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 In Vitro Anti-inflammatory agent 35 (compound 5a27) (10 μM; 30 min) inhibits the production of proinflammatory cytokines (IL-6, TNF-α) induced by LPS (0.5 μg/mL; 24 h) without cytotoxicity in mouse primary macrophages (MPMs). Anti-inflammatory agent 35 inhibits the production of IL-6, TNF-α with IC50s of 2.23 μM and 2.40 μM, respectively. Anti-inflammatory agent 35 (10 μM; 30 min) significantly inhibits LPS-induced activation in RAW 264.7 mouse macrophages. And it markedly inhibits p-p38 and p-ERK, decreases IκB level, indicating the suppression of MAPK and NF-κB signaling. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell 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. In Vivo Anti-inflammatory agent 35 (compound 5a27) (50 mg/kg; po; single dose, monitored 0-25 min) has a better bioavailability than curcumin . Anti-inflammatory agent 35 (10 mg/kg; ip; once daily for 1 week) improves LPS-induced ALI by inhibiting inflammation in mice model . The pharmacokinetic parameters in rats Route Dose (mg/kg) AUC (0-t) (μg/L·h) AUC (0-∞) (μg/L·h) MRT (0-t) (h) MRT (0-∞) (h) t 1/2 (h) T max (h) CLz/F (L/h/kg) Vz/F (L/kg) C max 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 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: ALI mouse model (C57BL/6 mice) 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. Form:Solid IC50& Target:p38 MAPK ERK I-kappaBalpha IL-6 p65 NF-κB