Anti-inflammatory Effect Of Thymoquinone Research Articles

Immunomodulatory and AntiInflammatory Effect of Thymoquinone on Rat Liver and Kidneys

Immunomodulatory and AntiInflammatory Effect of Thymoquinone on Rat Liver and Kidneys

Anti-Inflammatory Effects of Thymoquinone in Atherosclerosis: A Mini Review

Atherosclerosis poses serious health problems and increases the risk of various cardiovascular diseases, including myocardial infarction, heart failure, ischemic stroke, and peripheral arterial disease. Atherosclerosis patients require long-term medications to prevent complications, some of which are costly and may result in unwanted adverse reactions. Natural products have emerged as potential sources of bioactive compounds that provide health benefits in cardiovascular diseases. Increased inflammation and vascular remodeling have been associated with atherosclerosis pathogenesis. The molecules involved in signaling pathways are considered valuable targets for new treatment approaches. Therefore, this review aimed to summarize the available evidence of the anti-inflammatory effects of thymoquinone, the major active compound isolated from Nigella sativa L., via inflammatory signaling pathways in atherosclerosis. Specifically, nuclear factor-κB and mitogen-activated protein kinase signaling pathways were considered. Furthermore, the potential toxic effects elicited by thymoquinone were addressed. These findings suggest a potential role of thymoquinone in managing atherosclerosis, and further studies are required to ascertain its effectiveness and safety profile.

Protection Against Blood-Brain Barrier Permeability as a Possible Mechanism for Protective Effects of Thymoquinone Against Sickness Behaviors Induced by Lipopolysaccharide in Rats

Background: Blood-brain barrier (BBB), as well-known protection for the brain, plays an active role in normal homeostasis. It might be changed by a range of inflammatory mediators to have a role in sickness behaviors. Objectives: Regarding the anti-inflammatory effects of thymoquinone (TQ), its protection against BBB permeability, as a possible mechanism for protective effects against sickness behaviors elicited by lipopolysaccharide (LPS), was evaluated in rats. Methods: The animals were grouped as follows and treated (n = 10 in each): (1) control (saline); (2) LPS 1 mg/kg, was injected two hours before behavioral tests for two weeks; (3-5) 2, 5, and 10 mg/kg TQ, respectively was injected 30 min before LPS injection. Open-field (OF), elevated plus-maze (EPM) and Forced Swimming test (FST) were done. Finally, the animals were anesthetized to evaluate for BBB permeability using Evans blue (EB) dye method. Results: Compared with control, LPS decreased the peripheral distance and crossing and also total crossing and distance in OF, (P < 0.01 - P < 0.001). The central crossing and distance and central time in all three treatment groups were more than LPS (P < 0.05 - P < 0.001). LPS also reduced the entries and the time spent in the open arm while increased the time spent in the closed arm in EPM (P < 0.05 - P < 0.001). The effects of LPS were reversed by TQ (P < 0.05 - P < 0.001). In FST, the immobility time and active time were increased and decreased by LPS compared with control (P < 0.001), respectively. In all three TQ-treated groups, the active and climbing times were more while the immobility time was fewer than the LPS (P < 0.05 - P < 0.001). The animals of the LPS group showed more EB dye content in their brain tissue than the control group (P < 0.05 - P < 0.001). TQ significantly reduced EB dye content of the brain tissues (P < 0.05 - P < 0.001). Conclusions: According to this study, protection against BBB permeability as a possible mechanism for the protective effects of TQ against sickness behaviors induced by LPS might be suggested.

