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Black Cumin (Nigella sativa), which belongs to the botanical family of Ranunculaceae, commonly grows in Eastern Europe, the Middle East, and Western Asia. Its ripe fruit contains tiny black seeds, known as “Al-Habba Al-Sauda” and “Al-Habba Al-Barakah” in Arabic and black seed or black cumin in English. Seeds of Nigella sativa are frequently used in folk medicine in the Middle East and some Asian countries for the promotion of good health and the treatment of many ailments. However, data for the cardiovascular benefits of black cumin are not well-established. We reviewed the literature from 1960 to March 2012 by using the following key words: “Nigella sativa,” “black seeds,” and “thymoquinone.” Herein, we discussed the most relevant articles to find out the role of Nigella sativa in the cardiovascular diseases spectrum especially when there is a paucity of information and need of further studies in human to establish the utility of Nigella sativa in cardiovascular system protection.
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REVISED PROOF
1
2
3Cardiovascular Benefits of Black Cumin (Nigella sativa)
4Adel Shabana Ayman El-Menyar
5Mohammad Asim Hiba Al-Azzeh
6Hassan Al Thani
7
8ÓSpringer Science+Business Media, LLC 2012
9Abstract Black Cumin (Nigella sativa), which belongs to
10 the botanical family of Ranunculaceae, commonly grows
11 in Eastern Europe, the Middle East, and Western Asia. Its
12 ripe fruit contains tiny black seeds, known as ‘‘Al-Habba
13 Al-Sauda’’ and ‘‘Al-Habba Al-Barakah’’ in Arabic and
14 black seed or black cumin in English. Seeds of Nigella
15 sativa are frequently used in folk medicine in the Middle
16 East and some Asian countries for the promotion of good
17 health and the treatment of many ailments. However, data
18 for the cardiovascular benefits of black cumin are not well-
19 established. We reviewed the literature from 1960 to March
20 2012 by using the following key words: ‘Nigella sativa,’’
21 ‘‘ black seeds,’’ a n d ‘‘ thymoquinone.’ Herein, we discussed
22 the most relevant articles to find out the role of Nigella
23 sativa in the cardiovascular diseases spectrum especially
24 when there is a paucity of information and need of further
25
studies in human to establish the utility of Nigella sativa in
26
cardiovascular system protection.
27
28
Keywords Nigella sativa Black seeds Thymoquinone 29
Cardiovascular Cumin
30
Introduction
31
Complementary and alternative medicine has become
32
popular worldwide over the past 20 years [1]. The seeds of
33
Black cumin (Nigella sativa) were among the accompa-
34
nying articles found in the tomb of Egyptian Pharaoh
35
Tutankhamen [2]. Thus, Nigella sativa (NS) probably had
36
an important role in the practices of the ancient Egyptians
37
[3], who described it as a panacea (cure for problems and
38
diseases). The historical references to these seeds are also
39
present in some of the oldest religious and medical texts.
40
For example, Hippocrates and Dioscorides referred them as
41
‘Melanthion’’ and were identified and described by Lin-
42
naeus in 1753 [4]. The Bible describes black seed as the
43
‘curative black cumin’’ (Isaiah 28:25, 27 NKJV) [4]. Seeds
44
of NS are the common drug used in islamic prophet’s
45
medicine, since prophet Muhammad (PBUH) stated that it
46
is the remedy for every disease except death (Sahih Buk-
47
hari 7:591) [5]. It is stated that he himself [PBUH] used to
48
take these seeds with honey syrup for therapeutic purpose
49
[6]. Ibni Sina, known in the West as Avicenna, also
50
referred NS as the seed ‘‘that stimulates the body’s energy
51
and helps recovery from fatigue’’ in his great book ‘‘The
52
Canon of Medicine’’ [7].
53
NS is widely used as a medicinal herb, not to be mis-
54
taken with common cumin seed (Cuminum cyminum) that
55
belong to the botanical family Umbelliferae [4]. NS is a
56
spice that grows in the Middle Eastern region and in
A1 A. Shabana
A2 Deparment of Cardiology, Hamad Medical Corporation, Doha,
A3 Qatar
A4 A. Shabana A. El-Menyar (&)
A5 Department of Clinical Medicine, Weill Cornell Medical School,
A6 PO Box 24144, Doha, Qatar
A7 e-mail: aymanco65@yahoo.com
A8 A. El-Menyar M. Asim
A9 Clinical Research, Trauma section, Hamad Medical Corporation,
A10 Hamad General Hospital, PO Box 3050, Doha, Qatar
A11 H. Al-Azzeh
A12 Al-Ghad Technology for Food Additives [MVM(Path)],
A13 Amman, Jordan
A14 H. Al Thani
A15 Department of Vascular Surgery, Hamad Medical Corporation,
A16 Doha, Qatar
Cardiovasc Toxicol
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57 Western Asian countries including India, Pakistan, and
58 Afghanistan. It is known by different names. For example,
59 in Arabic it is termed as ‘‘Habbah Sawda’’ [black seed] or
60 ‘Habbat el Baraka’’ (Seeds of blessing). In India, it is
61 called ‘‘Kalonji,’’ while in China it is known as ‘‘Hak Jung
62 Chou’’ [8]. The plant belongs to the Ranunculaceae family
63 of flowering plants, including multiple species, among
64 which NS is the most extensively investigated for thera-
65 peutic purposes [8]. Figure 1shows NS plant, flowers, and
66 seeds.
67 During the last two decades, most of the studies dealt
68 with the volatile oil of the seeds and its major constituents
69 (i.e., the two purified components of NS seed, thymoqui-
70 none and dithymoquinone). These studies revealed a mul-
71 tirange of actions that covered almost all known diseases of
72 the human body systems [9].
73 Traditional Uses
74 Traditionally, the seeds and oil were used in several diseases.
75 The seeds are used as a pungent, carminative, emmenagogue ,
76 galactagogue, aromatic, stimulant, appetizer, diuretic, anthel-
77 mintic, digestive, febrifuge, expectorant, abortifacient, and
78
diaphoretic. They were also used in ascites, cough, jaundice,
79
fever, piles, anorexia, dyspepsia, flatulence, dysentery,
80
diarrhea, and amenorrhea and in the treatment of worms and
81
skin eruptions [4,9,10].
82
Commonly, the seeds were used as a spice and food
83
preservative. In folk medicinal practices, they are ingested
84
with food or mixed with honey [4]. Several beneficial
85
pharmacological effects have been attributed to various
86
crude or purified components of these seeds including
87
antihistaminic, antihypertensive, hypoglycemic, antifungal,
88
anti-inflammatory, and immunity booster along with sig-
89
nificant antineoplastic activities [1116]. These studies
90
collectively provide early indication that further develop-
91
ment of agents derived from NS seeds could be useful in
92
modern medicine [4].
93
The Chemical Composition of the Seeds and Oil
94
The chemical composition of the NS seed is diverse and
95
contains amino acids, carbohydrates, fixed and volatile oils,
96
alkaloids, saponins, and many other compounds [4,9,17].
