Traditional Medicine Research doi: 10.

12032/TMR20210118216

Traditional Indian Medicine

Phytochemical composition, therapeutical and pharmacological

potential of Nigella sativa: a review
Nivedita Manoharan1, Dheepthi Jayamurali1, Rajeshwari Parasuraman1, Sathya Narayanan Govindarajulu1*

1
Department of Physiology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani,
Chennai, Tamil Nadu 600113, India.

*Corresponding to: Sathya Narayanan Govindarajulu. Dr. ALM Post Graduate Institute of Basic Medical Sciences,
Department of Physiology, University of Madras, State University, Chennai, No.2A, Taramani Link Road, IRT Road,
Taramani, Chennai Zone, Tamil Nadu 600113, India. E-mail: drgsathyanarayanan@gmail.com

Highlights

This review explores the phytochemical, therapeutical and pharmacological potentials of medicinal herb
Nigella sativa.

Tradition

Nigella sativa is a well-known medicinal herb in ancient Ayurveda, Siddha, Chinese, Arab and Unani Tibb.
Nigella sativa is cultivated in South East Asia and Middle East countries, it is used in the treatment of
various airway disorders, digestive disorders, and rheumatism. Nigella sativa was considered to cure any
disease except death in prophetic medicine and it is first mentioned in Book of Isaiah in 8th century B.C.E. It
is also said by one of the earliest herbalists “the herb from heaven”. In the 10th century, Canon of Medicine
by Avicenna has mentioned the importance of black seeds in improving body energy. Nigella sativa has also
been mentioned in the Holy Bible for its healing property and characterized as Melanthion (little black seed)
by Hippocrates and Disoscorides in first century C.E. Nigella sativa and its oil have a folklore usage in
Indian and Arabian customs as food and medicine.

Submit a manuscript: https://www.tmrjournals.com/tmr 1

doi: 10.12032/TMR20210118216 REVIEW
Abstract
Plants naturally produce chemical compounds, which are used to endorse health and fight against diseases and have
been used traditionally. Nigella sativa (N. sativa) has a broad spectrum of usage in traditional folk medicines and
it’s a well-known medicinal herb in ancient Ayurveda, Siddha, Chinese, Arab and Unani Tibb. N. sativa stimulates
the body with its natural vitalizing process and cures the disease. Phytochemically, N. sativa seed contains a wide
range of fixed oils, proteins, alkaloids, saponin and essential oils. Most of the medicinal properties of N. sativa are
due to the presence of the quinone constituent. Among the constituents of N. sativa, thymoquinone is one of the
predominant bioactive compounds. The aim of this review is to explore the phytochemical, therapeutical and
pharmacological potentials of N. sativa. N. sativa reported to have many therapeutical and pharmacological actions
which includes antioxidant, antimicrobial, antidiabetic, anticancer, anti-inflammatory, immunomodulator,
cardioprotective, antihyperlipidemic, pulmonary protective, hepatoprotective, nephroprotective, gastroprotective,
diuretics, anti-osteoporotic, dermatologic, neuroprotective effects and also has stimulative action on the
reproductive system. N. sativa seeds and its derivatives have to be isolated and further investigations should be
done using animal models and clinical trials to understand its novel molecular mechanism of action. So, N. sativa
and the plant derived constituents can be used in the production of new drug and to treat several diseases.
Keywords: Nigella sativa, Phytochemistry, Therapy, Pharmacology

Author contributions:
Sathya Narayanan Govindarajulu, Nivedita Manoharan and Dheepthi Jayamurali developed the idea for the study
and directed the article and collected the data on chemical structures and its pharmacological activities.
Rajeswari Parasuraman did the data collection on history, taxonomy, figures and plagiarism checking. All
authors read and approved the final version of the manuscript.
Competing interests:
The authors declare no conflicts of interest.
Acknowledgments:
Authors would like to thank Department of Physiology, University of madras, Chennai, India for providing the
facilities to support this research activity.
Abbreviations:
N. sativa, Nigella sativa; TQ, thymoquinone; NSO, N. sativa oil; TBHQ, tert-butyl hydroquinone; GSH-Px,
glutathione peroxidase; DMH, 1,2-dimethylhydrazine; MDA, malondialdehyde; CAT, catalase; SOD, superoxide
dismutase; NSE, N. sativa extract; IFN-γ, interferon-γ; ALT, alanine aminotransferase; STZ, streptozotocin;
5-LO, 5-lipoxygenase; TNF-α, tumour necrosis factor α; IL, interleukin; CP, cisplatin; MPO, myeloperoxidase;
TOS, total oxidative status; OSI, oxidative stress index; TAC, total antioxidant capacity; GABAergic,
gamma-aminobutyric acid-releasing; GABA, gamma-aminobutyric acid; Aβ, amyloid-β peptide; PTZ,
pentylenetetrazole; MES, maximal electroshock; I/R, ischemia reperfusion; PCO, polycystic ovary; SPF, sun
protective factor.
Citation:
Manoharan N, Jayamurali D, Parasuraman R, Govindarajulu SN. Phytochemical composition, therapeutical and
pharmacological potential of Nigella sativa: a review. Tradit Med Res. 2021;6(4):32. doi:
10.12032/TMR20210118216.
Executive editor: Rui-Wang Zhao.
Submitted: 03 August 2020, Accepted: 18 January 2021, Online: 02 March 2021.

