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TABLE 7.2 A Recent Research Summary of N. sativa Extract or TQ Loaded Nanoformulations for the Treatment of Various Types of Cancers
https://t.me/medicina_free
Nanoformulation Drug Excipients Cell Line Types Conclusive Remarks References
Nanogel-based Thymoquinone (TQ) Myristic Human breast High drug-targeting potential Dehghani et al.,
nanoparticle acid-chitosan adenocarcinoma cell and efficiency demonstrates 2015
(MA-chitosan) line (MCF7) anticancer activity.
Nanoparticles Thymoquinone (TQ) Poly (lactide- Colon (HCT-116), TQ into nanoparticles Ravindran et
co-glycolide) breast (MCF-7), and enhances its anti-proliferative, al., 2010
(PLGA), stabilizer- prostrate cancer cells and chemosensitizing effects
polyethylene glycol (PC-3) and multiple
(PEG)-5000 myeloma (U-266)
cells
Nanoemulsion
Nanostructured Thymoquinone (TQ) Mixture of solid lipid Liver Cancer Anticancer effects on the Haron et al.,
Lipid Carrier and liquid lipid Cell-Hep3B Hep3B 2018
(NLC)
Nanoemulsion
Nanocarrier Thymoquinone (TQ) Pluronic F127 (5.0 MCF7 cells Sustained delivery of TQ for Shaarani et al.,
PEGylated Thymoquinone (TQ) Polyvinylpyrrolidone Mammary carcinoma Non-toxicity and effectivity Bhattacharya et
nanoparticles (PVP) + polyethylene cell lines (MCF-7, of PEG4000-TQ-Nps against al., 2015
N. sativa extracts +
doxorubicin
N. sativa essential oil
Phosphate-buffered Human MCF-7 Promising and potential Mahmoud et
saline (pH 7.4) + breast cancer cells therapeutic modality al., 2013
lipid aliquots
Non-ionic surfactant MCF-7 breast cancer Potential application in breast Periasamy et
+ emulsifier cells cancer therapy al., 2016
polysorbate 80
wt.%) and Pluronic cancer 2017
F68
glycol (PEG) 4000 HBL-100) cancer cell migration.
164
Biomarkers as Targeted Herbal Drug Discovery
Nigella sativa
https://t.me/medicina_free
+ NCLN 2%/food (Group 4), normal control (Group 5). Administration of
NCLN and NCLN+NS for 7 weeks, decreased malondialdehyde (MDA)
level compared to the diabetic control. Moreover, in the untreated diabetic
control and NS groups, the level of total antioxidant capacity (TAC) was
increased when compared to the normal control group. Additionally, the
level of superoxide dismutase (SOD) decreased in the NS+NCLN group in
comparison to the NS and NCLN groups (p < 0.01). It was concluded that
discrete supplementation of NS and NCLN produced more efficient antioxidative effects when compared to the combined supplementation of NS
and NCLN (Omidi et al., 2017). Table 7.3 describes about various antioxidant studies, which has been conducted on N. sativa extract or TQ loaded
nanoformulation such as nanoemulsion, nanoparticles, etc.
Alcoholic extract of N. sativa is a strong antidepressant. Moreover, the
anxiolytic activity was demonstrated with the increase in serotonin (5-HT)
and decrease in hydroxyindole acetic acid (5-HIAA) levels in the rat brain.
The increased level of 5-HT in rats improved learning and memory capacity
and augmented the tryptophan levels. The neuroprotective effects were due
to the antioxidant, free radical scavenging and anti-inflammatory capacities
of N. sativa. It may also act as anticonvulsant (Ahmad et al., 2013). The
results of thymoquinone rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE), and the conventional emulsion were studied
on the high fat or cholesterol diet (HFCD) fed rats. Various proteins and
enzymes levels such as amyloid-β (Aβ) generation; amyloid-β precursor
protein (APP) processing, γ-secretases of presenilin 1 (PSEN1), β-secretase
1 (BACE1), and presenilin 2 (PSEN2), Aβ degradation; Aβ transportation;
insulin-degrading enzyme (IDE), receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein 1 (LRP1)
was estimated in brain tissues. TQRFNE were found to reduce the brain Aβ
fragment length 1–40 and 1–42 (Aβ40 and Aβ42) levels, which could further
N. sativa extract effects on lactate dehydrogenase (LDH), TAC, catalase
(CAT), myeloperoxidase (MPO), total oxidative status (TOS), aspartate
TABLE 7.3 A Recent Research Summary of Antioxidant Activities on N. sativa Extract or TQ Loaded Nanoformulations
https://t.me/medicina_free
Nanoformulations Drug Excipients Study Conducted Conclusive Remarks References
Nanoemulsion Thymoquinone (TQ) Tween-80, triolein high fat-cholesterol Improving total Ismail et al., 2017
diet-induced rats antioxidant status and
antioxidants genes
expression levels
Nanoemulsions
enriched with gold
nanoparticle
N. sativa oil +
Calendula officinalis
extract
Gold nanoparticles Black seed extract Hydrogen
lipoic acid + gold
(Chloroauric acid)
tetrachloroaurate
In vitro cellular
investigations
Antioxidant and wound Guler et al., 2014
healing activity
NA Antioxidant activities Fragoon et al.,
2012
tetrahydrate
(HAuCl
Nanoparticles Thymoquinone (TQ) PAG CCl mediated Benefit of the Verma et al., 2013
(p-aminophenyl- hepatotoxicity in rats antioxidant property of
·4H O)
4 2
4
1-thio-β-d- TQ without any toxicity.
