title: Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells.
abstract: BACKGROUND
  Traditional Mongolian medicine (TMM) uses preparations from herbs as one form of medication for the treatment of a diversity of diseases including diabetes mellitus (DM). We evaluated the effect of extracts from the plant Leonurus sibiricus L. (LS), used in TMM to treat typical symptoms of type 2 DM, on insulin secretion, electrophysiological properties, intracellular calcium concentration and cell proliferation of INS-1E insulinoma cells under standard cell culture conditions (SCC; 11.1mM glucose).
  
  
  METHODS
  Insulin secretion was measured by ELISA, electrical properties were assessed by whole cell patch clamping, intracellular calcium concentration (Cai) by Fluo-4 time lapse imaging, insulin receptor expression was verified by RT-PCR and cell proliferation assessed by CellTiter-Glo® cell viability assay.
  
  
  RESULTS
  Insulin released from INS-1E cells into the culture medium over 24h was significantly increased in presence of 500 mg/L aqueous LS extract (LS OWE) as well as methanolic LS extract (LS MeOH/H2O) but not in the presence of the butanol-soluble extract (LS MeOH/BuOH). Acute application of LS OWE resulted in a depolarization of the cell membrane potential paralleled by an initial increase and subsequent decline and silencing of action potential frequency, by KATP channel inhibition, persisting depolarization and an increase in Cai. The electrophysiological effects were comparable to those of 100 μM tolbutamide, which, however failed to elevate insulin secretion under SCC. Furthermore all LS extracts stimulated INS-1E cell proliferation.
  
  
  CONCLUSIONS
  The finding that extracts from Leonurus sibiricus L. enhance insulin secretion and/or foster cell proliferation may provide possible explanations for the underlying therapeutic principles in the empirical use of LS-containing formulations in DM and DM-related disorders as applied in TMM.
authors: Institute of Physiology and Pathophysiology, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria. Electronic address: sabine.schmidt@pmu.ac.at.
authors: S
authors: S
authors: Schmidt
authors: M
authors: M
authors: Jakab
authors: S
authors: S
authors: Jav
authors: D
authors: D
authors: Streif
authors: A
authors: A
authors: Pitschmann
authors: M
authors: M
authors: Zehl
authors: S
authors: S
authors: Purevsuren
authors: S
authors: S
authors: Glasl
authors: M
authors: M
authors: Ritter
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma; D031332:Leonurus; D056785:Medicine, Mongolian Traditional; D010190:Pancreatic Neoplasms; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts
keywords: AP; ATP-sensitive K(+) conductance/currents; Ca(i); DM; DM-related disorders; DMrD; Diabetes; Diabetes mellitus; Flavonoids; GLUT-4; IK(ATP); IR; LS; LS MeOH/H(2)O; LS OWE; LSMeOH/BuOH; Leonurus sibiricus L.; Leonurus sibiricus original water extract; Leonurus sibiricus purified methanolic extract; Leonurus sibiricus water-soluble part of the methanolic extract; Phytochemistry; Polyphenols; SCC; T2DM; TMM; TOL; Traditional Mongolian Medicine; Traditional medicine Asia and Oceania; Type 2 Diabetes mellitus; V(mem); WHO; World Health Organization.; action potential; cell membrane potential; glucose transporter isoform 4; insulin receptor; intracellular calcium concentration; standard cell culture condition; tolbutamide; type 2 diabetes mellitus