Natural therapeutic approach of Nigella sativa (Black seed) fixed oil in management of Sinusitis.

Sinusitis is associated with inflammation and infections of air-filled cavities of sinuses. The aim of this study was to evaluate the potential efficacy of Nigella sativa seed fixed oil in management of sinusitis. The information was extracted from accessible international databases, traditional books, electronic resources, and unpublished data.
RESULTS: The results of investigations on N. sativa seed fixed oil showed its therapeutic potential in treatment of sinusitis by its anti-inflammatory, antioxidant, antihistaminic, immune-modulator, antimicrobial and analgesic effects. The use of N. sativa seed fixed oil can inhibit the inflammation of sinuses and respiratory airways, microbial infections and finally help the patients suffering from clinical symptoms of sinusitis such as coryza, nasal congestion, headache, neck pain, earache and toothache. Clinical studies are required to evaluate its efficacy in patients with sinusitis in future.

Introduction

The air-filled cavities of sinuses is one of host defense system, which act by classical, pseudostratified and ciliated columnar epithelium. When one or more of paranasal sinuses become inflamed, sinusitis occurs. Classically, there are four types of sinusitis including acute, sub-acute, chronic and recurrent ones. The infection of paranasal sinuses, which occur 10 days and less than 4 weeks is defined as acute sinusitis. The inflammatory diseases of sinuses, much similar to asthma is chronic sinusitis. Viral upper respiratory infection leads to inflammation of sinuses, damaging the mucosa and defective performance of cilia, which prone the environment to bacterial infections. Rhinoviruses, Streptococcus pneumonia, Haemophilus influenza, and Moraxella catarrhalis are the majority pathogens of acute sinusitis 2, 3. In spite of inflammatory nature of acute sinusitis, the involved bacterial pathogens of acute sinusitis, Staphylococcus aureus, coagulase negative Staphylococci are found in chronic sinusitis . Postnasal drip, greenish nasal discharge, nasal congestion, tenderness of the face under the eyes or at the bridge of the nose, frontal headaches, pain in teeth, cough and fever are common symptoms of sinusitis. Antibiotics (amoxicillin, doxycycline, cephalexin and cefadroxil, etc.) are prescribed for 85-98% of patients with acute sinusitis 5, 6, 7. Nasal corticosteroids, and anti-histamines are used in patients with sneezing or rhinitis. Corticosteroids and antibiotics are used in chronic sinusitis . The appearance of antibiotic resistant pathogens to chemical agents along with the adverse effects of drugs encourage the scientists to search among the medicinal plants. One of popular plants in traditional medicines for management of sinusitis and clinical symptoms is Nigella sativa seeds.

Nigella sativa, a member of Ranunculaceae family is commonly known as black seed. N. sativa seed with a rich historical and religious background is the miracle curative herb for all ailments, except the death. N. sativa seeds are used widely for extraction of fixed oil. N. sativa seeds were used by Dioscorides as diuretic, emmenagogue, galactopoietic. Avicenna in the “Canon of Medicine” used the black seed for stimulating the body's energy and helping recovery from fatigue and dispiritedness. It was a remedy for coryza. Frying the seeds in oil and putting in the lint and putting on forehead, relieves the headache. Soaking the seeds in the vinegar for one night and crushing them and smelling was a remedy for chronic headache . In Middle East countries, N. sativa seed oil is used as antiseptic, local analgesic and for treatment of asthma, bronchitis, rheumatism and other inflammatory diseases . Algerians take the roasted seeds with butter for cough, and with honey for colic, Arabians use its seed as lactagogue, soaking in rose oil as eye drops for eye infections. Indian people use the seed tincture for anorexia, diarrhea, dyspepsia and fever or seed fixed oil in sesame oil for dermatosis. N. sativa is anthelmintic, carminative, emmenagogue and stimulant in Ayurvedic. Sniffing the cloth containing the mixture of N. sativa seed with melted butter is used by Ethiopians for headache. Indonesians combine N. sativa seed with astringent medicines for abdominal disorders. The seed extract is used for treatment of liver ailments. The poultice seeds is used by Malayans for treatment of abscesses, headache, nasal ulcers, orchitis and rheumatism. In North Africans, mixture of N. sativa seed with honey is used as morning aperitif. Unani Medicine consider the plant as abortifacient, diuretic, anthelmintic and emmenagogue and good treatment for cough, fever, jaundice, pulmonosis and sore eyes. In Yemen, the seeds are used for hemorrhoids .

