Molecular mechanisms underlying the antidiabetic effects of mulinum spinosum root decoction.

BERRUEZO,S; PAVAROTTI, M; ALVAREZ, MS; SCAPINI, C; CREMER, C; CASTRO C

Congreso; XXXIX Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2021

Sociedad de Biología de Cuyo

A bitter decoction prepared from the root of Mulinum spinosum, popularly known as “neneo”, it is traditionally attributed antiglycemic properties. However, the molecular mechanisms that underline this effect remain unknown. The aim of this work was to analyze whether aqueous extracts from “neneo” roots enhance insulin sensitivity in in vivo experiments as a possible molecular mechanism. Cytotoxicity was tested in vascular smooth muscle cells using MTT tetrazolium reduction assay, and GLUT-4 translocation, as a measure of Insulin Sensitizing, was performed in L6 myoblast cell. As a diabetic animal model, adult male C57BL/6 mice were fed with a 20% w/v fructose (Fru) in drinking water combined with 30% w/w high fat diet (HFD) over a period of 12 weeks. “Neneo” root extracts (3 or 6 g/kg/day) were administered in drinking water along with Fru-HFD. Mice were weighted weekly, glucose tolerance test was determined at the end of the treatment period, and adipose tissue was collected after sacrifice. Translocation of GLUT4 from intercellular compartment to plasma membrane as surface level of GLUT4myc, was measured by an antibody-coupled assay. “Neneo” root extract (0.5–10 mg/mL) did not affect cell viability, only higher concentrations (20 and 50 mg/mL) significantly reduced 10% fetal calf serum-induced proliferation. In the presence of 25 nM insulin, GLUT4 quantification on the membrane cell of L6 cells was higher than controls (P < 0.01). The addition of “neneo” root extract (1 mg/mL) during 60 min, significantly enhanced translocation of insulin sensitive glucose transporters-4, in skeletal muscle cells (P < 0.05). After 10 weeks, mice fed a Fru-HFD treated with “neneo” significant decreased body weight gain compared to the Fru-HFD group (P < 0.01). After 120 min of intraperitoneal injection of 2 g/kg body weight of glucose, blood glucose levels in Fru-HFD fed mice treated with “neneo” extract, significantly decreased compared with Fru-HFD group (P < 0.01). Histological examination of mesenteric adipose tissue showed a significant reduction of adipocyte perimeter and area after “neneo” intake compared with Fru-HFD group (P < 0.01). In conclusion, our results show for the first time a possible molecular mechanism of action underlying the antidiabetic effect attributable to “neneo” extract consumption