Skip to main content
NCBI home page
Avicenna Journal of Phytomedicine logoLink to Avicenna Journal of Phytomedicine
. 2015 Jul-Aug;5(4):333–340.

The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats

Abbasali Abbasnezhad 1, Parichehr Hayatdavoudi 1, Saeed Niazmand 1,*, Maryam Mahmoudabady 2
PMCID: PMC4587602  PMID: 26445713

Abstract

Objective:

Oxidative stress plays an important role in the etiology of diabetic complications. Diabetes impairs hippocampus neurogenesis, synaptic plasticity, and learning. The aim of this study was to investigate the effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in STZ-induced diabetic rats' hippocampus.

Materials and Methods:

Diabetes induced by 60 mg/kg STZ, i.p, and the rats were divided into five experimental groups (n=8-10 in each group) including control (received 0.5 ml normal saline), untreated STZ-diabetic (received 0.5 ml normal saline), and treated rats received Nigella sativa extract (200 and 400 mg/kg) or metformin (300 mg/kg) by gavage for 42 days. Serum glucose concentration and body weight as well as hippocampus tissue malondialdehyde and thiol levels were determined by calorimetric assay.

Results:

Serum glucose level in the diabetic rats treated with 200 mg/kg Nigella sativa extract at the days 24 and 45 decreased in comparison to untreated diabetic group (p<0.05, p<0.01, respectively). Weight loss was significantly different between metformin and Nigella sativa extract at the dose of 200 and 400 mg/kg (p<0.05). Thiol content of hippocampus increased by 200 mg/kg Nigella sativa extract in comparison to untreated diabetic group (p<0.05). Malondialdehyde content of hippocampus reduced by Nigella sativa extract, 200 mg/kg (p<0.001), 400 mg/kg (p<0.05), and metformin (p<0.05) in comparison to the untreated diabetic group.

Conclusion:

The results of the present study showed that hydroalcoholic extract of the Nigella sativa decreased oxidative stress in hippocampus of the STZ-induced diabetic rats. Nigella sativa at the dose of 200 mg/kg was more effective to reduce oxidative stress in hippocampus of rats.

Key Words: Diabetes mellitus, Nigella sativa, Oxidative stress, Hippocampus, Rat

Introduction

Diabetes mellitus is a common metabolic illness that is accompanied by high blood glucose concentration as a result of the lack of insulin or the presence of insulin resistance in peripheral tissues or both (momin et al., 2013 ▶; Dalia and Hafez, 2013 ▶). the complications of diabetes are major health problems in developing and developed countries, (Dalia and Hafez, 2013 ▶). Cerebral complications of diabetes are primarily due to the direct effects of chronic hyperglycemia. The hippocampus is involved in learning and memory and is particularly vulnerable to alterations in cerebral glucose supply. Hippocampal neurogenesis, synaptic plasticity, and learning are impaired in the diabetic rats (Amin et al., 2013 ▶; Stranahan et al., 2008 ▶). Diabetes in rats leads to reorganization of hippocampal synapses and dendrites. Moreover, glucocorticoid reactivity is increased in response to stress (Magariños and McEwen, 2000 ▶). Furthermore, low corticosterone levels can prevent the impairment of learning and memory in diabetes (Stranahan et al., 2008 ▶). According to magnetic imaging resonance (MRI) studies, even in well- controlled diabetic patients the hippocampus is destroyed (Yin et al., 2013 ▶).

High blood glucose concentration induces oxidative stress (Capellini et al., 2010 ▶). Free radicals possess one or more unpaired electrons in their outer electronic orbits. ROS (reactive oxygen species) such as superoxide anion (O2−), hydroxyl radical (OH−), hydrogen peroxide (H2O2), and singlet oxygen (1O2) are highly reactive. Free radicals and ROS are produced in normal physiological processes (Leong et al., 2013 ▶). It is already known that oxidative stress occurs when there is an imbalance between ROS production and antioxidant defense system (Ceretta et al., 2012 ▶). Therefore, oxidative stress plays a key role in the etiology of the diabetes and its complications (Kanter et al., 2004).

