Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Phytochemistry. 2022 Feb;194:113023. doi: 10.1016/j.phytochem.2021.113023. Epub 2021 Nov 25.
Six undescribed protoberberine derivatives including two pairs of enantiomers, named yanhusanines G-L, along with fifteen reported protoberberine alkaloids, were isolated from the tubers of Corydalis yanhusuo. Among them, yanhusanines H-L feature a unique 13,13a-seco skeleton which is rare in nature. Their structural elucidations were achieved by extensive spectroscopic analysis and quantum chemistry calculations. A biogenetic route for yanhusanines H-L was proposed. Bioassay results showed that yanhusanine J exhibited potent inhibitory effect against the nitric oxide (NO) production in lipopolysaccharide (LPS) induced RAW 264.7 cells (IC = 2.25 ± 1.32 μM). Western blot analysis demonstrated that yanhusanine J exerted its anti-inflammatory effect via suppressing the nuclear factor kappa B (NF-κB) pathway, together with the decrease of the inflammatory factors TNF-α, IL-6 and IL-1β. Furthermore, molecular simulation docking indicated that yanhusanine J had strong interaction with the active site of the inducible nitric oxide synthase (iNOS) protein.
从延胡索块茎中分离得到了 6 种未被描述的原小檗碱衍生物，包括 2 对对映异构体，命名为延胡索沙林宁 G-L，以及 15 种已报道的原小檗碱生物碱。其中，延胡索沙林宁 H-L 具有独特的 13,13a-断骨架，在自然界中较为罕见。通过广泛的光谱分析和量子化学计算确定了它们的结构。提出了延胡索沙林宁 H-L 的生物合成途径。生物测定结果表明，延胡索沙林宁 J 对脂多糖 (LPS) 诱导的 RAW 264.7 细胞中一氧化氮 (NO) 的产生具有很强的抑制作用 (IC = 2.25 ± 1.32 μM)。Western blot 分析表明，延胡索沙林宁 J 通过抑制核因子 kappa B (NF-κB) 途径发挥抗炎作用，同时降低炎症因子 TNF-α、IL-6 和 IL-1β。此外，分子模拟对接表明，延胡索沙林宁 J 与诱导型一氧化氮合酶 (iNOS) 蛋白的活性位点具有很强的相互作用。
