Zingerone improves the immune responses in an animal model of breast cancer.

OBJECTIVES: The potent anti-tumorigenic effects were attributed to ginger and there are some reports regarding the anti-cancer and immunomodulatory properties ginger-derived components. This study aimed to investigate the effects of zingerone on some immune-related parameters in an animal model of breast cancer. METHODS: The breast cancer was established in female BALB/c mice using a carcinogenic 4T1 cell line. At day 10 after cancer induction, tumor-bearing mice were divided into five groups and treated intraperitoneal (daily from days 11-30) with saline or zingerone (at doses 10, 20, 50 and 100 mg/kg/day). The mice were sacrificed on day 31 and the number of splenic Th1- and Treg cells, the expression of IFN-γ and TGF-ß in the blood mononuclear cells, the antibody production against sheep red blood cell (SRBC) were determined using flow cytometry, real time-PCR and a standard hemagglutination assay, respectively. RESULTS: Zingerone at doses 50 and 100 mg/kg enhanced the number of splenic Th1 cells (p<0.03 and 0.007, respectively); at doses 10, 20, 50 and 100 mg/kg reduced the number of splenic Treg cells (p<0.02, 0.01, and 0.01, respectively), at doses 50 and 100 mg/kg enhanced the expression of IFN-γ (p<0.03), at doses 50 and 100 mg/kg reduced the expression of TGF-ß, at doses 50 mg/kg reduced the titer of anti-SRBC antibody (p<0.05). CONCLUSIONS: Zingerone improve the T cell-mediated and antibody responses in a mouse model of breast cancer. The immunotherapeutic potentials of zingerone in cancers need more considerations.

Effect of Treatment with Thyme Extract on Urinary Levels of Melatonin in an Experimental Autoimmune Encephalomyelitis Mouse Model.

BACKGROUND: Thymus vulgaris, or thyme belongs to the Lamiaceae family of aromatic plant species and has established antioxidant and anti-inflammatory properties. We examined the association between thyme extract treatment to recovered urinary levels of melatonin, a hormone with neuroprotective effects, in mice induced with EAE. METHODS: Eight B6 mice induced with EAE were randomized into two groups and exposed to either 50 mg/kg of thyme extract or PBS. After EAE induction, mice were injected i.p every other day from day 0 to 21. Four B6 mice without EAE were considered the healthy control group. Urine samples were collected consecutively for two 24 h periods on day 19 and 20. We examined whether thyme extract treatment modified urinary melatonin sulfate concentration (ng/mL) in EAE-induced mice using an ELISA. RESULTS: The clinical score and body weight in thyme-treated EAE group were significantly lower in comparison to the EAE control group at indicated time points. The urinary melatonin concentration was significantly lower in the EAE control group compared to the healthy mice. There was no significant difference between thyme-treated and EAE groups regarding the urine melatonin concentration. CONCLUSION: Our results show that exposing EAE mice to thyme extract improved their clinical symptoms, however, there was no significant effect on urinary melatonin concentration.

Effect of ß-D-Mannuronic Acid (M2000) on Oxidative Stress Enzymes' Gene Using Healthy Donor Peripheral Blood Mononuclear Cells for Evaluating the Anti-Aging Property.

OBJECTIVE: This research aimed to study the anti-aging and anti-inflammatory effects of low and high doses of the ß-D-mannuronic (M2000) on gene expression of enzymes involved in oxidative stress (including SOD2, GST, GPX1, CAT, iNOS, and MPO) in peripheral blood mononuclear cells (PBMCs) of healthy donors under in vitro conditions. METHODS: The PBMCs were separated and the RNAs were then extracted and the cDNAs synthesized, and expression levels of the mentioned genes were detected by qRT-PCR. RESULTS: Our results indicated that the high dose of this drug could significantly reduce the expression level of the SOD2 gene compared to the lipopolysaccharide (LPS) group (p < 0.0001). Moreover, it was found that the high dose of this drug could significantly decrease the expression level of the GST gene compared to the LPS group (p < 0.0001). However, no significant reductions were observed in expression levels of the CAT and GPX1 genes compared to the LPS group. Furthermore, our data revealed that the level of iNOS and MPO gene expression was significantly reduced, in both doses of M2000, respectively, compared to the LPS group (p < 0.0001). CONCLUSION: This research showed that M2000 as a novel NSAID with immunosuppressive properties could modify oxidative stress through lowering expression levels of the SOD2, GST, iNOS, and MPO genes compared to the healthy expression levels, with a probable reduction of the risk of developing inflammatory diseases related to age and aging.

Beneficial effects of Thymus vulgaris extract in experimental autoimmune encephalomyelitis: Clinical, histological and cytokine alterations.

