Accepted Manuscript

Title: Effects of Black Seed (Nigella Sativa) on Metabolic

Parameters in Diabetes Mellitus: A Systematic Review

Author: Javad Heshmati Nazli Namazi

PII: S0965-2299(15)00027-8
DOI: http://dx.doi.org/doi:10.1016/j.ctim.2015.01.013
Reference: YCTIM 1425

To appear in: Complementary Therapies in Medicine

Received date: 7-8-2014

Revised date: 22-1-2015
Accepted date: 30-1-2015

Please cite this article as: Heshmati J, Namazi N, Effects of Black Seed (Nigella Sativa)
on Metabolic Parameters in Diabetes Mellitus: A Systematic Review, Complementary
Therapies in Medicine (2015), http://dx.doi.org/10.1016/j.ctim.2015.01.013

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1 Highlights

2  Nigella sativa can improve glycemic status in diabetes models

3  Nigella sativa can improve lipid profiles in diabetes models

 Nigella sativa can be used as a complementary therapies in diabetes mellitus

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6 Effects of Black Seed (Nigella Sativa) on Metabolic Parameters in Diabetes Mellitus: A

7 Systematic Review

8 Javad Heshmati a, Nazli Namazi*b

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9 Health Care Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

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10 Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

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14 *Corresponding Author: Nutrition Research Center, Tabriz University of Medical
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15 Sciences, Tabriz, Iran; E-mail:nazli.namazi@yahoo.com

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23 Abstract

24 Background: Current evidence indicated beneficial effects of some medicinal herbs on

25 metabolic parameters. Nigella sativa is an example of herbs which can ameliorate

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26 metabolic factors in diabetes mellitus. Despite several narrative review studies on medicinal

27 properties of NS, it seems that there is no systematic review to summarize effects of NS on

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28 glucose homoeostasis and lipid profile in diabetes mellitus. Therefore, the aim of present

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29 study was to review effects of Nigella sativa on metabolic parameters in diabetes mellitus.

30 Methods: Pubmed, Science Direct, Google scholar and Springer databases were searched

31
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from 1995 till January 2014. Key words were included: Nigella Sativa, black Seed,
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32 diabetes, glucose level, lipid and Insulin. Searching was limited to articles with English

33 language. Review articles, case reports, abstract in symposium and congress, studies on
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34 Nigella sativa mixed with other plants were excluded. Based on critically appraise,
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35 eligibility of included articles were evaluated.

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36 Results: Finally 19 eligible articles (2 human trials, 14 animal models and 3 in vivo/in vitro
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37 studies) were selected. They indicated that Nigella sativa can modulate hyperglycemia and

38 lipid profile dysfunction with various potential mechanisms including its antioxidant
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39 characteristics and effects on insulin secretion, glucose absorption, gluconeogenesis and

40 gene expression. Some studies compared effects of various types (extract, oil, powdered) of

41 Nigella sativa with each other and they reported different characteristics with various types

42 of black seed.

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43 Conclusion: Nigella sativa can improve glycemic status and lipid profile in diabetes

44 models. However, more clinical trials are necessary to clarify beneficial effects of Nigella

45 sativa, its effective type and dosage for diabetes management and its complications.

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46 Introduction

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47 Diabetes mellitus (DM) is a global health concern characterized by impairment in insulin

48 secretion or insulin action. According to an International Diabetes Federation (IDF) report,

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49 the prevalence of diabetes was 171 million in 2001 and it is expected to increase to 366

50 million by 2030 (1). Following the metabolic dysfunction in DM, the risk of developing

51
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cardiovascular diseases, dyslipidemia, infection, morbidity and mortality can increase (2,
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52 3). For controlling diabetes, various treatments including diet, life style changes,

53 biochemical and herbal medicine in combine or alone have been used (4, 5). Many
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54 populations consume complementary and alternative medicine and there is high tendency to
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55 use medicinal herbs for diabetes treatment in worldwide (6). Due to side effects of some

56 chemical drugs and high tendency of people to consume medicinal herbs, World Health
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57 Organization (WHO) persuades researchers to study efficacy and side effects of herbs with
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58 potential therapeutic properties (7).