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Fig. 1

Nigella sativa fixed oil in management of clinical symptoms of sinusitis.

Fixed oils is extracted for edible purposes, flavoring foods, preservatives in confectioneries, stabilizing of edible fats and pharmaceutical applications. According to traditional uses of N. sativa seed for treatment of headache, fever, cough and coryza, N. sativa seed fixed oil has a good potency for treatment of sinusitis. In this review article, we evaluate the therapeutic potency of N. sativa fixed oil in management of sinusitis and its symptoms.

Chemical composition of N. sativa seed fixed oil

The therapeutic effects of herbal medicines has direct correlation with their chemical compositions. Before everything, we evaluate the chemical composition of N. sativa seed oil in this section.

The seeds contain amino acids, proteins, carbohydrates, 0.4-1.49% essential oil, 30-44.21% fixed oil, sterols (cholesterol, campestrol, stagmasterol, α-spinasterol, β-sitosterol) , alkaloids (nigellidine, nigellimine, nigellicine), saponins and crude fiber, minerals (calcium, iron, sodium, potassium) . Thymoquinone (26.8-54.8%), p-cymene (14.7-38.0%), longifolene (1.2-10.2%), α-thujene (1.3-10.1%), carvacrol (0.5-4.2%), α-cubebene (0.4-3%), α-pinene (0.2-2.4%), limonene (0.7-2.3%), β-pinene (0.4-3.0%), sabinene (0.2-1.6%) were the main components of N. sativa seed essential oil . Linoleic acid make up 50% of fixed oil, followed by oleic acid (25%), palmitic acid (18%). Thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone) is present at concentration of 3.5-8.7 mg/g in fixed oil 15, 16.

The potential efficacy of N. sativa fixed oil in treatment of sinusitis

The anti-histaminic, anti-oxidant and anti-inflammatory effects of N. sativa seed fixed oil

Sinusitis is associated with inflammation of sinus cavities as the result of an irritant or triggering the body's histamine responses. Therefore, the anti-inflammatory, anti-histaminic and antioxidant effects of N. sativa seed fixed oil may explain one of mechanisms related to its efficacy in reducing the inflammation of sinuses and respiratory airways.

In animal model of allergic asthma, cyclooxygenase and 5-lipoxygenase pathways of rat peritoneal leukocytes inhibited by N. sativa fixed oil, by inhibition of thromboxane B2 and leukotriene B4 metabolites . Lung inflammation was improved and peripheral blood eosinophil count was decreased by N. sativa fixed oil . Oral administration of fixed oil in animal models significantly decreased the leukocyte, platelet counts .

The anti-inflammatory effects of N. sativa seed fixed oil is related to thymoquinone, nigellone, thymohydroquinone. Low concentration of Nigellone has been proved to inhibit the histamine release . 500 mg N. sativa seed fixed oil in the form of capsule is used as anti-histamine agent . N. sativa seed fixed oil, thymoquinone and nigellone dose dependently inhibited the formation of 5-lipoxygenase products and 5-hydroxy-eicosa-tetra-enoic acid (5-HETE) from polymorphonuclear leukocytes . Thymoquinone has exhibited anti-histaminic, anti-inflammatory and immunoboosting effects .

Rather than, the anti-inflammatory effects of N. sativa seed fixed oil in mice and rat animal models, N. sativa seed fixed oil reduced the serum levels of TNF-α and high sensitivity C-reactive protein in calorie restricted obese women . Furthermore, oral administration of 1 g N. sativa seed fixed oil in patients suffering from rheumatoid arthritis for 8 weeks increased the serum levels of IL-10 without any changes in TNF-α . The anti-inflammatory effects of daily administration of 0.5 ml N. sativa seed fixed oil for 30 days were associated with significant suppression of nasal mucosal congestion, turbinate hypertrophy, nasal itching, mucosal pollar and sneezing attacks of patients suffering from allergic rhinitis . In nasal congestion, the mucosa of nose and para-nasal sinuses becomes swollen, and this condition is associated with edema, mucus secretion and difficult breathing. The inflammatory disorders like sinusitis, otitis, bronchitis or asthma may be the reason of nasal congestion. Therefore, the significant suppression of nasal congestion may improve the clinical sign of sinusitis. The clinical evidence about preventive and bronchodilatory effects of N. sativa seed fixed oil on obstructive respiratory diseases are attributed to its anti-inflammatory, and antioxidant effects of its oil or oil components . This beneficial effects of N. sativa seed fixed oil in sinusitis could be attributed to these anti-inflammatory and antioxidant effects. The anti-inflammatory effects of N. sativa seed fixed oil is attributed to its antioxidant activity. The antioxidant effects of N. sativa seed fixed oil were confirmed 16, 26. Therefore, the antioxidant, anti-histaminic and anti-inflammatory effects of N. sativa seed fixed oil and main components decrease the inflammation of sinuses and respiratory airways, and inhibit the nasal congestion, edema, coryza as the clinical signs of sinusitis.