The protective effects of thymoquinone on lung damage caused by cigarette smoke

Chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation that usually is caused by exposure to noxious particles or gases. Thymoquinone (TQ) prevents the production of inflammatory mediators, such as thromboxane B2 and leukotriene, by altering arachidonic acid metabolism. We investigated the preventive and curative effects of TQ on lung damage in rats caused by cigarette smoke (CS). We used 50 adult male rats, 30 of which were exposed to CS every day for 3 months. TQ in dimethylsulfoxide (DMSO) was administered intraperitoneally (i.p.) every day to ten animals to investigate the protective effects of TQ, and to ten other animals during the last 21 days to investigate the curative effect. Ten rats received saline for the last 21 days. Ten subjects were untreated controls. Ten controls that were not exposed to CS received TQ for the last ten days. Serum IL-8, IL-6, IL-1β and MMP-9 levels were measured using ELISA. IL-1β and IL-8 levels were elevated in the group exposed to CS compared to controls. IL-8 levels were decreased in the group that received only TQ compared to controls, which indicated the anti-inflammatory effect of TQ. The apoptotic index (AI) was increased in all groups that were exposed to CS compared to controls. The AI index was decreased in the group that received TQ for the last 21 days compared to the other CS groups. AI was increased in the group that received TQ daily compared to the other CS groups. Our findings indicate that TQ exerts curative effects for the inflammation caused by CS and may prevent apoptosis if administered in appropriate doses; however, long term TQ or DMSO exposure may produce cumulative toxic effects.

Immunomodulatory and Anti-inflammatory Effects of Thymoquinone.

The immunomodulatory properties of Nigella sativa seed, as a basis of its clinical applications by many cultures have been reviewed. Thymoquinone (TQ) is one of the major bioactive components of the volatile oil of N. sativa seeds. The review on immunomodulatory and anti- inflammatory effects of TQ was focused on published literature in the English language. The literature search was conducted in the following databases: PubMed (2004-2017), Scopus (2004-2017) and Google Scholar (2004-2017). The keywords used were the following terms: thymoquinone, immunomodulation, inflammation, autoimmune and asthma. The present investigations provide a comprehensive review of the ability of TQ to modulate inflammation and immune-related disorders in the various important disease states. This finding showed that TQ has anti-inflammatory properties that prevent the biosynthesis of important mediators in inflammatory processes and asthma such as 5-LO, COX, PGD2 and LTs. TQ also reduced LPS-induced proinflammatory cytokines such as interleukins (ILs) and TNF-α. In addition, TQ showed immunomodulatory role in the cellular and humoral immunity. This study also found that TQ improves imidacloprid toxicity through reducing oxidative stress and increasing chemokinesis, chemotaxis, phagocytic activity, antibody levels and the hemagglutination of immunoglobulins as well as by reducing serum MDA levels and hepatic enzymes. The study indicated the beneficial effects of TQ in immune-related diseases, however, well designed clinical trials in humans are required to confirm these effects.

The anti-inflammatory effects of thymoquinone in a rat model of allergic rhinitis

The anti-inflammatory effects of thymoquinone in a rat model of allergic rhinitis

The anti-inflammatory and antioxidant effects of thymoquinone on ceruleine induced acute pancreatitis in rats.

The aim of this study is to investigate the potential antioxidant and anti-inflammatory effects of thymoquinone (TQ) on ceruleine induced acute pancreatitis. A total of 14 male Wistar albino rats were divided into 2 groups as follows: (1) normal saline-treated group and (2) thymoquinone- treated groups. For achieving acute pancreatitis, intraperitoneal (IP) cerulein, a stable cholecystokinin (CCK) analogue, was applied in a 50 mcg/kg dose 2 times in one-hour interval in total. One hour after last ceruleine injection, IP 2 ml/kg isotonic saline solution was applied to the saline group and IP 5 mg/kg TQ was applied. The rats were sacrificed by decapitation 12 h after the last injection of last medication. Blood samples were taken, and serum interleukin-1β (IL-1β), amylase, lipase pancreatic, total antioxidant capacity (TAC), total oxidant status (TOS), and pancreatic Schoenberg scores were determined. Oxidative stress index (OSI) was calculated for each group. Results are given as mean ± SD. A value of p < 0.05 was accepted as statistically significant. SPSS for Windows v15.0 was used for statistical analyses. The increased serum amylase, lipase levels and histopathological scoring of pancreatic tissue showed that acute pancreatitis was present in both groups. Furthermore, serum IL-1β level was significantly reduced in TQ administered group (p < 0.05). Although serum TAC level was high and TOS level was low, those changes were not statistically significant. Nevertheless, OSI index, which was driven from TOS/TAC, was significantly low in TQ groups (p < 0.05). Although TQ partially ameliorated the acute pancreatitis in terms of histopathological evaluations, the main effect of it was brought about by reducing the hemorrhage in acute pancreatitis (p < 0.05). In this study, it was shown that TQ can reduce the inflammation and has a positive effect on the oxidative status of organism in inflammatory cases such as acute pancreatitis. This is consistent with partial amelioration of acute pancreatitis in rats given TQ (Tab. 2, Fig. 4, Ref. 31).