97
The chemical analysis of NS total oil showed the presence
98
of both fixed and volatile oil. The major component was
Fig. 1 Nigella sativa whole plant, flower, and seeds
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99 the fixed oil, whereas the volatile oil ranged from 0.4 to
100 0.7 % of the seeds’ weight. The chemical composition of
101 black seed fixed oil includes mixture of oils such as lino-
102 leic, oleic, linolenic, arachidic, palmitoleic, eicosadienoic,
103 palmitic, stearic and myristic acid [9,18].
104 Specific chemical analyses of the volatile oil started
105 around 50 years ago and were complemented by most
106 recent reports, using different chromatography techniques
107 for separating components of the oil samples. They showed
108 the presence of many components, including thymoqui-
109 none [the major active principle of NS and constitutes
110 about 30 % of its volatile oil or ether extract], carvacrol,
111 tanethole, and 4-terpineol, and all of them have demon-
112 strated respectable radical scavenging activity. The oil
113 samples showed variable antioxidant activity that was
114 attributed mainly to the variable composition of these
115 constituents [4,1921].
116 Since last four decades, various researchers have
117 investigated the pharmacological actions of the whole
118 seeds of NS (crushed powder or an extract) worldwide. The
119 aqueous, ethanolic, methanolic, petroleum ether, hexane,
120 and ethereal extracts were studied mainly in animals, and
121 to a lesser extent in humans. The most widely studied
122 component of black seed is the volatile oil and its con-
123 stituent thymoquinone [9,17].
124 Cardiovascular Effects of NS
125 The Effect of NS on Diabetes Mellitus and Metabolic
126 Syndrome
127 The hypoglycemic and antidiabetic effects of NS have been
128 reported in several in vitro and in vivo studies (animal
129 studies) but few have been performed on humans [2224].
130 Both pancreatic and extra-pancreatic mechanisms have
131 been proposed for such effects.
132 Animal models for type I diabetes have been mainly
133 induced by streptozotocin injection (with or without nico-
134 tinamide) or by cadmium treatment. The mechanisms
135 underlying the hypoglycemic effect of NS and its compo-
136 nents have been suggested to be mainly due to the pres-
137 ervation of beta cell integrity in the islets of Langerhans
138 with partial regeneration/proliferation of beta cells leading
139 to increased insulin levels [2528]. However, in other
140 studies, the hypoglycemic effects were not paralleled by
141 stimulation of insulin release, suggesting extra-pancreatic
142 actions of NS [29]. This was also supported by evidence of
143 a decrease in hepatic gluconeogenesis in another study
144 [30]. In addition to hypoglycemic effects, NS oil and thy-
145 moquinone have been found beneficial in correcting
146 experimental diabetic neuropathy, which makes it a pos-
147 sible potential therapeutic agent for neuropathy [31,32].
148
The benefit of NS has been validated in type II diabetes
149
in animal models as well as human subjects. Multiple
150
molecular targets and several mechanisms of action have
151
been suggested to explain such benefit. In animal studies,
152
NS was found to inhibit intestinal glucose absorption in
153
vitro and in vivo, stimulate insulin release from pancreatic
154
islets, and exert an insulin-sensitizing actions in skeletal
155
muscles, adipocytes, and liver cells through the activation
156
of AMPK (adenosine monophosphate-activated protein
157
kinase) pathway, as well as PPARc(peroxisome prolifer-
158
ator-activated receptor gamma), and increasing muscle
159
GLUT4 (glucose transporter 4) content [24,3336].
160
Few human studies have been published in the literature
161
assessing the effect of NS on glycemic control in patients
162
with type II diabetes mellitus as well as patients with
163
insulin resistance syndrome [23,37]. Bamosa and
164
coworkers administrated NS seeds to diabetic patients for
165
3 months and assessed their glycemic control. They found
166
that NS in a dose of 2 g/day could be a beneficial adjuvant
167
to oral hypoglycemic agents in these patients [23]. Qidwai
168
et al. [38] have also found favorable effect of NS seeds on
169
blood sugar and serum lipids in adults, but results were not
170
statistically significant.
171
Najmi et al. carried out a prospective study on 60 met-
172
abolic syndrome patients. The patients were divided into
173
two groups of 30 each. All patients were advised fixed
174
doses of statin and metformin tablets for a period of
175
6 weeks. In the second group, NS oil of 2.5 ml twice daily
176
was added for a period of 6 weeks. Fasting and postpran-
177
dial blood glucose, fasting lipid profile, and waist cir-
178
cumference were recorded before the therapy and after the
179
completion of the therapy. The results showed that the
180
second group had significant improvement in levels of
181
fasting blood sugar as well as total cholesterol and low-
182
density lipoprotein cholesterol (LDL-C). In summary, NS
183
therapy may prove to be promising in the prevention and
184
treatment of the insulin resistance syndrome [37].
185
Effect of NS on Lipid Profile
186
Several studies have reported favorable effects of NS on
187
lipid profile.
188
In cholesterol-fed animals, thymoquinone significantly
189
induced a reduction in total cholesterol, LDL-C, triglyc-
190
eride [TG], and thiobarbituric acid-reactive substances’
191
concentrations, with increase in high-density lipoprotein
192
cholesterol [HDL-C] levels [39]. Similar findings were
193
observed using NS powder and oil in other studies [35,
194
4042]. Zaoui et al. [42] found that oral treatment with NS
195
oil decreased serum cholesterol and TG levels in normal
196
rats by 15.5 and 22 %, respectively.
197
Also, oral administration of powdered black seeds to
198
hypercholesterolemic patients at the dose of one gram daily
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199 for 2 months significantly reduced the total cholesterol,
200 TG, and LDL-C levels and increased the HDL-C level [43].
201 Bamosa et al. [44] reported decreased levels of glucose
202 and cholesterol in healthcare professionals treated with 2
203 gram of NS capsules twice daily. In a recent study by
204 Tasawar et al. 8 subjects were divided into two groups
205 through random stratification. One group was given NS and
206 statin, while the second group was given only statin daily.
207 Fasting blood samples were taken before and after 2 and
208 6 month’s treatment. In the first group, total cholesterol,
209 LDL-C, and triglycerides decreased significantly after the
210 treatment by 14.58, 23, and 15.16 %, respectively. Also,
211 there was significant increase in HDL-C (by 3.18 %) after
212 6 months, compared to the second group. This study
213 showed that NS is helpful in normalization of the lipid
214 profile and in turn prevents cardiovascular disorders [45].
215 Moreover, Dehkordi and Kamkhah [46] observed a
216 significant reduction in serum total cholesterol and LDL-C
217 in patients with mild hypertension after 8 weeks of black
218 seed extract oral administration.
219 The hypolipidemic effect of NS does not seem to be due
220 to one component only, but rather to the synergistic action
221 of its different components, including thymoquinone,
222 sterols, flavonoids, and the high content of polyunsaturated
223 fatty acids [17]. Several mechanisms have been postulated
224 to explain this hypolipidemic effect, which includes inhi-
225 bition of de novo cholesterol synthesis or stimulates bile
226
acid excretion. It is well known that both actions reduce
227
serum cholesterol levels [44,47]. Another mechanism
228
depends on NS antioxidant role affecting nonenzymatic
229
lipid peroxidation [22,48].