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59 Current evidence demonstrated beneficial effects of some medicinal herbs such as Urtica

60 dioica, Trigonella foenum, Silybum marianum and Nigella sativa (NS) for controlling

61 glucose level and lipid profile in diabetes models (8-10). NS or Black seed is one of the

62 medicinal plants with anti-hyperglycemia and anti-hyperlipidemia characteristics (11). It is

63 a plant of Ranunculaceae family which grows widely in many Middle Eastern countries. Its

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64 seed colored black and taste bitter (12). NS has many different chemical ingredients

65 including Thymocinon (TQ), essential fatty acids particularly linoleic and oleic acid, trans-

66 anethole, p-cymene, alpha pinene, limonene, and carvone. It is used in traditional medicine

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67 in different forms such as powder, oil and extract (12, 13). Previous studies indicated many

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68 medical characteristics of black seed including antimicrobial, anti-inflammatory and

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69 antioxidative effects (14, 15) . Also anti-diabetic effects of black seed have been reported

70 in several studies (16-18). Despite several narrative review studies on medicinal properties

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71 of NS, it seems that there is no systematic review to summarize glucose homoeostasis and

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72 lipid profile effects of NS in diabetes mellitus. Therefore, the aim of present study was to

73 evaluate effects of Nigella sativa on glycemic status and lipid profile in DM.
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74 Article selection
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75 We searched databases of Pubmed, Science Direct, Google scholar and Springer from 1995
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76 till January 2014. Key words were selected based on Mesh terms. They were included:

77 “Nigella sativa” or “black Seed” or “black cumin” and “diabetes”, “glucose level”, “lipid”,
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78 and “Insulin”. Also we hand searched references of articles. Two reviewers extracted data
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79 independently, and then titles and abstracts of each article were assessed to delete
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80 duplication data. Any irrelevant papers were excluded. The remaining articles were

81 reviewed to determine compatibility with the inclusion criteria. Searching was limited to

82 articles with English language. Review articles, case reports, abstract in symposium and

83 congress, articles about effects of NS mixed with other plants were excluded. After

84 critically appraise of articles, 19 articles were selected (Fig 1). Characteristic of studies

85 have been summarized in Table 1.

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86 Summary of studies and potential mechanisms

87 Studies were classified into three groups: human, animal and in vivo/in vitro studies.

88 1. Human studies

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89 Based on the criteria, two human studies were found (16, 17). Kaatabi et al evaluated

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90 different dosage of powdered NS (1, 2 and 3 gr/day) in patients with type 2 diabetes. They

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91 indicated that 1 g/day NS increased high-density lipoprotein cholesterol (HDL-c) levels

92 after 12 weeks. Two and 3g/day of black seed significantly decreased total cholesterol

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93 (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) levels and

94 increased HDL-C concentration. Increasing dosage from 2 to 3gr/day did not indicate
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95 higher improvement in lipid profile (16). Also Bamosa et al demostrated that only 2g/day

96 NS seed decreased fasting blood sugar (FBS), 2 hours postprandially glucose (2-hPG),
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97 glycosylated hemoglobin (HbA1c) and insulin resistance without any renal or hepatic side
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98 effects in patients with type 2 diabetes after 3 months (17).

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99 2. Animal studies
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100 Of 19 selected articles, 14 studies evaluated effects of NS in animal models. Meral et al

101 indicated that 20 ml/kg aqueous extract of NS orally decreased glucose level and
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102 improved antioxidant status in diabetic rabbits after two months (19). In Saleh Mansi et

103 al study, oral treatment with 20 ml/kg aqueous extract of NS elevated insulin levels in

104 diabetic rats after 15 days (15). It also affect glucose metabolism through the inhibition

105 of hypothalamus-pituitary-adernal axis. Based on Kaleem et al study, oral

106 administration of 300 mg/kg ethanol extract of NS decreased lipid peroxidation and

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107 antioxidant enzymes levels in diabetic rats after 30 days (20). In Houcher et al study,

108 intra peritoneal 810 mg/kg/day crude methanol extract and 2.5 ml/kg/day NS oil

109 decreased glucose and increased total antioxidant capacity (TAC) concentrations in

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110 diabetic rats after 25 days (21). Kanter et al demonstrated that 50 mg/kg thymoquinone

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111 orally in diabetic rats increased activities of mitochondria in leukocytes, energy

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112 metabolism and insulin levels after 20 days intervention (14, 22-24). Also Salama et al

113 concluded that oral treatment with 500 mg/kg NS oil in diabetic rat model decreased

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114 glucose level and increased insulin, C-peptide pyruvate dehydrogenase and TAC

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115 concentrations (25). Based on Alimohamadi et al study, only injection low dose

116 (5mg/kg) of hydroalcoholic extract of NS showed positive effects on regeneration of

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117 pancreatic beta cells, therefore in diabetic rats insulin secretion increased and FBS

118 levels decreased (26). Also Sultan et al reported that added 4% fixed oil and 0.3%
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119 essential oil of NS to the diet reduced glucose and Malondialdehyde (MDA) levels,
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120 improved lipid profile and enhanced body antioxidant capacity in diabetic rats. They
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121 reported that essential oils were more effective than fixed oils to reduce oxidative
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122 damages after 56 days in rats (18).

