Preventive effects of Salvia officinalis leaf extract on insulin resistance and inflammation in a model of high fat diet-induced obesity in mice that responds to rosiglitazone

Background. Salvia officinalis (sage) is a native plant to the Mediterranean region and has been used for a long time in traditional medicine for various diseases. We investigated possible anti-diabetic, anti-inflammatory and anti-obesity effects of sage methanol (MetOH) extract in a nutritional mouse model of obesity, inflammation and insulin resistance, as well as its effects on lipolysis and lipogenesis in 3T3-L1 cells. Methods. Diet-induced obese (DIO) mice were treated for five weeks with sage methanol extract (100 and 400 mg kg(-1)/day bid), or rosiglitazone (3 mg kg(-1)/day bid), as a positive control. Energy expenditure, food intake, body weight, fat mass, liver glycogen and lipid content were evaluated. Blood glucose, and plasma levels of insulin, lipids leptin and pro-and anti-inflammatory cytokines were measured throughout the experiment. The effects of sage MetOH extract on lipolysis and lipogenesis were tested in vitro in 3T3-L1 cells. Results. After two weeks of treatment, the lower dose of sage MetOH extract decreased blood glucose and plasma insulin levels during an oral glucose tolerance test (OGTT). An insulin tolerance test (ITT), performed at day 29 confirmed that sage improved insulin sensitivity. Groups treated with low dose sage and rosiglitazone showed very similar effects on OGTT and ITT. Sage also improved HOMA-IR, triglycerides and NEFA. Treatment with the low dose increased the plasma levels of the antiinflammatory cytokines IL-2, IL-4 and IL-10 and reduced the plasma level of the proinflammatory cytokines IL-12, TNF-alpha, and KC/GRO. The GC analysis revealed the presence of two PPARs agonist in sage MetOH extract. In vitro, the extract reduced in a dose-related manner the accumulation of lipid droplets; however no effect on lipolysis was observed. Conclusions. Sage MetOH extract at low dose exhibits similar effects to rosiglitazone. It improves insulin sensitivity, inhibits lipogenesis in adipocytes and reduces inflammation as judged by plasma cytokines. Sage presents an alternative to pharmaceuticals for the treatment of diabetes and associated inflammation.