Transcript Black seed

BENEFITS OF NIGELLA SATIVA IN
ONCOLOGY
2nd INTERNATIONAL CONFERENCE ON QUALITY MEDICATION
IN PROPHETIC MEDICINE
KSA
EHAB ELNAKOURY
CLINICAL ONCOLOGY
07-04-2016
‫قال رسول هللا صلى هللا عليه و سلم‬
‫" عليكم بهذه الحبة السوداء ‪ ،‬فإن فيها شفاء‬
‫سام ”‬
‫من ك ّل داء إال ال َّ‬
‫رواه البخاري (‪ )5688‬ومسلم (‪)2215‬‬
Cancers account for 20-25% of deaths in clinical
practices.
Attempts to cure or palliate cancer employ 4
basic methods:
 Surgery
 Radiotherapy
 Chemotherapy.
 Targeted therapy
N. sativa
whole plant, flower& seeds
• IT grows to 20-30-cm tall ,with finely divided,linear
leaves.
• Flowers are delicate, and usually colored pale blue and
white, with five to ten petals.
• The seed is used as a spice.
• The plant has been found to be salt tolerent and
may be considered a glycophyte (Hajar et al.,
1996).
• The spicy seeds from this plant have proclaimed
medicinal usage dating back to the ancient
Egyptians, Greeks and Romans.
• In his Canon of Medicine Avicenna states 'the
black seed act as an expectorant, it stimulates the
body's energy and helps recovery from fatigue
and dispiritedness.
• Traditional folk medicine has been safely using
black seeds since the time of the Egyptian
Pharaohs.
• Black seed oil was found in the tomb of the
Egyptian Pharaoh Tutankhamen, which
indicates that the oil probably had an
important role in ancient Egyptian practices.
Black Seed: Seed of Blessing,” By The Institute of Tibb Medicine, Johannesburg, South Africa, Published in
Awareness Magazine, September/October
2000. http://www.awarenessmag.com/sepoct0/SO0_BLACK_SEED.HTM
• Archeologists also found black seeds mixed
with honey and bee’s wax in a pilgrim flask
from the Old Hittite Period level of Boyalı
Höyük (Mound), dating from around 1650 BC,
in north-central Turkey.
B. Saliha, T. Sipahib, E. Oybak Dönmezc; “Ancient nigella seeds from Boyalı Höyük in north-central Turkey,” Journal of
Ethnopharmacology, Volume 124, Issue 3, 30 July 2009, Pages 416–420, PMID: 19505557.
Traditionally
• There is a common Islamic belief that black
seed is a panacea for all ailments, but cannot
prevent aging or death.
Blackseed 840 Braz J Med Biol Res 40(6) 2007 L. Ait Mbarek
et al. www.bjournal.com.br
•
•
Also identified as the curative black cumin in
the Holy Bible and is described as Melanthion
by Hippocrates and Dioscorides and as Gith by
Pliny .
. Worthen DR, Ghosheh OA, Crooks PA. The in vitro anti-tumor activity of some crude and purified components of
blackseed, Nigella sativa L. Anticancer Res 1998; 18: 1527-1532
Nigella sativa
• Among various medicinal plants, N.Sativa (Family
Ranunculaceae) is emerging as a miracle herb with a
rich historical and religious background since many
researches revealed its wide spectrum of
pharmacological potential.
• Native to Southern Europe, North Africa and
Southwest Asia and it is cultivated in many countries
in the world like Middle Eastern Mediterranean
region, South Europe, India, Pakistan, Syria, Turkey,
Saudi Arabia.
•
Khare CP. Encyclopedia of Indian medicinal plants. NewYork: Springes-Verlag Berlin Heidelberg; 2004.