230
Antiatherogenic Effects of NS
231
Al-Naqeep et al. studied the effect of black seeds powder
232
and oil on atherosclerosis in diet-induced hypercholester-
233
olemic rabbits in comparison with statin. Figure 2shows
234
the antiatherogenic potential of NS seed as well as oil in
235
rabbits. The investigators broadly divided the study animals
236
into two groups: the first group with normal diet and the
237
second group with cholesterol-supplemented diet. The
238
second group was further subdivided into three groups, that
239
is, (a) no treatment, (b) administration of NS seed/oil, and
240
(c) administration of hypocholesterolemic agent (simva-
241
statin). They found that feeding rabbits with NS either
242
(powder or oil) significantly improve lipid profile after 2, 4,
243
6, and 8 weeks compared with the control group. Exami-
244
nation of aortic intima at the end of the 8th week showed
245
significant inhibition of plaque formation. Furthermore, the
246
intima : media ratio was significantly decreased in the NS
247
supplemented groups compared with the control group [40].
248
Nader and colleagues, in another study, found similar
249
beneficial effects of thymoquinone on lipid profile of
250
cholesterol-fed rabbits, with histopathological evidence of
Fig. 2 The antiatherogenic potential of Nigella sativa seeds and oil (modified from ref. [40]: Al-Naqeep et al.: (2011) Evidence-Based
Complementary and Alternative Medicine), Hindawi publishing Corporation
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251 protection against hypercholesterolemia-induced aortic
252 tissue damage [39].
253 In addition to its beneficial actions on atherosclerosis
254 (through modulating major risk factors as diabetes melli-
255 tus and dyslipidemia), NS has been investigated for its
256 effect on the progression of monocyte-derived macro-
257 phage growth [49]. Such macrophages have been shown to
258 uptake oxidized LDL, becoming foam cells in the blood
259 vessel wall, accelerating the local inflammatory response
260 that eventually leads to atherosclerotic plaque formation
261 [50]. Mat et al. isolated primary human monocytes from
262 whole blood and treated them with NS oil. The finding of
263 this study provided preliminary support on regulation of
264 cell growth and differentiation in monocyte and mono-
265 cyte-derived macrophages by NS oil. NS was found to
266 exert its effects via decreasing the productions of pro-
267 inflammatory mediators secreted by primary macrophage
268 [49].
269 Effect of NS on Endothelial Dysfunction
270 Endothelial dysfunction is a pathological condition that
271 contributes to the pathogenesis of several cardiovascular
272 diseases and has been found in patients with dyslipidemia,
273 hypertension, diabetes mellitus, obesity, atherosclerosis,
274 and aging as well. All such conditions are associated with
275 overproduction of reactive oxygen species in the arterial
276 vessel wall [51,52]. A recent data, mainly targeting aging-
277 related endothelial dysfunction, demonstrated that thymo-
278 quinone improved endothelial function at least in part,
279 through inhibition of oxidative stress and normalization of
280 the angiotensin system [52].
281 Antiplatelet Effects of NS
282 The methanol-soluble portion of oil prepared by com-
283 pressing NS seeds has been used by Enomoto et al. and
284 discovered to have strong inhibitory effects on arachidonic
285 acid-induced platelet aggregation. Some isolated com-
286 pounds from the oil had stronger potency than aspirin [53].
287 Effect of NS on Heart Rate and Blood Pressure
288 Controversial findings have been reported regarding car-
289 diovascular actions of NS or its active ingredients. Some
290 studies reported no effect on blood pressure levels in ani-
291 mals or humans, whereas others showed a dose-dependent
292 decrease in the arterial blood pressure and heart rate in
293 normal or spontaneously hypertensive rats [12,54,55].
294 El-Tahir et al. [55] suggested that such cardiovascular
295 depressant effects were mediated mainly centrally via
296 indirect and direct mechanisms that involved both
297 5-hydroxytryptaminergic and muscarinic mechanisms.
298
NS was also effective in decreasing the elevated heart
299
rate in cadmium-treated rats [26]. Khattab and Nagi [56]
300
studied the effects of thymoquinone in rats after chronic
301
inhibition of nitric oxide synthesis with N[omega]-nitro-
302
L-arginine methyl esters [L-NAME] and concluded that
303
thymoquinone is effective in protecting rats against
304
L-NAME-induced hypertension and renal damage, possibly
305
via antioxidant activity.
306
One of the few studies in the literature conducted on
307
humans showed that NS extract administration for
308
2 months to patients with mild hypertension reduced both
309
systolic and diastolic blood pressures in a dose-dependent
310
manner [46]. Favorable effects of the seeds on blood
311
pressure have also been reported in another human study
312
by Qidwai et al. [38].
313
Effect on Cardiac Mass and Contractility
314
El-Bahai et al. reported evidence of physiological
315
improvement and beneficial cardiac hypertrophy in rats
316
provoked by long-term NS supplementation. NS supple-
317
mentation induced moderate overall cardiac hypertrophy.
318
The isolated perfused hearts of NS-treated rats showed
319
enhanced levels of baseline peak tension [57]. Further-
320
more, the supplementation of NS demonstrated encourag-
321
ing resulted on intrinsic cardiac contractile properties
322
without evidence of increased cardiac work load or energy
323
consumption in vivo [58].
324
Other studies showed the effects of NS (aqueous and
325
macerated extracts) on heart rate and contractility of the
326
isolated heart in guinea pigs. The results showed a potent
327
inhibitory effect of both extracts on heart rate and con-
328
tractility that was comparable or even higher than that of
329
diltiazem. It may be either due to calcium channel inhibi-
330
tory action or an opening effect on potassium channels of
331
the isolated heart [59,60].
332
Cardioprotective Effects of NS Against Chemical
333
Toxicity
334
Cyclosporine A is the most frequently used agent in
335
transplant surgery and in the treatment of autoimmune
336
diseases. However, the drug has multiple adverse effects
337
including hypertension, cardiotoxicity, and vascular endo-
338
thelial dysfunction [61,62]. Ebru et al. [63] studied the
339
effects of NS oil on cyclosporine A-induced cardiomyop-
340
athy and showed that pretreatment with NS oil decreased
341
the subsequent cyclosporine A injury in rat heart, with
342
normalized cardiac histopathology, decreased lipid perox-
343
idation, improvement in antioxidant enzyme status and
344
cellular protein oxidation.
345
Cyclophosphamide is another chemotherapeutic agent
346
with known cardiotoxic effects. Nagi et al. examined the
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347 possible protective effects of thymoquinone against
348 cyclophosphamide-induced cardiotoxicity in rats. Interest-
349 ingly, thymoquinone supplementation resulted in a com-
350 plete reversal of all the biochemical changes (in blood and
351 in heart tissues) induced by cyclophosphamide to their
352 normal values. Results of this study suggest that beneficial
353 effects of thymoquinone are attributed to its antioxidant
354 properties as well as its ability to improve the mitochon-
355 drial function and energy production in heart tissues [64].
