Thymoquinone and T- cell immunity

Dr. Weeks’ Comment:  Wow!  
“…These results suggest that TQ has a beneficial effect in conditioning T cells in vitro for adoptive T-cell therapy against cancer and infectious disease…”
“…The oil and certain active ingredients showed beneficial immunomodulatory properties, augmenting the T cell– and natural killer cell-mediated immune responses…” 
“…Although BSO treatment decreased both number and cytolytic function of NK cells on day 3 of infection, it increased numbers of Mφ and CD4(+) T cells…”
“… The aqueous extract attenuated the CCl(4) -induced liver damage likely due to the decrease of proinflammatory cytokines and T-cell proliferation…”
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Br J Biomed Sci. 2011;68(3):131-7.

Thymoquinone, the active ingredient of Nigella sativa seeds, enhances survival and activity of antigen-specific CD8-positive T cells in vitro.

Abstract

Recent preclinical and clinical studies provide evidence that adoptive transfer of in vitro activated T cells can results in significant antitumour responses in vivo upon acquisition of certain survival and homing properties during in vitro activation. Based on recent studies showing in vivo antioxidant effects of thymoquinone (TQ), the active ingredient of Nigella sativa seeds, this study aims to determine whether or not TQ can increase survival and sustain the expression of the homing receptor CD62L in antigen-specific T cells in vitro. The results showed that stimulation of OT-1 (transgenic CD+) T cells with OVA antigen resulted in activation, as shown by a decrease in the surface expression of CD62L which coincided with significant apoptosis measured three and five days after antigen stimulation. Addition of low concentrations of TQ during CD85+ T-cell activation resulted in enhanced survival of the activated T cells and sustained expression of CD62L. These effects coincided with enhancement in the capability of CD8+ T cells to produce the effector cytokine interferon-gamma (IFNgamma). These results suggest that TQ has a beneficial effect in conditioning T cells in vitro for adoptive T-cell therapy against cancer and infectious disease.

Int Immunopharmacol. 2005 Dec;5(13-14):1749-70. Epub 2005 Jul 1.

Immunomodulatory and therapeutic properties of the Nigella sativa L. seed.

Abstract

A larger number of medicinal plants and their purified constituents have been shown beneficial therapeutic potentials. Seeds of Nigella sativa, a dicotyledon of the Ranunculaceae family, have been employed for thousands of years as a spice and food preservative. The oil and seed constituents, in particular thymoquinine (TQ), have shown potential medicinal properties in traditional medicine. In view of the recent literature, this article lists and discusses different immunomodulatory and immunotherapeutic potentials for the crude oil of N. sativa seeds and its active ingredients. The published findings provide clear evidence that both the oil and its active ingredients, in particular TQ, possess reproducible anti-oxidant effects through enhancing the oxidant scavenger system, which as a consequence lead to antitoxic effects induced by several insults. The oil and TQ have shown also potent anti-inflammatory effects on several inflammation-based models including experimental encephalomyelitis, colitis, peritonitis, oedama, and arthritis through suppression of the inflammatory mediators prostaglandins and leukotriens. The oil and certain active ingredients showed beneficial immunomodulatory properties, augmenting the T cell– and natural killer cell-mediated immune responses. Most importantly, both the oil and its active ingredients expressed anti-microbial and anti-tumor properties toward different microbes and cancers. Coupling these beneficial effects with its use in folk medicine, N. sativa seed is a promising source for active ingredients that would be with potential therapeutic modalities in different clinical settings. The efficacy of the active ingredients, however, should be measured by the nature of the disease. Given their potent immunomodulatory effects, further studies are urgently required to explore bystander effects of TQ on the professional antigen presenting cells, including macrophages and dendritic cells, as well as its modulatory effects upon Th1- and Th2-mediated inflammatory immune diseases. Ultimately, results emerging from such studies will substantially improve the immunotherapeutic application of TQ in clinical settings.

Int J Immunopharmacol. 2000 Sep;22(9):729-40.

Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection.