© 2021 By Authors. Published by TMR Publishing Group Limited. This is an open access article under the CC-BY
license (http://creativecommons.org/licenses/BY/4.0/).
2 Submit a manuscript: https://www.tmrjournals.com/tmr
Traditional Medicine Research doi: 10.12032/TMR20210118216
diuresis, bronchitis, asthma, epilepsies, paralysis,
Background inflammatory diseases, fatty liver, diabetes,
cardiovascular diseases, conjunctivitis, ammenorhea,
Plants are known for their medicinal properties for anorexia, pain such as chronic headaches and back
centuries and they have been used globally to cure and pain. They are also applied directly in blister, nasal
avert diseases, infections, and infestation [1]. There are abscesses, orchitis, eczema, and swollen joints [2, 7, 8,
numerous plants which have active bioactive 14, 15]. Most of the pharmacological and therapeutical
compounds with therapeutic characteristic [2]. Plant properties of N. sativa are due to the presence of the
species with a long history of pharmacological and quinone constituent, in which thymoquinone (TQ) is a
phytochemical properties leads to the safe use of the one of the major bioactive compounds of the essential
herb and development of drug [3]. In recent years, oil [2]. The aim of this review is to explore the
there has been increasing interest in the usage of phytochemical, therapeutical, and pharmacological
natural products because they are cost effective, they potentials of N. sativa.
have various therapeutic properties and also because of
the connotation of side effects to man-made drugs [4].
In the course of time, almost 25% of drugs are reliable
plants based; another 25% are chemically altered plant
based products [5, 6]. Among several medicinal plants,
Nigella sativa (N. sativa) has wide-ranging therapeutic
effect and they are also reported for their significant
uses [7]. N. sativa not only known for their medicinal
properties, but they are also widely used as spices and
flavoring agents in a variety of foods [8]. N. sativa has
broad antiquity in different civilization as a miracle Figure 1 The whole plant of N. sativa L. and
herb for promoting the body for its natural healing medicinal seeds N. sativa, Nigella sativa.
process [9]. The herb was considered to cure any
disease except death in prophetic medicine [5] and it is Table 1 Taxonomy of N. sativa
first mentioned in Book of Isaiah in 8th century B.C.E.
[10]. This miraculous herb was considered as “the herb Scientific classification [16, 17]
from heaven” by the ancient herb specialists Avicenna Kingdom Plantae
(10th century) [8]. Archeological evidence reported that
in the tomb of Tutankhamen the herb was sited [10]. N. Division Magnoliophyta
sativa is traditionally used in Ayurveda, Siddha,
Chinese, Arab and Unani Tibb [2, 11]. Class Magnoliopsida
Nigella is a genus of about 20 species of annual
Order Ranunculales
plants in the family Ranunculaceae (Table 1). The
common titles applied to members of this genus are Family Ranunculaceae
“devil-in-a-bush” or “love in a mist” [12]. N. sativa
grows in loamy soils mainly in South Europe, North Genus Nigella
Africa, and South-West Asia and also cultivated in
Middle East Mediterranean region [11, 13]. It is an Species N. sativa
annual flowering plant which grows up to 20–90 cm N. sativa, Nigella sativa.
tall, finely divided leaves, the leaf segment narrowly
linear or threadlike. The flowers are delicate, and Phytochemical composition
usually colored white, yellow, pink, pale blue or pale
purple with 5–10 petals. The ripe fruit has large and In different varieties of seeds, various bioactive
inflated capsule which is composed of 3–7 united compounds were identified and stated in many studies.
follicles, each containing numerous seeds. The seeds Among them, the most important bioactive compounds
are small dicotyledons, trigonus, angular, regular are TQ (30%–48%), thymohydroquinone,
tubercle, 2–3.5 mm × 1–2 mm black externally and dithymoquinone, p-cymene (7%–15%), carvacrol
white inside, slightly aromatic with pungent bitter taste (6%–12%), 4-terpineol (2%–7%), t-anethol (1%–4%),
(Figure 1) [7, 12] sesquiterpene longifolene (1%–8%), α-pinene and
Biological activities and therapeutical uses of N. thymol etc. N. sativa also contains some other
sativa were widely studied in the ancient period. N. compounds in trace amounts. The seeds have two types
sativa seeds and oil are traditionally used to treat of alkaloids; that is isoquinoline
several diseases. N. sativa was well-known for its alkaloids-nigellicimine and nigellicimine-N-oxide, and
medicinal properties as they are used in rheumatism, pyrazol alkaloids or indazole ring bearing alkaloids
jaundice, dyspepsia, ulcer, helminthic infections, piles, which include nigellidine and nigellicine. The seeds
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doi: 10.12032/TMR20210118216
also contain α-hederin (water soluble pentacyclic
triterpene) and saponin (potential anticancer agent) [18,
19]. In trace amounts other compounds like carvone,
limonene, citronellol were also found. The seeds of N.
sativa also contain protein (26.7%), fat (28.5%),
carbohydrates (24.9%), crude fiber (8.4%) and total
ash (4.8%). The seed also contains good amount of
various vitamins and minerals like Cu, P, Zn, Fe and
carotene which is converted by the liver to vitamin A
[18, 20].
In some research these seeds are also reported to
contain rich unsaturated fatty acids, mainly linoleic
acid (50%–60%), oleic acid (20%), eicodadienoic acid
(3%) and dihomolinoleic acid (10%). Saturated fatty
acids (palmitic, stearic acid) are about 30% or less.
α-sitosterol is a major sterol, which is 54% of the total
sterols, followed by stigmasterol (6.6%–20.9% of total
sterols) [21–23]. In few other studies it is reported that
the other components includes nigellone,
avenasterol-5-ene, avenasterol-7-ene, campesterol,
cholesterol, citrostadienol, cycloeucalenol, gramisterol,
lophenol, obtusifoliol, stigmastanol, stigmasterol-7-ene,
β-amyrin, butyro-spermol, cycloartenol,
24-methylenecycloartanol, taraxerol, tirucallol, 3-O-(β-
D-xylopyranosyl(1→3)-α-L-rhamnopyranosyl(1→2)-α
REVIEW
-L-arabino-pyranosyl)- 28 - O- (α-L- rhamnopyranosyl-
(1→4)-β-glucopyranosyl(1→6) - β-D-gluco-pyranosyl)
hederagenin, volatile oil (0.5%–1.6%), fatty oil
(35.6%–41.6%), oleic acid, esters of unsaturated fatty
acids with C15 and higher terpenoids, esters of
dehydrostearic and linoleic acid, aliphatic alcohol,
β-unsaturated hydroxy ketone, hederagenin glycoside,
melanthin, melanthigenin, tannin, resin, protein,
reducing sugar, glycosidal saponin, 3-O-(β-D-
xylopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→2)-β-
D-glucopyranosyl)-11-methoxy-16, 23-dihydroxy-28-
methy-lolean-12-enoate, stigma-5, 22-dien-3-β-D-
gluco-pyranoside, cycloart-23-methyl-7, 20,
22-triene-3β, 25-diol, nigellidine-4-O-sulfite, N. mines
A3, A4, A5, C, N. mines A1, A2, B1, and B2 [20, 24,
25–27]. The phytochemical composition of some of
the components of N. sativa (Table 2) (Figure 2)
Pharmacological activity of N. sativa
In last few decades, extensive research was conducted
on N. sativa seed extracts and its bioactive compounds
to study its therapeutical and pharmacological actions
on multiple diseases. The following are the medleys of
some research.

Table 2 Chemical composition of N. sativa seeds

Group Components Reference

Arachidonic, eicosadienoic, linoleic, linolenic, oleic, palmitic,

Fixed oil (32%–40%)
Volatile oil (0.40%–0.45%)
Proteins (16.0%–19.9%)
stearic, myristic acid, cholesterol, campesterol, stigmasterol, [27–31]
β-sitosterol, α-spinasterol, steryl esters, steryl glucosides
Nigellone, TQ, thymohydroquinone, dithymoquinone, thymol,
[32–35]
carvacrol, 2-(2-methoxypropyl)-5-methyl-1, 4-benzenediol
Alanine, valine, glycine, isoleucine, leucine, proline, threonine,
serine, aspartic acid, methionine, phenylalanine, glutamic acid, [29]
tyrosine, lysine, arginine

Alkaloids Nigellicine, nigellidine, nigellimine-N-oxide [19, 36]

Coumarins 6-methoxy-coumarin, 7-hydroxy-coumarin, 7-oxy-coumarin [37]

Saponins Hederagenin [38, 39]

DL-α-tocopherol, DL-β-tocopherol, all-trans-retinol, vitamin

Vitamins [40, 41]
B1, vitamin B6, niacin, folic acid

Minerals (1.8%–3.7%) Calcium, phosphorous, potassium, sodium and iron [18, 29]

Carbohydrates (33.9%)
Fiber (5.5%) – –
Water (6.0%)
TQ, thymoquinone; N. sativa, Nigella sativa; –, not mentioned.

