Possible therapeutic effects of Nigella sativa and its thymoquinone on COVID-19

Figures & data

Table 1. Antiviral effects of N. sativa and TQ.

Type of plant Extract	Effective doses	Model of study	Effects	Reference
N. Sativa oil	100 μg/100 μL	MCMV	Inhibited the virus titres in spleen and liver 3 and significantly reduced the viral load in the liver and spleen. Raising IFN-γ serum level and increasing numbers of CD4+ helper T cells	Salem and Hossain (2000)
Fed diets of N. Sativa	2%, 4% and 6%	H9N2 AIV	Significantly increased the body weight and reduced mortality was observed in turkeys. Significantly lower virus titre than those in control group. Moreover, fed diets of N. sativa increased the expression levels of IFN-γ mRNA compared to the control group.	Umar et al. (2016)
N. sativa oil	Capsule (450 mg)	HCV patients	Significant decreased the viral load and also improvement of the oxidative stress due to augmented total antioxidant activity. N. sativa oil also improved RBC, platelet counts, total protein and albumin in HCV patients	Barakat et al. (2013)
Fed diets of TQ	5 g/kg	H9N2 AIV	Significantly increased antibody titre against H9N2 and increased gene expression of IFN-γ. TQ also reduced virus shedding and enhanced immune responses in treated animals that lead to suppress pathogenesis of H9N2 viruses	Umar et al. (2016)

MCMV: murine cytomegalovirus; H9N2 AIV: H9N2 avian influenza virus; HCV: hepatitis C virus.

Table 2. Anti-inflammatory and immuno-modulatory effects of N. sativa.

Type of plant extract	Effective doses	Model of study	Effects	Reference
Ethanolic extract	1000 µg/mL	Splenocytes cells	IL-4 and IFN-γ	Gholamnezhad et al. (2015)
Aqueous extract	2 µg/mL	PBMC cells	TNF-α, IL-1β and IL-4 IL-8	Haq et al. (1999)
	100 µg/mL	Splenocytes cells	IL-6, TNF-α, and NO IL-4 and IL-10	Majdalawieh et al. (2010)
	0.5 µg/mL	Human lymphocyte	IL-1β and IL-3	Haq et al. (1995)
Ethanolic extract	200 mg/kg, p.o.	Rat	IL-6, IL-10 and TNFα IL-4	Gholamnezhad et al. (2014)
Hydroethanolic	2500 mg/L, p.o.	Guinea pigs	IL-4, IFN-γ	Boskabady, Keyhanmanesh et al. (2011)
	80 mg/L, p.o.	Guinea pigs	Neutrophil number and restored the IL-4 and IFN-γ changes	Boskabady, Vahedi et al. (2011)
Volatile oil	2.10 µg, i.m	Rat	Splenocytes and neutrophils counts Peripheral lymphocytes and monocytes	Islam et al. (2004)
Aqueous extract	2.8 g/kg,bw	Rat	The expression of transforming growth factor beta 1 (TGF β1)	Noor et al. (2015)
Diet of N. sativa	5%	Rainbow trout	Serum protein and total Ig levels	Dorucu et al. (2009)
Supplement of N. sativa oil	10 mg/kg, p.o.	Human	Production of prostaglandin E2	Salem (2005)
Capsule of N. sativa oil	40 mg/kg/day, p.o.	Human	IgE, eosinophil count, endogenous cortisol in plasma and urine	Kalus et al. (2003)

IL: interleukins; IFN-γ: interferon gamma; TNF-α: tumour necrosis factors alpha; PBMC: peripheral blood mononuclear cell; TGF β1: transforming growth factor beta 1; Ig: immunoglobulin.

Figure 1. The possible anti-inflammatory and immunomodulatory effects of N. sativa and TQ on COVID-19 induced acute respiratory distress syndrome (ARDS).

Table 3. Anti-inflammatory and immuno-modulatory effects of TQ.