Immunomodulatory effects of N. sativa seed fixed oil

The immunomodulatory effects of N. sativa may be another reason for its beneficial effects in sinusitis. Oral N. sativa seed fixed oil enhanced humoral immune responses by reduction in IgA, IgM and C3 levels . The immunomodulatory effects of N. sativa seed fixed oil is not related to the effects on Th1 and Th2 cell responsiveness to allergen stimulants . N. sativa seed fixed oil decreased the serum IgG1, IgG2a, IL-2, IL-12, IL-10, IFN-γ and inflammatory cells in lung tissue of murine model of allergic asthma . 5 ml/kg/day injected N. sativa seed fixed oil for 17 days in CD1 albino mice decreased IgG and serum IL-2 and IL-12 , also 4 ml/kg/day injected N. sativa seed fixed oil in OVA sensitized BALB/c mice for 7 days decreased total IgE, IgG1 and OVA IgG1, mRNA expression of IL-4, IL-5, IL-6 and TGF-β1 from lung cells and nitric oxide, eosinophils, macrophages and lymphocytes , Thymoquinone decreased leukotriene , OVA IgE & IgG1, IL-4, IL-5, IL-13, IFN-c, eosinophils , blood IFN-γ in mice animal models and cell lines. N. sativa seed fixed oil can ameliorate the cellular immunological changes due to chloramphenicol . Weak immune system is the cause of recurrent sinus infections that make the body vulnerable to infections, increase the mucus production, chronic swelling of the mucous membranes, that finally leads to sinus pain. Therefore, the immunomodulatory effects of N. sativa seed fixed oil can prevent the secondary infections, headache and other clinical signs of sinusitis.

Antimicrobial effects of N. sativa fixed oil

Sinusitis especially acute ones is associated with viral and bacterial infections. Therefore, the antimicrobial activity of N. sativa fixed oil against pathogenic microorganisms can be useful in patients with sinusitis. The antiviral effects of thymoquinone, N. sativa seed fixed oil against avian influenza virus (H9N2) and murine cytomegalovirus infection model were confirmed, respectively. N. sativa seed fixed oil had stimulatory effects on CD4+ T lymphocytes in murine BALB/c cytomegalovirus model. It decreased the virus titers in spleen and liver and increased the serum IFN-γ level and MΦ number and function . The antifungal activity of thymoquinone against Candida sp. (C. albicans, C. krusei, C. tropicalis), dermatophytes (Epidermophyton fluccosum, Microsporum canis, M. gypseum, Trichophyton interdigitale, T. mentagrophytes and T. rubrum) were the subject of some studies. Thymoquinone exhibited strong antimicrobial properties against Gram negative and positive bacteria with MIC values in the ranges of 8-512 μg/ml 39, 40, 41, and had synergistic effects with particular antibiotics and act as resistant modifiers 39, 40, 41, 42. 0.1% w/w N. sativa seed fixed oil is used as potent food preservative . Although, in vitro studies have introduced N. sativa seed fixed oil as broad extended antimicrobial agents, but other studies are required to evaluate its antimicrobial effects against the involved pathogens in sinusitis.

Analgesic effects of N. sativa fixed oil

As we noted before, there is a connection between sinusitis and pain in ear, teeth, jaw, throat, neck and so on. Therefore, the analgesic effects of N. sativa seed fixed oil can suppress some clinical symptoms in patients suffering from sinusitis.

