Anti-inflammatory agent 35

Anti-inflammatory agent 35 (compound 5a27) is an orally active curcumin analogue with anti-inflammatory activity. Anti-inflammatory agent 35 blocks mitogen-activated protein kinase (MAPK) signaling and p65 nuclear translocation of NF-kB. Anti-inflammatory agent 35 also inhibits yellow neutrophil infiltration and pro-inflammatory cytokine production. Anti-inflammatory agent 35 significantly attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vivo[1].

Signaling Pathways >> Immunology/Inflammation >> Interleukin Related

Signaling Pathways >> MAPK/ERK Pathway >> p38 MAPK

Research Areas >> Inflammation/Immunology

Signaling Pathways >> MAPK/ERK Pathway >> ERK

Signaling Pathways >> Stem Cell/Wnt >> ERK

p38 MAPK

ERK

I-kappaBalpha

IL-6

p65

NF-κB

Anti-inflammatory agent 35 (化合物 5a27) (10 μM；30 分钟) 抑制 LPS (0.5 μg/mL；24 小时) 对促炎细胞因子 (IL-6、TNF-α) 产生的诱导作用，对小鼠原代巨噬细胞没有细胞毒性。Anti-inflammatory agent 35 抑制 IL-6、TNF-α 的产生，IC50 分别为 2.23 μM 和 2.40 μM[1]。 Anti-inflammatory agent 35 (10 μM；30 分钟) 显着抑制 RAW 264.7 小鼠巨噬细胞中 LPS 诱导的激活。并且它显着抑制 p-p38 和 p-ERK，降低 IκB 水平，表明对 MAPK 和 NF-κB 信号的抑制[1]。 Western Blot Analysis[1] Cell Line: RAW 264.7 mouse macrophages Concentration: 10 μM Incubation Time: 30 min; followed by incubation with 0.5 μg/mL LPS for another 30 min Result: Decreased the phosphorylation of p38 and ERK. And down-regulated IκB (inhibitor of NF-κB), inhibits the transcription of TNF-α, IL-6, IL-1β, ICAM-1.

Anti-inflammatory agent 35 (化合物 5a27) (50 mg/kg；口服；单剂量，监测 0-25 分钟) 比姜黄素 (HY-N0005) 具有更好的生物利用度[1]。 Anti-inflammatory agent 35 (10 mg/kg；腹腔注射；每天 1 次，共 1 周) 通过抑制小鼠模型中的炎症改善 LPS 诱导的 ALI[1]。 在大鼠中的药代动力学参数[1] Route Dose (mg/kg) AUC(0-t) (μg/L·h) AUC(0-∞) (μg/L·h) MRT(0-t) (h) MRT(0-∞) (h) t1/2 (h) Tmax (h) CLz/F (L/h/kg) Vz/F (L/kg) Cmax p.o 50 231.2 325.6 7.8 12.3 6.7 3.3 5062.6 827.1 113.3 i.v 5 34.3 122.4 11.3 19.9 0.2 0.1 404.4 59.5 16.4 Animal Model: ALI mouse model (C57BL/6 mice)[1] Dosage: 10 mg/kg Administration: Intraperitoneal injection, once daily for 1 week; 30 min later every dose, followed by 5 mg/kg LPS, intratracheal injection Result: Significantly normalized the wet/dry ratio of lungs.

[1]. Qian J, et al. Design and synthesis novel di-carbonyl analogs of curcumin (DACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI). Eur J Med Chem. 2019 Apr 1;167:414-425.