The imbalance between pro and anti-inflammatory cytokines plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Thymus vulgaris (thyme) as a traditional medicinal plant has been reported to exert antimicrobial, antioxidant, and anti-inflammatory effects. Therefore, this study evaluated the modulatory effects of Thymus vulgaris on the clinical symptoms, histopathological scores, and the production of some anti-inflammatory (TGF-ß, IL-4, and IL-10) and pro-inflammatory (IFN-γ, IL-6 and IL-17) cytokines in EAE model. EAE was induced by MOG35-55 peptide and mice were treated intra-peritoneally (i.p) with phosphate buffered saline (PBS) in the control group or thyme extract (50 or 100 mg/kg of body weight, every other day) in thyme-treated EAE groups, from day 0 to +21 of post MOG immunization. Mice were sacrificed at day 22, and splenocytes were isolated and re-stimulated in vitro with MOG in order to measure the cytokine production and proliferation of re-stimulated cells by enzyme linked immunosorbent assay (ELISA) method and WST-1 reagent, respectively. The clinical symptoms and histopathological scores of the CNS were lower in thyme-treated than EAE control group. Furthermore, the production of IFN-γ and IL-6 by splenocytes was lower in thyme-treated EAE than in the control group. The production of IL-10 and TGF-ß increased in mice treated with thyme extract compared to the control group. In this study, we showed for the first time that the immunomodulatory effects of Thymus vulgaris in EAE model. Thus, the possible therapeutic potential of thyme for treatment of MS could be considered in future research.

Therapeutic potentials of ginger for treatment of Multiple sclerosis: A review with emphasis on its immunomodulatory, anti-inflammatory and anti-oxidative properties.

Multiple sclerosis (MS) is characterized by chronic inflammatory response-induced demyelination of the neurons and degeneration of the axons within the central nervous system (CNS). A complex network of immunopathological-, inflammatory- and oxidative parameters involve in the development and advancement of MS. The anti-inflammatory, immunomodulatory and anti-oxidative characteristics of the ginger and several of its components have been indicated in some of experimental and clinical investigations. The possible therapeutic potentials of ginger and its ingredients in the treatment of MS may exert mainly through the regulation of the Th1-, Th2-, Th9-, Th17-, Th22- and Treg cell-related immune responses, down-regulation of the B cell-related immune responses, modulation of the macrophages-related responses, modulation of the production of pro- and anti-inflammatory cytokines, down-regulation of the arachidonic acid-derived mediators, interfering with the toll like receptor-related signaling pathways, suppression of the inflammasomes, down-regulation of the oxidative stress, reduction of the adhesion molecules expression, and down-regulation of the expression of the chemokines and chemokine receptors. This review aimed to provide a comprehensive knowledge regarding the immunomodulatory-, anti-inflammatory and anti-oxidative properties of ginger and its components, and highlight novel insights into the possible therapeutic potentials of this plant for treatment of MS. The review encourages more investigations to consider the therapeutic potentials of ginger and its effective components for managing of MS.

Ginger Extract Modulates the Expression of Chemokines CCL20 and CCL22 and Their Receptors (CCR6 and CCR4) in the Central Nervous System of Mice with Experimental Autoimmune Encephalomyelitis.

Background Chemokines facilitate the leukocytes infiltration into the central nervous system (CNS) which is an essential step in the pathogenesis of multiple sclerosis. Ginger has also a broad anti-inflammatory properties. The aim was to evaluate the effects of ginger extract on the expression of CCL20 and CCL22 and their receptors (CCR6 and CCR4, respectively) in experimental autoimmune encephalomyelitis (EAE). Material and Methods Female C57BL/6 mice used for EAE induction by immunization with myelin oligodendroglial glycoprotein. Then, the EAE mice were treated with PBS or ginger extract, from day +3 to +30. At day 31, mice were scarified and the expression of CCL20 and CCL22 and their receptors in the spinal cord measured using real time-PCR. Results The expression of CCL20, CCL22 and CCR4 in the spinal cord of PBS-administrated EAE mice was significantly higher than healthy group (P<0.04, P<0.05 and P<0.02, respectively). In 200- and 300 mg/kg ginger extract-treated EAE mice, the expression of CCL20, CCL22 and CCR4 were significantly reduced as compared with PBS-administrated EAE group (P<0.04, P<0.01 and P<0.002 for 200 mg/kg ginger extract and P<0.01, P<0.005 and P<0.004 for 300 mg/kg ginger extract, respectively). The CCR6 expression in EAE mice treated with 200- or 300 mg/kg ginger extracts was lower than PBS-administrated EAE mice (P<0.01 and P=0.07, respectively). Conclusion Treatment of EAE mice with ginger extract down-regulate the expression of CCL20 and CCL22 and their receptors in EAE mice. The possible therapeutic potential of ginger for treatment of MS can be considered in future investigations.