Thymoquinone Inhibits IL-1β-Induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing NF-κB and MAPKs Signaling Pathway.

Thymoquinone, an active ingredient isolated from Nigella sativa, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effect of thymoquinone on IL-1β-stimulated osteoarthritis chondrocytes remains unclear. In this study, we designed to investigate the anti-inflammatory effects and elucidated the underlying mechanism of thymoquinone on IL-1β-stimulated human osteoarthritis chondrocytes. The effects of thymoquinone on inflammatory mediators COX-2, iNOS, NO, PGE2, as well as MMP-1, MMP3, MMP13 production were detected. The results demonstrated that thymoquinone concentration-dependently inhibited IL-1β-induced COX-2, iNOS, NO, and PGE2 production. Thymoquinone also suppressed IL-1β-induced MMP-1, MMP3, and MMP13 production. We found that thymoquinone significantly inhibited IL-1β-induced NF-κB activation and IκBα degradation. In addition, thymoquinone was found to suppress IL-1β-induced mitogen-activated protein kinases (MAPKs) activation. In conclusion, thymoquinone inhibited IL-1β-induced inflammatory mediator production by inhibition of NF-κB and MAPKs signaling pathways in osteoarthritis chondrocytes. Thymoquinone may be a potential agent in the treatment of osteoarthritis.

Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells

Thymoquinone (TQ), the main pharmacological active ingredient within the black cumin seed (Nigella sativa) is believed to be responsible for the therapeutic effects on chronic inflammatory conditions such as arthritis, asthma and neurodegeneration. In this study, we evaluated the potential anti-inflammatory role of TQ in lipopolysaccharide (LPS)-stimulated BV-2 murine microglia cells. The results obtained indicate that TQ was effective in reducing NO2− with an IC50 of 5.04μM, relative to selective iNOS inhibitor LNIL-l-N6-(1-iminoethyl)lysine (IC50 4.09μM). TQ mediated reduction in NO2− was found to parallel the decline of iNOS protein expression as confirmed by immunocytochemistry. In addition, we evaluated the anti-inflammatory effects of TQ on ninety-six (96) cytokines using a RayBio AAM-CYT-3 and 4 cytokine antibody protein array. Data obtained establish a baseline protein expression profile characteristic of resting BV-2 cells in the order of osteopontin>MIP-1alpha>MIP-1g>IGF-1 and MCP-I. In the presence of LPS [1ug/ml], activated BV-2 cells produced a sharp rise in specific pro-inflammatory cytokines/chemokine's IL-6, IL-12p40/70, CCL12 /MCP-5, CCL2/MCP-1, and G-CSF which were attenuated by the addition of TQ (10μM). The TQ mediated attenuation of MCP-5, MCP-1 and IL-6 protein in supernatants from activated BV-2 cells were corroborated by independent ELISA. Moreover, the data obtained from the RT2 PCR demonstrated a similar pattern where the LPS mediated elevation of mRNA for IL-6, CCL12/MCP-5, CCL2/MCP-1 were significantly attenuated by TQ (10μM). Also, in this study, consistent data were obtained for both protein antibody array densitometry and ELISA assays. In addition, TQ was found to reduce LPS mediated elevation in gene expression of Cxcl10 and a number of other cytokines in the panel. These findings demonstrate the significant anti-inflammatory properties of TQ in LPS activated microglial cells. Therefore, the obtained results might indicate the usefulness of TQ in delaying the onset of inflammation-mediated neurodegenerative disorders involving activated microglia cells.