4 Submit a manuscript: https://www.tmrjournals.com/tmr

Traditional Medicine Research
Figure 2 Chemical structure of components
Antioxidant activity
Essential oil of N. sativa was tested for its antioxidant
activity by thin-layer chromatography screening
methods, in which TQ and the components carvacrol,
t-anethole, and 4-terpineol confirmed upright radical
scavenging property. They were also effective •OH
radical scavenging agents in the assay for
non-enzymatic lipid peroxidation in liposomes and the
deoxyribose degradation assay. This indicates that N.
sativa seeds can be used in the treatment of various
diseases [42]. TQ, the natural main constituent of N.
sativa oil (NSO), and a synthetic structurally related
tert-butyl hydroquinone (TBHQ) were studied in vitro.
Both TQ and TBHQ powerfully inhibited
iron-dependent microsomal lipid peroxidation in a
concentration-dependent manner with median
inhibitory concentration (IC50) values of 16.8 and 14.9
mM, respectively. TQ was more active than TBHQ as
a superoxide anion scavenger with IC50 of 3.35 mM
compared to 18.1 mM for TBHQ [43]. Both N. sativa
and essential oil was effective in enhancing the
antioxidant indices against potassium bromate induced
oxidative stress by significantly increasing the
glutathione-S-transferase, glutathione reductase, and
glutathione peroxidase (GSH-Px) [17].
Likewise, the methanolic extract and volatile oil
fractionated from N. sativa seed oil in atherogenic
suspension fed rats have been reported to have
replenished the plasma total antioxidant power by an
average of 88% against free radical [44]. The
modulatory effect of TQ on erythrocyte lipid
peroxidation and antioxidant status during
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doi: 10.12032/TMR20210118216
1,2-dimethylhydrazine (DMH)-induced colon
carcinogenesis after initiation in male Wistar rats was
studied in which pretreatment of TQ refurbished the
increased level of malondialdehyde (MDA) and
conjugated diene levels, and augmentation of enzyme
activities like catalase (CAT), GSH-Px, and superoxide
dismutase (SOD) activities due to exposure to DMH.
TQ was a useful compound preventing DMH-induced
erythrocyte damages [45].
Antimicrobial activity
N. sativa extract (NSE) is reported to have effective
antibacterial activity against gram-positive
(Staphylococcus aureus) and gram-negative
(Pseudomonas aeruginosa and Escherichia coli)
species. The extract showed a synergistic effect with
streptomycin and gentamycin and also showed
addictive action with spectinomycin, erythromycin,
tobramycin, doxycycline, chloramphenicol, nalidixic
acid, ampicillin, lincomycin, and
sulphamethoxyzole-trimethoprim combination. These
outcomes suggested the antimicrobial efficacy of the
extract [46]. The methanolic extract of N. sativa seed
shows a greater inhibition zone for gram-positive
bacteria (Streptococcus pyogene) and gram-negative
bacteria (Pseudomonas aeruginosa, Klebseilla
pneumoniae and Proteus vulgaris) [47]. TQ revealed a
significant antibacterial activity majorly against
gram-positive cocci with MICs values ranging from 8
to 32 μg/mL showed the minimum biofilm inhibition
concentration at 22 and 60 μg/mL for Staphylococcus
aureus and Staphylococcus epidermidis, respectively
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doi: 10.12032/TMR20210118216
[48].
The effect of essential oil and extract of N. sativa
mainly TQ proved its potent antifungicidal activity on
different dermatophyte strains like Trichophyton
entagrophytes, Microsporum canis and Microsporum
gypseum [49]. The aqueous extract of N. sativa
exhibits an inhibitory effect against candidiasis and the
study also validates that a 5-fold decrease in candida in
kidneys, 8-fold in the liver, and 11-fold in the spleen
was observed in post-treated mice [50]. Two novel
defensins Ns-D1 and Ns-D2 were isolated and
sequenced from N. sativa seeds. These defensins show
strong antifungal activity towards several
phytopathogenic fungi [51].
Using murine cytomegalovirus model, antiviral
effect of NSO was studied in which NSO exhibited
complete inhibition of virus titer in the liver and spleen
on day 3 of infection and coincided with the serum
level of rising interferon-γ (IFN-γ), macrophages, and
CD4+ T cells. On the 10th day of infection, the virus
titer was undetectable in the liver and spleen of NSO
treated mice. The result exhibited a striking antiviral
activity against murine cytomegalovirus mediated by
increase in macrophages and IFN-γ production [52].
NSO was given for Schistosoma mansoni infected
mice for two weeks, which showed diminished number
of worms in the liver and also reduced in ova
deposition in the liver and intestine. The infected mice
also produced a rise in serum activity of L-alanine
aminotransferase (ALT), gamma-glutamyl transferase,
with a low increase in alkaline phosphatase level,
while reduced serum albumin level, administration of
NSO was partially successful. When NSO along with
praziquantel was administered, it showed a reduction
in the dead ova number in comparison with
praziquantel alone seen. The results suggested that
NSO plays a role in the modification caused by
Schistosoma mansoni [53]. Anti-plasmodial activity of
various plant extract was performed among that N.
sativa showed a 100% inhibition of the parasite growth
(Plasmodium falciparum) at a concentration ≤ 50
μg/mL [54]. Efficacy of NSO against Hymenolepis
nana, a causative agent of zoonosis diseases mice was
used in this study to check the inhibitory effect of NSO
dose-dependent against the causative agent. The
efficacy of the 5 mL/kg NSO dose against
Hymenolepis nana attained 100% 14 days after
treatment; the efficacy of the 2.5 mL/kg NSO does
attain an efficacy of 100% 21 days after treatment. It
indicates that NSO unveils efficacy against
Hymenolepis nana [55].
Anti-diabetic activity
The effect of N. sativa and TQ on histopathological
changes of the sciatic nerve was evaluated. The
treatment with N. sativa and TQ showed a sharp
decrease in elevated serum glucose and an increase in
lowered serum insulin concentration in streptozotocin
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REVIEW
(STZ) induced diabetic rats. The treatment with N.
sativa and TQ increased the area of insulin
immunoreactive beta cells significantly. Only fewer
morphological changes were seen in diabetic animals
treated with N. sativa and TQ. The ultra-structural
features of axon also showed a remarkable
improvement suggesting the utility of N. sativa and TQ
as a potential treatment on peripheral neuropathy in
STZ induced diabetic rats [56].
The effect of hydrochloric extract of NSE at high
dosage did not exhibit any effect. But this extract at
low doses has a hypoglycemic effect and ameliorative
effect on the regeneration of pancreatic islets and
maybe also is used as a therapeutic agent in the
management of diabetes mellitus [57]. N. sativa and its
constituent TQ possess maximum anti-diabetic
potential towards hepatic gluconeogenesis, glucose
absorption in the intestine, blood glucose level,
simulates glucose induced secretion of insulin from
beta cells in the pancreas, improves glucose tolerance
as efficiently as metformin so far it has not shown
significant adverse effects and has very low toxicity
[58].
Anti-cancer activity
This study investigates the anticancer activity of NSO
and petroleum ether extract of N. sativa against a
human lung cancer cell line. NSO (0.10, 0.25, 0.50,
and 1.00 mg/mL) and NSE (0.25, 0.50, and 1.00
mg/mL) were added to the cell line and kept for 24h.
NSE and NSO significantly reduce the viability of
cells and alter the cellular morphology of A-549 cells
in a concentration dependent manner [59]. In another
study, NSE obtained by various seed thermal
processing was examined in-vitro for their
anti-proliferative activity in mouse colon carcinoma
cells and TQ content. At various thermal processing
25 °C, 50 °C, 100 °C, or 150 °C, the seeds were heated
at 50 °C, 100 °C, or 150 °C produced oil with a strong
ability to inhibit tumor cell growth and a higher TQ
content and inhibits the NF-κB signaling pathway [60].
The research suggesting that TQ induced apoptosis
through a p53-independent pathway with the
expression of p21 and cell cycle arrest at S phase in
human colon cancer cells [61]. TQ treated to DLD-1
(human colon cancer cell line) increased the
phosphorylation of mitogen-activated protein kinases
extracellular signal-regulated kinase and c-Jun
N-terminal kinase, but not of p38. It provides the
evidence linking the pro-oxidant effects of TQ with its
apoptotic effects in colon cancer and shows a
protective role of mitogen-activated protein kinases
[62].
Anti-inflammatory property
NSO, nigellone, and TQ were evaluated for their effect
on the formation of 5-lipoxygenase (5-LO) product