Bioactive compound	Effective doses	Model of study	Effects	Reference
TQ	10 μM	Mast cells	IL-5 and IL-13 mRNA expression	El Gazzar (2007)
	20 μM	Dendritic cells	IL-10, IL-12, and TNFα Caspase 3 and caspase 8	Xuan et al. (2010)
	25 μM	KBM-5 cells	NF-κB activation, anti-apoptotic, and angiogenic gen	Sethi et al. (2008)
	75 μM	(PDA) cells	IL-1β, TNFα, MCP-1, and COX-2	Chehl et al. (2009)
	3 mg/kg, i.p.	Guinea pigs	IL-4 IFN-γ	Rana Keyhanmanesh et al. (2014)
	3 mg/kg, i.p.	Mice	LTB4 and LTC4, IL-4, IL-5 and IL-13 IL-10	El Gazzar, El Mezayen, Marecki et al. (2006)
	3 mg/kg, i.p.	Mice	IgE and IgG1, IL-4, IL-5, and IL-13 and IFN-γ	El Gazzar, El Mezayen, Nicolls (2006)
	20 mg/kg, p.o.	Rat	IL-2 and T cell proliferation	Badr et al. (2011)
	5 or 10 mg/kg, i.p.	Rat	IL-6, TNF-α, and NO metabolites	Bargi et al. (2017)
	10, 20, and 40 mg/kg/day, p.o.	Rat	Amyloid-β (Aβ) formation and accumulation, and also decreased TNF-α and IL-1β	Abulfadl et al. (2018)

KBM-5: myeloid leukaemia cell line; PDA: pancreatic ductal adenocarcinoma cells; NF-κB: nuclear factor-κB; MCP-1: monocyte chemoattractant protein-1; COX-2: cyclooxygenase-2; LTB4: leukotriene B4; LTC4: leukotriene C4; NO: nitric oxide.

Salem ML, Hossain MS. 2000. Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection. Int J Immunopharmacol. 22(9):729–740.

 PubMed Web of Science ®Google Scholar

Umar S, Shah MA, Munir MT, Yaqoob M, Fiaz M, Anjum S, Kaboudi K, Bouzouaia M, Younus M, Nisa Q, et al. 2016. Synergistic effects of thymoquinone and curcumin on immune response and anti-viral activity against avian influenza virus (H9N2) in turkeys. Poult Sci. 95:1513–1520.

 PubMed Web of Science ®Google Scholar

Barakat EMF, El Wakeel LM, Hagag RS. 2013. Effects of Nigella sativa on outcome of hepatitis C in Egypt. World J Gastroenterol. 19:2529–2536.

 PubMed Web of Science ®Google Scholar

Gholamnezhad Z, Rafatpanah H, Sadeghnia HR, Boskabady MH. 2015. Immunomodulatory and cytotoxic effects of Nigella sativa and thymoquinone on rat splenocytes. Food Chem Toxicol. 86:72–80.

 PubMed Web of Science ®Google Scholar

Haq A, Lobo PI, Al-Tufail M, Rama NR, Al-Sedairy ST. 1999. Immunomodulatory effect of Nigella sativa proteins fractionated by ion exchange chromatography. Int J Immunopharmacol. 21(4):283–295.

 PubMed Web of Science ®Google Scholar

Majdalawieh AF, Hmaidan R, Carr RI. 2010. Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J Ethnopharmacol. 131(2):268–275.

 PubMed Web of Science ®Google Scholar

Haq A, Abdullatif M, Lobo PI, Khabar KS, Sheth KV, Al-Sedairy ST. 1995. Nigella sativa: effect on human lymphocytes and polymorphonuclear leukocyte phagocytic activity. Immunopharmacology. 30(2):147–155.

 PubMedGoogle Scholar

Gholamnezhad Z, Boskabady MH, Hosseini M. 2014. Effect of Nigella sativa on immune response in treadmill exercised rat. BMC Complement Alternat Med. 14:1–11.

 PubMed Web of Science ®Google Scholar

Boskabady M-H, Keyhanmanesh R, Khameneh S, Doostdar Y, Khakzad M-R. 2011. Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs. J Zhejiang Univ Sci B. 12(3):201–209.