123 3. In vivo/In vitro studies

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124 According to the criteria, finally 4 in vivo/ in vitro studies were evaluated. They

125 indicated that NS can play anti-hyperglycemic roles and improve glucose metabolism

126 and lipid profile with various mechanisms. In Rchid et al trial, effects of subfractions of

127 NS with different dosages (0.01, 0.1, 1 and 5 mg/ml) on pancreatic cells of rats were

128 studied. They reported that stimulating effect of NS extract on insulin secretion is

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129 stronger in whole extract or basic subfractions, and acidic subfractions only indicated

130 stimulating effects in higher dosage (27). Meddah et al indicated that aqueous extract

131 of NS (0.1 pg/ml t0 100 ng/ml for in vitro) could inhibit glucose absorption directly and

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132 in vivo study showed that 2 g/kg aqueous extract of NS improved glucose tolerance in

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133 diabetic rats after 6 weeks. They compared NS effects with 300 mg/kg/day and no

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134 significant differences were observed between two groups (28). Based on Andaloussi et

135 al study, ethanol extract of NS can act as an agonist PPAR-gamma and induce insulin-

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136 like effects on skeletal muscle cells and adiposities (29). Also Abdelmeguid et al

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137 reported that single intraperitoneal of aqueous extract and NS oil act as a protective

138 factor against oxidative stress in vivo and in vitro studies and they decreased glucose
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139 levels in diabetic rats (13). Besides mentioned mechanisms, Alimohammadi et al

140 demonstrated that 20 mg/kg NS extract had no significant effects on glucose levels, but
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141 5 mg/kg of hydroalcoholic NS extract showed therapeutic effects on blood sugar in

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142 diabetic rats by ameliorating beta cells and increasing insulin secretion (26).
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143 In the present study, we reviewed effects of NS on glycemic status and lipid profile in DM.
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144 It seems only two studies evaluated effects of NS in patients with diabetes. But these two

145 clinical studies were open label trials without placebo-control group.
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146 Animal and in vivo/in vitro studies evaluated effects of various forms of NS (extract, oil,

147 powered) in diabetes models. Although, they indicated beneficial effects of NS on glycemic

148 status and lipid profile in diabetes models, but efficacy of NS on various indicators of

149 glycemic status and lipid profile were different. Differences in the chemical composition of

150 NS in different regions and preparation are related to the pharmacological activity.

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151 Potential mechanisms of ameliorating glycemic indices and lipid profile are discussed as

152 follow:

153 I. Antioxidant characteristics

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154 In most studies, possible anti-hyperglycemia and anti-hyperlipidemia effects of NS

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155 were attributed to its antioxidants components. TQ and dithymoquinone are the main

156 antioxidant components in NS (30). Black seed in all forms of usage, such as ingestion

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157 and injection can improve body antioxidant defense. Some studies indicated that NS

158 can elevate TAC and antioxidant enzymes and decrease lipid peroxidation (13, 18-21,

159
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25). Reduction in oxidative stress help to regeneration of pancreatic beta cells (22),
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160 preserving integrity of pancreatic beta-cells, increasing numbers of islets and their

161 diameters (26), reduction in insulin resistance (17), increasing in insulin secretion (15,
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162 26) ,(27) and inhibition of advanced glycation end product (31). Reduction in free
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163 radicals directly and indirectly can trigger lipid metabolism. Antioxidant components

164 can prevent lipid peroxidatinon and improve enzyme function which participates in
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165 lipid metabolism (32). Besides, glycemic improvement can modulate lipid dysfunction
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166 particularly in patients with diabetes (33).

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167 II. Insulin secretion: TQ and other antioxidant components of NS can increase insulin

168 secretion by improving energy metabolism in mitochondria and it can reduce

169 liver damages in diabetic rats. Also, NS can improve the intracellular pathways

170 of insulin receptors. It can participate in rising insulin concentration and

171 inhibition hypothalamus-pituitary adrenal axis (15).