from polymorphonuclear leukocytes. IC50 values of
Traditional Medicine Research
inhibition of 5-LO for NSO and TQ were similar at 25
µg/mL and 0.2 µg/mL. The IC50 value of
5-hydroxy-eicosa-tetra-enoic acid production from
NSO, nigellone, and TQ are 24 µg/mL, 11.9 µg/mL,
and 0.36 µg/mL respectively. It shows part of the effect
of oil, nigellone, and TQ in ameliorating inflammatory
disease [63]. The NSO and TQ both inhibit the
eicosanoid generation in leukocytes through the
inhibition of cyclo-oxygenase and 5-LO pathways of
arachidonate metabolism. This shows that NSO and
TQ can be used in the treatment of rheumatism and
related inflammatory diseases [64]. In a comparative
study of ethanolic extract of N. sativa and diclofenac
sodium (an anti-inflammatory drug), the extract
significantly reduces the paw inflammatory response in
albino rats. The ethanolic extract of N. sativa has a
potent anti-inflammatory effect in albino rats however,
this effect is moderately less but prolonged than that
produced by diclofenac sodium [65]. Experimental
autoimmune encephalomyelitis is a well-established
animal model for multiple sclerosis. NSO treated
animals ameliorated the clinical signs and suppressed
inflammation and also enhanced remyelination in the
hippocampus. N. sativa could be used as a protective
agent or an aide in treatment for encephalomyelitis
even when the treatment started after the appearance of
the first clinical signs [66].
Immunomodulatory activity
A report showed that alloxan induced diabetic rats
showed a significant increase in monocytes and
granulocytes and a significant decrease in the
proliferation capacity of lymphocytes and tumour
necrosis factor α (TNF-α), interleukin (IL)-4, and IL-8
levels in the diabetic group. When these rats were
treated with N. sativa induced significant amelioration
in monocytes and granulocytes, with a significant
increase in lymphocyte TNF-α, IL-4, and IL-8 levels.
It showed the potential effect of N. sativa as an
immunomodulator [67]. At different concentrations,
ethanolic extract of N. sativa, TQ and dexamethasone
has effect on cell viability, proliferation, IL-4, and
IFN-γ secretion in nonstimulated, phytohemagglutinin
and (concavaline A)-stimulated splenocytes.
Dexamethasone treated animals indicated suppression
in cell viability, IFN-γ, and IL-4 secretion in
non-stimulated and stimulated splenocytes while
extract and TQ reduced the viability and inhibited the
proliferation of stimulated and non-stimulated
splenocytes concentration-dependently. The higher
concentration of extract and TQ reduced the secretion
of IL-4/IFN-γ ratio in both stimulated and
non-stimulated cells, while the higher concentration of
TQ produced same effect on stimulated cells. N. sativa
and TQ showed a cytotoxic inhibitory effect on rat
splenocytes, T-helper 1 and T-helper 2 cytokines
concentration-dependently. It shows the cytotoxic and
immunomodulatory effect of N. sativa and TQ [68].
Submit a manuscript: https://www.tmrjournals.com/tmr
doi: 10.12032/TMR20210118216
Likewise, dexamethasone induced immune suppressed
male rabbits showed a decreased in phagocytic activity
while NSE reported to increase the phagocytic activity
by stimulating the immune cells and increase the
immune potentiality [69]. The radioprotective effect of
Nigella crude oil against the hemopoietic adverse
effect of gamma irradiation was evaluated. NSO
administered before irradiation significantly
normalized the increased MDA concentration and
plasma GSH-Px, CAT, and erythrocyte SOD activities
and produced significant regeneration in spleen and
thymus lymphoid follicles, thus having a promising
natural radioprotective activity against the
immunosuppressive and oxidative effect of ionizing
radiation [70].
Cardioprotective activity
The effect of N. sativa supplementation for two months
to normal rats on cardiac hemodynamics in vivo, the
ionotropic and chronotropic properties of the isolated
hearts in vitro, and the cardiac responsiveness to
progressive adrenergic stimulation by isoproterenol
were studied in which the results indicated the intrinsic
cardiac contractile properties without evidence of
increased cardiac workload or energy consumption in
vivo makes N. sativa an inotriopic agent [71]. This
shows the cardioprotective effect of NSO on lead
induced cardiotoxicity. The results showed produced
significant normalization of the physiological
parameters and restored the histological structure and
decreased the cyclooxygenase-2 expression of the
heart. NSO intake has cardioprotective potential
through its ability to decrease pro-inflammatory
cytokines, oxidative stress, and cardiac tissue damage
[72]. Myocardial injury was induced in rats by
cisplatin (CP) and showed a significant increase in
congestion, edema, and pyknotic nuclei in myocardial
fibres and decrease the expression of antiapoptotic
protein B cell lymphoma-2. CP along with TQ was
administered and it showed attenuating cardiomyocyte
necrosis and apoptosis by increasing B cell
lymphoma-2 expression [73].
Anti-hyperlipidemic effects
N. sativa was given to hyperlipidemia rats and there
was significantly reduced cholesterol and triglycerides
with adequate safety profile. This shows the
effectiveness of N. sativa to treat hyperlipidemia [74].
A similar study was conducted in which
hyperlipidemic rats were treated with the methanolic
extract N. sativa and volatile oil. Both extract and
volatile oil have TQ common which effectively
ameliorate the hypolipidemic activity via hepatic
3-hydroxy-3-methylglutaryl-coenzyme A reductase
pathway. Methanolic extract and volatile oil both can
be used as a hypolipidemic agent [75]. Another study
also confirms N. sativa antihyperlipidemic effect by a
significant decrease in total cholesterol, low-density
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lipoprotein, and triglyceride [76].
Pulmonary protective activity
The study examines the beneficial effect of NSO on
pulmonary aspirations in experimental lung injury in
rats. The volatile oil treated rats showed significant
inhibition of inflammatory pulmonary responses,
reduced peribronchial inflammatory cell infiltration,
alveolar septal infiltration, alveolar edema, alveolar
exudate, alveolar macrophages, interstitial fibrosis,
granuloma, and necrosis formation. It also showed a
significant reduction in the activity of inducible nitric
oxide synthase and a rise in surfactant protein D in
lung tissue of different pulmonary aspiration models
after N. sativa therapy. N. sativa can subside lung
injury and have potential clinical use [77]. The relaxant
effect of n-hexane, dichloromethane, methanol, and the
aqueous fraction of N. sativa (0.8, 1.2, 1.6 and 2.0 g%)
was compared with theophylline (0.2, 0.4, 0.6 and 0.8
mM). The relaxant effect of different concentrations of
methanol and dichloromethane fraction and n-hexane
was significantly greater. It showed the potent effect of
N. sativa was mainly due to lipid fractions [78]. The
effect of nigellone and TQ on the trachea and their
influence on respiratory clearance was studied. In the
study, the effect of Ba++ carbachol and leukotriene
induced tracheal contraction and the transport of
fluorescence dye rhodamin B concerning ciliary action
was also studied using microdialysis. Nigellone and
the higher concentration of TQ had a concentration
dependent effect on the trachea and the contraction
induced by leukotrience-d4 were inhibited by nigellone
and TQ. The mucociliary effect of nigellone was
higher than TQ. It is suggested that nigellone is more
effective than TQ and can be used in the treatment of
respiratory diseases [79].
Gastro-protective activity
The NSO showed a promising effect on necrotizing
enterocolitis. The histopathology, apoptosis evaluation,
and severity of bowel damage were significantly lower
and tissue GSH-Px and superoxide levels were
preserved where MDA and myeloperoxidase (MPO)
were lowered in necrotizing enterocolitis. This shows
the potent antioxidant, anti-inflammatory;
antiapoptotic properties of NSO and thus seems to be a
potentially promising agent for protecting intestinal
tissues from severe damage [80]. The gastric effect of
N. sativa powder was noticed in alcohol induced
gastric lesions in mice. There was a significant
increase in gastric secretion whereas a significant
decrease in gastric volume and reported a vigorous
improvement in gastric disorders treated by N. sativa
[81]. The anti-ulcer effect of N. sativa aqueous
suspension against necrotizing agent which induces
gastric ulcer was studied. N. sativa significantly
ameliorates the ulcer severity and basal gastric ulcer
secretion N. sativa treatment appears to reinforce the
8 Submit a manuscript: https://www.tmrjournals.com/tmr
REVIEW
mucosal barrier, which is the first line of defense
against endogenous and exogenous ulcerogenic agents.
