sarrafzadegan N, Asgary S, Ghannadi A. Clinical Evaluation of NS Seeds for the Treatment of Hyperlipidemia: A randomized, placebo controlled clinical trial. Med Arh 2012;66:198-200.  Back to cited text no. 31
    
32.
Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol 1998;81:7B-12B.  Back to cited text no. 32
    
33.
Kaatabi H, Bamosa AO, Lebda FM, Al Elq AH, Ali I. Al-Sultan AI. Favorable impact of NS seeds on lipid profile in type 2 diabetic patients. J Family Community Med 2012;19:155-61.  Back to cited text no. 33
    
34.
Zhao J, Quan-Xin Y, Kong W, Hai-Cheng G, Sun B, Ya-Qin X, et al. The urotensin II receptor antagonist, urantide, protects against atherosclerosis in rats. Exp Ther Med 2013;5:1765-9.  Back to cited text no. 34
    
35.
Omidi H, Khorram S, Mesgari M, Asghari-Jafarabadi M, Tarighat-Esfanjani A. Effects of separate and concurrent supplementation of Nano-sized clinoptilolite and NS on oxidative stress, anti-oxidative parameters and body weig htin rats with type 2 diabetes. Biomed Pharmacother 2017;96:1335-40.  Back to cited text no. 35
    
36.
Pencina MJ, Navar-Boggan AM, D'Agostino RB Sr., Williams K, Neely B, Sniderman AD, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med 2014;370:1422-31.  Back to cited text no. 36
    
37.
El Rabey HA, Al-Seeni MN, Bakhashwain AS. The antidiabetic activity of NS and propolis on streptozotocin-induced diabetes and diabetic nephropathy in male rats. Evid-Based Complement Alternat Med 2017;2017:5439645.  Back to cited text no. 37
    
38.
Pourghassem-Gargari B, Ebrahimzadeh-Attary V, Rafraf M, Gorbani A. Effect of dietary supplementation with NS L. on serum lipid profile, lipid peroxidation and antioxidant defense system in hyperlipidemic rabbits. J Med Plants Res 2009;3:815-21.  Back to cited text no. 38
    


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