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172 III. Gluconeogenesis: NS can decrease gluconeogenesis which contributes to

173 hyperglycemia in diabetes models (26), (13). TQ can decrease expression of

174 gluconeogenic enzymes (glucose-6-phosphtse and fructose 1,6 bisphosphatase)

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175 and hepatic glucose production (21).

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176 IV. Gene expression: It has been indicated that ethanol extract of NS is an agonist of

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177 PPAR-gamma gene and NS can increase PPAR-gamma activity more than 50%

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178 at dose of 200 μg/ml (29). Also, TQ can increase uptake of LDL-c by up-

179 regulation of hepatic receptors of LDL-c. It can inhibit 3-hydroxy-3-

180

181 synthesis of cholesterol (30). an

methylglutaryl- coenzyme A (HMG-CO-A) reductase gene and suppress
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182 V. Glucose absorption
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183 Meddah et al indicated that ingestion of aqueous extract of NS reduced glucose

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184 absorption in diabetic rats. It seems that NS can inhibit sodium-glucose co-transporter.
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185 Second potential mechanism may be suppressive effects of polyphenol ingredients on

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186 transporter of glucose absorption (28).

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VI. Reduction in body weight

188 Le et al indicated that a 4-week intragastric gavage with petroleum ether extract of NS
189 caused a 25% reduction in food intake. Also it improved lipid profile and insulin sensivity
190 in rats. They concluded that petroleum ether extract of NS has a slight anorexic effect
191 which cause reduction in food intake and body weight. Also it can activate Mitogen-
192 activated protein kinases (MAPK) and Protein kinase B (PKB) pathways which are
193 involved in insulin-sensitizing action (34). Also Kaleem et al reported that 300 mg/day

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194 ethanolic extract of NS decreased body weight in streptozocin-induced diabetic rats after 30
195 days (20). Based on Haque et al study, 5ml NS oil decreased body weight and body mass
196 index (BMI) after 6 weeks in subjects with metabolic syndrome (35). Based on Najmi et al
197 study, 500mg/day NS for 2 months decreased body weight in subjects with metabolic

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198 syndrome (36). Constituents of NS mainly TQ and lipase enzyme in NS can involve in anti-

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199 obesity effects of NS (37). Moreover, Bamosa et al indicated that NS can decrease insulin
200 resistance in subjects with T2DM. Reduction in insulin resistance can involve in faster

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201 losing weight (17). Losing weight can be a potential mechanism for improving glucose
202 status and lipid profile in DM. However, more studies are needed to clarify weight-

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203 lowering effects of NS in DM.

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204 Future prospects

205 Despite positive effects of NS on metabolic parameters in diabetes models, limited clinical
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206 trials with no placebo group evaluated anti-hyperglycemia and anti-hyperlipidemia effects

207 of NS. For future studies, double-blind placebo-controlled randomized clinical trials were
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208 suggested to evaluate NS on glucose homeostasis and lipid concentrations in DM.

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209 Conclusion
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210 Nigella Sativa can improve glucose homeostasis and lipid profiles in diabetes models with

211 various potential mechanisms. Modulation of metabolic parameters in DM can prevent

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212 diabetes complications including atherosclerosis and cardiovascular diseases. Therefore,

213 NS can be used as a complementary therapies in DM. But due to differences in models,

214 chemical compositions of difference sources of NS, dosage, and duration of intervention, it

215 is difficult to determine effective type and dosage of NS in diabetes management. More

216 studies are suggested to clarify effective type and dosage of NS in patients with diabetes.

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217

218 Conflict of Interest

219 Authors declared no conflict of interest

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220

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221 References

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222 [1]. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes
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224 [2]. Zoungas S, Chalmers J, Ninomiya T, Li Q, Cooper ME, Colagiuri S, et al.
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253 [14]. Kanter M, Akpolat M, Aktas C. Protective effects of the volatile oil of Nigella
254 sativa seeds on β-cell damage in streptozotocin-induced diabetic rats: a light and electron
255 microscopic study. J Molecular Histol 2009; 40(5-6):379-85.
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259 2005; 8(8):1152-56.

