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1.
Article in English | MEDLINE | ID: mdl-31622213

ABSTRACT

BACKGROUND: This study aimed to investigate the effects of guluronic acid (G2013) on blood sugar, insulin, and gene expression profile of oxLDL receptors (SR-A, CD36, LOX-1, and CD68) in the experimental model of diabetes. METHODS: 18 Sprague Dawley rats were randomly assigned to three groups of healthy control, diabetic control, and G2013 group. Diabetes was induced through intraperitoneal (IP) injection of 60 mg/kg streptozotocin. The subjects were IP treated with 25 mg/kg of G2013 per day for 28 days. The body weight, food intake, fasting blood glucose and insulin were measured. In addition, the expression of mentioned genes was investigated through quantitative real-time PCR. RESULTS: The data showed that the final weight increased significantly in the G2013-treated subjects compared to the diabetic control (p < 0.05). The results indicated that final food intake significantly reduced in the G2013-treated subjects compared to the diabetic control (p < 0.05). The study findings also suggested that the final fasting blood glucose significantly reduced in the G2013-treated group, whereas the final fasting serum insulin level significantly increased in this group compared to the diabetic control (p < 0.05). Moreover, the gene expression levels of SR-A, CD36, LOX-1, and CD68 in the G2013 group significantly reduced compared to the diabetic control (p < 0.05). CONCLUSION: This study showed that G2013, could reduce blood glucose and increase insulin levels and reduce the gene expression level of oxLDL receptors. In addition, it may probably play an important role in reducing the severity of diabetes-induced inflammatory symptoms.


Subject(s)
Angiogenesis Inducing Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Hexuronic Acids/therapeutic use , Hypoglycemic Agents/therapeutic use , Uronic Acids/therapeutic use , Animals , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/pathology , Male , Random Allocation , Rats , Rats, Sprague-Dawley
2.
Article in English | MEDLINE | ID: mdl-31729947

ABSTRACT

BACKGROUND: Regarding the leukocytes infiltration into the synovium of Rheumatoid Arthritis (RA) patients is mostly mediated by chemokine ligands and receptors, and following the efficient and motivating results of international Phase III clinical trial of ß-D-Mannuronic acid (M2000) patented EP067919 (2017), as a novel anti-inflammatory drug, in patients with RA, the present research was designed. OBJECTIVES: This study aimed to assess the oral administration effects of this new drug on gene expression of some chemokine receptors and ligands, including CXCR4, CXCR3, CCR2, CCR5 and CCL2/MCP-1 in PBMCs of patients with active form of RA. METHODS: Twelve patients suffering from RA, with inadequate response to conventional drugs were selected (Clinical trial identifier IRCT2017100213739N10) and 1000mg/day of M2000 was orally administrated to them for 12 weeks. The mRNA expression of target molecules was then evaluated in PBMCs of the patients before and after treatment with M2000 using real-time PCR and was compared to healthy controls. Patents related to this study were also reviewed. RESULTS: The results showed that M2000 was able to significantly down-regulate the mRNA expression of CXCR4, CCR2 and CCL2/MCP-1 in the PBMCs of the RA patients. It should be noted that the gene expression situation of the target molecules was in coordinate with the clinical and paraclinical assessments in the patients. CONCLUSION: Taken together, the results of this investigation revealed the part of molecular and immunological mechanisms of drug Mannuronic acid (M2000) in the treatment of RA, based on chemokine ligands and receptors mediated processes.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Arthritis, Rheumatoid/drug therapy , Chemokines/metabolism , Hexuronic Acids/administration & dosage , Administration, Oral , Adolescent , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arthritis, Rheumatoid/genetics , Female , Gene Expression Regulation/drug effects , Hexuronic Acids/pharmacology , Humans , Leukocytes, Mononuclear/drug effects , Male , Middle Aged , Patents as Topic , Receptors, Chemokine/genetics , Young Adult
3.
Article in English | MEDLINE | ID: mdl-29879894

ABSTRACT

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat the pathological pain and inflammation through inhibition of cyclooxygenase (COX) enzyme and disruption of the synthesis of prostaglandins (PGs). The α-L-guluronic acid (G2013) patented (PCT/EP2017/067920), as a novel NSAID with the immunomodulatory property, has been shown its positive effects in experimental models of multiple sclerosis and anti-aging. OBJECTIVE: This study was aimed to investigate the effects of G2013 on the gene expression and activity of COX-1/COX-2 enzymes in order to introduce a novel NSAID for the treatment of inflammatory diseases. METHOD: The mRNA expression levels of COX-1/COX-2 were measured by qRT-PCR. The PGE2 concentration in culture media was determined using ELISA method. RESULTS: Our results demonstrated that the low and high dose of G2013 could significantly reduce the gene expression of COX-1 and COX-2, as compared to the control treated with LPS (p < 0.05). In addition, data showed that 5, 50 and 500 mMol/ml doses of this drug can significantly the reduce activities of COX-1 and COX-2, as compared to the control treated with LPS and AA (p < 0.0001). CONCLUSION: This study revealed that G2013, as a novel NSAID with the immunomodulatory property, is able to reduce the gene expression and activity of COX-1/COX-2 enzymes. According to the findings, this agent might be categorized and introduced as a novel NSAID for the treatment of inflammatory diseases.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Immunologic Factors/pharmacology , Inflammation/drug therapy , Leukocytes, Mononuclear/drug effects , Uronic Acids/pharmacology , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cells, Cultured , Cyclooxygenase 1/genetics , Cyclooxygenase 2/genetics , Female , Gene Expression Regulation/drug effects , Hexuronic Acids , Humans , Immunologic Factors/therapeutic use , Leukocytes, Mononuclear/physiology , Male , Middle Aged , RNA, Messenger/genetics , Uronic Acids/therapeutic use
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