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The oral administration of drug β-d-mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial. Patients (n = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment. In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo. The results of this multinational, phase III clinical trial provided a potent evidence base for the use of β-d-mannuronic acid as a new highly safe and efficient drug in the treatment of RA.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis. EAE is mainly mediated by adaptive and innate immune responses that leads to an inflammatory demyelization and axonal damage. The aim of the present research was to examine the therapeutic efficacy of D-aspartic acid (D-Asp) on a mouse EAE model. EAE induction was performed in female C57BL/6 mice by myelin 40 oligodendrocyte glycoprotein (35-55) in a complete Freund's adjuvant emulsion, and D-Asp was used to test its efficiency in the reduction of EAE. During the course of study, clinical evaluation was assessed, and on Day 21, post-immunization blood samples were taken from the heart of mice for the evaluation of interleukin 6 and other chemical molecules. The mice were sacrificed, and their brain and cerebellum were removed for histological analysis. Our findings indicated that D-Asp had beneficial effects on EAE by attenuation in the severity and delay in the onset of the disease. Histological analysis showed that treatment with D-Asp can reduce inflammation. Moreover, in D-Asp-treated mice, the serum level of interleukin 6 was significantly lower than that in control animals, whereas the total antioxidant capacity was significantly higher. The data indicates that D-Asp possess neuroprotective property to prevent the onset of the multiple sclerosis.

Introduction: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. The aim of the present research was to examine the therapeutic efficacy of Peg interferon alpha 2a (Peg-IFN I±-2a) as a serine protease inhibitor on EAE model. Material and methods: EAE induction was performed in female C57BL/6 mice by myelin oligodendrocyte glycoprotein (35-55) (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion, and Peg-IFN I±-2a was used for the treatment of EAE. During the course of the study, clinical evaluation was assessed, and on day 21 post-immunisation blood samples were taken from the heart of mice for evaluation of IL -6, and enzymatic and non-enzymatic antioxidants. The mice were sacrificed and the brains and cerebellums were removed for histological analysis. Results: Our findings indicated that Peg-IFN I±-2a had beneficial effects on EAE by attenuation of the severity and a delay in the onset of disease. Histological analysis showed that treatment with Peg-IFN I±-2a can reduce inflammation criteria. Moreover, in Peg-IFN I±-2a-treated mice the serum level of IL-6 was significantly less than in controls, and total antioxidant capacity was significantly more than in the control animals. Conclusions: These data indicate that Peg-IFN I±-2a as an anti-serine protease with immunomodulatory properties may be useful for the treatment of MS. © 2018 Termedia Publishing House Ltd. All rights reserved.

This study was carried out to elucidate the therapeutic efficacy of a new antimalarial drug, artemether, in adriamycin-induced nephropathy. To induce experimental nephrosis, adriamycin was given on...

Multiple sclerosis (MS) is a chronic, neurodegenerative disease that causes central nervous system (CNS) demyelination and affects approximately 2 million people worldwide. The aim of the present study was to test the therapeutic effect of ethylene diamine tetra acetic acid (EDTA) in an experimental model of MS. The experiment was done on male C57BL/6 mice aged 6-8 weeks. The experimental autoimmune encephalomyelitis (EAE) was induced using 250 microg of the MOG35-55 peptide emulsified in CFA and injected subcutaneously on day 0 over two flank areas. In addition, 250 ng of pertussis toxin in 400 microl PBS was injected i.p. on days 0 and 2. In the treatment group, EDTA was administered i.p. at a dose 75 mg/kg/day. The mice were sacrificed 21 days after EAE induction and blood samples were taken from their hearts. The brains of mice were removed for histological analysis and their isolated splenocytes were cultured.Our results showed that treatment with EDTA caused a significant delay in the time of onset and a significant reduction in severity of the EAE. Histological analysis indicated that there was not any plaque in the group of EDTA-treated mice whereas 5 +/- 1 plaques were detected in controls. The density of mononuclear infiltration in the CNS of EDTA-treated mice was lower than controls. In the group of EDTA-treated mice, using the FRAP test, total serum antioxidant power was high and significant in comparison to the controls. Moreover, the serum level of nitric oxide in the treatment group was significantly less than the control group, and, also, the levels of IFN-gamma in the cell culture supernatant of treated mice splenocytes was lower than control group. These data indicate that EDTA therapy can effectively attenuate EAE progression.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that leads to an inflammatory demyelination, axonal damage, and progressive neurologic disability that affects approximately 2.5 million people worldwide. The aim of the present research was to test the therapeutic effect of Aloe vera in experimental model of MS. All experiments were conducted on C57BL/6 male mice aged 6-8 weeks. To induce the experimental autoimmune encephalomyelitis (EAE), 250 microg of the myelin oligodendrocyte glycoprotein 35-55 peptide emulsified in complete freund's adjuvant was injected subcutaneously on day 0 over two flank areas. In addition, 200 ng of pertussis toxin in 100 microL phosphate buffered saline was injected intraperitoneally on days 0 and 2. The therapeutic protocol was carried out intragastrically using 120 mg/kg/day Aloe vera from 7 days before to 21 days after EAE induction. The mice were killed 21 days after EAE induction. The brains of mice were removed for histological analysis and their isolated splenocytes were cultured. The results indicated that treatment with Aloe vera caused a significant reduction in severity of the disease in experimental model of MS. Histological analysis showed 3 +/- 2 plaques in Aloe vera-treated mice compared with 5 +/- 1 plaques in control group. The density of mononuclear infiltration in the CNS of Aloe vera-treated mice (500 +/- 200) was significantly less in comparison to 700 +/- 185 cells in control group. Moreover, the serum level of nitric oxide in treatment group was significantly less than control animals. The level of interferon-gamma in cell culture supernatant of treated mice splenocytes was lower than control group, whereas decrease in serum level of interleukin-10 in treatment group was not significant in comparison with control mice. These data indicate that Aloe vera therapy can attenuate the disease progression in experimental model of MS.