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260 [16]. Kaatabi H, Bamosa AO, Lebda FM, Al Elq AH, Al-Sultan AI. Favorable impact of
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266 [18]. Sultan MT, Butt MS, Karim R, Zia-Ul-Haq M, Batool R, Ahmad S, et al. Nigella
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271 Concentration, Lipid Peroxidation, Anti-Oxidant Defence System and Liver Damage in
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273 [20]. Kaleem M, Kirmani D, Asif M, Ahmed Q, Bano B. Biochemical effects of Nigella
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275 [21]. Houcher Z, Boudiaf K, Benboubetra M, Houche B. Effects of Methanolic Extract
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276 and Commercial Oil of Nigella sativa L. on Blood Glucose and Antioxidant Capacity in
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278 [22]. Kanter M. Effects of Nigella sativa and its major constituent, thymoquinone on
279 sciatic nerves in experimental diabetic neuropathy. Neurochem Res. 2008 Jan;33(1):87-96.
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281 [23]. Kanter M, Coskun O, Korkmaz A, Oter S. Effects of Nigella sativa on oxidative
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284 [24]. Kanter M, Meral I, Yener Z, Ozbek H, Demir H. Partial regeneration/proliferation
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286 diabetic rats. Tohoku J Exp Med 2003; 201 (4):213-9.

287 [25]. Salama RHM. Hypoglycemic effect of lipoic acid, carnitine and Nigella sativa in
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289 [26]. Alimohammadi S, Tavakoli M, Hobbenaghi R, Khadivar F, Javanbakht J, Akbari H.
290 Protective and antidiabetic effects of extract from Nigella sativa on blood glucose
291 concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study
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293 [27]. Rchid H, Chevassus H, Nmila R, Guiral C, Petit P, Chokaırid M, et al. Nigella
294 sativa seed extracts enhance glucose-induced insulin release from rat-isolated Langerhans
295 islets. Fundam Clin Pharmacol 2004; 18:525–9

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296 [28]. Meddah B, Ducroc R, El Abbes Faouzi M, Eto B, Mahraoui L, Benhaddou-

297 Andaloussi A, et al. Nigella sativa inhibits intestinal glucose absorption and improves
298 glucose tolerance in rats. J Ethnopharma 2009; 121(3):419-24.
299 [29]. Benhaddou‐Andaloussi A, Martineau L, Vallerand D, Haddad Y, Afshar A, Settaf
300 A, et al. Multiple molecular targets underlie the antidiabetic effect of Nigella sativa seed
301 extract in skeletal muscle, adipocyte and liver cells. Diabetes Obes Metab 2010; 12(2):148-

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303 [30]. Fararh KM, Ibrahim AK, Elsonosy YA. Thymoquinone enhances the activities of
304 enzymes related to energy metabolism in peripheral leukocytes of diabetic rats. Res Vet
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306 [31]. Jack N. Losso, Hiba A. Bawadi, Madhavi Chintalapati. Inhibition of the formation
307 of advanced glycation end products by thymoquinone. Food Chemistry 2011; 128:55-61.
[32]. Yin H, Xu L, Porter NA. Free radical lipid peroxidation: mechanisms and analysis.

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309 Chem Reviews 2011;111 (10):5944-72.
310 [33]. Kendall DM, Rubin CJ, Mohideen P, Ledeine J-M, Belder R, Gross J, et al.
311 Improvement of Glycemic Control, Triglycerides, and HDL Cholesterol Levels With

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312 Muraglitazar, a Dual Peroxisome Proliferator-Activated Receptor Activator, in Patients
313 With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy A double-
314 blind, randomized, pioglitazone-comparative study. Diabetes Care 2006; 29(5):1016-23.
315 [34]. Le P.M, Benhaddou-Andaloussi A, Elimadi A, Settaf A, Cherrah Y, Haddad P.S.
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316 The petroleum ether extracts of Nigella sativa seeds exert insulin sensitizing and lipid
317 lowering action in rats. J Ethnopharmacol 2004; 94(2-3): 251-259.
318 [35]. Haque S. F, Najmi M.N.A. Indigenous herbal product Nigella sativa proved
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319 effective as an anti-obesity therapy in metabolic syndrome. Int J Med Res 2011; 1(3), 173-
320 176.
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321 [36]. Najmi A, Haque S. F, Naseeruddin M, Khan R. A. Effect of Nigella Sativa oil on
322 various clinical and biochemical parameters of metabolic syndrome. Int J Dia Dev Ctries
323 2008; 16: 85-87.
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324 [37]. Akova A, Ustun G. Activity and adsorption of lipase from Nigella sativa seeds,
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325 Biotechnol Lett 2000; 22(5):355-359

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327
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329

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Fig 1: Trend of screening and choosing articles

Records identified through Additional records identified

Identification

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database searching through other sources

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(n =61) (n =6)

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Records after duplicates removed
(n =40)

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Screening

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Records screened Records excluded
(n = 29) (n = 11)
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Full-text articles excluded
Full-text articles assessed (n =10)
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for eligibility
Eligibility

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(n = 29)
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Included

Studies included in
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qualitative synthesis
(n = 19)

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Table 1- Summary table of Nigella sativa actions and its pharmacological effects.