The anti-ulcer effect of N. sativa is possibly
prostaglandin-mediated or via its antioxidant and
anti-secretory activities [82]. A report on murine colitis
induced by administration of dextran sodium sulfate
and treated with TQ showed amelioration of
colitis-related damage and significant reduction in
colonic MPO activity and MDA levels and elevation in
glutathione levels. It can be concluded that the
antioxidant and anti-inflammatory effects of TQ can
ameliorate inflammatory bowel disease [83].
Hepato-protective effect
In hepatic ischemia-reperfusion injury, N. sativa was
infused intraperitoneally and there was a significant
reduction in aminotransferase, ALT, lactate
dehydrogenase levels, total oxidative status (TOS),
oxidative stress index (OSI), and MPO and a
significant increase in total antioxidant capacity (TAC)
and histological tissue damage was milder in N. sativa
treated rats [84]. In a similar study, bile duct ligation
induces cholestatic liver injury in rats on treatment
with N. sativa decreased the liver enzymes level, TOS,
OSI, and MPO and increased TAC levels significantly.
N. sativa treated rats with biliary obstruction resulted
in inhibition of necro-inflammation through
attenuation of improved neutrophil infiltration and
oxidative stress in liver tissue [85]. In a study about CP
induced hepatotoxicity, CP treatment caused an
increase in ALT, aminotransferase, and lipid
peroxidation, and decreased antioxidants and activities
of various carbohydrate metabolism and membrane
enzymes. NSO administration to CP rats showed
reduced liver damage. NSO protected the CP induced
hepatotoxicity by improving energy metabolism and
strengthening antioxidant defense mechanisms [86]. In
this study, cadmium induces hepatotoxicity which
significantly increased antioxidant enzymatic activities
and protein carbonyl it also reduced glutathione
content, and pretreatment with TQ showed an
attenuating effect on protein oxidation and
rejuvenation of depleted antioxidants of the cellular
fraction. It shows the modulatory role of TQ in the
liver [87].
Nephro-protective effect
A study was conducted to investigate about the
gentamicin induced nephrotoxicity and the protective
effect of NSO against gentamicin. Plasma creatinine
and urea levels are significantly decreased in both
higher and lower dosages of N. sativa also there were a
significant reduction in MDA and nitric oxide
generation and increased SOD and GSH-Px activities
and renal damage was also reduced histopathologically.
This implies N. sativa acts as a potent scavenger of
free radicals to prevent gentamycin induced
nephrotoxicity [88]. In similar study on paracetamol
Traditional Medicine Research
induced nephrotoxicity and protective role of ethanolic
extract of N. sativa. There was a significant decrease in
creatinine, urea, MDA and significant increase in SOD
and glutathione levels in the kidney. It suggested that
the anti-inflammatory and antioxidant effect of NSE,
as a potential therapeutic candidate for nephrotoxicity
[89]. Hyperlipidemic nephropathy induced by
doxorubicin in rats showed a significant decrease in
serum urea, triglycerides, total cholesterol and there
was an elevation of non-protein sulfhydryl content and
CAT activity upon TQ treatment in the kidney. The
data suggest that due to the high antioxidant potential
of TQ there was a suppression of doxorubicin induced
nephropathy and TQ might be used as a protective
agent of proteinuria and hyperlipidemia associated
nephrotic syndrome [90]. The report on TQ in
cadmium induced nephrotoxicity, in rats there was a
marked reduction in cadmium toxicity and the
architecture of the kidney was preserved and in
immunohistochemical analysis. TQ also produced a
marked decrease in the expression of NF-кB in renal
tissues and there was a significant decrease in
apoptotic cells and lipid peroxidation. The finding
suggested the nephro-protective potential of TQ might
be due to anti-oxidant and anti-apoptotic properties
[91].
Diuretic like effect
The diuretic effect of aqueous extract of N. sativa in
rats in dose dependent manner (i.e., 10, 30 and 50
mg/kg) with the reference group received furosemide
(10 mg/kg), showed a significant diuretic, kaliuretic
and natriuretic effects with no change in urinary pH.
The diuretic index value showed good diuretic activity
in NSE. The higher dosage of NSE significantly
elevated the urinary volume and modified the
concentration of urinary electrolytes; there were no
signs of acute toxicity. N. sativa has a strong potential
to be used as a diuretic agent [92].
Anti-osteosporotic effect
Osteoporotic effect of N. sativa was studied in STZ
induced diabetic rats. STZ treated rats showed a
significant reduction in body weight and serum
alkaline phosphate. Radiological changes were
observed in femur like decreased bone density, bone
softening, and cortical thinning. Histological changes
like degeneration of osteoblast and osteocytes,
multiple osteoporotic cavities, reduced collagen fibres,
and irregular bone surface were also observed.
Morphometrically, it showed a significant reduction in
osteoblast number and immunohistochemically, there
was reduced osteopontin protein in the bone matrix. In
N. sativa treated rats, there was the improvement of
biochemical, radiographic, histological,
morphometrical, and immunohistochemical. N. sativa
ameliorates diabetic changes in bone [93]. A similar
study was conducted on STZ induced diabetic rats
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doi: 10.12032/TMR20210118216
which can cause diabetic osteopenia. The analysis
showed combined treatment with N. sativa and human
parathyroid hormone showed enhanced bone mass and
biomechanical behavior [94]. The protective role of N.
sativa on osteoporosis produced by ovariectomy in rats.
In ovariectomy rats, there was a reduction in plasma
calcium level and elevation in alkaline phosphate,
amino terminal collagen type 1 telopeptide, MDA,
nitrates, TNF-α, and IL-6. These changes were
reversed in N. sativa treated rats and the histological
changes of tibias shown discontinuous eroded bone
trabeculae with widened spaces in ovariectomy rats
and a decrease in both cortical and trabecular bone
thickness were also reversed in N. sativa treated. There
was no mononuclear cellular infiltration and
congestion of blood vessels was seen in N. sativa
treated rats. This shows N. sativa as a potent
anti-osteoporotic agent, which can be due to its high
content of unsaturated fatty acid as well as antioxidant
and anti-inflammatory properties [95].
Neuro-protective effect
A study was conducted to investigate the effect of
hydro-alcoholic extract of N. sativa and TQ on
lipopolysaccharide induced depression-like behavior in
rats. In which N. sativa was given in two different
doses (200 and 400 mg/kg of NSE) and TQ (40 mg).
Two hours before conducting the forced swim test,
lipopolysaccharide (100 µg/kg) was administered and
NSE and TQ was administered the day before starting
the experiment. In open field apparatus, N. sativa and
TQ treated showed a lowered immobility time,
crossing the number of peripheral and higher central
crossing numbers when compared to
lipopolysaccharide alone. It shows that N. sativa of
hydro-alcoholic extract and TQ have a beneficial effect
on anti-depression [96]. Repeated administration NSO
for four weeks exhibited significant motor activity
which shows the anxiolytic behavior. The
concentration of serotonin (5-hydroxytryptamine) was
increased and there was a decrease in the levels of
5-hydroxyindoleacetic acid in the brain and tryptophan
levels were significantly increased in the brain and
plasma. This study shows that N. sativa can be a
promising drug for antidepressant and anxiolytic [97,
98]. To study the role of gamma-aminobutyric
acid-releasing (GABAergic) and nitriergic modulation
in the anxiolytic effect of TQ, stress was given by
immobilizing the rats for 6 hours and behavioral
analysis was tested through the elevated plus maze and
light/dark test. TQ was administered in two different
doses (10 and 20 mg/Kg). TQ in higher doses
decreased plasma nitrite and reversal of decreased
brain gamma-aminobutyric acid (GABA) content [99].
Using the Morris water maze test scopolamine
induced spatial memory impairment and the effect of N.
sativa of hydro-alcoholic extract was evaluated. Two
different doses of NSE were given (200 and 400 mg/kg)
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doi: 10.12032/TMR20210118216
and scopolamine (2 mg/kg) was induced 30 min before
Morris water maze test. In N. sativa (400 mg/kg) there
was significantly shorter travel path level and latency
when compared with scopolamine. In brain cortical
tissues, acetylcholinesterase activity showed a
significantly increase in scopolamine group and
significantly decrease in NSE treated when compared
