부산대학교 도서관

Herein, we demonstrate that butein (1) can prevent swelling in a murine lymphedema model by suppressing tumor necrosis factor α (TNF-α) production. Butein derivatives were synthesized and evaluated to identify compounds with in vitro anti-inflammatory activity. Among them, 20 μM of compounds 7j , 7m , and 14a showed 50% suppression of TNF-α production in mouse peritoneal macrophages after lipopolysaccharide stimulation. Compound 14a , exhibited the strongest potency with an in vitro IC 50 of 14.6 μM and suppressed limb volume by 70% in a murine lymphedema model. The prodrug strategy enabled a six-fold increase in kinetic solubility of compound 1 and five-fold higher levels of active metabolite in the blood for compound 14a via oral administration in the pharmacokinetics study. We suggest that the compound 14a could be developed as a potential therapeutic agent targeting anti-inflammatory activity to alleviate lymphedema progression. Image 1 • Inflammation affects progression of acquired lymphedema. • The compounds 8s and 14s significantly showed anti-inflammatory activity in vitro. • The compound 14a suppressed limb volume by 70% compared to control in animal model. • Enhancing blood level of active ingredient improved suppression of lymphedema. [ABSTRACT FROM AUTHOR]