*4.3. Effect on Diabetes and Obesity*

Maqui dietary supplementation has been shown to have positive effects on fasting glucose and insulin levels in human and mouse models of type 2 diabetes and obesity. Maqui standardized extract showed a significant reduction in glycemia in 10 volunteers with moderate glucose intolerance [73]. It was shown that obese mice induced by a high-fat diet and supplemented with lyophilized Maqui had better insulin response capacity, less weight gain, and greater thermogenic activity [74].

The effect of Maqui anthocyanins on a murine model of type 2 diabetes was studied. Oral administration of these anthocyanins improved fasting blood glucose levels and glucose tolerance in hyperglycemic obese C57BL/6J mice, fed a high-fat diet. On the other hand, it also improved the negative regulation of the gluconeogenic enzyme glucose-6-phosphatase stimulated by insulin and decreased glucose production. Additionally, delphinidin-3-*O*-sambubioside-5-*O*-glucoside was shown to dose-dependently lower fasting blood glucose levels in obese C57BL/6J mice [75].

Maqui berries are commercially extracted to produce a standardized polyphenolic extract, which contains 25% delphinidin, the most abundant anthocyanin in this fruit. The extract has other constituents, phenolic acids, flavonols (quercetin, rutin, myricetin, and flavanols (catechins and epicatechins). Maqui berry extract is marketed worldwide as Delphinol® and is distributed by the company Maqui New Life (MNL, trademark owner), based in Santiago, Chile, and Cham, Switzerland [76]. Delphinol® is a nutritional supplement with the ability to naturally control postprandial glycemia through the inhibition of the sodium and glucose cotransporter in the small intestine. An investigation carried out on ten volunteers with moderate glucose intolerance, using a double-blind, placebo-controlled, crossover study model, showed the effect of Delphinol® on glucose. This supplement significantly inhibited non-desired changes in postprandial blood glucose levels, 60 and 90 min after ingestion of boiled rice [73]. Alvarado et al. showed that the effects of Delphinol® on basal glycemia and insulinemia could be related to the inhibition of intestinal glucose transporters, as well as an incretin-mediated effect or by improving sensitivity to insulin [77].

Additionally, the role of Maqui extracts has been highlighted not only in preventing diabetes but also in preventing and treating obesity. A high-fat diet supplemented with a regular dose of Maqui berries shows better insulin response and less weight gain. In addition, a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, the formation of multilocular lipid droplets, and thermogenesis in subcutaneous white adipose tissue (scWAT) is evidenced. These findings highlighted the role of this berry in preventing or treating type 2 diabetes and obesity-related diseases, as well as their metabolic complications [74].

Alpha-glucosidase inhibition is considered one of the measures to regulate type 2 diabetes [69]. Gironés-Vilaplana et al. (2014) reported that EC50 values of glucosidase inhibition for açai and Maqui berries were in the range of 0.33–2.14 mg/mL, while for strawberry pomace the values were not so influential, which shows once again the potential of Maqui over other berries [69,78]. Maqui has shown potent postprandial glycemic lowering effects at a single dose of approximately 1000 μmol GAE of polyphenols derived from Maqui berry extract and lemon juice, following carbohydrate (glucose and rice) ingestion [79]. A similar dose was also effective in lowering postprandial blood glucose (induced by ingestion of 25 g glucose) by ingestion of coffee containing 2.5 mmol/L chlorogenic acid (a total amount of 1000 μmol chlorogenic acid) [79,80]. Table 2 summarizes the clinical studies that link Maqui with cardiovascular protection. These results show the effect of different extracts of this berry on cardiovascular risk factors (glucose index, obesity, diabetes, among others). Some studies showed the biological activity of the Maqui extract, while others relate the biological potential with the presence of some compounds of a mainly phenolic nature.

**Table 2.** Cardioprotective role of Maqui: clinical studies.



diglucoside.