Retraction. Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models.

Many studies have been carried out in recent years on the pharmacological effects of nigella sativa seeds that have uncovered their antiinflammatory and immunological effects. The objective of this study was to explore the antiinflammatory effects of thymoquinone on arthritis in rat models. Rats with arthritis induced by Freund's incomplete adjuvant were assigned into five groups: group 1: controls 0.9% NaCl (n = 7); group 2: 2.5 mg/kg thymoquinone (n = 7); group 3: 5 mg/kg thymoquinone (n = 7); group 4: Bacilli Chalmette Guerin (BCG) 6 × 105 CFU (n = 7); group 5: methotrexate 0.3 mg/kg (n = 7). Signs of inflammation on the claw and radiological signs were searched for and TNF-alpha and IL-1beta were measured. The results of control and other groups were compared. As a result, thymoquinone, confirmed clinically and radiologically, suppressed adjuvant-induced arthritis in rats. Copyright © 2006 John Wiley & Sons, Ltd.

Antioxidative and Anti-inflammatory Effect of Thymoquinone in an Acute Pseudomonas Prostatitis Rat Model

Introduction: The aim of this study is to investigate the potential antioxidant and anti-inflammatory effects of thymoquinone (TQ) to improve acute bacterial prostatitis (ABP) induced by Pseudomonas aeruginosa. Material and Methods: A total of 42 male Wistar albino rats were divided into 7 groups as follows: control, ABP (24, 48, and 72 h), and TQ-ABP (24, 48, and 72 h). The prostate tissue samples were assayed for prostate tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities. Sections were examined for characteristic histological changes, and a histological scoring system was used. Results: When the ABP groups given TQ (24, 48, and 72 h) were compared to the ABP groups not given TQ, the levels of MDA and NO and the GPX activity were found to be significantly lower in the groups given TQ. Concerning SOD values, the TQ-ABP-72 group was lower in comparison with the ABP-72 and control groups, but statistically higher than the TQ-ABP-48 group (p < 0.05). Concerning CAT activity, only the TQ-ABP-72 and ABP-72 groups had a significant difference with the control group. TQ improved prostate histology significantly only in the TQ-ABP-24 group compared to the ABP-24 group (p < 0.001). Conclusion: Our study demonstrated for the first time that ABP induced by P. aeruginosa had an oxidative effect on prostate tissue and could regress following TQ administration as shown with the biochemical and histological findings.

Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation

Thymoquinone (TQ), the main active constituent of the volatile oil extracted from Nigella sativa's seeds, has been reported to have an anti-inflammatory and immune stimulatory effect on bronchial asthma and inflammation. However, little is known about the factors and mechanisms underlying these effects. In the present study, we examined the effect of TQ on airway inflammation in a mouse model of allergic asthma. Intraperitoneal injection of TQ before airway challenge of ovalbumin (OVA)-sensitized mice resulted in a marked decrease in lung eosinophilia and the elevated Th2 cytokines observed after airway challenge with OVA antigen; both in vivo, in the bronchoalveolar lavage (BAL) fluid and in vitro, following stimulation of lung cells with OVA. TQ also decreased the elevated serum levels of OVA-specific IgE and IgG1. Histological examination of lung tissue demonstrated that TQ significantly inhibited allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells. While TQ showed a significant effect in inhibiting IL-4, IL-5 and IL-13 and some effect in inducing IFN-γ production in the BAL fluid, it did show a slight effect on in vitro production of IL-4 by cultured lung cells stimulated with OVA antigen. These data suggest that TQ attenuates allergic airway inflammation by inhibiting Th2 cytokines and eosinophil infiltration into the airways; thus demonstrating its potential anti-inflammatory role during the allergic response in the lung.