Barati Anis, Jamshidi Ahmad Reza, Ahmadi Hossein, Aghazadeh Zahra, Mirshafiey Abbas
Department of Immunology, School of Public Health.
Iranian Institute for Health Sciences Research, Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Drug Des Devel Ther. 2017 Mar 30;11:1027-1033. doi: 10.2147/DDDT.S129419. eCollection 2017.
Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on , , and gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the expression levels of , , and . The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease and levels but also increase and levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier: IRCT2014011213739N2).
类风湿关节炎(RA)是最常见的慢性炎症性关节炎,其特征为关节疼痛、肿胀和破坏,最终导致残疾。改善病情抗风湿药(DMARDs)和生物药物可干扰疾病进程。在本研究中,评估了新型非甾体抗炎药β-D-甘露糖醛酸(M2000)兼具免疫抑制、抗炎及抗氧化作用时,对12例类风湿关节炎患者的 、 、 和 基因表达的影响。此前,由海藻酸钠(天然产物;专利号:DEU: 102016113018.4)提取的M2000已在多发性硬化症、类风湿关节炎和肾病综合征的实验模型中显示出显著疗效。本研究针对12例对传统治疗反应不佳的类风湿关节炎患者进行。在该试验期间,允许患者继续进行除非甾体抗炎药之外的传统治疗。M2000以每日两次、每次500 mg的剂量口服给药,持续12周。在治疗前后采集外周血单个核细胞(PBMCs)以评估 、 、 和 的表达水平。基因表达结果显示,M2000具有显著疗效,在治疗12周后,它不仅能显著降低 和 的水平,还能提高 和 的水平。此外,基因表达结果与临床和临床前评估结果一致。总之,M2000作为一种天然新型药物,对类风湿关节炎患者具有治疗和免疫抑制特性(标识符:IRCT2014011213739N2)。