to scopolamine group. After inducing scopolamine,
MDA concentration was higher and decreased cortical
thiol content was observed. In pretreated with NSE
showed significant elevation in thiol content and
reduction in MDA. N. sativa of hydro-alcoholic extract
showed decreased acetylcholinesterase activity and
oxidative stress in the brain. It shows the folk belief
about the beneficial effect of N. sativa [100]. During
neonatal and juvenile growth on learning and memory,
the effect of N. sativa was investigated. In which
neonates were tested in morris water maze, where
reduced time latency and distance traveled to reach the
platform and there was a decrease in MDA
concentration in hippocampal tissues and elevated total
thiol content in the brain. This shows the positive
effect of learning and memory in neonatal and juvenile.
This may be due to the antioxidant effect of N. sativa
[101]. NSO enhancement of spatial working memory
performance was assessed using a radial arm maze.
NSO treated rats exhibited no hindrance in the spatial
memory performance. The results exhibited a declined
mean number of errors was observed in NSO treated
rats. It shows the ability of NSO to enhance learning
and memory [10]. The possible beneficial effect of N.
sativa in comparison to methylprednisolone on
experimental spinal cord injury was studied. Spinal
cord injury was performed by placing an aneurysm clip
extradural at T11-12. In spinal cord injury, there was a
significant elevation of MDA and protein carbonyl
levels and reduced SOD, GSH-Px, and CAT enzyme
activities when compared to control. The study
suggested the NSO neuroprotective and restorative
effect on secondary pathochemical actions after spinal
cord injury [102].
Ethanolic extract of N. sativa was shown to have
antiparkinson activity in chlorpromazine induced rats.
The NSE was given in two different doses (200 and
400 mg/kg) and it reduced the cataleptic score.
Levodopa, carbidopa, and N. sativa elevated the
depleted level of reduced glutathione and total protein
and decreased the elevated levels of thiobarbituric acid
reactive substances and nitrite preferably at higher
doses of NSE. Due to its anti-cataleptic and
neurochemical response, N. sativa is shown to have
antiparkinson activity [103]. The study to investigate
the role of TQ on unilateral intrastriatal
6-hydroxydopamine-lesioned rats induces
Hemi-Parkinson was conducted. After 1 week of the
lesion, apomorphine caused contralateral rotations, a
reduction in the number of neurons on the left side of
substantia nigra pars compacta was observed, MDA
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REVIEW
and nitrite levels in the midbrain were increased and
SOD were reduced in 6-hydroxydopamine lesions. But
in pretreated TQ there was significant progress in
turning behavior, prevented the loss of substantia nigra
pars compacta neurons, and lowered MDA levels. The
effect of TQ may be partially due to the attenuation of
lipid peroxidation and it can provide benefit along with
other therapies, in neurodegenerative disorder
including Parkinson’s disease [104]. Another study
was conducted to investigate the protective role of TQ
against Alzheimer’s amyloid-β peptide (Aβ). Cultured
hippocampal and cortical neurons were treated with
Aβ1-12 and TQ. TQ treated efficiently attenuated
Aβ1-12 induced toxicity by enhancing cell viability.
TQ inhibited mitochondrial membrane potential
depolarization and reactive oxygen species generation
caused by Aβ1-12. TQ also restored synaptic vesicle
recycling inhibition, partially reversed firing activity.
The study suggested that TQ may be a promising drug
for Alzheimer’s disease [105].
The current study suggested the epileptiform of N.
sativa in penicillin induced epilepsy and the mediation
of neurotransmitters in epilepsy. In
electroencephalographic data pretreated N. sativa
suppressed penicillin induced seizures by abolishing
85% high voltage spike discharges and there was the
elevation of serotonin and reduced dopamine in the
cerebral cortex, cerebellum, caudate nucleus, and
midbrain. Decreased norepinephrine was observed
only in the cerebral cortex. N. sativa administration
selectively alters the monoamine level in the different
brain regions and similar to the anticonvulsive pattern
shown by diazepam. The study suggests that N. sativa
has promising anticonvulsant action [106]. Another
study was conducted N. sativa aqueous extract, fixed
oil, volatile oil, and its components TQ and p-cymene
using pentylenetetrazole (PTZ) and maximal
electroshock (MES) induced convulsions. All the
constituents of N. sativa showed a protective effect
against PTZ-induced convulsion except fixed oil.
Volatile oil and its constituent effectively suppressed
MES-induced convulsion. All constituents showed a
varying degree of minimal neurological deficit in the
chimney test and TQ may be responsible for this act.
GABAergic transmission is indicated as a pathway in
the antiepileptic effect through the GABAA receptor.
Combination of valproate with TQ showed
potentiation of valproate and reduction of median
effective dose in both PTZ and MES induced
convulsions. TQ can be used as an adjunct with
valproate in seizure therapy [107]. In another study
action of intra-cerebroventricular injection of TQ in
PTZ induced convulsion. TQ was administered in two
different doses 200 and 400 µM in PTZ induced
convulsion and resulted in prolongation of onset and
reduced duration of tonic-clonic seizures and the
lethality of doses was 45% and 50% respectively. The
study also includes about GABAA receptor and opioid
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Traditional Medicine Research
receptors and the action of TQ through flumazenil and
naloxone. TQ showed anticonvulsant activity, maybe
an opioid receptor-mediated increase in GABAergic
tone [108].
In a study with the albino mice, the analgesic effect
of ethanolic extract of N. sativa was assessed using
acetic acid induced writhing test. When compared to
diclofenac sodium, N. sativa possessed significant
analgesic activity [109]. In another study to assess the
antinociceptive effect of NSO and TQ on dose
dependent effect in response to the hot-plate test,
tail-pinch test, acetic acid, and in the early phase of the
formalin test, TQ showed a promising action. TQ
attenuates the nociceptive response in the early and
late phases of the formalin test. Naloxone significantly
blocked NSO and TQ induced antinociception in the
early phase of the formalin test. Furthermore, naloxone
(µ1 opioid receptor antagonist), naloxonazine or
к-opioid receptor antagonist, nor-binaltorphimine
significantly reversed TQ induced antinociception in
the early phase but not in the late phase of the formalin
test while naltrindole (δ-opioid receptor antagonist) did
not affect either phase. This shows that NSO and TQ
might have act via the supraspinal opioid system,
particularly µ1 and к-opioid receptor subtypes [110].
Effect on male reproduction system
A study was conducted to evaluate the role of TQ on
testicular toxicity induced by methotrexate. In
methotrexate, there was an elevation in TAC, and MPO
activity and TQ treated animals showed a reduced TAC
and prevent the increase in MPO activity. In
histological studies, methotrexate showed an
interstitial space dilatation, edema, severe disruption of
the seminiferous epithelium, and reduced diameter of
seminiferous dilatation, and TQ treated reversed the
changes significantly. The study suggests that TQ may
decrease the destructive effects of methotrexate on
testicular tissues [111]. Another study investigated the
protective effect of N. sativa against
cyclophosphamide-induced toxicity on reproduction.
The cyclophosphamide-induced alone showed a
reduced weight of testis, epididymides, and sperm
count. In N. sativa treated there was increased sperm
count may be due to the antioxidant property of the
plant which acts on the germline. N. sativa restored the
histological architecture of testis and protective
property against oxidative damage induced by
cyclophosphamide. N. sativa also promotes acrosome
reaction during fertilization [112]. The study examines
the protective role of TQ on unilateral testicular
ischemia reperfusion (I/R) injury in mice. In testicular
torsion, there was increased TOS, OSI, and MDA
levels. In TQ treated torsion group there was decrease
in TOS, OSI, and MDA and did not affect total
oxidative capacity and MPO activity, significantly
reduced histological damage associated with I/R injury
[113]. The study was conducted to know the effect of
Submit a manuscript: https://www.tmrjournals.com/tmr
doi: 10.12032/TMR20210118216
TQ on testosterone and leutinizing hormone levels in
STZ induced diabetic rats. There was a decrease in
testosterone and leutinizing hormone in diabetic rats