Abstract

In this study, antiviral effect of black seed oil (BSO) from Nigella sativa was investigated using murine cytomegalovirus (MCMV) as a model. The viral load and innate immunity mediated by NK cells and Mφ during early stage of the infection were analyzed. Intraperitoneal (i.p.) administration of BSO to BALB/c mice, a susceptible strain of MCMV infection, strikingly inhibited the virus titers in spleen and liver on day 3 of infection with 1×10(5) PFU MCMV. This effect coincided with an increase in serum level of IFN-gamma. Although BSO treatment decreased both number and cytolytic function of NK cells on day 3 of infection, it increased numbers of Mφ and CD4(+) T cells. On day 10 of infection, the virus titer was undetectable in spleen and liver of BSO-treated mice, while it was detectable in control mice. Although spleen of both control and BSO-treated mice showed similar CTL activities on day 10 after infection, serum level of IFN-gamma in BSO-treated mice was higher. Furthermore, BSO treatment upregulated suppressor function of Mφ in spleen. These results show that BSO exhibited a striking antiviral effect against MCMV infection which may be mediated by increasing of Mφ number and function, and IFN-gamma production.

 

Biomed Sci Instrum. 2009;45:274-9.

Amelioration of chronic relapsing experimental autoimmune encephalomyelitis (cr-eae) using thymoquinone – biomed 2009.

Abstract

Axonal damage, demylination and inflammation of the central nervous system are the major pathological features of the human multiple sclerosis (MS). MS is thought to be due to abnormal T cell mediated immune response. Oxidative stress plays an important role in the advancement of MS. The management of oxidative stress by outlining central role of reduced glutathione. In our experiment we used Experimental autoimmune encephalomyelitis (EAE) animal model that mimic human MS and tested the effect of Thymoquinone (TQ), an oil constituent of Nigella Sativa also known as black seed. Thirty female mice of strain C57BL/6J and aged between 6 to 12 weeks were placed into 3 groups of 10 and were given Myelin Oligodendrocyte Glycoprotein (MOG) subcutaneously (SC) to induce EAE. Group A was the control group. Group B received MOG (SC) and TQ intraperiotoneally (IP) from day 1 till day 50. Group C received MOG (SC) and TQ (IP) on the appearance of first sign and symptoms of chronic relapsing EAE (CR-EAE). All Mice were examined daily for behavioral deficits and all euthanized and sacrificed on day 50. Preliminary result showed that TQ due to its antioxidant effect is almost 90% preventive and 50% curative in CR-EAE. This result could assist further studies on the mechanism of action of TQ in CR-EAE and explore the possibility of treating the human chronic relapsing multiple sclerosis phase.

Drug Test Anal. 2011 Apr;3(4):245-54. doi: 10.1002/dta.225. Epub 2011 Feb 9.

Phytochemical and biological investigation of the extracts of Nigella sativa L. seedwaste.

Abstract

Different extracts of Nigella sativa L. seed waste; aqueous (AE) 200 mg/kg, ethanol 70% (EE) 250 mg/kg and hexane (HE) 10 mg/kg, were evaluated for their hepatoprotective activities. They were administered orally, once daily, for 5 consecutive days. On day 5, liver injury was induced in animals by a single i.p. injection of carbon tetrachloride (10 mg/kg b. w. of 0.25% (v/v). Hepatoxicity produced, was evaluated by both biochemical and histopathological investigations. The aqueous extract attenuated the CCl(4) -induced liver damage likely due to the decrease of proinflammatory cytokines and T-cell proliferation. This was noticed by a significant decrease in both serum and tissue cytokines; tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ) and interlukin-beta (IL-1β), in the markers of liver functions; bilirubin and glutamic pyruvic transaminase (GPT) and in the oxidative stress markers; malondialdehyde (MDA) and glutathione content (GSH). Fractionation of this extract was performed and its component, protein, saponin, and polyphenol fractions were evaluated by appropriate analytical procedures. The crude protein of the seed waste reached 36.85% while protein fingerprint showed four bands ranging from 91.97 KD and 29.00 KD. The saponin content was evaluated through the determination of the haemolytic index and reached 15.56 mg/g dry powder. Finally, Folin Ciocalteu method was used for the determination of the total polyphenols. The same biochemical and histopathological studies were again performed on the different fractions of the aqueous extract; protein fraction (PF) 10 mg/kg, saponin fraction (SF) 5 mg/kg and polyphenol fraction (FF) 10 mg/kg. The biochemical changes were improved only by the protein fraction (PF) of the seed waste of Nigella sativa. This was manifested by a significant reduction in both serum and tissue cytokines in the liver markers and in the oxidative stress markers. Moreover, liver histopathology showed that (PF) reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, hepatic necrosis and fibrous connective tissue proliferation induced by CCl(4) in mice. From this study, it is concluded that the protein fraction of the aqueous extract of Nigella sativaseed waste exhibited a promising hepatoprotective effect in the management of different liver disorders.

 

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