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

Abstract

Blockage of the human ether-à-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 ∼50% of hERG current inhibition at 100 μg/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 μM, 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 μg (2) in the daily recommended dose.

Statistical mixture design investigation for extraction and quantitation of aporphine alkaloids from the leaves of Unonopsis duckei R.E. Fr. by HPLC–MS/MS

“…Limits for the present method are similar to those reported in other methods using LC–MS/MS for a variety of alkaloids, for instance, five alkaloids (piperine, piperlonguminine, Δα,β‐dihydropiperlonguminine, pellitorine and piperanine) in Piper longum L. and Piper nigrum L, five active alkaloids (vinblastine, vindoline, ajmalicine, catharanthine, and vinleurosine) in Catharanthus roseus , four pyrrolizidine alkaloid (senecionine, seneciphylline, senecionine‐ N ‐oxide and seneciphylline‐ N ‐oxide) in Petasites hybridus extract, and the antiplasmodial alkaloid carpaine in Carica papaya . LOD and LOQ observed herein and in these mentioned studies are in ng/mL, whereas studies using ultraviolet (UV)‐based detectors report values in μg/mL …”

“…Figure 3(D these mentioned studies are in ng/mL, whereas studies using ultraviolet (UV)-based detectors report values in μg/mL. 17,18 In order to evaluate intraday variation, quality control (QC) solutions were analysed in triplicate, and also run on three different days to determine interday variation. (Table 4).…”

A Comprehensive Review on Chemical Profiling of Nelumbo Nucifera: Potential for Drug Development

“…Anti-pyretic potential of ethanolic extract from N. nucifera stalks was evaluated on normal body temperature and yeast induced pyrexia in rats. It was found that the extract caused significant lowering of body temperature in both Nuciferine Hepato-protective (Ma et al, 2015, Anti-cancer (Liu et al, 2015, Anti-inflammatory , Insulin secretagogue (Nguyen et al, 2012), (Hu et al, 2010), Antipsychotic (Farrell et al, 2016), Anti-melanogenesis (Morikawa et al, 2016), hERG blocker (Grienke et al, 2015) 3…”

“…Grienke et al, 2015) 4 (s)-armepavine Auto-immune(Ka et al, 2010) (Liu et al, 2007), hepatic fibrosis(Weng et al, 2012), Cell cycle arrest(Liu et al, 2004), SLE(Liu et al, 2006), Anti-melanogenesis(Morikawa et al, 2016) 5 …”

Inhibitory effects of three bisbenzylisoquinoline alkaloids on lipopolysaccharide-induced microglial activation

“…1). 4 These three bisbenzylisoquinoline alkaloids are reported to possess a wide range of biological activities including anticarcinogenesis, [5][6][7] anti-arrhythmia, 8,9 anti-hypertension, 10 sedation, 11 and anti-depression.…”