Combretum lanceolatum flowers extract shows antidiabetic activity through activation of AMPK by quercetin

Abstract

The present study evaluated the antidiabetic activity of the Combretum lanceolatum Pohl ex Eichler, Combretaceae, flowers extract (ClEtOH) in diabetic rats. Streptozotocin-diabetic rats were divided into four groups: diabetic control, diabetic treated with 500 mg/kg of metformin and diabetic treated with 250 or 500 mg/kg of ClEtOH for 21 days. The treatment of diabetic rats with 500 mg/kg of ClEtOH promoted an increase in the weight of liver, white adipose tissues and skeletal muscles, improving body weight gain. Diabetic rats treated with 500 mg/kg of ClEtOH also presented reduction in glycemia, glycosuria and urinary urea levels, and increase in liver glycogen content. HPLC chromatogram showed that quercetin is the major compound in the extract. The phosphorylation levels of adenosine monophosphate-activated protein kinase were increased in liver slices incubated in vitro with 50 µg/mL of ClEtOH, similarly to the incubation with metformin (50 µg/mL) or quercetin (10 µg/mL). The antihyperglycemic effect of ClEtOH was similar to that of metformin and appears to be through inhibition of gluconeogenesis, since urinary urea was reduced and skeletal muscle mass was increased. These data indicate that the antidiabetic activity of the Combretum lanceolatum extract could be mediated, at least in part, through activation of adenosine monophosphateactivated protein kinase by quercetin

Combretum lanceolatum flowers ethanol extract inhibits hepatic gluconeogenesis: an in vivo mechanism study

“…These results confirm previous findings regarding the antidiabetic activity of ClEtOH (Dechandt et al 2013), allowing the investigation of the hepatic mechanisms of action of the extract.…”

“…Previous studies demonstrated that ClEtOH reduced plasma glucose levels in STZ-diabetic rats after 21 d of treatment; the extract also reduced the urinary urea levels and the mass loss of soleus and EDL skeletal muscles (Dechandt et al 2013), indicating a possible role in the inhibition of gluconeogenesis. Attempting for this, the present study showed that at least part of the antihyperglycaemic effect of ClEtOH is related to the reduction of the hepatic glucose output, since its production was reduced in liver of diabetic rats treated with ClEtOH.…”

“…In this way, our data confirm that ClEtOH led to AMPK activation, since its phosphorylation levels were increased in liver of diabetic rats treated with the extract (Figure 3). Quercetin, the major constituent of ClEtOH, can be mentioned as responsible for the AMPK activation; the in vitro incubation of liver slices with quercetin, ClEtOH or metformin increased the AMPK phosphorylation (Dechandt et al 2013). In agreement with these findings, Sato et al (2013) also observed that the phosphorylation of AMPK was increased in liver from adult offspring rats of protein-restricted dams that received quercetin during lactation, which could be a beneficial mechanism against the long-term metabolic disturbances related to malnutrition during gestational periods.…”

“…Among these, Combretum lanceolatum Pohl (Combretaceae), commonly known as ''pombeiro-vermelho'' can be cited as largely distributed in the Brazilian Pantanal. Recent studies by Dechandt et al (2013) demonstrated that the treatment of streptozotocin (STZ)-diabetic rats with the C. lanceolatum flowers ethanol extract (ClEtOH) for 21 d improved various parameters classically altered in diabetes, including a decrease in the blood and urinary glucose levels. In addition, a decrease in the urinary urea and an increase in the weight of soleus and extensor digitorum longus (EDL) muscles were also observed, suggesting that the extract could be acting, at least in part, through reduction in the hepatic gluconeogenesis.…”

“…Also, the beneficial effects of the treatment with ClEtOH were very similar to that promoted by metformin. Furthermore, in vitro incubations of liver slices with ClEtOH or with metformin were able to stimulate adenosine monophosphate-activated protein kinase (AMPK) (Dechandt et al 2013).…”