Ginger Extract Reduces the Expression of IL-17 and IL-23 in the Sera and Central Nervous System of EAE Mice.

BACKGROUND: IL-17/IL-23 axis plays an important role in the pathogenesis of several autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). The immunomodulatory properties of ginger are reported in previous studies. OBJECTIVE: To evaluate the effects of ginger extract on the expression of IL-17 and IL-23 in a model of EAE. METHODS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein and then treated with PBS or ginger extracts, from day +3 to +30. At day 31, mice were scarificed and the expression of IL-17 and IL-23 mRNA in spinal cord were determined by using real time-PCR. The serum levels of cytokines were measured by ELISA. RESULTS: The mRNA expression of IL-17, IL-23 P19 and IL-23 P40 in CNS and serum levels of IL-17 and IL-23 were significantly higher in PBS-treated EAE mice than non-EAE group (p<0.003, p<0.001, p<0.001, p<0.05 and p<0.01, respectively). In 200 mg/kg ginger-treated EAE mice the mRNA expression of IL-17, P19 and P40 in CNS and serum IL-23 levels were significantly decreased as compared to PBS-treated EAE mice (p<0.05, p<0.001, p<0.001 and p<0.05, respectively). Moreover, 300 mg/kg ginger-treated EAE group had significantly lower expression of IL-17, P19 and P40 in CNS and lower serum IL-17 and IL-23 levels than PBS-treated EAE group (p<0.02, p<0.001, p<0.001, p<0.03 and p<0.004, respectively). CONCLUSION: Ginger extract reduces the expression of IL-17 and IL-23 in EAE mice. The therapeutic potential of ginger for treatment of MS could be considered in further studies.

Vitamin D Modulates the Expression of IL-27 and IL-33 in the Central Nervous System in Experimental Autoimmune Encephalomyelitis (EAE).

BACKGROUND: It has been reported that vitamin D has broad anti-inflammatory and immunomodulatory effects. OBJECTIVE: To evaluate the effects of vitamin D on the expression of IL-27 and IL-33 in a model of experimental autoimmune encephalomyelitis (EAE). METHODS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein mixed with complete Freund's adjuvant. The mice were administered with PBS or olive oil, intraperitoneally, in the control groups and vitamin D (200 ng every two days) in the treatment group, from day +3 to +30. At day 31, the mice were scarified and their spinal cords and brains were harvested. The expression of the IL-27 and IL-33 mRNA in the spinal cord was measured using real time-PCR. RESULTS: In PBS- or olive oil-treated EAE mice the expression of IL-27 P28 mRNA was significantly lower than that in the healthy control group (p<0.002). In both PBS- and olive oil-treated EAE groups, the expression of IL-27 EBI3 mRNA was also lower than that observed in the healthy group, but the differences were not significant. In vitamin D-treated EAE group, the expression of IL-27 P28 and IL-27 EBI3 were significantly higher compared with the olive oil-treated EAE groups (p<0.002 and p<0.04, respectively). The expression of IL-33 was significantly higher in PBS-or olive oil-treated EAE groups compared with healthy mice (p<0.05 and p<0.02, respectively). Vitamin D significantly decreased the expression of IL-33 compared with PBS- or olive oil-treated EAE mice (p<0.04, p<0.02, respectively). The PBS- or olive oil -treated EAE mice showed the clinical symptoms of EAE at days 9 and 10, respectively. The vitamin D-treated EAE group exhibited the symptoms at day 12 post immunization. The maximum mean clinical score and mean pathological scores were also significantly lower in vitamin D-treated EAE group, in comparison with PBS- or olive oil treated EAE mice (p<0.001). CONCLUSION: Vitamin D may modulate the expression of IL-27 and IL-33 in the spinal cord of EAE mice and also ameliorate the clinical symptoms of the disease.

Impact of opium on the serum levels of TGF-ß in diabetic, addicted and addicted-diabetic rats.

BACKGROUND: Several cells of immune system such as regulatory T cells and macrophages secrete transforming growth factor-ß (TGF-ß) in response to different stimuli. This cytokine has inhibitory effect on immune system and diminished production of this cytokine is associated with autoimmune disorders. OBJECTIVE: The aim of this study was to evaluate the influence of opium addiction on serum level of TGF-ß in male and female diabetic and non-diabetic Wistar rats. METHODS: This experimental study was performed on normal, opium addicted, diabetic and addicted-diabetic male and female rats. Serum level of TGF-ß was measured by ELISA. RESULTS: The results of our study indicated that the mean serum level of TGF-ß in female addicted rats was significantly increased compared to control group (p<0.004). Conversely, in male addicted rats the mean serum level of TGF-ß was lower compared with control (p<0.065). CONCLUSION: Our results suggest that opium and its derivatives have differential inductive effects on the cytokine expression in male and female rats.