and TQ treated has resulted in increased testosterone
and leutinizing hormone level was not significant with
other groups [114].
A study was conducted to investigate the effect of
alcoholic extract of N. sativa on the fertility of male
rats. At two different doses (0.5 and 1.5 g/kg) N. sativa
was given and the results revealed that significant
decrease of excitation time and the significant increase
in body weight, reproductive parameters (seminiferous
tubules thickness and diameters, the account of
spermatogonia, primary and secondary spermatocytes,
spermatids, free spermatozoa, the account of Sertoli
and Leydig cells, diameter of Leydig cells and the
height of epithelial cells entirely covered epididymal
caudal), protein concentration, testosterone and follicle
stimulating hormone and decrease in leutinizing
hormone and cholesterol. This study suggested that
daily oral administration improves male fertility [115].
In a similar study, the alcoholic extract of N. sativa
was evaluated in the reproductive system of the male
rat. The extract was given at two doses (200 and 400
mg/kg body weight) and the results showed a
significant difference in testes and epididymides
weight, sperm count, epididymal sperm reserve, daily
sperm production, blood testosterone concentration,
leutinizing hormone, and fertility index in both the
lower dose group and the higher group as compared to
the control group. The study suggested that a higher
dose could increase fertility potential, leutinizing
hormone, and testosterone concentration in male rats
[116]. Another study was conducted to examine the
role of aqueous extract of N. sativa (300 mg/kg) for 60
days. The treated group showed a significant increase
in reproductive organ weight, sperm motility, and
count in cauda epididymides, testicular ducts, and
secretary activities of seminal vesicle and ventricular
prostate and also increased spermatogenesis activity
observed in seminiferous tubule. The results confirm
that long term ingestion of N. sativa increases the
effect on fertility and reproductive system in male rats
[117].
Effect on female reproductive system
A study was conducted to evaluate the effect of N.
sativa on experimentally induced I/R injury in rat
ovaries. After 3 hours of ischemia, the bilateral
vascular clips were removed. N. sativa (500 mg/kg)
was given 2.5 hours after induction of reperfusion. The
results showed that I/R injury has increased MDA and
MPO activity, while a significant reduction in SOD
activity and glutathione levels when compared to sham
was observed. N. sativa before I/R reversed MDA,
MPO, SOD, and glutathione activity and I/R increase
the serum levels of IL-1, IL-6, and TNF-α while
treated with N. sativa reduced the serum levels of these
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doi: 10.12032/TMR20210118216
cytokines. The report shows the effectiveness of N.
sativa in reversing the tissue damage [118]. A study
was conducted to validate the effect of TQ in
polycystic ovary (PCO) rats both in vivo and in vitro.
In vivo study, PCO rat model treated with TQ showed
significant restoration of normal physio-molecular
behavior of the ovary, like reduced cysts formation,
increased ovulation rate, and normalization of key
ovarian factors (like TNF-α stimulated gene/protein 6,
hyaluronan, hyaluronan-binding protein 1,
cycloocygenases 2, matrix metalloproteinases
(membrane type 1-matrix metalloproteinase, matrix
metalloproteinases 9 and 2)), tissue inhibitor of
metalloproteinases 1 and 2, and gelatinases matrix
metalloproteinases 9 and 2 activity during follicular
maturation. In vitro study, NF-кB nuclear translocation,
cycloocygenases 2, and reactive oxygen species
expression were inhibited via TQ supplementation in
RU486-treated KK1 cells. Due to the TQ modulatory
effect on NF-кB signaling, elevates normal ovarian
phenotype and physiological function in the PCO
model, demonstrating its potential to cure PCO in rats
[119]. The study describes the effect of aqueous extract
of N. sativa on the endometrium of the female
reproductive system. N. sativa was given at doses of
0.2/100 g showed an increase in uterine wet weight,
with intense and persistent diffuse of endometrial
hypertrophy and enhanced glandulogenesis when
compared to the control group. The aqueous extract of
N. sativa acts via stimulating the endogenous release
of estrogen and progesterone [120].
According to the report of Aqel and Shaheen, the
volatile oil of N. sativa inhibited the spontaneous
movement of uterine smooth muscles and also the
contraction induced by oxytocin stimulation in rat and
guinea pig [121]. It may be due to blocking of calcium
influx via voltage dependent Ca2+ channel and
receptor-operated Ca2+ channel by N. sativa, thus
proving the anti-oxytocic potential. When hexane
extract of N. sativa was given orally to experimental
rats it prevented the pregnancy in experimental rats at
a dose of 2 g/kg daily on day’s 1–10 postcoitum. The
active hexane extract exhibited only mild uterotrophic
activity when compared to ethinylestradiol, but was
without any estrogenicity in the immature rat bioassay
[122]. In another study the postcoital anti-implantation
activity of ethanolic extract of N. sativa at three
different doses (100, 200 and 400 mg/kg) were studied.
The results showed that the anti-implantation effect
and fertility index showed the increased impairment of
fertility at a higher dosage. The anti-fertility showed a
significant difference in all doses. The data suggested
that N. sativa can be used as a postcoital contraceptive
in female rats [123].
Dermatological and cosmetics
Trichophyton verrucosum isolated from cattle suffering
from trichophytosis suspected animals indicated hair
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REVIEW
loss, scurf scales, crusts, and keratinization. On
treatment with NSE in combination with enilconazole
on the infected area showed a strong anti-fungal
activity. This study has suggested the usage of N.
sativa as an adjunctive or alternative agent in the
treatment of dermatophytosis [124]. The effect of NSE
and TQ on pigmentation activity was studied by
isolating melanophores from Hemidactylus flaviviridis.
They were assayed using mean melanospore size index
and their response was recorded. The study suggested
that N. sativa and TQ mimic the action of
acetylcholine in melanin diffusion leading to skin
darkening via stimulation of cholinergic receptors of
muscarinic nature in the melanophores of
Hemidactylus flaviviridis. N. sativa and TQ have a
novel melanogenic for its clinical application in skin
disorders such as hypopigmentation or vitiligo [125].
In vitro sun protective factor (SPF) for NSO was
evaluated using optometrics, LLC, SPF-290S
instruments. The protection factor was calculated by
the wavelength range from 290–400 nm as per United
States Food and Drug Administration standards. Since
the SPF value of N. sativa was more than 2 it can be
formulated for sunscreen [126].
Currently, many researches are conducted on herbal
products to use as an alternative medicine for several
diseases due to their efficacy, safety and low cost.
Among many medicinal plants, N. sativa has a broad
spectrum in traditional folk medicines. N. sativa also
promotes the body with its natural reviving process
and cures the disease. N. sativa has many positive
effects when used as remedies and/or as an adjunct for
various diseases integrating by different systems of the
body. N. sativa seed contains wide-ranging of fixed
oils, proteins, alkaloids, flavonoids, tannins, saponin,
and essential oils, thus proving its multiple
mechanisms of action behind its therapeutical potential
[127]. TQ is considered to be the most active
constituent of N. sativa and has reported exhibiting
potent antioxidant, anti-inflammatory, analgesic,
neuro-protective, hepatoprotective, nephroprotective,
and anti-cancer properties [128]. N. sativa also has
other constituents which also serve to enhance its
medicinal property. Since the complex synergic
activity of the constituents improves the state of
cellular nutrition, and gradually improves vitality [129].
The pharmacological perspective of N. sativa can be
because of conspicuous antioxidant properties [130].
Several in vitro and in vivo studies are piloted in N.
sativa and its constituents. But still, the mechanism of
action is unclear in some perception. The plant
composition in therapeutic and pharmacological
potentials is very much essential for advancing the
research on other beneficial and unknown features. So,
N. sativa and the plant derived constituents can be used
to treat several diseases [16]. The consolidated
pharmacological actions of N. sativa is given below
(Figure 3).
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Traditional Medicine Research doi: 10.12032/TMR20210118216

