Nigella sativa (Black Cumin) Seed Extract Alleviates Symptoms of Allergic Diarrhea in Mice, Involving Opioid Receptors

The incidence of food hypersensitivity and food allergies is on the rise and new treatment approaches are needed. We investigated whether N. sativa, one of its components, thymoquinone, or synthetic opioid receptor (OR)-agonists can alleviate food allergy. Hence, ovalbumin (OVA) -sensitized BALB/c-mice were pre-treated either with a hexanic N. sativa seed extract, thymoquinone, kappa- (U50'4889) or mu-OR-agonists (DAMGO) and subsequently challenged intra-gastrically with OVA. All 4 treatments significantly decreased clinical scores of OVA-induced diarrhea. N. sativa seed extract, thymoquinone, and U50'488 also decreased intestinal mast cell numbers and plasma mouse mast cell protease-1 (MMCP-1). DAMGO, in contrast, had no effect on mast cell parameters but decreased IFNγ, IL-4, IL-5, and IL-10 concentration after ex vivo re-stimulation of mesenteric lymphocytes. The effects on allergy symptoms were reversible by OR-antagonist pre-treatment, whereas most of the effects on immunological parameter were not. We demonstrate that N. sativa seed extract significantly improves symptoms and immune parameters in murine OVA-induced allergic diarrhea; this effect is at least partially mediated by thymoquinone. ORs may also be involved and could be a new target for intestinal allergy symptom alleviation. N. sativa seed extract seems to be a promising candidate for nutritional interventions in humans with food allergy.

[1]  F. Rahim,et al.  Herbal treatment of allergic rhinitis: the use of Nigella sativa. , 2011, American journal of otolaryngology.

[2]  S. Prescott,et al.  Food allergy: Riding the second wave of the allergy epidemic , 2011, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[3]  H. Fahmi,et al.  Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis , 2011, Journal of cellular biochemistry.

[4]  Ş. Çetinel,et al.  Protective Effects of Black Cumin (Nigella sativa) Oil on TNBS-Induced Experimental Colitis in Rats , 2011, Digestive Diseases and Sciences.

[5]  L. Yu,et al.  Fatty acid profile, thymoquinone content, oxidative stability, and antioxidant properties of cold-pressed black cumin seed oils , 2010 .

[6]  Udaya Sankar Kadimi,et al.  Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxide , 2010, Journal of food science and technology.

[7]  Zhiwei Wang,et al.  Review on Molecular and Therapeutic Potential of Thymoquinone in Cancer , 2010, Nutrition and cancer.

[8]  K. Gee,et al.  Thymoquinone-induced Neu4 sialidase activates NFκB in macrophage cells and pro-inflammatory cytokines in vivo , 2010, Glycoconjugate Journal.

[9]  M. Boskabady,et al.  Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. , 2010, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[10]  M. S. Butt,et al.  Nigella sativa: Reduces the Risk of Various Maladies , 2010, Critical reviews in food science and nutrition.

[11]  A. Zuercher,et al.  Polyphenol‐enriched apple extract attenuates food allergy in mice , 2010, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[12]  L. Shek,et al.  Allergies in Asia: differences in prevalence and management compared with Western populations , 2010, Expert review of clinical immunology.

[13]  A. Mercenier,et al.  Allergen‐specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice , 2009, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[14]  L. Bielory,et al.  Complementary and alternative medicine: herbs, phytochemicals and vitamins and their immunologic effects. , 2009, The Journal of allergy and clinical immunology.

[15]  S. Fein,et al.  Maternally Reported Food Allergies and Other Food-Related Health Problems in Infants: Characteristics and Associated Factors , 2008, Pediatrics.

[16]  S. Ramesh.  Food Allergy Overview in Children , 2008, Clinical reviews in allergy & immunology.

[17]  S. H. Arshad,et al.  Original article: Prevalence and cumulative incidence of food hypersensitivity in the first 3 years of life , 2007, Allergy.

[18]  Aamir Ahmad,et al.  From here to eternity - the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond. , 2008, Cancer therapy.

[19]  S. Sirohi,et al.  μ-Opioid Receptor Up-Regulation and Functional Supersensitivity Are Independent of Antagonist Efficacy , 2007, Journal of Pharmacology and Experimental Therapeutics.

[20]  S. Collins,et al.  Lymphocyte-mediated regulation of beta-endorphin in the myenteric plexus. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

[21]  Elena F. Verdu,et al.  Lymphocyte-mediated regulation of β-endorphin in the myenteric plexus , 2007 .

[22]  S. Dreskin,et al.  Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma. , 2006, Biochimica et biophysica acta.

[23]  S. Dreskin,et al.  Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation. , 2006, International immunopharmacology.

[24]  R. Stead,et al.  Vagal influences over mast cells , 2006, Autonomic Neuroscience.

[25]  A. Zuercher,et al.  Food products and allergy development, prevention and treatment. , 2006, Current opinion in biotechnology.

[26]  M. Kanter,et al.  The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage , 2006, Archives of Toxicology.