Nigella sativa is a plant from the Ranunculaceae family (Ahmad et al., 2013 ▶). The seeds contain 36–38% fixed oils, 0.4–2.5% essential (volatile) oil, proteins, alkaloids, and saponins (Ali and Blunden, 2003 ▶). The Nigella sativa is well- known for its potent antioxidative effects (Leong et al., 2013 ▶), hence it can protect the brain from the oxidative stress following lipid peroxidation in transient global ischemia of the brain (Azzubaidi et al. 2012 ▶).

Moreover, Nigella sativa can prevent the impairment of spatial memory after scopolamine administration and reducing the AChE (acetylcholinesterase) activity as well as oxidative stress of the brain tissue in rats (Mohammadpour et al., 2013 ▶).

Therefore, the present study was designed to investigate the effects of a hydroalcoholic extract of the Nigella saliva seed on the oxidative stress due to the STZ-induced diabetes in the hippocampus of rats.

Materials and Methods

Plant material and preparation of the extract

The Nigella sativa seeds were purchased from a local herbal shop in Mashhad, Khorasan province, Iran and identified by botanists in the herbarium of the Ferdowsi University of Mashhad (voucher No. 176-2013-9). The seeds were powdered and soaked in 2 L of a hydroalcoholic solution (50% ethanol, 50% water) for 48 h at room temperature. The extraction solution was subsequently filtered and dried using an oven at 40 °C for 72 h. The dried extract was dissolved in the distilled water to obtain the doses of 200 and 400 mg/kg.

Chemicals and drugs

All chemicals were of analytical grade. Streptozotocin (STZ) was obtained from Sigma (Germany). Serum glucose concentrations were determined using Pars Azmun kits (Tehran, Iran) by a photometer

Animals and induction of diabetes

Male Wistar rats (250–280 g, 10 weeks old) were housed on a 12 h light-dark cycle, under constant temperature (22±1 oC) and free access to standard laboratory diet and drinking water. All experiments were performed under the license of the Ethics Committee of Mashhad University of Medical Sciences (MUMS) according to the standards of caring and using of the experimental animals.

To induce diabetes, streptozotocin (60 mg/kg, i.p.) was injected at a single dose . We confirmed the development of the diabetes by measuring the blood glucose levels in tail blood samples of the 12 h fasted.rats. The rats with the blood glucose level≥250 mg/dl were considered diabetic.

Experimental design

The rats were randomly assigned to six groups (n=8-10 in each group): control (C), diabetic (D), diabetic-metformin (DM), diabetic-extract (DE). The C and D groups received normal saline, DM group received metformin (300 mg/kg) and DE groups (DE-200 and DE-400) received the Nigella sativa seed extract (200 and 400 mg/kg) by a gavege tube for 6 weeks.

Preparation of rat hippocampus tissue

At the end of the experiment, the animals were anesthetized deeply with ether and euthanized by decapitation with a guillotine. The Hippocampus was rapidly dissected out on ice and stored at -80 °C. The hippocampus samples were homogenized in ice-cold KCl (150 mM) for determination of malondialdehyde (MDA) and thiol levels

Malondialdeyde ( MDA) assays

MDA level is an index of lipid peroxidation. MDA reacts with thiobarbituric acid (TBA) as a TBA reactive substance (TBARS) and produces a red complex.

Briefly, 1 ml of the homogenate was added to the 2 ml of a solution containing TBA/trichloroacetic acid (TCA) /hydrochloric acid) (HCL), and then it was boiled in a water bath for 40 minutes. The solution remained to reach to the room temperature, then it was centrifuged at 1000 g for 10 minutes. The absorbance of the supernatant was read at 535 nm (Sharma, 2006 ▶). The MDA concentration was calculated according to the following equation.

