Department of Chemistry, Amrit Campus, Tribhuvan University, Kathmandu 44613, Nepal; International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Ibaraki 305-0044, Japan.
International Center for Young Scientists (ICYS), National Institute for Materials Science (NIMS), Namiki 1-1, Tsukuba, Ibaraki, 305-0044, Japan.
Bioorg Chem. 2022 Apr;121:105686. doi: 10.1016/j.bioorg.2022.105686. Epub 2022 Feb 16.
Nine different isoquinoline alkaloids, berberine, govaniadine, stylopine, adlumine, adlumidine, bicuculline, sanguinarine, protopine and californidine have been evaluated for their effects on a cellular model of hepatocyte for their effect on low density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression compared to simvastatin. Berberine, californidine and govaniadine induced LDLR with an effect similar to 2.5 µM simvastatin. Californidine and berberine at tested doses reduced the expression of PCSK9, with an opposite behaviour to simvastatin on this target. Govaniadine, on the other hand, showed a statin-like effect, although less potently, by increasing both LDLR and PCSK9 levels. Berberine californidine and govaniadine were then tested on the same cellular model to assess possible effect of reduction of total cholesterol, compared to simvastatin. All compounds were able to reduce total cholesterol level in the hepatocytes.
已评估了 9 种不同的异喹啉生物碱、小檗碱、戈瓦宁碱、斯图洛普碱、阿杜林、阿杜米德、二氢巴马丁、血根碱、原阿片碱和加利福尼亚定碱，以研究它们对低密度脂蛋白受体 (LDLR) 和前蛋白转化酶枯草溶菌素/克氏蛋白酶 9 (PCSK9) 表达的影响，与辛伐他汀相比。小檗碱、加利福尼亚定碱和戈瓦宁碱诱导 LDLR 的作用与 2.5 μM 辛伐他汀相似。加利福尼亚定碱和小檗碱在测试剂量下降低了 PCSK9 的表达，与辛伐他汀在该靶点上的作用相反。另一方面，戈瓦宁碱表现出类似他汀类药物的作用，尽管效力较弱，通过增加 LDLR 和 PCSK9 水平。然后在相同的细胞模型上测试小檗碱、加利福尼亚定碱和戈瓦宁碱，以评估与辛伐他汀相比降低总胆固醇的可能效果。所有化合物均能降低肝细胞中的总胆固醇水平。