356 Doxorubicin is a mainstay of cancer chemotherapy
357 despite its clinical limitations that arise from its cardio-
358 toxicity and the high incidence of multidrug resistance.
359 Recent studies revealed a protective effect of thymoqui-
360 none against doxorubicin-induced cardiotoxicity [6567].
361 The superoxide scavenging and antilipid peroxidation may
362 explain such effect [67].
363 Cardioprotective Effect of NS Against
364 Hyperhomocysteinemia (HHcy)
365 HHcy is associated with higher risks of coronary, periph-
366 eral, and cerebral artery disease through the induction of a
367 pathogenic state of oxidative stress. El-Saleh et al. dem-
368 onstrated that under the state of induced HHcy in rats, there
369 were significant increases in the plasma levels of triglyc-
370 erides, lipid peroxidation, and cholesterol and in the
371 activities of glutathione peroxidase and superoxide dis-
372 mutase with a significant depression of the total antioxidant
373 status. All of these effects were almost totally blocked by
374 prior treatment with thymoquinone or black seed oil [68].
375 In summary, the beneficial effects of NS, either seeds or
376 its purified constituent, could be contributed to their cyto-
377 protective and antioxidant actions and to their effect on
378 some mediators of inflammation [17]. Table 1shows the
379 experimental and clinical data for the effect of NS on the
380 cardiovascular system. Table 2summarizes the mechanism
381 of actions of NS on the heart.
382 Main Noncardiac Pharmacological Activities of NS
383 Antioxidant Activity
384 Thymoquinone and NS seed extracts have been shown to
385 demonstrate antioxidant property through different mecha-
386 nisms in several recent reports [74,75]. Thymoquinone
387 could act as a free radical and superoxide radical scavenger.
388 In addition, it preserves the activity of various antioxidant
389 enzymes such as catalase, glutathione peroxidase, and glu-
390 tathione-S-transferase [74]. It has been shown that thymo-
391 quinone could inhibit iron-dependent microsomal lipid
392 peroxidation successfully in rats with doxorubicin-induced
393 hyperlipidemic nephropathy [65,76]. Sayed-Ahmed and
394
Nagi have investigated the probable protective effects of
395
thymoquinone against gentamicin-induced nephrotoxicity.
396
Supplementation with thymoquinone resulted in significant
397
decline in reduced glutathione and increased levels of glu-
398
tathione peroxidase, catalase, and ATP. That study also
399
showed complete reversal of the gentamicin-induced
400
increased blood urea nitrogen, creatinine, thiobarbituric
401
acid-reactive substances, and total nitrate/nitrite to normal
402
range [77]. Both NS oil and thymoquinone can protect gastric
403
mucosa from acute alcohol-induced mucosal injury, which is
404
partly attributed to their free radical scavenging activity [78].
405
Furthermore, ethanolic extracts may protect against radia-
406
tion-induced oxidative damage in mice [79].
407
Hepatoprotective Activity
408
Thymoquinone and other NS seed extracts are also known
409
to have hepatoprotective activity in various settings.
410
In an animal study by Yildiz et al. NS treatment was
411
found to protect the rat liver against hepatic ischemia–
412
reperfusion injury. This may have clinical implications to
413
some hepatic surgeries and in hepatic transplantation where
414
ischemia reperfusion injuries are considered significant
415
problem [80].
416
Another recent animal study showed that NS adminis-
417
tration had protective effects on cholestatic liver injury in
418
rats. The authors suggested that the underlying mechanism
419
of action might involve attenuation of enhanced neutrophil
420
infiltration and oxidative stress in the liver tissue [81].
421
Furthermore, NS and components have been found to
422
protect the liver against the effects of several toxins,
423
including tert-butyl hydroperoxide, carbon tetrachloride,
424
aflatoxin B, and lead [8285]. The attenuated liver damage
425
may be due to the decrease in pro-inflammatory cytokines
426
and T-cell proliferation as described by Michel et al. [86].
427
Finally, thymoquinone supplementation reduced liver
428
dysfunction induced by endotoxemia in rats, partly via anti-
429
apoptotic and antioxidant activities. This was proven through
430
both biochemical and pathological examination [87].
431
Anti-Inflammatory Activity
432
The NS oil and thymoquinone have been found to exhibit
433
potent anti-inflammatory effects on several inflammation-
434
based models through the suppression of prostaglandins
435
and leukotrienes [88]. Asthma and rheumatoid arthritis are
436
examples of chronic inflammatory disorders involving a
437
range of inflammatory mediators and different pathways
438
[4]. In a recent clinical trial, 29 asthmatic adults were
439
randomly divided into two groups; a control group and
440
treatment group with NS seed extract with a 3-month fol-
441
low-up. It was observed that asthma symptoms, frequency
442
of asthmatic attacks, and pulmonary function test values in
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Table 1 Recent clinical and experimental studies for the effect of Nigella sativa on the cardiovascular system
References Type of
study
Study population NS component used Results
Le et al. [35] In vivo Rats Petroleum ether extract of NS for 4 weeks There is a reduction in TG and increase in HDL
Najmi et al. [37] Human 60 pts with metabolic
syndrome
2 gps; all given metformin and statin
while NS oil added in one group for
6 weeks
NS group shows significant improvement in TC, LDL, and fasting blood
sugar
Qidwai et al. [38] Human 123 pts with dyslipidemia Powdered black seeds in capsules versus
placebo
Black seeds have favorable effects on almost all lipid variables
Nader et al. [39] In vivo Cholesterol-fed rabbits Propolis or TQ Administration of TQ with cholesterol-enriched diet significantly reduced
TC, LDL-C, and TG, while that increased HDL-C concentration. Early
atherosclerotic changes were observed in high-cholesterol control group
that did not receive TQ
Al-Naqeeb et al. [40] In vivo Rabbits NS seed and oil NS significantly reduced TC and LDL-C and also enhanced HDL-C levels. In
addition, plaque formation was significantly inhibited while the
intima : media ratio was significantly reduced with NS
El-Dakhakhny et al.
[41]
In vivo Rats Oral NS oil for 4 weeks There is a significant decrease in serum total cholesterol, LDL, and TG and
increase in serum HDL
Zaoui et al. [42] In vivo Rats NS Oil for 12 weeks There is a significant decrease in TC and TG
Bhatti et al. [43] Human 10 pts with
hypercholesterolemia
NS seed powder for two ms There is a significant reduction in TC, TG, and LDL and increase in HDL-C
Tasawar et al. [45] Human 80 pts with stable CAD Pts were 2 gps, (statin ?NS capsules]
and (statin only) for 6 ms
NS group had significant decrease in total cholesterol, LDL, and triglycerides
with significant increase in HDL-C levels compared with the other group.
