Maharjan Binita, Rossi Ilaria, Sut Stefania, Shrestha Timila, Shrestha Lok Kumar, Hill Jonathan P, Ariga Katsuhiko, Benetazzo Veronica, Adorni Maria Pia, Papotti Bianca, Shrestha Shyam Sharan, Shrestha Ram Lal Swagat, Ferri Nicola, Dall'Acqua Stefano
Department of Chemistry, Amrit Campus, Tribhuvan University, Kathmandu, 44600, Nepal.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Chem Biodivers. 2024 Dec;21(12):e202401388. doi: 10.1002/cbdv.202401388. Epub 2024 Oct 28.
Four new alkaloids Chaeronepaline-A (1), Chaeronepaline-B (2), Chaeronepaline-C (3), and Chaeronepaline-D (4) were isolated from Corydalis chaerophylla D.C. collected from Nepal and their structures were elucidated by spectroscopic data, 1D, 2D NMR and mass spectrometry. The structures were established as 3,12- Dimethoxy-5,6-dihydroisoquinolino [2,1-b] isoquinolin- 7- ium- 2, 9- diol (1), 7-Methyl-2,3 : 11,12-bis(methylenedioxy)-7,13a-secoberbin-13-14-epoxide (2), 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline (3) and 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline-N-oxide (4). The new alkaloids were tested in human hepatoma cell line to assess their ability to modulate the expression of low-density lipoprotein receptor (LDL-R), of proprotein convertase subtilisin/kexin 9 (PCSK9) and to affect cellular cholesterol biosynthesis with the aim to evaluate their potential hypocholesterolemic effect. Results indicated that compounds 2 and 3 upregulate the LDLR, and inhibited the cholesterol biosynthesis with compound 2, which also reduced the secretion of PCSK9 by Huh7 cells. These in vitro data indicated a potential hypocholesterolemic effect of compound 2 that requires further in vivo validation.
从采自尼泊尔的碎叶紫堇（Corydalis chaerophylla D.C.）中分离得到了4种新生物碱，即碎叶紫堇碱A（1）、碎叶紫堇碱B（2）、碎叶紫堇碱C（3）和碎叶紫堇碱D（4），并通过光谱数据、一维和二维核磁共振以及质谱对其结构进行了阐明。其结构确定为3,12 - 二甲氧基 - 5,6 - 二氢异喹啉并[2,1 - b]异喹啉 - 7 - 鎓 - 2,9 - 二醇（1）、7 - 甲基 - 2,3 : 11,12 - 双亚甲基二氧基 - 7,13a - 裂环小檗碱 - 13 - 14 - 环氧化物（2）、7 - 甲基 - 5,6,7,8 - 四氢 - 8H - 螺[9,14 - 二羟基 - 11,12 - 亚甲基二氧基 - 茚满 - 异喹啉]（3）和7 - 甲基 - 5,6,7,8 - 四氢 - 8H - 螺[9,14 - 二羟基 - 11,12 - 亚甲基二氧基 - 茚满 - 异喹啉] - N - 氧化物（4）。对这些新生物碱在人肝癌细胞系中进行了测试，以评估它们调节低密度脂蛋白受体（LDL - R）、前蛋白转化酶枯草溶菌素/kexin 9（PCSK9）表达的能力以及对细胞胆固醇生物合成的影响，旨在评估它们潜在的降胆固醇作用。结果表明，化合物2和3上调了LDLR，并抑制了胆固醇生物合成，其中化合物2还降低了Huh7细胞中PCSK9的分泌。这些体外数据表明化合物2具有潜在的降胆固醇作用，需要进一步进行体内验证。
