PMID- 26035250 OWN - NLM STAT- MEDLINE DCOM- 20151207 LR - 20220727 IS - 1520-5118 (Electronic) IS - 0021-8561 (Linking) VI - 63 IP - 23 DP - 2015 Jun 17 TI - Human Ether-a-go-go Related Gene (hERG) Channel Blocking Aporphine Alkaloids from Lotus Leaves and Their Quantitative Analysis in Dietary Weight Loss Supplements. PG - 5634-9 LID - 10.1021/acs.jafc.5b01901 [doi] AB - Blockage of the human ether-a-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 approximately 50% of hERG current inhibition at 100 mug/mL. Chromatographic separation resulted in the isolation and identification of (-)-asimilobine, 1, nuciferine, 2, O-nornuciferine, 3, N-nornuciferine, 4, and liensinine, 5. In agreement with in silico predicted ligand-target 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 muM, 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 mug (2) in the daily recommended dose. FAU - Grienke, Ulrike AU - Grienke U AD - daggerInstitute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria. FAU - Mair, Christina E AU - Mair CE AD - daggerInstitute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria. FAU - Saxena, Priyanka AU - Saxena P FAU - Baburin, Igor AU - Baburin I FAU - Scheel, Olaf AU - Scheel O AD - #Cytocentrics Bioscience GmbH, Tannenweg 22k, 18059 Rostock, Germany. FAU - Ganzera, Markus AU - Ganzera M AD - daggerInstitute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria. FAU - Schuster, Daniela AU - Schuster D AD - perpendicularInstitute of Pharmacy/Pharmaceutical Chemistry, Computer-Aided Molecular Design Group, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria. FAU - Hering, Steffen AU - Hering S FAU - Rollinger, Judith M AU - Rollinger JM AD - daggerInstitute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria. LA - eng GR - W 1232/FWF_/Austrian Science Fund FWF/Austria PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150609 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - 0 (Alkaloids) RN - 0 (Anti-Obesity Agents) RN - 0 (Aporphines) RN - 0 (Ether-A-Go-Go Potassium Channels) RN - 0 (Plant Extracts) RN - 0 (Potassium Channel Blockers) RN - 13NS2KTD6H (aporphine) SB - IM MH - Alkaloids/*chemistry/pharmacology MH - Animals MH - Anti-Obesity Agents/*chemistry/pharmacology MH - Aporphines/*chemistry/pharmacology MH - Cell Line MH - Dietary Supplements/*analysis MH - Ether-A-Go-Go Potassium Channels/*antagonists & inhibitors/metabolism MH - Humans MH - Nelumbo/*chemistry MH - Plant Extracts/*chemistry/pharmacology MH - Plant Leaves/*chemistry MH - Potassium Channel Blockers/*chemistry/pharmacology MH - Xenopus OTO - NOTNLM OT - Nelumbo nucifera OT - cardiotoxic risk OT - dietary supplement OT - hERG OT - lotus OT - nuciferine OT - patch clamp assay OT - weight loss EDAT- 2015/06/03 06:00 MHDA- 2015/12/15 06:00 CRDT- 2015/06/03 06:00 PHST- 2015/06/03 06:00 [entrez] PHST- 2015/06/03 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - 10.1021/acs.jafc.5b01901 [doi] PST - ppublish SO - J Agric Food Chem. 2015 Jun 17;63(23):5634-9. doi: 10.1021/acs.jafc.5b01901. Epub 2015 Jun 9.