N. sativa is commonly known as Black
Seed
• Other Names: 31
• Ajenuz, Aranuel, Baraka, Black Cumin, Black
Caraway, Charnuska, Cheveux de Vénus,
Cominho Negro, Comino Negro, Cumin Noir,
Fennel Flower, Fitch, Graine de Nigelle, Graine
Noire, Kalajaji, Kalajira, Kalonji, La Grainer Noire,
Love in a Mist, Mugrela, Nielle, Nigella sativa,
Nigelle de Crête, Nigelle Cultivée, Nutmeg Flower,
Poivrette, Roman-Coriander, Schwarzkummel,
Small Fennel, Toute Épice, Upakuncika.
Chemical composition of fixed &
volatile oil
Thymoquinone (TQ): The major component of
the volatile oil; ~ 0.2%w/v in fixed oil
Thymohydroquinone: A crystalline substance
resulting from refrigeration of the volatile oil
Nigellone: The carbonyl polymer of TQ
Nigellimine: An isoquinoline alkaloid, found in
trace amounts in the seeds
Sterols: Cholesterol, Campesterol, Stigmasterol,
 -sitosterol,  -spinasterol
Thymoquinone
It is the Bioactive component of Nigella Sativa
with documented:
Anti-inflammatory
Anti-histaminic
Anti-diabetic
Analgesic
Anticancer
Fatty acid composition of the fixed oil of
Nigella sativa seeds
Linoleic
Palmitic
54.00 - 58.13 %
11.97 - 14. 64%
Oleic
Eicosadienoic
Stearic
3.45 - 25.67%
2.69 - 2.87%
2.45 - 2.97%
Alpha-linolenic
Arachidic
Myristic
0.47 - 0.97%
0.20 - 0.25%
0.20 - 0.23
• Plants are invaluable sources of new medications.
• There is an enormous historical legacy regarding
the use of plant preparations in folk medicine .
Suffness M, Douros J. Methods in drugs development. De Vita Jr and Busch H (Editors), Drugs of plant origin. New York: Academic Press;
1982.
• Studies on plants used in ethn-omedicine have
led to the discovery of many valuable drugs
such as vincristine, navelbine, taxol,
camptothecin, etc.
Nadkarni K. Crocus sativus, Nigella sativa. In: Nadkarni KM (Editor), Indian materia medica. Bombay: Popular
Prakashan; 1976. p 386- 411
Clinical Trial .gov
• 9 studies found for NIGELLA SATIVA
Black Seeds have been used to Treat
Cancer for Thousands of Years
• In two separate 2011 studies, Chinese and Saudi Arabian
researchers reviewed the scientific literature for the use of
black seed oil , with cancer.
• They reported that black seed oil has been used as a
traditional medicine for centuries.
• Effective against many diseases such as cancer,
cardiovascular complications, diabetes, asthma, kidney
disease, etc.
• It is a safe and effective agent against cancer in the blood
system, lungs, kidneys, liver, prostate, breast, cervix, and
skin.
•
•
Khan MA1, Chen HC, Tania M, Zhang DZ.; “Anticancer activities of Nigella sativa (black cumin),” Afr
J Tradit Complement Altern Med. 2011, PMID: 22754079.
Randhawa MA1, Alghamdi MS.; “Anticancer activity of Nigella sativa (black seed) – a review,” Am J
Chin Med. 2011, PMID: 22083982.
Black Seed &Radiation Therapy
Black Seed Oil is An Important Aid to
Radiation Treatments
• In a 2014 study, Turkish researchers reported
how black seed oil could potentially be helpful
to people receiving radiation treatment for
cancer.
• They indicated that many cancer patients
treated with radiation therapy suffer severe
side effects during and after treatment.
Black Seed Oil is An Important Aid to
Radiation Treatments
• This study investigated the effects of irradiation and the
addition of black seed oil on the oxidant/antioxidant system
in the liver tissue of irradiated rats.
• They exposed some of the rats to a single dose of gamma
radiation.
• One group of rats received one gram of black seed oil per
kilogram of body weight one hour before the radiation and
received a daily dose afterward for 10 days.
