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Explore the various benefits of Nigella Sativa, a medicinal plant used in traditional medicine, in the field of oncology. Discover its potential in preventing and treating cancer through its various active components.
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BENEFITS OF NIGELLA SATIVA IN ONCOLOGY2nd INTERNATIONAL CONFERENCE ON QUALITY MEDICATIONIN PROPHETIC MEDICINEKSA EHAB ELNAKOURY CLINICAL ONCOLOGY 07-04-2016
قال رسول الله صلى الله عليه و سلم " عليكم بهذه الحبة السوداء ، فإن فيها شفاء من كلّ داء إلا السَّام ” رواه البخاري (5688) ومسلم (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. sativawhole 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 tolerentand may be considered a glycophyte(Hajar et al., 1996). • The spicy seeds from this plant have proclaimed medicinal usage dating back to the ancientEgyptians, Greeksand Romans. • In his Canon of Medicine Avicennastates '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 BoyalıHöyük (Mound), dating from around 1650 BC, in north-central Turkey. B. Saliha, T. Sipahib, E. OybakDönmezc; “Ancient nigella seeds from BoyalıHöyük 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, NigelleCultivée, Nutmeg Flower, Poivrette, Roman-Coriander, Schwarzkummel, Small Fennel, TouteÉpice, 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 54.00 - 58.13 % Palmitic 11.97 - 14. 64% Oleic 3.45 - 25.67% Eicosadienoic 2.69 - 2.87% Stearic 2.45 - 2.97% Alpha-linolenic 0.47 - 0.97% Arachidic 0.20 - 0.25% Myristic 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-omedicinehave led to the discovery of many valuable drugs such as vincristine, navelbine, taxol, camptothecin, etc. NadkarniK. Crocus sativus, Nigella sativa. In: Nadkarni KM (Editor), Indian materiamedica. 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, Chineseand Saudi Arabian researchers reviewed the scientific literature for the use of black seed oil , with cancer. • They reportedthat 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 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.
RadioprotectiveAntioxidant 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).
RadioprotectiveAntioxidant 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.
RadioprotectiveAntioxidant 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 ExpClin Cancer Res. 2002 Sep, PMID: 12385575.
Anti-tumor properties of blackseedEvaluate the in vitro and in vivo anti-cancer effect of Nigella sativaseed 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 the30th 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-tumortreatment 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 tumorvolume at the site of induction. • The active principles and their metastasis-inhibiting 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 includingSilene(Silenenocturna), 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. ImmunopharmacolImmunotoxicol. 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, TQwas 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 stillnot clearly understood, however, some studies showed that TQ hasantioxidantrole and improves body's defense system, inducesapoptosisand 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 AlternMed. 2011;8(5 Suppl):226-32. doi: 10.4314/ • ajtcam.v8i5S.10. Epub 2011 Jul 3. • AKhanMA1, Chen HC, Tania M, Zhang DZ
Anti-metastasis effect of thymoquinone on human pancreatic cancer -CHINA • Thymoquinonesuppressed the migration and invasion of Panc-1 cells in a dose-dependent manner. • Administration of thymoquinonesignificantly reducedtumor metastasis compared to untreated control. • Furthermore, the expression of NF-kappaBand 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-kappaBand 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 XueXueBao. 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. sativalipidextract 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 50mg/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 inhibitstumorgrowth 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 anti-angiogenic 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 flowcytometershowed 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. • PLoSOne. 2014; 9(9): e107154.Published online 2014 Sep 8. doi: 10.1371/journal.pone.0107154PMCID: PMC4157832 • Archana Pandita,1Bhupender Kumar,2Siddharth 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-sensitivityvalues 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, treatment-associated 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-preventivepotential and may reduce the toxicity of standard antineoplastic drugs . • In fact, topical application of a blackseed extract inhibited the two stage initiation-promotion 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 • SalomiMJ, 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 (α-hederin) 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.