Dehkordi and
Kamkhah [46]
Human Pts with mild hypertension Oral NS seed extract supplement Daily use of NS seed extract for 2 months may have a blood pressure-
lowering effect in patients with mild hypertension in addition to significant
decline in TC and LDL-C levels
Khattab and Nagi [56] In vivo NO deficient hypertensive
rats
TQ Treatment of rats with TQ decreased the elevated creatinine and increased
GSH to normal levels and attenuates hypertension and renal damage in NO
deficient hypertensive rats
El-Bahai et al. [57] In vivo Rats NS oral supplementation (2 months) There is enhanced levels of baseline peak tension, heart rate, and myocardial
flow rate, with significant increase in the tension developed per gram of left
ventricular weight
Al-Hariri et al. [58] In vivo Rats NS oral supplementation (2 ms) There is favorable results of NS supplementation on the intrinsic contractile
properties without evidence of an increased cardiac work load or energy
consumption
Boskabady et al. [59] In vitro Guinea pig hearts Aqueous and macerated extracts from NS Extracts from NS reduces heart rate and contractility that was comparable
and even higher than that of diltiazem.
Ebru et al. [63] In vivo Rats NS oil Pretreatment with NS oil reduced the subsequent cyclosporine A
cardiotoxicity, by normalized cardiac histopathology, decrease in lipid
peroxidation, improvement in antioxidant enzyme status and cellular
protein oxidation
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443
the treatment group significantly improved. Moreover, the
444
usage of the conventional medications in the treatment
445
group decreased, while no changes were noticed in control
446
group [89].
447
NS has been found beneficial against rheumatoid
448
arthritis in both animal and human studies [90,91].
449
Antioxytocic Activity
450
Preliminary reports have suggested that NS oil exhibits a
451
reversible inhibition of uterine smooth muscle contraction
452
induced by oxytocin stimulation in animals [11].
453
Immunomodulatory and Cytotoxic Activity
454
The oil and some of the active ingredients of black seed
455
showed favorable immunomodulatory properties by aug-
456
menting the T cell and natural killer cell-mediated immune
457
responses [88]. The cytotoxic and immune-potentiating
458
effects of NS have been established in many in vivo and in
459
vitro studies [74].
460
The anticancer effects of thymoquinone are probably
461
mediated through different mechanisms, which could be
462
broadly categorized into two modes of action: first, antipro-
463
liferation and induction of cell death and apoptosis [9,92,93],
464
and second, antimetastasis/antiangiogenesis action [94,95].
465
In addition, it was found to modulate various molecular tar-
466
gets, including p53, PTEN (phosphatase and tensin homolog),
467
STAT3 (signal transducer and activator of transcription 3),
468
PPAR-c, activation of caspases, modulation of lipid peroxi-
469
dation, and generation of reactive oxygen species [74].
470
Other studies have also documented the specific effects of
471
NS extracts, especially thymoquinone on multiple targets of
472
cancer cell lines [9,94], suggesting that thymoquinone
473
deserves further extensive investigations for delineating its
474
role as an anticancer agent [4]. Thymoquinone significantly
475
decreased the proliferationof human breast, colon, pancreatic,
476
lung, and prostate cancer cells and also prevented their
477
metastasis without affecting normal cell proliferation [74,96].
478
Similar effects have been found on acute lymphoblastic leu-
479
kemia cell lines [97]. Figure 3shows the effect of thymo-
480
quinone on the lymphoid system in an experimental study.
481
The combination of thymoquinone or other NS compo-
482
nents with conventional chemotherapeutic drugs such as
483
cisplatin, ifosfamide, doxorubicin, gemcitabine, and oxa-
484
liplatin could enhance the therapeutic effect as well as
485
reduces the chemotoxicity [66,74,98101].
486
Antimicrobial Activity
487
NS and its oil exhibited strong antimicrobial activity
488
against E. coli,Pseudomonas aeruginosa, and others
489
[102104]. The ethanol extract of seeds has inhibited the
Table 1 continued
References Type of
study
Study population NS component used Results
Nagi et al. [64] In vivo Rats TQ TQ supplementation resulted in a complete reversal of all the biochemical
changes (including creatine kinase and cholesterol levels) induced by
cyclophosphamide
Ali et al. [69] In vivo Rats Seeds in different doses and durations up
to 14 days
All doses produced significant reduction in TC, TG, LDL-C. and HDL-C
with no linear dose- or time-dependent effects.
Dahri et al. [70] In vivo Rats NS oral Significant decrease in serum LDL-C level and increase in serum HDL-C
levels
Yar et al. [71] In vivo Rats NS oral for 1 m Short duration of NS administration caused moderate hypertrophy and
increased inotropic properties as well as maximal peak tension generation
upon progressive cardiac stress by isoproterenol infusion
Ragheb et al. [72] In vivo Rabbits TQ TQ attenuates hypercholesterolemic atherosclerosis in addition to a decrease
in serum lipids and oxidative stress
Sultan et al. [73] In vivo Rats NS fixed oil and essential oil Supplementation of oils was effective in reducing the abnormal values of
cardiac and liver enzymes caused by oxidative stress
LDL-C low-density lipoprotein cholesterol, TC total cholesterol, HDL-C high-density lipoprotein cholesterol, TG triglycerides, NS Nigella sativa,TQ thymoquinone, NO nitric oxide, pts
patients, gp group, ms months
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490 growth of methicillin-resistant Staphylococcus aureus
491 [105]. Thymoquinone was also found to prevent bacterial
492 biofilm formation against 11 human pathogenic bacteria
493 [106]. Similarly, antifungal activities of seeds and extracts
494 have been reported in several studies [107,108].
495 Anthelmintic Activity
496 NS was shown to have an antiparasitic activity against
497 tapeworm and schistosomiasis in infected mice [109,110].
498 Other Activities
499 Other reports include anticonvulsant, anxiolytic, antiuro-
500 lithiatic, analgesic, and antispasmolytic effects [111114].
501 Toxicology
502 No toxic effect of crushed black seed was observed by
503 administrating high doses of NS [28 g/kg orally] in rabbits
504
[115,116]. The seeds have very low degree of toxicity with
505
no significant adverse effects on liver or kidney functions;
506
however, two cases of contact dermatitis were detected
507
following topical use in humans [17]. In an animal study,
508
NS extracts were relatively nontoxic in acute toxicity test,
509
but the aqueous extract showed possible hepatic adverse
510
effects [117].
511
Zaoui et al. [115] studied the acute and chronic toxicities
512
of NS fixed oil in mice and rats. Changes in key hepatic
513
enzymes levels, including aspartate-aminotransferase, ala-
514
nine-aminotransferase, and gamma-glutamyltransferase
515
and histopathological modifications in the cardiac, hepatic,
516
renal, and pancreatic tissues were not observed in rats
517
treated with NS after 3 months of treatment. Although the
518
investigators reported a wide margin of safety for thera-
519
peutic doses of NS fixed oil, the count of leukocytes and
520
platelets decreased significantly, compared to control val-
521
ues, while hematocrit and hemoglobin levels increased
522
significantly. In another experimental study, Al-Ali et al.