galactopyranoside)
coated NIPAAM
(N-isopropyl
acrylamide)
Solid lipid
N. sativa essential oil
Hydrogenated palm NA Acts as antioxidant, Alhaj et al., 2010
nanoparticles (SLN) oil Softisan 154 + anti-inflammatory,
sorbitol anticancer, analgesic,
antimicrobial activities.
166
Biomarkers as Targeted Herbal Drug Discovery
Nigella sativa
https://t.me/medicina_free
aminotransferase (AST), alanine aminotransferase (ALT), and oxidative
stress index (OSI) depicts that it has potent hepatoprotective activity (Adam
et al., 2016). Hepatoprotective activity was observed by Verma et al.
with NTQ, where optimized nanocarriers system exploits the beneficial
antioxidant properties of TQ and minimizes its toxic effects. A targeted
delivery system was designed by the encapsulation of TQ (NTQ) in their
hydrophobic core of PAG (p-aminophenyl-1-thio-β-D-galactopyranoside)
coated with NIPAAM (N-isopropyl acrylamide) nanoparticles. The serum
and the biochemical analysis with the prepared nanoparticles (NTQ) showed
superior hepatoprotective activity of NTQ as compared to TQ (Verma et al.,
2013).
Another nanoformulation of TQ, (TQ-NLCs) was formulated using high-
pressure homogenization with ultrasonication methodology. Entrapment
efciency was found to be between 84.6 ± 5% and 96.2 ± 1.6%. An in-vivo
study revealed that TQ AUC0-t values were higher in animals treated with
NLCs, with a relative bioavailability of 2.03- and 3.97-fold higher than TQ
suspension. Histopathological and enzyme levels studies revealed a signicant decrease in both serum ALT and AST (305.0 ± 24.88 and 304.7 ± 23.55
U/mL, respectively) levels proving, the enhanced hepatoprotective effects of
TQ in rats (Elmowafy et al., 2016).
N. sativa was found to be a crucial herbal medicine in the attenuation of blood
glucose levels with increased insulin and C-peptide level in animal models.
TQ act as a potent antioxidant which plays a key role in the reduction of
tissue MDA levels, DNA damage, preserves pancreatic β-cell integrity and
mitochondrial vacuolization, and fragmentation. They exhibit an antihyperglycemic effect in rats although the effect of TQ loaded nanoformulation has
not been reported in the literature.
Rani et al. studied the effect of TQ loaded nanoformulation against strep-
tozotocin-nicotinamide induced type-2 diabetic rats and its comparative study
was conducted with Thymoquinone (TQ) and standard marketed antidiabetic
drugs, metformin. Nanoprecipitation technique and Box-Behnken statistical
analysis tool was exploited for the formulation of TQ and metformin loaded
polymeric nanocapsules (NCs) and optimization of a biocompatible polymer
and other excipients as variables respectively. Different doses of metformin
(150 mg/kg), TQ (20, 40, and 80 mg/kg) and their nanoformulations (80 mg/
168
https://t.me/medicina_free
Biomarkers as Targeted Herbal Drug Discovery
kg for metformin and 20, 40, and 80 mg/kg for thymoquinone) were administered to type-2 diabetic-induced rats for 21 successive days. Blood glucose
and BW were estimated every week for consecutively 3 weeks. Glycosylated
hemoglobin and serum lipid were measured on 22 days. Oral administration of TQ loaded NCs reported better antihyperglycemic effect in type-2
diabetic rats at a half dose as when to thymoquinone alone demonstrating the
profound utility of nanoformulations for dose reduction (Rani et al., 2018).
N. sativa and its extract act against Candida albicans and Madurella mycetomatis. The activity of the extracts of N. sativa was claimed to be potentially
more effective than antibiotics like amphotericin-B and griseofulvin against
Aspergillus niger, Fusarium solani, and Scopulariopsis brevicaulis. Moreover, TQ confirmed potential activity against Trichophyton spp., Epidermophyton spp., and Microsporum spp. Aqueous extracts of N. sativa showed
no antifungal activity. The plant extract of N. sativa caused a significant
inhibition of the growth of the fungi, Candida albicans (Aljabre et al., 2015).
