Six undescribed and six known bisbenzylisoquinoline alkaloids were isolated from the embryo of Nelumbo nucifera seeds. Their structures were fully characterized by a combination of ¹H, ¹³C NMR, 2D NMR, and HRESIMS analyses, as well as ECD computational calculations. The antiadipogenic activity of 11 alkaloids was observed in a dose-responsive manner, leading to the suppression of lipid accumulation in 3T3-L1 cells. Luciferase assay and Western blot analysis showed that the active alkaloids downregulated peroxisome proliferator-activated receptor gamma (PPARγ, a key antiadipogenic receptor) expression in 3T3-L1 cells. Analysis of the structure–activity relationship unveiled that a 1R,1′S configuration in bisbenzylisoquinoline alkaloids led to a notable enhancement in antiadipogenic activity. The resistance level against lipid accumulation highlighted a consistent pattern with the suppressive effect on the PPARγ expression. These activity results indicate that alkaloids from the embryo of N. nucifera seeds have a potential of antiobesity effects through PPARγ downregulation.

中文翻译：

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结构多样的双苄基异喹啉生物碱通过下调荷花种子胚中的 PPARγ 具有抗脂肪形成活性

从Nelumbo nucifera种子的胚中分离出六种未描述的和六种已知的双苄基异喹啉生物碱。^通过1 H、¹³ C NMR、2D NMR 和 HRESIMS 分析以及 ECD 计算的结合，对它们的结构进行了全面表征。以剂量响应方式观察到 11 种生物碱的抗脂肪形成活性，从而抑制 3T3-L1 细胞中的脂质积累。荧光素酶测定和蛋白质印迹分析表明，活性生物碱下调3T3-L1 细胞中过氧化物酶体增殖物激活受体 γ（ PPARγ ，一种关键的抗脂肪形成受体）的表达。结构-活性关系分析表明，双苄基异喹啉生物碱中的 1 R ,1′ S构型导致抗脂肪形成活性显着增强。对脂质积累的抵抗水平突出了与PPARγ表达抑制作用一致的模式。这些活性结果表明，N. nucifera种子胚中的生物碱通过下调PPARγ具有潜在的抗肥胖作用。