 PubMed Web of Science ®Google Scholar

Boskabady MH, Vahedi N, Amery S, Khakzad MR. 2011. The effect of Nigella sativa alone, and in combination with dexamethasone, on tracheal muscle responsiveness and lung inflammation in sulfur mustard exposed guinea pigs. J Ethnopharmacol. 137(2):1028–1034.

 PubMed Web of Science ®Google Scholar

Islam N, Begum P, Ahsan T, Huque S, Ahsan M. 2004. Immunosuppressive and cytotoxic properties of Nigella sativa. Phytother Res. 18(5):395–398.

 PubMed Web of Science ®Google Scholar

Noor NA, Fahmy HM, Mohammed FF, Elsayed AA, Radwan NM. 2015. Nigella sativa ameliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats. Int J Clin Exp Pathol. 8:6269.

 PubMed Web of Science ®Google Scholar

Dorucu M, Colak SO, Ispir U, Altinterim B, Celayir Y. 2009. The effect of black cumin seeds, Nigella sativa, on the immune response of rainbow trout, Oncorhynchus mykiss. Mediter Aquacult J. 2(1):27–33.

 Google Scholar

Salem ML. 2005. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol. 5(13–14):1749–1770.

 PubMed Web of Science ®Google Scholar

Kalus U, Pruss A, Bystron J, Jurecka M, Smekalova A, Lichius JJ, Kiesewetter H. 2003. Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. Phytother Res. 17(10):1209–1214.

 PubMed Web of Science ®Google Scholar

El Gazzar M. 2007. Thymoquinone suppresses in vitro production of IL-5 and IL-13 by mast cells in response to lipopolysaccharide stimulation. Inflamm Res. 56(8):345–351.

 PubMed Web of Science ®Google Scholar

Xuan NT, Shumilina E, Qadri SM, Götz F, Lang F. 2010. Effect of thymoquinone on mouse dendritic cells. Cell Physiol Biochem. 25:307–314.

 PubMed Web of Science ®Google Scholar

Sethi G, Ahn KS, Aggarwal BB. 2008. Targeting nuclear factor-κB activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Res. 6:1059–1070.

 PubMed Web of Science ®Google Scholar

Chehl N, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA. 2009. Anti‐inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB. 11:373–381.

 PubMed Web of Science ®Google Scholar

Rana Keyhanmanesh LP, Omrani H, Mirzamohammadi Z, Shahbazfar AA. 2014. The effect of single dose of thymoquinone, the main constituents of Nigella sativa, in guinea pig model of asthma. BioImpacts: BI. 4:75–81.

 PubMedGoogle Scholar

El Gazzar M, El Mezayen R, Marecki JC, Nicolls MR, Canastar A, Dreskin SC. 2006. Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation. Int Immunopharmacol. 6:1135–1142.

 PubMed Web of Science ®Google Scholar

El Gazzar M, El Mezayen R, Nicolls MR, Marecki JC, Dreskin SC. 2006. Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma. Biochim Biophys Acta. 1760:1088–1095.

 PubMed Web of Science ®Google Scholar

Badr G, Alwasel S, Ebaid H, Mohany M, Alhazza I. 2011. Perinatal supplementation with thymoquinone improves diabetic complications and T cell immune responses in rat offspring. Cell Immunol. 267:133–140.

 PubMed Web of Science ®Google Scholar

Bargi R, Asgharzadeh F, Beheshti F, Hosseini M, Sadeghnia HR, Khazaei M. 2017. The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress status and memory deficits induced by lipopolysaccharide in rats. Cytokine. 96:173–184.

 PubMed Web of Science ®Google Scholar

Abulfadl Y, El-Maraghy N, Ahmed AE, Nofal S, Abdel-Mottaleb Y, Badary O. 2018. Thymoquinone alleviates the experimentally induced Alzheimer’s disease inflammation by modulation of TLRs signaling. Hum Exp Toxicol. 37(10):1092–1104.

 PubMed Web of Science ®Google Scholar