N. sativa seed fixed oil as an opioid principle with an antagonizing effects on naloxone had been the strong antinociceptive actions in hot plate test, tail pinched test, acetic acid Writhing test models of mice and rats . N. sativa seed fixed oil loaded liposomes in hot plate test showed analgesic effects . The dose dependent analgesic response of 50-400 mg/kg N. sativa seed fixed oil (p.o) was confirmed in hot plate test, tail-pinch test, acetic acid induced writhing test and early phase of formalin test, while the systemic administration of thymoquinone showed antinociceptive effects in early and late phase of formalin test. The antinociceptive effects N. sativa seed fixed oil and thymoquinone in early phase of formalin test was blocked by naloxone. Also, the antinociceptive effects of thymoquinone in early phase of formalin test was suppressed by naloxone, naloxonazine, while naltrindole had no effects on nociceptive response of thymoquinone. Thymoquinone and N. sativa seed fixed oil decreased the antinociceptive effect of morphine, therefore, the antinociceptive effects of N. sativa seed fixed oil and thymoquinone is via indirect activation of k-opoid and supra-spinal μ1 receptor subtypes . The analgesic effects of N. sativa seed fixed oil confirm the scientific reason for traditional uses of it in headache and its novel potential in treatment of pain related to sinusitis.

Safety of N. sativa seed fixed oil

According to traditional believes, N. sativa had hot and dry temperament, therefore it can cause respiratory complications in hot temperament individuals. Processing the seeds with vinegar according to Iranian Traditional recommendation eliminate the related adverse effects due to its seed. Comparative study on the fixed oil from non-processed or processed N. sativa seed showed the same content of fatty acids, while thymoquinone was eliminated in processed seeds . Evaluating the safety of 0.3% oral N. sativa seed fixed oil for 8 weeks in rats, showed no significant changes in vital organs (heart, liver, pancreas, lungs, spleen, kidneys) to body weight ratio, red and white blood cells, cardiac enzymes, liver enzymes, urea, creatinine, albumin, A/G ratio and total protein . 200 mg/kg/day of N. sativa seed oil for 14 weeks revealed no histopathological changes in liver, kidneys, spleen, lungs, stomach, intestine, testes and accessory organs, and thyroid Gland . The LD50 of N. sativa seed fixed oil was 29 mL/kg in mice and rats. Intake of 2 mL/kg N. sativa seed fixed oil for 12 weeks had no clear organ damage, no fall in leukocyte and platelet counts . Supplementing the rats with 4% N. sativa fixed oil was associated with no harmful effects , while feeding female rats with 0.8 ml/daily N. sativa fixed oil caused a minor weight loss and through two pregnancies improved pups health . 500-1000 mg of N. sativa seed fixed oil, three times a day is recommended as typical dose. Sub-chronic and sub-acute of thymoquinone (10-100 mg/kg body weight) had been no toxicity and death . The LD50 for intraperitoneal and oral thymoquinone were 104.7 mg/kg and 870.9 mg/kg in mice and 794.3 and 57.5 mg/kg in rats .

Conclusion

N. sativa seed is valuable herbal medicine that is traditionally used for treatment of all diseases except the death. One component of N. sativa seed is its fixed oil rich in fatty acid oils and some valuable ingredients such as thymoquinone, nigellone, etc. N. sativa seed fixed oil has been used by traditional practitioners Avicenna, Dioscorides as treatment for headache, infections, coryza, and nasal congestion. Recent investigations on N. sativa seed fixed oil have exhibited that it has anti-inflammatory, anti-oxidant, anti-histaminic, antimicrobial, analgesic, and immunomodulator activities. These pharmacological activities make it as suitable candidates for treatment of sinusitis. The inflammatory effects of sinuses and airways inhibit by N. sativa seed fixed oil, also, its immunomodulatory and antihistaminic effects of oil prevent from secondary infections of sinuses and respiratory airways. Also, the antiviral and antibacterial effects of oil kill the pathogenic microorganisms. All of these activities along with analgesic effects of N. sativa seed fixed oil protect the patients against pain in ear, head, teeth and neck. Although, previous studies introduce N. sativa seed fixed oil as a potential treatment in management of sinusitis, large double blind clinical trials are required to compare the efficacy and safety of N. sativa seed fixed oil with current treatment in futures.

Conflict of interest

There was no conflict of interest.