Development of Drug Candidate for the Treatment of Lymphedema Using Natural Product and its Derivatives from Rhus verniciflua Strokes

옻나무(Rhus verniciflua Strokes) 주요 단일성분과 그 유도체를 이용한 다중기전 림프부종 치료제 후보물질 개발

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 IC₅₀ 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.