523
[21] reported LD50 values of 10–15 times and 100–150
524
times greater than doses of thymoquinone reported for its
Table 2 Summary of the
effects of Nigella sativa on the
heart
Direct effect Indirect effect
Inhibition of plaque formation Antidiabetic effect
Improves endothelial function Prevent and treat metabolic syndrome
Reduces intima/media ratio Reduction in total cholesterol, LDL,
and triglyceride
Inhibits arachidonic acid-induced
platelet aggregation
Increases HDL
Reduces elevated heart rate Antioxidant effect
Reduces BP in hypertensive condition Protects against L-NAME-induced
hypertension and renal damage
Inhibitory effect on contractility
Cardioprotection against chemotherapy Protect against hyperhomocysteinemia effects
Fig. 3 The effect of thymoquinone on the lymphoid system in
animal. aHyperplasia in the lymphoid follicle in the spleen white
bulb in thymoquinone-treated rats. bHyperplasia in the bronchial-
associated lymphoid tissue in the lung in thymoquinone-treated rats
(Courtesy from Haba Al-Azzeh)
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525 anti-inflammatory, antioxidant, and anticancer effects.
526 They concluded that thymoquinone is a relatively safe
527 compound, particularly when given orally.
528 Conclusion
529 The multiple uses of NS in folk medicine encouraged many
530 investigators to isolate its active components. A large
531 number of in vitro and in vivo studies have been conducted
532 on laboratory animals and a few in humans in order to
533 investigate its pharmacological properties and utilities in
534 different medical aspects. NS seeds and extracts have been
535 shown to have beneficial effect on diabetes mellitus, insulin
536 resistance syndrome, total lipid profile, and cardiovascular
537 system, as well as antiplatelet actions. In addition, pre-
538 treatment with NS oil decreased cyclosporine A, cyclo-
539 phosphamide, and doxorubicin injury in animal heart.
540 Based on the current review, it has been concluded that NS
541 has a broad spectrum of therapeutic potential especially in
542 cardiovascular diseases. Further, long-term human trials
543 are required to establish the therapeutic utility of this
544 ancient alternative medicine.
545
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800 70. Dahri, A. H., Chandiol, A. M., Rahoo, A. A., & Memon, R. A. (2005).
801 Effect of Nigella sativa [kalonji] on serum cholesterol of albino rats.
802 Journal of Ayub Medical College, Abbottabad, 17(2), 72–74.
803 71. Yar, T., El-Hariri, M., El-Bahai, M., et al. (2008). Effects of
804 Nigella sativa supplementation for one month on cardiac reserve
805 in rats. Indian Journal of Physiology and Pharmacology, 52(2),
806 141–148.
807 72. Ragheb, A., Elbarbry, F., Prasad, K., et al. (2008). Attenuation of
808 the development of hypercholesterolemic atherosclerosis by thy-
809 moquinone. International Journal of Angiology, 17(4), 186–192.
810 73. Sultan, M., Butt, M., Ahmad, R., et al. (2012). Supplementation
811 of Nigella sativa fixed and essential oil mediates potassium
812 bromate induced oxidative stress and multiple organ toxicity.
813 Pakistan Journal of Pharmaceutical Sciences, 25(1), 175–181.
814 74. Woo, C., Kumar, A., Sethi, G., & Tan, K. (2012). Thymoqui-
815 none: Potential cure for inflammatory disorders and cancer.
816 Biochemical Pharmacology, 83(4), 443–451.
817 75. Tripathi, Y., Chaturvedi, A., & Pandey, N. (2012). Effect of
818 Nigella sativa seeds extracts on iNOS through antioxidant
819 potential only: Crude/total extract as molecular therapy drug.
820 Indian Journal of Experimental Biology, 50(6), 413–418.
821 76. Badary, O. A., Abdel Naim, A. B., Abdel Wahab, M. H., &
822 Hamada, F. M. (2000). Induced hyperlipedimic nephropathy in
823 rats. Toxicology, 143(3), 219–226.
824 77. Sayed-Ahmed, M. M., & Nagi, M. N. (2007). Thymoquinone
825 supplementation prevents the development of gentamicin-
826 induced acute renal toxicity in rats. Clinical and Experimental
827 Pharmacology and Physiology, 34, 399–405.
828 78. Kanter, M., Demir, H., Karakaya, C., & Ozbek, H. (2005).
829 Gastroprotective activity of Nigella sativa L. oil and its con-
830 stituent, thymoquinone against acute alcohol-induced gastric
831 mucosal injury in rats. World Journal of Gastroenterology, 11,
832 6662–6666.
833 79. Rastogi, L., Feroz, S., Pandey, B. N., et al. (2010). Protection
834 against radiation-induced oxidative damage by an ethanolic
835 extract of Nigella sativa L. International Journal of Radiation
836 Biology, 86(9), 719–731.
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838 relieves the deleterious effects of ischemia reperfusion injury on
839 liver. World Journal of Gastroenterology, 14(33), 5204–5209.
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841 Nigella sativa on bile duct ligation induced-liver injury in rats.
842 Cell Biochemistry and Function, 28(1), 83–88.
843
82. Daba, M. H., & Abdel-Rahman, M. S. (1998). Hepatoprotective 844
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83. Nagi, M. N., Alam, K., Badary, O. A., et al. (1999). Thymo- 847
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(2011). Protective effect of pretreatment with thymoquinone 852
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Protective effect of Nigella sativa seeds against lead-induced 856
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properties of the Nigella sativa L. seed. International Immuno-
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89. Boskabady, M. H., Javan, H., Sajady, M., & Rakhshandeh, H. 868
(2007). The possible prophylactic effect of N. sativa seed extract 869
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90. Vaillancourt, F., Silva, P., Shi, Q., et al. (2011). Elucidation of 872
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augments thymoquinone-induced apoptosis and caspase activa- 881
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factor-{kappa}B activation pathway by thymoquinone: Role in 889
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apoptosis. Molecular Cancer Research, 6, 1059–1070. 891
95. Yi, T., Cho, S., Yi, Z., et al. (2008). Thymoquinone inhibits 892
tumor angiogenesis and tumor growth through suppressing AKT 893
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96. Kaseb, A. O., Chinnakannu, K., Chen, D., et al. (2007). Androgen 896
receptor and E2F-1 targeted thymoquinone therapy for hormone- 897
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97. Abusnina, A., Alhosin, M., Keravis, T., et al. (2011). Down- 899
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key event of p73 and UHRF1 deregulation in thymoquinone- 901
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909 in rodents and potentiates its antitumor activity. Canadian Journal
910 of Physiology and Pharmacology, 75(12), 1356–1361.
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913 activity in mice. Journal of Ethnopharmacology, 67(2), 135–142.
914 101. Banerjee, S., Kaseb, A., Wang, Z., et al. (2009). Antitumor
915 activity of gemcitabine and oxaliplatin is augmented by thy-
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918 102. Morsi, N. (2000). Antimicrobial effect of crude extracts of Ni-
919 gella sativa on multiple antibiotics-resistant bacteria. Acta Mi-
920 crobiologica Polonica, 49(1), 63–74.
