Effect of Polyphenolic Extract of Vachellia Farnesiana on Glycemic Response and Safety in Healthy Volunteers.

The increased consumption of high carbohydrate, processed, and non-fiber foods increases the risk of obesity and consequently the development of type 2 Diabetes Mellitus (DM2); therefore, one of the approaches in the prevention and treatment of these diseases has been focused on the management and reduction of the rate of absorption and metabolism of carbohydrates. DM2 is the result of chronic insulin resistance and loss of pancreatic ß-cell mass and function, which may be caused by glucotoxicity and lipotoxicity leading to apoptosis and dysfunction of these cells; the search for alternative therapies has focused research on secondary compounds from plant metabolism, particularly polyphenols (flavonoids), which have shown positive effects on postprandial blood glucose reduction (2). Polyphenols, defined as secondary metabolites produced by plants, can be found in flowers, vegetables, and fruits; they are generated as a defense mechanism against stress, cold, and UV radiation, among other factors. Polyphenols are classified into two large groups: 1) flavonoids and 2) non-flavonoids. An aromatic ring with a hydroxyl group characterizes the structure of polyphenols.

The consumption of polyphenolics around the world is highly variable; it has been reported that in France, the average consumption is between 283 and 1000 mg/day; in Spain, between 500 and 1000 mg/day; in Italy, it is close to 700 mg/day, and in South Korea an average of 320 mg/day, among others. The variety of dietary patterns worldwide will depend on the total amount of polyphenols consumed daily. The consumption of anthocyanins has been associated with preventing and managing DM2 by protecting against pancreatic beta-cell oxidation, decreasing carbohydrate digestion enzymes, and inhibiting advanced glycation products. Over time, polyphenols have been investigated in several experimental models and clinical trials, contributing to the knowledge of their application as potential preventive agents and in the treatment of chronic non-communicable diseases.

One of the essential compounds in this evidence is gallic acid; this polyphenol is found in vegetables, fruits, tea, and red wine; important biological activities have been reported in murine models in metabolic diseases such as DM2, in addition to the regulation of the peroxisome proliferation receptor (PPAR) in liver, muscle and adipose tissue; impacting on the reduction of serum glucose. Furthermore, in vitro studies have documented a crucial inhibitory activity of glycogen phosphorylase enzymes, which participates in the regulation of glycogen metabolism; a strategy that could be used as an antihyperglycemic agent, and another method could focus on the reduction of the alpha-glucosidase enzyme, which participates by reducing carbohydrate absorption at the intestinal level.

The study of another flavonoid present in tomatoes, tubers, oranges, apples, green and black tea, potatoes, and in plants such as Vachellia farnesiana has been quercetin; this component is mainly absorbed in the intestine with low intensity in the portal vein. In subjects with DM2, this compound showed a decrease in serum glucose peaks after administering a single dose of 200 mg of quercetin, a phenomenon that extended during the three hours of follow-up of glucose concentration compared to the placebo group. A meta-analysis reported that oral administration of quercetin >500 mg/day for eight weeks decreased fasting plasma glucose concentration in patients with metabolic syndrome. In another trial, quercetin was administered for eight weeks at 250 mg/day in patients with DM2, significantly decreasing LDL levels and increasing total antioxidant capacity. However, it showed no change in plasma glucose compared to a placebo group, suggesting that the dose was insufficient. Other compounds identified with antihyperglycemic effects are caffeic, gallic, ferulic, and vanillic acids, flavones (rutin), and flavanones (naringenin).

Glucose uptake in peripheral tissues can be affected by the presence of polyphenol compounds through different effects such as: 1) inhibition of monoglyceride digestive enzymes (alpha-amylase and alpha-glucosidase), these digestive enzymes will decrease glucose uptake and 2) reduction of glucose uptake through inhibition of sodium-dependent glucose transporters 1 (SGLT1) and 2 (SGLT2) located in the proximal tubules of the kidney, 3) in addition to stimulation of insulin secretion and protection of beta-pancreatic cells 4) and finally through inhibition of SGLT2 transporters located not only in the renal tubules; but also in other tissues.