• Another group received the radiation treatment and was
given a saline solution instead of black seed oil.
• The control group was not irradiated.
Black Seed Oil is An Important Aid to
Radiation Treatments
• The analysis of the data shows that black seed oil
reduces oxidative stress markers and has antioxidant
effects, which also augments the antioxidant capacity
in the liver tissue of rats.
• Thus, the use of black seed oil before radiation
treatment, and for 10 days afterward, protected the
rats from some of the harmful effects of radiation.
] Cikman O1, Ozkan A, Aras AB, Soylemez O, Alkis H, Taysi S, Karaayvaz M.;
“Radioprotective Effects of Nigella Sativa Oil Against Oxidative Stress in Liver
Tissue of Rats Exposed to Total Head Irradiation,” J Invest Surg. 2014 Mar 28,
PMID: 24679182.
Radioprotective
Antioxidant activities
• The properties of the seed oil of Nigella sativa have been
tested on the liver of Swiss albino mice.
• The experiments were done on four sets of animals that
comprised of
a control group,
an irradiated group,
a Nigella sativa treated group and
a Nigella sativa irradiated group by measuring the changes in
DNA, RNA, glutathione (GSH) and superoxide dismutase (SOD) in
the liver of each group of animals (Abdel Salam et al., 1998).
Radioprotective
Antioxidant activities
• It was found that only those group of animals
which recieved Nigella sativa oil prior to
irradiation showed significant improvement
in DNA, RNA, SOD and GSH profiles.
• All the non-protected animals that were
irradiated demised after 14 days whereas the
subjects pretreated with Nigella sativa oil
experienced longevity and 60% of them lived
for a maximum of 34 days.
Radioprotective
Antioxidant activities
• On the basis of these results it has been
suggested that a nutritional supplement of
the black seed extract may offer better
protection to the human body against
oxidative damage than supplementation with
synthetic antioxidants.
Bee honey and Nigella grains
• Egyptian researchers studied the protective effect
of bee honey and Nigella grains on the oxidative
stress and cancer that was created by exposing
rats to a strong carcinogen.
• After the four groups of rats were exposed to the
carcinogen,
• some groups were fed black seeds or
• honey, and one group was fed
• both black seeds and honey.
• Control group.
The rats were evaluated after 6 months.
Bee honey and Nigella grains
• The rats that ate black seeds received an 80%
protection against oxidative stress and cancer
formation.
• Whereas the rats that ate a daily dose of
both honey and black seeds were protected
100% against oxidative stress, inflammatory
responses, and cancer formation.
•
Mabrouk GM1, Moselhy SS, Zohny SF, Ali EM, Helal TE, Amin AA, Khalifa AA.; “Inhibition of
methylnitrosourea (MNU) induced oxidative stress and carcinogenesis by orally administered bee honey
.
and Nigella grains in Sprague Dawely rats” J Exp Clin Cancer Res. 2002 Sep, PMID: 12385575
Anti-tumor properties of blackseed
Evaluate the in vitro and in vivo anticancer effect of Nigella sativa seed
extracts
•
•
•
•
Brazilian Journal of Medical and Biological Research (2007) 40: 839-847
ISSN 0100-879X3Laboratory of Ecophysiology, Faculty of Sciences Semlalia, Cadi-Ayyad University,
Marrakech, Morocco
L. Ait Mbarek1,H. Ait Mouse1, N. Elabbadi1,M. Bensalah1, A. Gamouh1,R. Aboufatima3,A. Benharref2, A. Chait3,M. Kamal1,
A. Dalal3and A. Zyad1
Results
• clearly showed that the injection of the
essential oil into the tumor site significantly
inhibited solid tumor development.
• Indeed, on the 30th day of treatment, the
tumor volume of the control animals was 2.5
± 0.6 cm3, whereas the tumor volumes of the
essential oil-treated animals were 0.22 ±
0.1CM3 .
