Human Ether-脿-go-go Related Gene (hERG) Channel Blocking Aporphine Alkaloids from Lotus Leaves and Their Quantitative Analysis in Dietary Weight Loss Supplements

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• 作者：Ulrike Grienke ; Christina E. Mair ; Priyanka Saxena ; Igor Baburin ; Olaf Scheel ; Markus Ganzera ; Daniela Schuster ; Steffen Hering ; Judith M. Rollinger
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2015
• 出版时间：June 17, 2015
• 年：2015
• 卷：63
• 期：23
• 页码：5634-5639
• 全文大小：277K
• ISSN：1520-5118

文摘

Blockage of the human ether-脿-go-go related gene (hERG) channel can result in life-threatening ventricular tachyarrhythmia. In an in vitro screening of herbal materials for hERG blockers using an automated two-microelectrode voltage clamp assay on Xenopus oocytes, an alkaloid fraction of Nelumbo nucifera Gaertn. (lotus) leaves induced 鈭?0% of hERG current inhibition at 100 渭g/mL. Chromatographic separation resulted in the isolation and identification of (鈭?-asimilobine, 1, nuciferine, 2, O-nornuciferine, 3, N-nornuciferine, 4, and liensinine, 5. In agreement with in silico predicted ligand鈥搕arget interactions, 2, 3, and 4 revealed distinct in vitro hERG blockages measured in HEK293 cells with IC₅₀ values of 2.89, 7.91, and 9.75 渭M, respectively. Because lotus leaf dietary weight loss supplements are becoming increasingly popular, the identified hERG-blocking alkaloids were quantitated in five commercially available products. Results showed pronounced differences in the content of hERG-blocking alkaloids ranging up to 992 渭g (2) in the daily recommended dose.