MDA concentration (M) = Absorbance / (1.56 × 105 cm-1 M-1)

The MDA levels are expressed per gram of tissue.

Thiol assays

DTNB (2,2'-dinitro-5,5'-dithiodibenzoic acid) reagent, which reacts with the SH group, was used to determine the total thiol groups. The produced yellow complex has a peak absorbance at 412 nm. Briefly, 50 μL of tissue homogenates was added to 1 ml Tris-EDTA) ethylene diaminetetraacetic acid) buffer (pH=8.6) and the absorbance was read at 412 nm against Tris-EDTA buffer alone (A1). Then, 20 µl of a 10 mM solution of DTNB was mixed with the solution and stored in the room temperature for 15 minutes and the absorbance was read again (A2). The absorbance of the DTNB reagent was also read as blank (B) (Sharma JB, 2006 ▶). The thiol levels were determined using a spectrophotometric method based on the use of Ellman’s reagent (DTNB solution) and the results were expressed per gram of tissue.

Total thiol concentration (mM) = (A2 – A1 – B) × 1.07) / 0.05 × 14.150)

Plasma glucose concentration

Serum fasting blood glucose concentrations were measured in four different time periods: before STZ injection, at the third day, 24 days after STZ injection (when the diabetes was confirmed), and at the sixth weeks (45th day).

Data analysis

The Results are expressed as mean±SEM. Statistical analyses were performed using the one-way ANOVA followed by the Tukey’s test, and statistical significance was defined as p<0.05.

Results

The serum glucose concentration increased in days 3, 24, and 45 in the D group compared to the C group (p<0.001), while it didn’t show significant difference between DM and D group in the same days. On the other hand, serum glucose concentration reduced at the days 24 and 45 in the DE-200 compared to the D group (p<0.05, p<0.01, respectively) (Table 1).

Table 1.

Effect of Nigella sativa seed extract on the average serum concentration of glucose (mg/dl) in the STZ-induced diabetic rats.

Group Day 0 Day 3 Day 24 Day 45
C 86.10±2.62 86.10±2.62 87.38±4.31 84.48±3.96
D 82±2.11 335.2±17.54*** 293.39±7.82*** 300.54±10.40***
DM 98.46±1.67 302.43±10.32*** 278.99±26.11*** 267.60±21.31***
DE-200 91.91±5.89 347.33±69*** 190.99±21.28*#× 168.75±24.32##×
DE-400 91.65±4.05 334.24±5.30*** 258.74±28.72*** 227.47±27.40*
Open in a new tab

Data are expressed as mean ± SEM. n=8 in the D group and n=10 in all other groups.

*

p<0.05

***

p<0.001 compared to C group.

#

p<0.01

##

p<0.001 compared with the D group.

×

p<0.05 comparison between DM and DE-200 groups. Statistical analyses were made using the one-way ANOVA followed by the Tukey’s test.

According to the present results, the weight was increased in the C group (p<0.001) and decreased in the D (p<0.01) and treated diabetic groups (p<0.05) compared to the day zero. Also, in the untreated and treated diabetic groups, the weight was reduced in the days 24 and 45 compared to the control group (p<0.001).But, there was not any significant difference between the untreated diabetic group and treated diabetic groups. However, within treatment groups, 400 mg/kg of the extract was the most effective dose in reducing the weight (p<0.05) (Figure 1).

Figure 1.

Figure 1

Open in a new tab

The effect of Nigella sativa extract on the prevention of weight loss in the STZ-induced diabetic rats. n=8 in D group and n=10 in all other groups. *** p<0.001 compared with C group after 24 days. ### p<0.001 compared with C group after 45 days. + p<0.05 comparison between DE-400 and DE-200 groups in 24 days. × p<0.05 comparison between DM and DE-400 groups after 24 days. Statistical analyses were made using the one-way ANOVA followed by the Tukey’s test

The results showed that the thiol content of hippocampus decreased in D group (p<0.001), DM group (p<0.01), and DE- 400 (p<0.001) compared to C group. Thiol concentration of hippocampus was significantly increased by Nigella sativa extract 200 mg/kg (p<0.05) in comparison to untreated diabetic group (Figure 2).