Results indicate for the first time that intra-tumor
treatment of tumor-bearing mice with essential oil
may have led to the inhibition of metastasis
development .
• These results demonstrate either that the
essential oil has an anti-metastatic activity in
mice or that it inhibits or delays metastasis by
rapid reduction of primary tumor volume at the
site of induction.
• The active principles and their metastasisinhibiting mechanism still need to be identified.
Evaluation of immunomodulatory effect of three
herbal plants growing in Egypt
(supportive care in cancer manag.)
A group of medicinal plant including Silene (Silene nocturna), Black
seed (Nigella sativa) and Chamomile (Matricaria chamomilla)were
examined for their immunomodulatory effect in mice.
Two groups of mice were immunosuppressed with cyclophosphamide,
the one which pretreated with the plants extracts significantly
(P < 0.01) restored their resistance against lethal infection with the
predominately granulocyte-dependant Candida albicans.
Treatment (intraperitoneal injection) with five doses of methanolic
extract for each plant was found to enhance the total white blood cells
count (up to 1.2 × 10(4) cells/mm.
Evaluation of immunomodulatory effect of three
herbal plants growing in Egypt
(supportive care in cancer manag.)
Bone marrow cellularity also increased significantly
(P < 0.01) after the administration of the extract of
each of three test plants.
These results confirm the immunomodulatory
activity of Silene, Black seed, and Chamomile
extracts and may have therapeutic implications in
prophylactic treatment of opportunistic infections
and supportive treatment in oncogenic cases.
Immunopharmacol Immunotoxicol. 2011 Mar;33(1):141-5. doi: 10.3109/08923973.2010.487490. Epub 2010 May 27.
Ghonime M, Eldomany R, Abdelaziz A, Soliman H
Thymoquinone inhibits cancer metastasis by downregulating TWIST1
expression to reduce epithelial to mesenchymal transition
• Proteins that promote Epithelial to Mesenchymal
Transition (EMT) are associated with cancer metastasis.
• Inhibition of EMT regulators may be a promising
approach in cancer therapy.
• In this study, TQ was used to treat cancer cell lines to
investigate its effects on EMT-regulatory proteins and
cancer metastasis.
• It shows that TQ inhibited cancer cell growth,
migration and invasion in a dose-dependent manner.
•
Khan MA, Tania M, Wei C, Fu S, Cheng J, Xu J, Fu. Oncotarget. 2015 Aug 14;6(23):19580-91.
anticancer activities of Nigella sativa
(black cumin)
• The molecular mechanisms behind its anti-cancer role is
still not clearly understood, however, some studies showed
that TQ has antioxidant role and improves body's defense
system, induces apoptosis and controls Akt pathway.
• Although the anti-cancer activity of N. sativa components
was recognized thousands of years ago but proper scientific
research with this important traditional medicine is a
history of last 2∼3 decades.
• There are not so many research works done with this
important traditional medicine and very few reports exist in
the scientific database
•
•
•
Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):226-32. doi: 10.4314/
ajtcam.v8i5S.10. Epub 2011 Jul 3.
AKhan MA1, Chen HC, Tania M, Zhang DZ
Anti-metastasis effect of
thymoquinone on human pancreatic
cancer -CHINA
• Thymoquinone suppressed the migration and
invasion of Panc-1 cells in a dose-dependent
manner.
• Administration of thymoquinone significantly
reduced tumor metastasis compared to
untreated control.
• Furthermore, the expression of NF-kappaB and
MMP-9 in tumor tissues was also suppressed
after treatment with thymoquinone.
Anti-metastasis effect of thymoquinone
on human pancreatic cancer -CHINA
• Taken together, the results indicate that
thymoquinone exerts anti-metastatic activity on
pancreatic cancer both in vitro and in vivo, which
may be related to down-regulation of NF-kappaB
and its regulated molecules such as MMP-9
protein.
• Consequently, these results provide important
insights into thymoquinone as an antimetastatic
agent for the treatment of human pancreatic
cancer.
