Marisa Azevedo

Metformin-like effect of salvia officinalis (common sage) : is it useful in diabetes prevention?

Common sage (Salvia officinalis L.) is among the plants that are claimed to be beneficial to diabetic patients, and previous studies have suggested that some of its extracts have hypoglycaemic effects in normal and diabetic animals. In the present study, we aimed to verify the antidiabetic effects of an infusion (tea) of common sage, which is the most common form of this plant consumed. Replacing water with sage tea for 14 d lowered the fasting plasma glucose level in normal mice but had no effect on glucose clearance in response to an intraperitoneal glucose tolerance test. This indicated effects on gluconeogenesis at the level of the liver. Primary cultures of hepatocytes from healthy, sage-tea-drinking rats showed, after stimulation, a high glucose uptake capacity and decreased gluconeogenesis in response to glucagon. Essential oil from sage further increased hepatocyte sensitivity to insulin and inhibited gluconeogenesis. Overall, these effects resemble those of the pharmaceutical drug metformin, a known inhibitor of gluconeogenesis used in the treatment and prevention of type 2 diabetes mellitus. In primary cultures of rat hepatocytes isolated from streptozotocin (STZ)-induced diabetic rats, none of these activities was observed. The present results seem to indicate that sage tea does not possess antidiabetic effects at this level. However, its effects on fasting glucose levels in normal animals and its metformin-like effects on rat hepatocytes suggest that sage may be useful as a food supplement in the prevention of type 2 diabetes mellitus by lowering the plasma glucose of individuals at risk.

Ursolic acid and luteolin-7-glucoside improve lipid profiles and increase liver glycogen content through glycogen synthase kinase-3.

In the present study, two phytochemicals – ursolic acid (UA) and luteolin‐7‐glucoside (L7G) – were assessed in vivo in healthy rats regarding effects on plasma glucose and lipid profile (total cholesterol, HDL and LDL), as well as liver glycogen content, in view of their importance in the aetiology of diabetes and associated complications. Both UA and L7G significantly decreased plasma glucose concentration. UA also significantly increased liver glycogen levels accompanied by phosphorylation of glycogen synthase kinase‐3 (GSK3). The increase in glycogen deposition induced by UA (mediated by GSK3) could have contributed to the lower plasma glucose levels observed. Both compounds significantly lowered total plasma cholesterol and low‐density lipoprotein levels, and, in addition, UA increased plasma high‐density lipoprotein levels. Our results show that UA particularly may be useful in preventable strategies for people at risk of developing diabetes and associated cardiovascular complications by improving plasma glucose levels and lipid profile, as well as by promoting liver glycogen deposition. Copyright

Sage Tea Drinking Improves Lipid Profile and Antioxidant Defences in Humans

Salvia officinalis (common sage) is a plant with antidiabetic properties. A pilot trial (non-randomized crossover trial) with six healthy female volunteers (aged 40–50) was designed to evaluate the beneficial properties of sage tea consumption on blood glucose regulation, lipid profile and transaminase activity in humans. Effects of sage consumption on erythrocytes’ SOD and CAT activities and on Hsp70 expression in lymphocytes were also evaluated. Four weeks sage tea treatment had no effects on plasma glucose. An improvement in lipid profile was observed with lower plasma LDL cholesterol and total cholesterol levels as well as higher plasma HDL cholesterol levels during and two weeks after treatment. Sage tea also increased lymphocyte Hsp70 expression and erythrocyte SOD and CAT activities. No hepatotoxic effects or other adverse effects were observed.

