A High-Content Screen for the Identification of Plant Extracts with Insulin Secretion-Modulating Activity.

Roland Hager,Marcus Iken,Peter Lanzerstorfer,Josef Ranner,Nicole Ollinger,Cathrina Neuhauser,Julian Weghuber,Johannes Pitsch,Jakob Kerbl-Knapp,Corinna Dawid,Verena Mittermeier-Kleßinger

doi:10.3390/ph14080809

Abstract

Bioactive plant compounds and extracts are of special interest for the development of pharmaceuticals. Here, we describe the screening of more than 1100 aqueous plant extracts and synthetic reference compounds for their ability to stimulate or inhibit insulin secretion. To quantify insulin secretion in living MIN6 β cells, an insulin–Gaussia luciferase (Ins-GLuc) biosensor was used. Positive hits included extracts from Quillaja saponaria, Anagallis arvensis, Sapindus mukorossi, Gleditsia sinensis and Albizia julibrissin, which were identified as insulin secretion stimulators, whereas extracts of Acacia catechu, Myrtus communis, Actaea spicata L., Vaccinium vitis-idaea and Calendula officinalis were found to exhibit insulin secretion inhibitory properties. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to characterize several bioactive compounds in the selected plant extracts, and these bioactives were retested for their insulin-modulating properties. Overall, we identified several plant extracts and some of their bioactive compounds that may be used to manipulate pancreatic insulin secretion.

Highlights

Metabolic diseases are global health problems that are rapidly increasing worldwide.In this regard, energy metabolism represents a key player that is controlled by insulin secretion from pancreatic β cells
Mouse MIN6 β cells were used based on an assay described by Kalwat et al [20], which was adapted for our high-content screening approach
Using higher concentrations of glucose led to a decrease in insulin secretion, which is in line with other studies [21,22]

Summary

Introduction

Metabolic diseases are global health problems that are rapidly increasing worldwide. In this regard, energy metabolism represents a key player that is controlled by insulin secretion from pancreatic β cells. Elevated glucose levels induce intracellular energy and metabolic processes with a subsequent increase in the ATP/ADP ratio followed by the closure of ATP-triggered potassium (KATP ) channels. Voltage-dependent Ca2+ channels (VDCCs) are activated, allowing Ca2+ influx; this increase in cytosolic Ca2+ concentration initiates GSIS. This triggering pathway is followed by a time-dependent increase in insulin secretion [2,3]

Methods

Results

Conclusion