Figure 2.

Figure 2

Open in a new tab

The effect of Nigella sativa extract on the thiol concentration in the hippocampus of the STZ-induced diabetic rats. n=8 in the untreated diabetic group and n=10 in all other groups. ** p<0.01 and *** p<0.001 compared with C group. # p<0.01compared with D group. Statistical analyses were made using the one-way ANOVA followed by the Tukey’s test.

In D group (p<0.001) and group DE-400 (p<0.05), the malondialdehyde (MDA) content of the hippocampus increased in comparison to the C group. However, malondialdehyde was reduced in the groups of DE-200 (p<0.001), DE-400 (p<0.05), and DM (p<0.05) in comparison to the D group (Figure 3).

Figure 3.

Figure 3

Open in a new tab

The Effect of Nigella sativa extract on the malondialdehyde (MDA) level in the hippocampus of the STZ-induced diabetic rats. n=8 in the untreated diabetic group and n=10 in all other groups. * p<0.05 and *** p<0.001 compared with the C group. # p<0.01 and ### p<0.001 compared with the D group. + p<0.05 comparison between DE-400 and DE-200 groups. Statistical analyses were made using the one-way ANOVA followed by the Tukey’s test.

Discussion

In this study, the ethanolic extract of the Nigella Sativa, 200 mg/kg, was effective in reducing the blood glucose level after 24 days (p=0.025), and this reduction persisted and was even more pronounced (p=0.003) until the day 45 without affecting the weight.

It has been shown that hyperglycemia leads to elevated amount of the reactive oxygen species (ROS) (Maiese et al., 2007 ▶), and ROS plays a substantial role in the development of the diabetes mellitus and its complications (Maritim et al., 2003 ▶; Huber et al., 2006 ▶; Sani et al., 2012 ▶). Furthermore, hyperglycemia compromises the cerebral blood flow and brain glucose metabolism (Christopher et al., 2006 ▶).

Nigella Sativa has been reported to possess antidiabetic activity (Muhammad Tauseef Sultan et al., 2014 ▶). It has been reported that fixed, essential oil, methanolic extract, and commercial oil of Nigella Sativa stimulate the insulin secretion (Muhammad Tauseef Sultan et al., 2014 ▶; Houcher et al., 2007 ▶) as well as the hepatic alterations of the enzymes of the gluconeogenesis pathway (Houcher et al., 2007 ▶). Increasing of the insulin resistance in peripheral tissues (Samane, 2006 ▶), inhibition of glucose absorption in small intestine (Meddah, 2009 ▶), reduction of AGE (advanced glycation end-products) accumulation (Fararh, 2004 ▶), activation of the AMPK (AMP-activated protein kinase) pathway, and the increased expression of Muscle Glut4 (Benhaddou-Andaloussi, 2011 ▶) have also been demonstrated as mechanisms that Nigella sativa can reduce the blood glucose levels. Moreover, reduction of deteriorations of the pancreatic beta cell’s shape have been reported to occur as a result of the antioxidative properties of the Nigella Sativa management in STZ- diabetic rats (Ahmad et al, 2013 ▶).

So far, phenolic compounds especially flavonoids have been known to be responsible for antioxidative properties of the medicinal plants (Ramkissoon et al., 2013 ▶), and flavonoids have shown positive effects to decrease the blood glucose levels (Moradabadi et al., 2013 ▶). Nigella Sativa contains flavonoids (Al-okaily et al., 2012 ▶) and thymoquinone (TQ), the major effective component, (Alhebshi et al., 2013 ▶) that can restore the antioxidant levels to normal (Salem, 2005 ▶) and diminish blood glucose level (Badr G, 2011 ▶).