•
•
•
Yao Xue Xue Bao. 2011 Aug;46(8):910-4.
[Article in Chinese]
Wu ZH, Chen Z, Shen Y, Huang LL, Jiang P.
The cytotoxic effects of different N. sativa seed
extracts as an adjuvant therapy to doxorubicin on
human breast cancer cells
• The study showed N. sativa lipid extract is
cytotoxic to human breast cancer cells with
LC50 of 2.720 ± 0.232 mg/mL, while its
aqueous extract cytotoxicity exhibited when
the applied concentration is high as about 50
mg/mL.
Mahmoud SS, Torchilin VP. Hormetic/cytotoxic effects of Nigella sativa seed alcoholic and aqueous extracts on
MCF-7 breast cancer cells alone or in combination with doxorubicin. Cell Biochem Biophys.2012;25(7):1392–
1398.
The antitumor and anti-angiogenic
effects of TQ on osteosarcoma
• Induced a higher percentage of growth inhibition and apoptosis in
the human osteosarcoma cell line compared to that of control.
• It was found that TQ significantly inhibit osteosarcoma cell growth.
Moreover, the expression of cleaved caspase-3 and Smac were
upregulated in SaOS-2 cells after treatment with TQ.
• Conclusion: effectively inhibits tumor growth and angiogenesis
both in vitro and in vivo.
• Therefore, inhibition of NF-κB and downstream effector molecules
is a possible underlying mechanism of the antitumor and antiangiogenic activity of TQ in osteosarcoma.
•
Peng L, Liu A, Shen Y, Xu HZ, Yang SZ, Ying XZ, et al. et al. Antitumor and anti-angiogenesis effects of thymoquinone
on osteosarcoma through the NF-κB pathway. Oncol Rep. 2013;29(2):571–578.
The cytotoxicity of TQ in human
cervical squamous carcinoma cells
• TQ was found to be more cytotoxic towards cervical
squamous carcinoma cells compared to cisplatin.
• Interestingly, TQ was less cytotoxic towards the normal
cells .
• Cell cycle analysis performed by flowcytometer
showed a significant increase in the accumulation of
TQ-treated cells at sub-G1 phase, indicating induction
of apoptosis by the compound.
• TQ was more potent than cisplatin in elimination of
cervical squamous carcinoma cells via apoptosis with
down-regulation of Bcl-2 protein.
•
Ng WK, Yazan LS, Ismail M. Thymoquinone from Nigella sativa was more potent than cisplatin in
eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein. Toxicol In
vitro.2011;25(7):1392–1398.
Synergistic Combination of Gemcitabine and Dietary Molecule
Induces Apoptosis in Pancreatic Cancer Cells and Down
Regulates PKM2 Expression
•
In order to optimize a possible synergistic combination of
Gemcitabine (GCB) with dietary molecules, Betuilnic acid (BA)
and Thymoquinone (TQ), stand-alone IC50 dose of GCB, BA
and TQ was calculated for pancreatic cancer cell lines.
•
PLoS One. 2014; 9(9): e107154.
Published online 2014 Sep 8. doi: 10.1371/journal.pone.0107154
PMCID: PMC4157832
Archana Pandita,1 Bhupender Kumar,2 Siddharth Manvati,1 Samantha Vaishnavi,1 Shashank K. Singh,3,* and Rameshwar N. K. Bamezai2
•
Materials and Methods
• Cell Lines, maintenance and reagents
• Human pancreatic cancer cell lines, were
cultured.
Treatment profile and Cell viability
assay
• Cells were exposed to different concentrations
of BA, TQ and GCB, alone and in combinations.
• Chemo-sensitivity values were expressed as %
cell viability of the drug concentration that
inhibited 50% cell growth
Cells in the lower right quadrant, represented apoptosis; and in the
upper right quadrant, necrosis or post apoptotic necrosis
Results
• demonstrated that TQ, BA and GCB
potentiate cytotoxicity with human pancreatic
cancer cell lines.