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Author/date Subject Source Dosage Intervention Duration Results

Sultan et al, diabetic rats Malaysia 4.0% fixed oil Fixed and essential NS oil 56 days Hypoglycemic effects

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2014 ↑HDL-C level
0.3% essential oil
↑Total antioxidant capacity and glutathione

ed ↓MDA , TC, TG and LDL-c levels

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Alimohamma diabetic rats Iran 5, 10, and 20 Hydroalcholic NS extract 32 days 5mg/kg: ↓ FBS

di et al, 2013 mg/kg ↑ Insulin secretion

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↑Pancreatic islets, cells and their diameter

1 gr/day: - TC, LDL-C, TG; ↑HDL-C

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Kaatabi et al, diabetic man Saudi Arabia 1, 2 and 3 gr /day Powdered NS 12 wk

2012 & woman

2 gr/ day: ↓TC, TG and LDL-C; ↑ HDL

3 gr/ day: ↓ TC, TG and LDL-C; ↑HDL;

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Not more effective than 2gr/day

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Salama, et al, diabetic rats Saudi Arabia 500 mg/kg NS Oil 30 days ↓Glucose concentration

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2011 ↑ Insulin and C-peptide

↑ TAC

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Fararh et al, diabetic rats Egypt 50 mg/kg/day Thymoquinone 20 days ↓ Plasma glucose, TC, TG

2010
↑ Insulin concentration , malate

ed dehydrogenase in leukocytes
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Bamosa et al, Type 2 Saudi Arabia 1,2,3gr/day NS Seeds 3 months 2gr/day: ↓ FBS, HbA1C
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2010 diabetes ↓ 2 hPG

subjects ↓Insulin resistance

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↑ beta-cell function

Abdelmeguid diabetic rats Egypt 2mL⁄kg and 5% Aqueous extract and NS 30 days ↓ Serum glucose after 10 days

, et al, 2010 aqueous extract; oil ↑ Insulin concentration after 20 days

0.2 mL⁄ kg oil, 3 ↑ SOD level with extract and thymoquinone

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mg⁄mL

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thymoquinone

an
Meddah et rat jejunum Morocco In vitro: 0.1 Aqueous extract of NS 6 wk In vitro: Inhibition of glucose absorption and

al, 2009 pg/ml-100 ng/ml In vivo: glucose tolerance and body weight

M
improvement
In vivo: 2 gr/kg

Andaloussi et C2C12

al , 2009 skeletal
Morocco

ed - Ethanol extract of NS 18 hr ↑Glucose uptake in skeletal cells and

adiposities
pt
muscle cells
ce

and 3T3-L1

adiposities
Ac

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ip
cr
Kanter et diabetic rats Turkey 0.2 ml/kg/day Volatile oil of NS 30 days Partial regeneration/ proliferation of

us
al,2009, pancreatic beta-cells,

an
2008, 2005,
↓GSH, glucose level and serum nitric oxide
2003
↑Insulin level, SOD and Catalase levels

M
60 days

ed ↓Lipid peroxidation and GSH

pt
Houcher et diabetic rats Algeria 810mg/kg/day Methanol extract of NS 25days ↓ Glucose level

al, 2007
ce

NS Oil
2.5ml/kg/day ↑ TAC
Ac

Kaleem et al, wister rats India 300 mg/kg/day Ethanol extract of NS 30 days ↑ Catalase, SOD and insulin levels

2006
↓Lipid peroxidation, GPX and glutathione,

↓Body weight

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Mansi et Male rats Jordan 20 mL/kg Aqueous extract of NS 3wk ↑Insulin level

us
al,2006
↓ Adrenocorticotropic hormone (ACTH)

an
Saleh et al, diabetic rats Jordan 20 ml/ kg/day Aqueous extract of NS 15 days ↑Insulin level

2005

M
↓ Glucose level

Rchid, et al, Rat - 0.01, 0.1, 1 and 5 Whole, basic and acidic 30min Whole and basic extract: ↑insulin release

2004 pancreatic

cells
ed
mg/mL subfractions of NS
pt
Meral et al, Male rabbits Turkey 20 ml/kg Aqueous extract of NS 2 months ↑GSH and ceruloplasmin concentrations
ce

2001 ↓ MDA and glucose levels

Ac

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