In this study, different doses of the hydroalcoholic extract of the Nigella Sativa significantly decreased the amount of MDA in the hippocampus of the diabetic group, although the dose of 200 mg/ kg was more potent than 400 mg/kg. Furthermore, the thiol content of the hippocampus showed significant increase only with 200 mg/kg of the extract. It was shown that AGE increased in diabetes and caused an oxidative stress (Goh, 2008 ▶). Since the dosage of 200 mg/kg of Nigella sativa extract had the most beneficial effects on reducing the blood glucose concentration, low levels of glucose AGE levels may explain the higher thiol content in the current study. It has been reported that oral Nigella Sativa oil increased MDA level in the cortex of rats in an experimental model of oxidative stress (Neveen and Iman, 2010 ▶). However, the hydroalcoholic extract of the Nigella Sativa has been reported to increase the thiol content and reduce the MDA level of the cortex in rats with memory impairment (Hosseini et al., 2014 ▶). In this study, it seems that hydroalcoholic extract of Nigella Sativa at the dose of 200 mg/kg restored antioxidative capacity in the hippocampus of STZ-induced diabetic rats. Therefore, the clinical studies in diabetic patients can be suggested for future investigations to reveal any potential benefit of Nigella Sativa seeds to prevent cerebral complications of diabetes mellitus, especially memory impairments.

Conclusion

The Nigella Sativa seeds extract showed antidiabetic and protective effects against the oxidative stress in the hippocampus of the STZ-induced diabetic rats.

Conflict of Interests

The authors declare that there is no conflict of interest regarding the publication of this paper.

Acknowledgment

The authors would like to thank the Research Affairs of Mashhad University of Medical Sciences for their financial support and Pharmacological Research Center of Medicinal Plants for preparation of the Nigella sativa seed extract.