921 103. Hanafy, M. S., & Hatem, M. E. (1991). Studies on the antimi-
922 crobial activity of Nigella sativa seed [black cumin]. Journal of
923 Ethnopharmacology, 34(2–3), 275–278.
924 104. Kokoska, L., Havlik, J., Valterova, I., et al. (2008). Comparison
925 of chemical composition and antibacterial activity of Nigella
926 sativa seed essential oils obtained by different extraction
927 methods. Journal of Food Protection, 71(12), 2475–2480.
928 105. Hannan, A., Saleem, S., Chaudhary, S., et al. (2008). Anti
929 bacterial activity of Nigella sativa against clinical isolates of
930 methicillin resistant Staphylococcus aureus. Journal of Ayub
931 Medical College, Abbottabad, 20(3), 72–74.
932 106. Chaieb, K., Kouidhi, B., Jrah, H., et al. (2011). Antibacterial
933 activity of thymoquinone, an active principle of Nigella sativa
934 and its potency to prevent bacterial biofilm formation. BMC
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936 107. Khan, M. A., Ashfaq, M. K., Zuberi, H. S., et al. (2003). The in
937 vivo antifungal activity of the aqueous extract from Nigella
938 sativa seeds. Phytotherapy Research, 17(2), 183–186.
939 108. Islam, S. K., Ahsan, M., Hassan, C. M., & Malek, M. A. (1989).
940 Antifungal activities of the oils of Nigella sativa seeds. Pakistan
941 Journal of Pharmaceutical Sciences, 2(1), 25–28.
942
109. Ayaz, E., Yilmaz, H., Ozbek, H., et al. (2007). The effect of 943
Nigella sativa oil against Aspiculuris tetraptera and Hymenol-
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28(11), 1654–1657. 946
110. Aboul-Ela, E. I. (2002). Cytogenetic studies on Nigella sativa
947
seeds extract and thymoquinone on mouse cells infected with 948
schistosomiasis using karyotyping. Mutation Research, 516,949
11–17. 950
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tylenetetrazol-induced kindling in mice. Neuropharmacology,
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49(4), 456–464. 954
112. Perveen, T., Haider, S., Kanwal, S., & Haleem, D. J. (2009). 955
Repeated administration of Nigella sativa decreases 5-HT 956
turnover and produces anxiolytic effects in rats. Pakistan
957
Journal of Pharmaceutical Sciences, 22(2), 139–144. 958
113. Hadjzadeh, M. A., Khoei, A., Hadjzadeh, Z., & Parizady, M. 959
(2007). Ethanolic extract of Nigella sativa L. seeds on ethylene 960
glycol-induced kidney calculi in rats. Urology Journal, 4(2), 961
86–90. 962
114. Aqel, M. B. (1993). Effect of Nigella sativa seeds on intestinal 963
smooth muscles. International Journal of Pharmacognosy, 31,964
55–60. 965
115. Zaoui, A., Cherrah, Y., Mahassini, N., et al. (2002). Acute and 966
chronic toxicity of Nigella sativa fixed oil. Phytomedicine, 9(1), 967
69–74. 968
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Acute and subchronic toxicity of thymoquinone in mice. Drug
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(2005). An investigation on LD50 and subacute hepatic tox- 973
icity of Nigella sativa seed extracts in mice. Pharmazie, 60(7), 974
544–547.
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... Thymoquinone is an inducer of antioxidant response; the inducer reacts with cysteine on Keap1, resulting in the release of Nrf2 from Keap1. GST as an antioxidant can protect liver cells from the influence of free radicals so that the SGOT-SGPT enzymes are within the normal range [34]. Nigella sativa as an antioxidant can prevent damage to the liver cells membrane due to oxidative stress. ...
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Cardiovascular diseases (CVD) are the leading causes of mortality worldwide. Flow‐mediated dilation (FMD) is a marker of vascular function. Beneficial cardiometabolic effects of Nigella sativa (N. sativa) have been observed. We evaluated the effect of N. sativa oil on FMD, plasma nitrite, and nitrate (NOx) as nitric oxide (NO) metabolites, and inflammatory markers in subjects with CVD risk factors. Fifty participants were randomly assigned to either the N. sativa (two capsules of 500 mg N. sativa oil) or the placebo group (two capsules of 500 mg mineral oil), for 2 months. The brachial FMD, plasma NOx, vascular cellular adhesion molecule‐1 (VCAM‐1), and intracellular adhesion molecule‐1 (ICAM‐1) were measured. FMD and plasma NOx levels was significantly increased in the N. sativa group compared to the placebo group (changes: 2.97 ± 2.11% vs. 0.71 ± 3.19%, p < 0.001 for FMD and 4.73 ± 7.25 μmol/L vs. 0.99 ± 5.37 μmol/L, p = 0.036 for plasma NOx). However, there was no significant difference in ICAM‐1 and VCAM‐1 levels between groups. Therefore, N. sativa oil improves vascular NO and FMD in subjects with cardiovascular risk factors. However, more studies are warranted to confirm the beneficial impacts of the N. sativa oil on vascular inflammation.
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Nigella sativa is an annual plant from Ranunculaceae family and was traditionally used as medicine by ancient civilizations for its wide therapeutic values. N. sativa is not only the source of healthy nutrition but also has the potential to be an alternative treatment option for different pathologies, from microbial infection to metabolic disease. Nigella seed is composed of a number of biologically active components that are being used in traditional medicines from antimicrobial remedy to cardiovascular diseases This chapter aims to provide readers understanding of complex composition, biological activities, adverse effects, and therapeutic propertiesof N. sativa. Further, seeds from Nigella are rich in nutrients such as proteins, fats, carbohydrates, vitamins, oils, minerals, fibers, etc., and contain a wide variety of saponins and alkaloids. Alkaloids, specially thymoquinone and its derivatives in Nigella, are rich in medicinal activities and are of therapeutic importance in many diseases. Recent research has identified several important active components of N. sativa such as thymoquinone, α-hederin, thymol, and others. However, thymoquinone is the principle active ingredient of Nigella and shows disease-altering biological properties, to name few, antioxidant, antimicrobial, antiinflammatory, antiproliferative, anticancer, and antimetastatic effects, suggesting potential therapeutic roles in many human pathologies. In addition, Nigella has been shown to be effective in immunomodulatory, antidiabetic, hepatoprotective, and neuroprotective activities and in neurological disorders. Derived from its antioxidant and also antiinflammatory action, Nigella has also been associated with the treatment of cardiovascular diseases. In conclusion, Nigella is a good candidate to be developed as a natural therapeutic agent for many pathologies and extensive studies are therefore, recommended. In addition, a better understanding of the mechanisms of Nigella’s therapeutic medicinal effects is needed, as well as knowledge of the best dose to be used, resulting in high efficacy, low toxicity, and better therapeutic effect against different diseases.
