Matsuda H, Kagerura T, Toguchida I, Ueda H, Morikawa T, Yoshikawa M
Kyoto Pharmaceutical University, Japan.
Life Sci. 2000 Apr 21;66(22):2151-7. doi: 10.1016/s0024-3205(00)00542-7.
The methanolic extract from the leaves of Laurus nobilis (bay leaf, laurel) was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages. Through bioassay-guided separation, fourteen known sesquiterpenes were isolated from the active fraction and were examined for ability to inhibit the NO production. Seven sesquiterpene lactones (costunolide, dehydrocostus lactone, eremanthine, zaluzanin C, magnolialide, santamarine and spirafolide) potently inhibited LPS-induced NO production (IC50 = 1.2 approximately 3.8 microM). Other sesquiterpene constituents also showed the inhibitory activity (IC50 > or = 21 microM), but their inhibitory activities were less than those of sesquiterpene lactones. Alpha-methylene-gamma-butyrolactone also showed inhibitory activity (IC50 = 9.6 microM), while mokko lactone and watsonol A etc., reductants of the alpha-methylene-gamma-butyrolactone moiety by NaBH4 or DIBAL, and a 2-mercaptoethanol adduct of dehydrocostus lactone showed little activity (IC50 > or = 18 microM). These results indicated that the alpha-methylene-gamma-butyrolactone moiety is important for the activity. Furthermore, costunolide and dehydrocostus lactone inhibited inducible nitric oxide synthase (iNOS) induction in accordance with induction of heat shock protein 72 (HSP 72). These results suggested that, as one of their mechanisms of action, sesquiterpene lactones induce HSP 72 thereby preventing nuclear factor-kappaB activation followed by iNOS induction.
人们发现，月桂叶的甲醇提取物能够抑制脂多糖（LPS）激活的小鼠腹腔巨噬细胞中一氧化氮（NO）的产生。通过生物测定导向分离，从活性部分分离出14种已知的倍半萜，并检测了它们抑制NO产生的能力。七种倍半萜内酯（木香烃内酯、脱氢木香内酯、艾里内酯、扎鲁扎宁C、厚朴内酯、圣塔马林和螺旋呋喃内酯）能有效抑制LPS诱导的NO产生（IC50 = 1.2至3.8 microM）。其他倍半萜成分也表现出抑制活性（IC50≥21 microM），但其抑制活性低于倍半萜内酯。α-亚甲基-γ-丁内酯也表现出抑制活性（IC50 = 9.6 microM），而莫克内酯和沃森醇A等通过NaBH4或DIBAL还原α-亚甲基-γ-丁内酯部分得到的产物，以及脱氢木香内酯的2-巯基乙醇加合物活性很小（IC50≥18 microM）。这些结果表明，α-亚甲基-γ-丁内酯部分对活性很重要。此外，木香烃内酯和脱氢木香内酯根据热休克蛋白72（HSP 72）的诱导抑制诱导型一氧化氮合酶（iNOS）的诱导。这些结果表明，作为其作用机制之一，倍半萜内酯诱导HSP 72，从而防止核因子-κB激活，进而防止iNOS诱导。