References

  1. Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Kishore K. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013;3:337–352. doi: 10.1016/S2221-1691(13)60075-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alhebshi AH, Gotoh M, Suzuki I. Thymoquinone protects cultured rat primary neurons against amyloid b-induced neurotoxicity. Bioch emical and Biophysical Research Communications. 2013;433:362–7. doi: 10.1016/j.bbrc.2012.11.139. [DOI] [PubMed] [Google Scholar]
  3. Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res. 17:299–305. doi: 10.1002/ptr.1309. [DOI] [PubMed] [Google Scholar]
  4. Al-okaily BN, Mohammed RS, Al-mzain KA, Khudair KK. Effect of Flavonoids Extracted from Black Cumin (Nigella sativa) and Vitamin E in Ameliorating Hepatic Damage Induced by Sodium Nitrate in adult male rats. Proceeding of the Eleventh Veterinary Scientific Conference. 2012:172–181. [Google Scholar]
  5. Amin SN, Younan SM, Youssef MF, Rashed LA, Mohamady I. A histological and functional study on hippocampal formation of normal and diabetic rats. F1000Res. 2013;2:151. doi: 10.12688/f1000research.2-151.v1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Azzubaidi MS, Saxena AK, Talib NA, Ahmed QU, Dogarai BB. Protective effect of treatment with black cumin oil on spatial cognitive functions of rats that suffered global cerebrovascular hypoperfusion. Acta Neurobiol. 2012;72:154–165. doi: 10.55782/ane-2012-1888. [DOI] [PubMed] [Google Scholar]
  7. Badr G, Alwasel S, Ebaid H, Mohany M, Alhazza I. Perinatal supplementation with thymoquinone improves diabetic complications and T cell immune responses in rat offspring. Cellular immunology. 2011;267:133–140. doi: 10.1016/j.cellimm.2011.01.002. [DOI] [PubMed] [Google Scholar]
  8. Benhaddou-Andaloussi A, Martineau L Fau - Vuong T, Vuong T Fau - Meddah B, Meddah B Fau - Madiraju P, Madiraju P Fau - Settaf A, Settaf A Fau - Haddad PS, et al. The In Vivo Antidiabetic Activity of Nigella sativa Is Mediated through Activation of the AMPK. Pathway and Increased Muscle Glut4 Content. 2011;2011(2011) doi: 10.1155/2011/538671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Capellini VK, Baldo C F, Celotto A C, Batalhão ME, Cárnio EC, Rodrigues AJ, Evora PRB. Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats. Arq Bras Endocrinol Metab. 2010;54:530–9. doi: 10.1590/s0004-27302010000600004. [DOI] [PubMed] [Google Scholar]
  10. Ceretta LB, Reus GZ, Abelaira HM, Ribeiro KF, Zappellini G, Felisbino FF, Quevedo J. Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan-induced diabetic rats. Exp Diabetes Res. 2012;2012:302682. doi: 10.1155/2012/302682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Christopher M, Ryan MIF, Julie A, Rood , Alexander R, Cobitz Brian, R Waterhouse, Mark WJ. Strachan Improving Metabolic Control Leads to Better Working Memory in Adults With Type 2 Diabetes. Diabetes Care. 2006;29:345–51. doi: 10.2337/diacare.29.02.06.dc05-1626. [DOI] [PubMed] [Google Scholar]
  12. Dalia A, Hafez Effects of Nigella sativa Oil and Thymoquinone on Renal Oxidative Stress and Apoptosis Rate in Streptozotocin-Diabetic Rats. J Am Sci. 2013;9:3. [Google Scholar]
  13. Fararh K, Atoji Y, Shimizu Y, Shiina T, Nikami H, Takewaki T. Mechanisms of the hypoglycaemic and immunopotentiating effects of Nigella sativa L oil in streptozotocin-induced diabetic hamsters. Res Veter Sci. 2004;77:123–9. doi: 10.1016/j.rvsc.2004.03.002. [DOI] [PubMed] [Google Scholar]
  14. Ghosheh OA, Houdi AA, Crooks PA. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L) J Pharm Biomed Anal. 1999;19:757–762. doi: 10.1016/s0731-7085(98)00300-8. [DOI] [PubMed] [Google Scholar]
  15. Goh SY, Cooper ME. The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab. 2008;93:1143–52. doi: 10.1210/jc.2007-1817. [DOI] [PubMed] [Google Scholar]
  16. Hosseini M, Mohammadpour T, Karami R, Rajaei Z, Sadeghnia HR, Soukhtanloo M. Effects of the hydro-alcoholic extract of Nigella Sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism. Chin J Integr Med. 2014:1–7. doi: 10.1007/s11655-014-1742-5. [DOI] [PubMed] [Google Scholar]
  17. Houcher Z, Boudiaf K, Benboubetra M, & Houcher B. Effects of methanolic extract and commercial oil of Nigella sativa L on blood glucose and antioxidant capacity in alloxan-induced diabetic rats. Pteridines. 2007;18:8–18. [Google Scholar]