[27]  J. Kerner,et al.  Gastrointestinal manifestations of food allergies in pediatric patients. , 2005, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[28]  S. Büyüköztürk,et al.  Nigella sativa (black seed) oil does not affect the T-helper 1 and T-helper 2 type cytokine production from splenic mononuclear cells in allergen sensitized mice. , 2005, Journal of ethnopharmacology.

[29]  H. Hosseinzadeh,et al.  Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. , 2005, Medical science monitor : international medical journal of experimental and clinical research.

[30]  M. Abdel-aziz,et al.  Effect of dexamethasone and Nigella sativa on peripheral blood eosinophil count, IgG1 and IgG2a, cytokine profiles and lung inflammation in murine model of allergic asthma. , 2005, The Egyptian journal of immunology.

[31]  M. Mansour,et al.  Inhibition of 5-lipoxygenase and Leukotriene C4 Synthase in Human Blood Cells by Thymoquinone , 2004, Journal of enzyme inhibition and medicinal chemistry.

[32]  J. Galligan,et al.  Function of opioids in the enteric nervous system , 2004, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[33]  H. Hosseinzadeh,et al.  Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. , 2004, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[34]  F. Finkelman,et al.  Mast cells are required for experimental oral allergen-induced diarrhea. , 2003, The Journal of clinical investigation.

[35]  C. Jackson,et al.  Butterbur, a herbal remedy, attenuates adenosine monophosphate induced nasal responsiveness in seasonal allergic rhinitis , 2003, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[36]  C. Gaveriaux-Ruff,et al.  Anti-inflammatory properties of the mu opioid receptor support its use in the treatment of colon inflammation. , 2003, The Journal of clinical investigation.

[37]  P. Peterson,et al.  Opioid G protein-coupled receptors: signals at the crossroads of inflammation. , 2003, Trends in immunology.

[38]  J. Simon,et al.  Topical treatment of atopic dermatitis with St. John's wort cream--a randomized, placebo controlled, double blind half-side comparison. , 2003, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[39]  U. Holzer‐Petsche,et al.  Involvement of μ‐ and κ‐, but not δ‐, opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea‐pig intestine , 2002 .

[40]  U. Holzer‐Petsche,et al.  Involvement of mu- and kappa-, but not delta-, opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea-pig intestine. , 2002, British journal of pharmacology.

[41]  J. Fahrenholz,et al.  Food allergy , 2002, Current treatment options in gastroenterology.

[42]  David R. Brown,et al.  δ-opioid receptors inhibit neurogenic intestinal secretion evoked by mast cell degranulation and type I hypersensitivity , 2001, Journal of Neuroimmunology.

[43]  O. Badary,et al.  Inhibitory effects of thymoquinone against 20-methylcholanthrene-induced fibrosarcoma tumorigenesis. , 2001, Cancer detection and prevention.

[44]  Kinzo Matsumoto,et al.  Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. , 2000, European journal of pharmacology.

[45]  L. Jan,et al.  Functional Dissociation of μ Opioid Receptor Signaling and Endocytosis Implications for the Biology of Opiate Tolerance and Addiction , 1999, Neuron.

[46]  P. Crooks,et al.  High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). , 1999, Journal of pharmaceutical and biomedical analysis.

[47]  H. Sampson.  Epidemiology of food allergy , 1996, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[48]  P. Houghton,et al.  Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. , 1995, Planta medica.

[49]  H. Matthes,et al.  The human delta-opioid receptor: genomic organization, cDNA cloning, functional expression, and distribution in human brain. , 1994, Molecular pharmacology.

[50]  G. Uhl,et al.  Human mu opiate receptor. cDNA and genomic clones, pharmacologic characterization and chromosomal assignment. , 1994, FEBS letters.

[51]  A Goldstein,et al.  Cloning and pharmacological characterization of a rat kappa opioid receptor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[52]  N. Chakravarty.  Inhibition of histamine release from mast cells by nigellone. , 1993, Annals of allergy.

[53]  R. Stead,et al.  Mast cells are closely apposed to nerves in the human gastrointestinal mucosa. , 1989, Gastroenterology.

[54]  V. Hruby,et al.  Antidiarrheal properties of supraspinal mu and delta and peripheral mu, delta and kappa opioid receptors: inhibition of diarrhea without constipation. , 1989, The Journal of pharmacology and experimental therapeutics.

[55]  Bock Sa.  Prospective Appraisal of Complaints of Adverse Reactions to Foods in Children During the First 3 Years of Life , 1987 .

[56]  S. Bock.  Prospective appraisal of complaints of adverse reactions to foods in children during the first 3 years of life. , 1987, Pediatrics.

[57]  V. Tandon,et al.  Tylophora indica in bronchial asthma--a double blind study. , 1979, The Indian journal of medical research.

[58]  J. Clain,et al.  A double-blind trial of loperamide in the treatment of chronic diarrhoea. , 1979, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[59]  G. Jaffé.  A Comparison of Lomotil and Imodium in Acute Non-Specific Diarrhoea , 1977, The Journal of international medical research.