Figure 3 Pharmacological potentials of N. sativa. N. sativa, Nigella sativa; iNOS, inducible nitric oxide synthase;
COX-2, cyclooxygenase-2; GABAergic, gamma-aminobutyric acid-releasing; AchE, acetylcholinesterase; GST,
glutathione-S-transferase; GSH-Px, glutathione peroxidase; AST, aminotransferase; ALT, alanine aminotransferase;
LDH, lactate dehydrogenase; LDL, low-density lipoprotein; SPF, sun protective factor; FSH; follicle stimulating
hormone; LH, leutinizing hormone.
sativa L.: uses in traditional and contemporary
Conclusion medicines-an overview [published online
February 6, 2020]. Acta Ecol Sin. 2020.
The medicinal plant N. sativa was broadly used as folk 3. Souza ENF, Williamson EM, Hawkins JA. Which
medicines and it has been reported to have many plants used in ethnomedicine are characterized?
therapeutical and pharmacological activities such as Phylogenetic patterns in traditional use related to
antioxidant, antimicrobial, anti-diabetic, anti-cancer, research efforts. Front Plant Sci. 2018;9:834.
anti-inflammatory, immunomodulatory, 4. Dias DA, Urban S, Roessner U. A historical
anti-osteoporotic, anti-hyperlipidemia and protective overview of natural products in drug discovery.
effect against cardiovascular system, pulmonary Metabolites. 2012;2(2):303–336.
system, pulmonary protective, gastrointestinal system, 5. Aftab A, Yousaf Z, Javaid A, et al. Nigella sativa
liver, kidney, skin, central nervous system and L. from traditional to contemporary medicine: a
reproductive system. In future research, the N. sativa review. Int J Biol Biotech. 2018;15:237–254.
seeds and its bioactive compounds should be isolated 6. Vuorela P, Leinonen M, Saikkuc P, et al. Natural
and investigated using animal models and clinical products in the process of finding new drug
trials to understand its novel molecular mechanism of candidates. Curr Med Chem.
action. It can be concluded that N. sativa is a valuable 2004;11(11):1375–1389.
medicinal plant that can be developed into 7. Ahmad A, Husain A, Mujeeb M, et al. A review
pharmaceutical and nutraceutical products to treat a on therapeutic potential of Nigella sativa: a
variety of diseases. miracle herb. Asian Pac J Trop Biomed.
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