  18. Huber JD, VanGilder RL, Houser K A. Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats. Am J Physiol Heart Circ Physiol. 2006;291:2660–2668. doi: 10.1152/ajpheart.00489.2006. [DOI] [PubMed] [Google Scholar]
  19. Leong XF, Rais Mustafa M, Jaarin K. Nigella sativa and Its Protective Role in Oxidative Stress and Hypertension. Evid Based Complement Alternat Med. 2013;2013:120732. doi: 10.1155/2013/120732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Magariños AM, McEwen BS. Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. P NATL ACAD SCI . 2000;20:11056. doi: 10.1073/pnas.97.20.11056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Maiese K, Morhan SD, Chong ZZ. Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus. Curr Neurovasc Res. 2007;4:63. doi: 10.2174/156720207779940653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Maritim AC, Sanders RA, Watkins JB. Diabetes, Oxidative Stress, and Antioxidants: A Review. J Biochem Molecul Toxicol. 2003;17:24–38. doi: 10.1002/jbt.10058. [DOI] [PubMed] [Google Scholar]
  23. Meddah B, Ducroc R, El Abbes Faouzi M, Eto B, Mahraoui L, Benhaddou-Andaloussi A, et al. Nigella sativa inhibits intestinal glucose absorption and improves glucose tolerance in rats. J Ethnopharmacol. 2009;121:419–24. doi: 10.1016/j.jep.2008.10.040. [DOI] [PubMed] [Google Scholar]
  24. Mohammadpour T, Hosseini M, Karami R, Rajaei Z, Soukhtanloo M, Sadeghnia HR. Effect of Nigella sativa on spatial memory deficit and oxidative stress. Iran Jl Neurol. 2013;12:138. [Google Scholar]
  25. Momin M, Momin S, Kurhade S, Mohebkhan , Butte K. 2013. Res phyochem pharmacho. Niglla sativa: Blessed seed;3:78–84. [Google Scholar]
  26. Moradabadi L, Kouhsari SM, Sani MF. Hypoglycemic Effects of Three Medicinal Plants in Experimental Diabetes: Inhibition of Rat Intestinal α-glucosidase and Enhanced Pancreatic Insulin and Cardiac Glut-4 mRNAs Expression. Iran J Pharm Res. 2013;12:387. [PMC free article] [PubMed] [Google Scholar]
  27. Muhammad Tauseef Sultan, Masood Sadiq Butt, Roselina Karim MZia-Ul-Haq, Rizwana Batool, Shakeel Ahmad, Feo a VD. Nigella sativa Fixed and Essential Oil Supplementation Modulates Hyperglycemia and Allied Complications in Streptozotocin-Induced Diabetes Mellitus. Evid Base Compl Alter Med. 2014;2014:1–8. doi: 10.1155/2014/826380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Neveen AN, Iman MM. Evaluation of antioxidant effect of Nigella sativa oil on monosodium glutamate-induced oxidative stress in rat brain. J Am Sci. 2010;6:13–19. [Google Scholar]
  29. Ramkissoon J, Mahomoodally M, Ahmed N, Subratty A. Antioxidant and anti–glycation activities correlates with phenolic composition of tropical medicinal herbs. Asian Pac J Trop Dis. 2013;6:561–569. doi: 10.1016/S1995-7645(13)60097-8. [DOI] [PubMed] [Google Scholar]
  30. Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L seed. International immunopharmacology. 2005;5:1749–1770. doi: 10.1016/j.intimp.2005.06.008. [DOI] [PubMed] [Google Scholar]
  31. Samane S, Noel J Fau - Charrouf Z, Charrouf Z Fau - Amarouch H, Amarouch H Fau - Haddad PS, Haddad PS. Insulin-sensitizing and anti-proliferative effects of Argania spinosa seed extracts. 2006;3:317–27. doi: 10.1093/ecam/nel015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sani MF, Kouhsari SM, Moradabadi L. Effects of Three Medicinal Plants Extracts in Experimental Diabetes: Antioxidant Enzymes Activities and Plasma Lipids Profiles inComparison with Metformin. Iran J Pharm Res. 2012;11:897. [PMC free article] [PubMed] [Google Scholar]
  33. Sharma JB, Sharma A, Bahadur A, Vimala N, Satyam A, Mittal S. Oxidative stress markers and antioxidant levels in normal pregnancy and pre-eclampsia. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2006;94:23–7. doi: 10.1016/j.ijgo.2006.03.025. [DOI] [PubMed] [Google Scholar]
  34. Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, Mattson MP. Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci. 2008;113:309–317. doi: 10.1038/nn2055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yin QQ, Pei JJ, Xu S, Luo DZ, Dong SQ, Sun MH, You L, Sun ZJ, Liu XP. Pioglitazone improves cognitive function via increasing insulin sensitivity and strengthening antioxidant defense system in fructose-drinking insulin resistance rats. 2013 doi: 10.1371/journal.pone.0059313. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Avicenna Journal of Phytomedicine are provided here courtesy of Mashhad University of Medical Sciences

RESOURCES