Laboratory of Functional Genomics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary.
Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.
Molecules. 2019 Apr 19;24(8):1546. doi: 10.3390/molecules24081546.
The incidence of inflammatory bowel disease (IBD) increases gradually in Western countries with high need for novel therapeutic interventions. Mannich curcuminoids, C142 or C150 synthetized in our laboratory, have been tested for anti-inflammatory activity in a rat model of TNBS (2,4,6-trinitrobenzenesulphonic acid) induced colitis. Treatment with C142 or C150 reduced leukocyte infiltration to the submucosa and muscular propria of the inflamed gut. C142 or C150 rescued the loss of body weight and C150 decreased the weight of standard colon preparations proportional with 20% less tissue oedema. Both C142 and C150 curcumin analogues caused 25% decrease in the severity of colonic inflammation and haemorrhagic lesion size. Colonic MPO (myeloperoxidase) enzyme activity as an indicator of intense neutrophil infiltration was 50% decreased either by C142 or C150 Mannich curcuminoids. Lipopolysaccharide (LPS) co-treatment with Mannich curcuminoids inhibited NF-κB (nuclear factor kappa B) activity on a concentration-dependent manner in an NF-κB-driven luciferase expressing reporter cell line. Co-treatment with LPS and curcuminoids, C142 or C150, resulted in NF-κB inhibition with 3.57 μM or 1.6 μM half maximal effective concentration (EC) values, respectively. C150 exerted a profound inhibition of the expression of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-4 (IL-4) in human PBMCs (peripheral blood mononuclear cells) upon LPS stimulus. Mannich curcuminoids reported herein possess a powerful anti-inflammatory activity.
炎症性肠病（IBD）的发病率在西方国家逐渐升高，这些国家对新型治疗干预措施的需求很高。我们实验室合成的 Mannich 姜黄素 C142 或 C150 已在 TNBS（2,4,6-三硝基苯磺酸）诱导的结肠炎大鼠模型中进行了抗炎活性测试。用 C142 或 C150 治疗可减少白细胞浸润到发炎肠道的粘膜下层和肌肉固有层。C142 或 C150 挽救了体重减轻，C150 使标准结肠制剂的重量减少了 20%，相应的组织水肿减少了 20%。C142 和 C150 两种姜黄素类似物均可使结肠炎症和出血病变的严重程度降低 25%。C142 或 C150 Mannich 姜黄素类似物可使结肠 MPO（髓过氧化物酶）酶活性降低 50%，这是中性粒细胞浸润强烈的指标。Mannich 姜黄素类似物与脂多糖（LPS）共同处理可在 NF-κB 驱动的荧光素酶表达报告细胞系中以浓度依赖性方式抑制 NF-κB（核因子 kappa B）活性。LPS 和姜黄素类似物，C142 或 C150 的共同处理导致 NF-κB 抑制，其半最大有效浓度（EC）值分别为 3.57 μM 和 1.6 μM。C150 对 LPS 刺激后的人外周血单核细胞（PBMC）中炎症细胞因子、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-4（IL-4）的表达有明显的抑制作用。本文报道的 Mannich 姜黄素类似物具有强大的抗炎活性。