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AIM: The seeds of the Nigella sativa plant have been used to promote health and fight disease for centuries, especially in the Middle East and in Southeast Asia. This plant has been a focus of much research. This clinical study was undertaken to know the adjuvant effect of N. sativa oil on various clinical and biochemical parameters of the insulin resistance syndrome. MATERIALS AND METHODS: This prospective study was conducted at a tertiary health care center in North India. After confirmation of diagnosis, 60 patients who fulfilled the inclusion and exclusion criteria were enrolled in this study. Written informed consent was taken from all the patients enrolled. Approval from the institutional ethical committee was also obtained. The patients were divided into two groups of 30 each. In group I (the standard group), patients were advised tablet atorvastatin 10 mg once a day and tablet metformin 500 mg twice a day for a period of 6 weeks. In group II (the N. sativa group), the patients were advised tablet atorvastatin 10 mg once a day, tablet metformin 500 mg twice a day, and N. sativa oil 2.5 ml twice daily for a period of 6 weeks. Fasting and postprandial blood glucose, fasting lipid profile, and waist circumference were recorded before therapy and after completion of therapy. RESULT: The treatment group showed significant (P < 0.05) improvement with reference to total cholesterol, low density lipoprotein cholesterol (LDL-C), and fasting blood glucose (P < 0.05). CONCLUSION: N. sativa oil was found to be effective as an add-on therapy in patients of insulin resistance syndrome. N. sativa oil has a significant activity in diabetic and dyslipidemic patients.
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The effect of 2 weeks daily treatment with 2 g Nigella sativa (N. sativa) on the blood levels of glucose, uric acid, cholesterol, triglycerides, BUN and creatinine was studied on 16 second year male medical students. Nine students took 2 capsules of 500 mg N. sativa twice daily and served as the test group. Seven students served as controls and took 2 capsules of 500 mg brown sugar twice daily. In the test group, the parameters which showed a significant decrease by the end of the first week of treatment were glucose (p < 0.01) and cholesterol (p = 0.05). However, both levels went up by the end of the second week of the treatment but remained below baseline. Creatinine was significantly elevated (p < 0.01) by the end of the first week. Uric acid showed a progressive but a nonsignificant decrease. A finding of interest was that the control group showed a progressive and significant increase in uric acid. It is concluded that N. sativa has a potential reducing effect on the blood levels of both glucose and cholesterol.
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The endothelium plays an obligatory role in a number of relaxations of isolated arteries. These endothelium-dependent relaxations are due to the release by the endothelial cells of potent vasodilator substances [endothelium-derived relaxing factors (EDRF)]. The best characterized EDRF is nitric oxide (NO). Nitric oxide is formed by the metabolism of L-arginine by the constitutive NO synthase of endothelial cells. In arterial smooth muscle, the relaxations evoked by EDRF are explained best by the stimulation by NO of soluble guanylate cyclase that leads to the accumulation of cyclic GMP. The endothelial cells also release an unidentified substance that causes hyperpolarization of the cell membrane (endothelium-derived hyperpolarizing factor, EDHF). The release of EDRF from the endothelium can be mediated by both pertussis toxin-sensitive (alpha2-adrenergic activation, serotonin, thrombin, aggregating platelets) and insensitive (adenosine diphosphate, bradykinin) G-proteins. In blood vessels from animals with regenerated endothelium, and/or atherosclerosis, there is a selective loss of the pertussis-toxin sensitive mechanism of EDRF-release which favors the occurrence of vasospasm, thrombosis and cellular growth.
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The present study has been carried out to determine the effects of Nigella saitva on the lipid profile in cardiac patients visited at Ch. Pervaiz Elahi Institute of Cardiology, Multan. The age of the subjects was 26-69 years. The eighty subjects were divided into two groups (interventional and non-interventional) through random stratification (n = 40/group) by weight. The interventional group given Nigella sativa and statin, non-interventional group given statin daily. Both groups were advised to take the recomended doses regularly for a period of six months and the patients were on usual care. Fasting blood samples were taken before and after two and six month's treatment. In interventional group, cholesterol decreased by (-14.58%), LDL (-23.00%), VLDL (-15.16%) and triglycerides (-15.16%) significantly (p<0.05) after the treatment, whereas there was significant increase (p<0.05) in HDL cholesterol (3.18%) after six months. In non-interventional group the cholesterol decreased by (+1.17%), LDL (-4.13%), VLDL (-3.10%) and triglycerides (-2.12%) non significantly (p>0.05) after the treatment, whereas there was significant increase (p<0.05) in HDL (+5.87) after six months. In conclusion, the Nigella sativa is effective to change the lipid profile significantly in a way which is beneficial to heart.
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The effects of acute and subchronic administration of thymoquinone (TQ), the main constituent of the volatile oil of the black seeds Nigella sativa, with significant cytoprotective properties, were studied in male Swiss albino mice.After acute oral administration, the LD50 value (95% CL) was 2.4 g/kg (1.52–3.77). Signs of toxicity at high doses were hypoactivity and difficulty in respiration. Twenty-four hours after TQ (2 and 3 g/kg) administration, a significant reduction in tissue (liver, kidneys, and heart) reduced glutathione (GSH) content was observed. Plasma urea and creatinine concentrations and the enzyme activities of alanine amino transferase (ALT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were significantly increased.In the subchronic study, mice received TQ in drinking water at concentrations of 0.01, 0.02, and 0.03% for 90 days with no resulting mortality or signs of toxicity. The average daily intake of the compound was approximately 30, 60, or 90 mg/kg/day. There were no changes of toxicological significance in body and organ weights, food and water intake, or urine and feces output. Tissue GSH, plasma concentrations of TP, urea, creatinine and triglycerides, and enzyme activities of ALT, LDH, and CPK were also not affected. Histological examination revealed no gross or microscopic tissue damage. TQ, however, produced a significant decrease in fasting plasma glucose level.The results indicate that the acute oral toxicity of TQ in mice is of a low order and it is generally well tolerated when given subchronically at doses previously shown to have cytoprotective activity. Drug Dev. Res. 44:56–61, 1998. © 1998 Wiley-Liss, Inc.
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A simple quantitative TLC method for the determination of thymoquinone in commercially available black seed oil obtained from Nigella Sativa L. (Ranunculaceae) using a scanning densitometer is described. Also the identification of thymol, dithymoquinone in this sample was established. The Rf values for thymoquinone, thymol and dithymoquinone are 0.77, 0.37 and 0.52 respectively. The identification of the thymoquinone spot, obtained from the methanol extract of oil is confirmed by GC/MS which is essentially identical to thymoquinone standard. The solvent system consisted of benzene: isopropyl ether (1:1). All the spots were visualised and quantitated at 254 nm. The method proposed is simple, reproducible with a lower limit of detection of 100 nmoles/ml and can be used in routine analysis of thymoquinone in black seed oil for quality control purposes.
Article
Abstract The spasmolytic effects of an ethanol extract and the volatile oil of Nigella sativa seeds were tested in vitro using isolated segments of rabbit jejunum. The ethanol extract and volatile oil inhibited spontaneous movements of the rabbit jejunum. Also, the volatile oil inhibited contractions of the rabbit jejunum which were induced by high potasium (K+) solution or acetylcholine. This inhibition was dose-dependent, reversible and not affected by the addition of calcium to the organ bath. These data suggest that the plant seed has an antispasmodic effect, possibly due to a calcium antagonistic activity.