• The clinical implications of this synergistic
interaction are paramount and include
improvements in efficacy, treatmentassociated toxicity, tolerability of therapeutic
regimens, and quality of life.
• These observations add an important value in
the possible clinical treatment with proposed
combinations, minimizing the dose of GCB,
and thereby decrease the risk of toxicity.
(OLDER AGE ).
TOPICAL APPLICATION
• Furthermore, blackseed preparations may
have a cancer chemo-preventive potential
and may reduce the toxicity of standard
antineoplastic drugs .
• In fact, topical application of a blackseed
extract inhibited the two stage initiationpromotion of skin carcinogenesis in mice .
•
Salomi NJ, Nair SC, Jayawardhanan KK, Varghese CD, Panikkar KR. Antitumour principles from Nigella sativa seeds. Cancer
Lett 1992; 63: 41-46
Malignant ascitis
• In fact, Salomi et al. , have shown that a crude
methanol extract of blackseed exhibited a strong
cytotoxic action on malignant ascitis, Dalton’s
ascites lymphoma and sarcoma 180 cells, with
minimal cytotoxicity to normal lymphocytes.
• These investigators have also described the
cytotoxic property of extracts of the seeds in vivo,
as shown by inhibition of the growth of
malignant ascitis in mice receiving 2 mg of the
extract per mouse per day for 10 days
•
Salomi MJ, Nair SC, Panikkar KR. Inhibitory effects of Nigella sativa and saffron (Crocus
sativus) on chemical carcinogenesis in mice. Nutr Cancer 1991; 16: 67-72.
• Furthermore, a new triterpene saponin (αhederin) recently isolated from blackseed
showed significant dose-dependent tumor
inhibition when given intraperitoneally for 7
days at 5 and 10 mg/kg to mice with formed
tumors .
•
Swamy SMK, Tan BKH. Extraction, isolation and characterization of anti-tumor principle,
alpha-Hederin, from the seeds of Nigella sativa. Planta Medica 2001; 67: 29-32
Improve Therapeutic Ratio of cisplatin
• Its use of as a chemotherapeutic agent to different kinds of
malignancies is well known to have side reactions such as
nephrotoxicity.
• The toxicity has been shown to be greatly reduced by using
cisplatin in combination with plant extracts which act as
protecting agents.
• Thus concurrent administration of cisplatin (3 mg/kg) with
a mixture comprising cysteine (20 mg/kg), vitamin E (2
mg/rat), an extract of Crocus sativus stigmas (50 mg/kg)
and Nigella sativa seed (50 mg/kg) in laboratory animal
experiments has produced a reduction in blood urea
nitrogenase and serum creatinine levels and an increase in
cisplatin-induced total serum lipids.
To go
• Black seeds and black seed oil have been
used for dozens of diseases with great
success ever since that time throughout a
large portion of the world.
• There are not so many research works done
with this important traditional medicine and
very few reports exist in the scientific
database.
To go
• Regarding its therapeutic use, the prophetic
acclaim that 'the black seed is a cure for all
the diseases' made some 1400 years ago by
prophet Muhammad appears to be
supported by the overwhelming evidence of
the detailed scientific enquiry that has shown
the black cumin to have a vast array of
diverse pharmacological activities.
To go
• They have been used for flavoring food and have been used as
daily tonics and remedies for thousands of years.
• Need not more test tube research or animal studies to prove that
black seeds are safe and effective in laboratory experiments.
• Proved effective as topical.intra-lesional,intra-peritoneal
&systemic therapy
• The research that we need involves the development of protocols
for using black seed oil in a clinical setting with cancer patients,
Large scale prospective validation.
• It is clear from the research that black seed oil and thymoquinone
are both effective against cancer and do not have harmful side
effects.
• It’s time for clinical trials.
THANK U