Nigellin – a functional food with multi-beneficial potential

Black seed extract has been historically used for different ailments. Black seed has a high food value, with adequate protein and essential fatty acids (EFAs), amino acids, and minerals. It is known to increase the activity of macrophages and help in phagocytosis (engulfing the invading pathogen). It is also known to be very helpful in allergies, allergic rhinitis, asthma, and eczema.

Sabinsa is pleased to introduce Nigellin®, a COSMOS approved and ECOCERT verified nutrient, prepared from the most revered medicinal seed, Nigella sativa (Black seed), with high thymoquinone content for general health and wellness. It is standardized to contain not less than 5% thymoquinone and up to 20%.

Immunomodulatory potential

Nigellone, present in black seed oil, protects from histamine-induced bronchial spasms (explaining its use to relieve asthma symptoms, bronchitis, and coughing) (Gilani AH. et al., 2001). Thymoquinone is an anti-inflammatory compound with positive effects on allergies and asthma. In a comparative clinical study, black seed steam inhalation was highly effective in relieving allergy symptoms (Al-Jawad FH. et al., 2012). In a randomized clinical trial, black seed oil could reduce nasal mucosal congestion, nasal itching, runny nose sneezing, and mucosal pallor within the first two weeks of consumption (Nikakhlagh S. et al., 2011).

The immunomodulatory activity of different black seed extracts was assessed by releasing mediators (IL-2, IL-6, PGE₂) in primary human T-lymphocytes, monocytes, and A549 human lung epithelial cells (Koshak AE. et al., 2018).

Thymoquinone-rich black seed extracts (Nigellin) showed the most remarkable effect on suppressing inflammatory mediators IL-2, IL-6, and PGE₂ release from human T-lymphocytes and marked suppression of IL-6 and PGE₂ release in human monocytes. On the other hand, the extract containing thymoquinone had a remarkable effect enhancing the release of PGE₂ from A549 human lung epithelial cells.

These results confirm that thymoquinone-rich black seed extract is helpful against asthma and allergic conditions. The beneficial effects are mediated by the suppression of pro-inflammatory mediators from human T-lymphocyte and monocytes and the possible bronchodilatory effect by enhancing PGE₂ release in A549 human lung epithelial cells.

Several experimental studies also reveal that thymoquinone inhibits cyclooxygenase and lipoxygenase enzymes, preventing the generation of eicosanoids. In addition, it further downregulates the expression of inflammatory cytokines, including interleukin IL-1, IL-6, TNFα, and iNOS, which can activate alveolar macrophages and neutrophils and increase pulmonary vascular permeability, releasing oxygen radicals and proteolytic enzymes (Hossen MJ. et al., 2017).

Metabolic health

Metabolic syndrome is a cluster of conditions that leads to heart disease, stroke, and type 2 diabetes. This is diagnosed when someone has high blood pressure, high blood sugar levels, excess body fat around the waist, and abnormal cholesterol or triglyceride levels (Wilborn C. et al., 2007).

In an in vitro study, Nigellin was found to increase glucose uptake by skeletal muscle cells and adipocytes, which was comparable to the effect of insulin (Fig.1) (Majeed M. et al., 2021).

Figure 1. Effects of Nigellin on glucose uptake by skeletal muscle cells and adipocytes (adapted from Majeed M. et al., 2021, patent).

Supplementation of Nigella sativa seeds significantly reduced fasting blood glucose (FBG), blood glucose level 2 hours postprandially (2 hPG), and glycosylated hemoglobin (HbA1c) without significant change in body weight (Bamosa AO. et al., 2010). In addition, Nigellin showed an inhibition of alpha-glucosidase enzyme with an IC₅₀ value of 28.78 μg/mL, which delays the absorption of carbohydrates from the small intestine and thus has a lowering effect on postprandial blood glucose and insulin levels. Therefore, black seed extract could be highly beneficial in reducing the complications associated with high blood sugar and help in maintaining excellent metabolic health.

Male health

Infertility resulting in childlessness is a social and clinical problem affecting couples worldwide. Among infertile couples, male factors contribute to more than half of all cases of childlessness. Several factors such as congenital diseases, hormonal imbalance, genetic and nutritional defects are among disorders in the normal function of the testicle which cause men’s infertility.

In a placebo-controlled clinical study, supplementation of 2.5 ml black seed oil (n=34) two times a day for two months showed sperm count, motility and morphology and semen volume, pH, and round cells were improved significantly in the black seed oil group (Fig. 2) compared with the placebo group. Hence, daily intake of 5 ml black seed oil for two months improves abnormal semen quality in infertile men without any adverse effects.

^{Figure 2. Semen quality after Black seed oil supplementation}

Conclusion

Black seed extract (Nigella sativa), the emerging antioxidant ingredient, has been traditionally used to manage numerous health conditions. The primary active constituent of Black seed, thymoquinone, exhibited potential healthy inflammation support via suppression of inflammatory mediators (IL-2, IL-6, PGE₂) and positive effects in asthma due to suppression of most active cytokines and broncho-dilatory effects. Several preclinical and clinical studies demonstrated that black seed extract helps manage healthy blood glucose levels, regulates blood cholesterol levels, and prevents oxidative stress, which helps in maintaining excellent metabolic health. Further, black seed oil intake improved male fertility without any adverse effects.

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_References:

_{Al-Jawad FH, Al-Razzuqi RAM, Hashim HM, and Ismael AH. Broncho-relaxant activity of Nigella sativa versus anthemis nobilis in chronic bronchial asthma: A comparative study of efficacy. IOSR Journal of pharmacy 2013; 2(4): 81-83.}

_{Bamosa AO, Kaatabi H, Lebda FM, Al Elq AM and Al-Sultan A. Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Indian J Physiol Pharmacol. 2010; 54 (4): 344–354.}

_{Kolahdooz M, Nasri S, Modarres SZ, Kianbakht S and Huseini HF. Effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men: A randomized, double-blind, placebo-controlled clinical trial. Phytomedicine 21: 901–905.}

_{Gilani AH, Aziz N, Khurram IM, Chaudhary KS and Iqbal A. Bronchodilator, spasmolytic and calcium antagonist activities of Nigella sativa seeds (Kalonji): A traditional herbal product with multiple medicinal uses. J Pak Med Assoc. 2001; 51(3): 115-120.}

_{Hossen MJ, Yang WS, Kim D, Aravinthan A, Kim JH and Cho JY. Thymoquinone: An IRAK1 inhibitor with in vivo and in vitro anti-inflammatory activities. Sci Rep. 2017; 7: 42995.}

_{Koshak AE, Yousif NM, Fiebich BL, Koshak EA and Heinrich M. Comparative Immunomodulatory Activity of Nigella sativa L. Preparations on pro-inflammatory mediators: a focus on asthma. Front Pharmacol.2018; 9: 1075. Majeed M, Nagabhushanam K and Mundkur L. Compositions for the management of hyperglycemia and related conditions. 2021. Journal name is missing}

_{Nikakhlagh S, Rahim F, Aryani FH, Syahpoush A, Brougerdnya MG and Saki N. Herbal treatment of allergic rhinitis: The use of Nigella sativa. Am J Otolaryngol. 2011; 32(5): 402-407.}

_{Wilborn C, Beckham J, Campbell B, Harvey T, Galbreath M, La Bounty P, Nassar E, Wismann J and Kreider R. Obesity: Prevalence, theories, medical consequences, management, and research directions. J Int Soc Sports Nutr. 2005; 2(2): 4–31.}