Size reduction of Amphotericin-B, Ketoconazole, and Thymoquinone was
attempted by the ball milling technique, and particle size was found to be 5
to 20 nm. The nanoparticulated drug and the conventionally available microstructured drug form were examined against Candida albicans yeast and
candida biofilm. Prepared nanosized drug particles were found to be two or
four times effective in both candida yeasts and candida biofilm (Randhawa
et al., 2015).
The clinical trial search was performed in the official site of clinical trial.gov
and found that there were no clinical trials conducted so far on the N. sativa
extract or TQ loaded nanoformulations. The pharmacological activities of N.
sativa are demonstrated in Table 7.4.
It has been more than half a century since TQ was extracted and identified from N. sativa although the limited study has been performed for the
TABLE 7.4 Various Clinical Studies and its Parameters of N. sativa
https://t.me/medicina_free
No.
NCT02816957
Beta Thalassemia
N. sativa
in children with Beta
Thalassemia
NCT01531062
Dyslipidemia
N. sativa black
on lipid profiles in sticky rice
elderly
NCT02307344
on nonalcoholic
Nonalcoholic
Steatohepatitis
N. sativa
Placebo
Steatohepatitis and
Steatosis
NCT01393054
Hypertension
N. sativa seed
seed extract on the
blood pressure with
Hypertension
NCT01735097
Effect of Nigella
Arsenical Keratosis
Vitamin E; N.
sativa in the sativa placebo
treatment of Palmer
Arsenical Keratosis
NCT00327054 Effectiveness of Hypercholesterolemia,
N. sativa seed
Nigella sativa in diabetes mellitus Univ Years
dyslipidemia
Metabolic syndrome X
Tanta Univ. 3–18 Phase 1 https://
Years clinicaltrials.
gov assessed
on 20
2018.
Indonesia 60 Years Phase 2
Univ. and
older
Hillel Yaffe 18 Years Not
Medical and Applicable
Center older
Indonesia 60 Years Phase 3
Univ and
older
Bangabandhu 18–60 Not
Sheikh Mujib Years Applicable
Medical Univ
Aga Khan 18–70 Phase 2
th
Dec
Nigella sativa
TABLE 7.4 (Continued)
https://t.me/medicina_free
No.
NCT03270280 Comparison Chronic periodontitis
N. sativa oil
Univ of 19–40 Phase 2 https://
of salivary Lahore Years clinicaltrials.
Interleukin-1β gov assessed
and matrix on 20
Metalloproteinase-8 2018.
levels with chronic
periodontitis
NCT03175757 Effects of turmeric Cholesterol Health Turmeric and Supplement 40–75 Not
and black cumin Black Cumin Formulators, Years Applicable
seed formulation on Seed placebo Inc
cholesterol levels
NCT01360957 Effect of Obesity Black cumin Shahid 16–60 Not
consumption of water extract Beheshti Univ. Years Applicable
black cumin extract
on weight loss in
overweight women
NCT02407262 Benefits of black Asthma Black seed Univ College, 18–65 Phase 2
seed oil on asthma oil|Placebo London; King Years
inflammation and Abdulaziz
outcomes Univ.
NCT03208790 Clinical evaluation Premalignant Lesion Thymoquinone Cairo Univ 18–75 Phase 2
of chemopreventive 200 mg|Placebo Years
thymoquinone oral capsule
th
Dec
170
Biomarkers as Targeted Herbal Drug Discovery
Nigella sativa
https://t.me/medicina_free
development and optimization of TQ loaded nanoformulations. N. sativa
has demonstrated potent in vitro and in vivo activities for several human
ailments. However, the low solubility and hence the bioavailability of the
active components limit its therapeutic potential. Therefore, several nanoformulations of the active components of N. sativa, particularly, TQ have
been developed to enhance their therapeutic usefulness. The nanoformulations demonstrated potent anti-inflammatory, antibacterial, anticancer,
antioxidant, hepatoprotective, and neuroprotective effects. The various
active components that have been isolated from N. sativa are thymoquinone, thymohydroquinone, dithymoquinone, thymol, carvacrol, nigellimine-N-oxide, nigellicine, nigellidine, etc., may cure various ailments
and disorders. Thus, the primary aim of developing nanoformulations is to
achieve increased solubilization of N. sativa or TQ. No clinical trials have
been trailed on the N. sativa extract or TQ loaded nanoformulations. We
assume this chapter will encourage to researchers for the development and
optimization of N. sativa extract or TQ loaded nanoformulations to unfold
its therapeutic potentials.
• alanine aminotransferase
• antioxidant
• cancer
• nano-formulations
•
• thymoquinone
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Asian Pacific Journal of Tropical Biomedicine, 3(5), 337–352.
Akhtar, M., et al., (2014). Neuroprotective study of Nigella sativa-loaded oral provesicular
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172
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Cells, Nanomed. and Biotech. doi: 10.1080/21691401.2018.1451873.
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Aqel, M., & Shaheen, R., (1996). Effects of the volatile oil of Nigella sativa seeds on the
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Atta-Ur-Rahman, (1995). Nigellidine-a new indazole alkaloid from the seed of Nigella sativa.
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