Rosmarinic acid, major phenolic constituent of Greek sage herbal tea, modulates rat intestinal SGLT1 levels with effects on blood glucose

SCOPE Previous results suggested that the effects of Salvia fruticosa tea (SFT) drinking on glucose regulation might be at the intestinal level. Here we aim to characterize the effects of SFT treatment and of its main phenolic constituent--rosmarinic acid (RA)--on the levels and localization of the intestinal Na+/glucose cotransporter-1 (SGLT1), the facilitative glucose transporter 2 and glucagon-like peptide-1 (GLP-1). METHODS AND RESULTS Two models of SGLT1 induction in rats were used: through diabetes induction with streptozotocin (STZ) and through dietary carbohydrate manipulation. Drinking water was replaced with SFT or RA and blood parameters, liver glycogen and the levels of different proteins in enterocytes quantified. Two weeks of SFT treatment stabilized fasting blood glucose levels in STZ-diabetic animals. The increase in SGLT1 localized to the enterocyte brush-border membrane (BBM) induced by STZ treatment was significantly abrogated by treatment with SFT, without significant changes in total cellular transporter protein levels. No effects were observed on glucose transporter 2, Na(+) /K(+) -ATPase or glucagon-like peptide-1 levels by SFT. Additionally, SFT and RA for 4 days significantly inhibited the carbohydrate-induced adaptive increase of SGLT1 in BBM. CONCLUSION SFT and RA modulate the trafficking of SGLT1 to the BBM and may contribute to the control of plasma glucose.

Effects on Liver Lipid Metabolism of the Naturally Occurring Dietary Flavone Luteolin-7-glucoside

Disruptions in whole-body lipid metabolism can lead to the onset of several pathologies such as nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs). The present study aimed at elucidating the molecular mechanisms behind the lipid-lowering effects of the flavone luteolin-7-glucoside (L7G) which we previously showed to improve plasma lipid profile in rats. L7G is abundant in plant foods of Mediterranean diet such as aromatic plants used as herbs. Results show that dietary supplementation with L7G for one week induced the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and of its target gene carnitine palmitoyl transferase 1 (CPT-1) in rat liver. L7G showed a tendency to decrease the hepatic expression of sterol regulatory element-binding protein-1 (SREBP-1), without affecting fatty acid synthase (FAS) protein levels. Although SREBP-2 and LDLr mRNA levels did not change, the expression of HMG CoA reductase (HMGCR) was significantly repressed by L7G. L7G also inhibited this enzymes in vitro activity in a dose dependent manner, but only at high and not physiologically relevant concentrations. These results add new evidence that the flavone luteolin-7-glucoside may help in preventing metabolic diseases and clarify the mechanisms underlying the beneficial health effects of diets rich in fruits and vegetables.

Salvia fruticosa tea drinking reduces the expression of sodium/glucose cotransporter 1 in enterocytes brush-border membrane of streptozotocin-induced diabetic rats

Diabetes mellitus is a metabolic disorder characterised by elevated plasma glucose concentrations, resulting from insufficient insulin secretion, insulin resistance or both. The prevalence of Type 2 diabetes mellitus is increasing worldwide and 366 million diabetic people are expected by 2030 [1]. Considering this increase in the prevalence of this disorder and a lack of an efficient treatment, there is a growing interest on the research of new bioactive compounds. One of the features of type 2 diabetes mellitus (T2DM) is an increase in Na+-dependent glucose transporter (SGLT1) expression in the brush-border membrane (BBM) of the enterocyte. This increases intestinal glucose absorption and aggravates hyperglycaemia [2]. Moreover, secretion of glucagon-like peptide1 (GLP-1), one of the enteroendocrine incretin hormones, and levels of insulin are reduced under a diabetic condition [3]. Salvia fruticosa is a medicinal plant to which antidiabetic properties have been attributed [4,5] and our previous results suggested an effect on control of blood glucose by reducing SGLT1 expression in brush-border membrane vesicles (BBMV) of rats after diet manipulation (unpublished data). In an attempt to characterise the antidiabetic effects of sage tea at the levels of intestinal epithelium and insulin secretion, normal and streptozotocin (STZ)-induced diabetic rats were used. S. fruticosa tea was given ad libitum, instead of water, for 14 days to the treated animals. Enterocyte SGLT1 and facilitative glucose transporter 2 (GLUT2) expression were evaluated by Western blotting. Effects on GLP-1 and islet regeneration (β cell insulin expression) were assessed by immunohistochemistry.