Electrophilic Agonists Modulate the Transient Receptor Potential Ankyrin-1 Channels Mediated by Insulin and Glucagon-like Peptide-1 Secretion for Glucose Homeostasis.

This pre-clinical study investigated the transient receptor potential ankyrin-1 (TRPA1) channels on modulating targets for glucose homeostasis using agonists: the electrophilic agonists, cinnamaldehyde (CIN) and allyl isothiocyanate (AITC), and the non-electrophilic agonist, carvacrol (CRV). A glucose tolerance test was performed on rats. CIN and AITC (5, 10 and 20 mg/kg) or CRV (25, 100, 300, and 600 mg/kg) were administered intraperitoneally (i.p.), and glycemia was measured. In the intestine, Glucagon-like peptide-1 (GLP-1) and disaccharidase activity were evaluated (in vivo and in vitro, respectively). Furthermore, in vivo and in vitro insulin secretion was determined. Islets were used to measure insulin secretion and calcium influx. CIN and AITC improved glucose tolerance and increased insulin secretion in vivo and in vitro. CRV was unable to reduce glycemia. Electrophilic agonists, CIN and AITC, inhibited disaccharidases and acted as secretagogues in the intestine by inducing GLP-1 release in vivo and in vitro and contributed to insulin secretion and glycemia. The effect of CIN on calcium influx in pancreatic islets (insulin secretion) involves voltage-dependent calcium channels and calcium from stores. TRPA1 triggers calcium influx and potentiates intracellular calcium release to induce insulin secretion, suggesting that electrophilic agonists mediate this signaling transduction for the control of glycemia.

Phenolic compounds of Eugenia involucrata (Myrtaceae) extracts and associated antioxidant and inhibitory effects on acetylcholinesterase and α-glucosidase.

Eugenia involucrata DC. (Myrtaceae), popularly known as "cereja-do-Rio-Grande", is a native tree from Brazil, popularly used as a hypoglycemiant. Crude hydroalcoholic extract (CHE) and fractions (insoluble (FI), dichloromethane (FDM), ethyl acetate (FEA) and butanol (FBu)) of leaves were assessed to determine the phenolic chemical composition by HPLC-ESI-MS/MS. 10 compounds were identified, being 7 new for this species: rutin, isoquercitrin, luteolin-7-O-rutinoside, mandelic acid, naringenin, luteolin-7-O-glucoside and salicylic acid. Extract and fractions showed inhibitory activity on acetylcholinesterase (AchE) enzyme (best result: IC50 = 44.19 µg mL-1, for FEA) and α-glucosidase (α-Glu) (best result: IC50 = 31.25 ± 0.15 µg mL-1, for CHE). The observed antioxidant and inhibitory activity on the AchE and α-Glu is due to, at least in part, the presence of phenolic compounds in the samples.