ABSTRACT
Astragalin is a flavonol glycoside with several biological activities, including antidiabetic properties. The objective of this study was to investigate the effects of astragalin on glycaemia and insulin secretion, in vivo, and on calcium influx and insulin secretion in isolated rat pancreatic islets, ex vivo. Astragalin (1 and 10 mg / kg) was administered by oral gavage to fasted Wistar rats and serum glucose and plasma insulin were measured. Isolated pancreatic islets were used to measure basal insulin secretion and calcium influx. Astragalin (10 mg/ kg) decreased glycaemia and increased insulin secretion significantly at 15-180 min, respectively, in the glucose tolerance test. In isolated pancreatic cells, astragalin (100 µM) stimulated calcium influx through a mechanism involving ATP-dependent potassium channels, L-type voltage-dependent calcium channels, the sarcoendoplasmic reticulum calcium transport ATPase (SERCA), PKC and PKA. These findings highlight the dietary coadjuvant, astragalin, as a potential insulin secretagogue that may contribute to glucose homeostasis.
Subject(s)
Calcium Signaling/drug effects , Glucose/metabolism , Hypoglycemic Agents/therapeutic use , Insulin Secretion/drug effects , Islets of Langerhans/metabolism , Kaempferols/therapeutic use , Animals , Calcium Channels, L-Type/metabolism , Cells, Cultured , Cyclic AMP-Dependent Protein Kinases/metabolism , Dietary Supplements , Homeostasis , Islets of Langerhans/pathology , KATP Channels/metabolism , Male , Protein Kinase C/metabolism , Rats , Rats, Wistar , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolismABSTRACT
1,8-Cineole is a terpenoid present in many essential oil of plants with several pharmacological and biological effects, including antinociceptive, smooth muscle relaxant and ion channel activation. Also, 1,8-cineole blocked action potentials, reducing excitability of peripheral neurons. The objective of this work was to investigate effects of 1,8-cineole on Na(+) currents (INa(+)) in dissociated superior cervical ganglion neurons (SCG). Wistar rats of both sexes were used (10-12 weeks old, 200-300g). SCG's were dissected and neurons were enzymatically treated. To study 1,8-cineole effect on INa(+), the patch-clamp technique in whole-cell mode was employed. 1,8-Cineole (6.0mM) partially blocked INa(+) in SCG neurons. The effect stabilized within â¼150s and there was a partial recovery of INa(+) after washout. Current density was reduced from -105.8 to -83.7pA/pF, corresponding to a decrease to â¼20% of control. 1,8-Cineole also reduced the time-to-peak of INa(+) activation and the amplitude and decay time constants of INa(+) inactivation. Current-voltage plots revealed that 1,8-cineole left-shifted the V1/2 of both activation and inactivation curves by â¼10 and â¼20mV, respectively. In conclusion, we demonstrate that 1,8-cineole directly affects Na(+) channels of the SCG by modifying several gating parameters that are likely to be the major cause of excitability blockade.
