Identification of Insulin-Mimetic Plant Extracts: From an In Vitro High-Content Screen to Blood Glucose Reduction in Live Animals.

Type 2 diabetes mellitus (T2DM) is linked to insulin resistance and a loss of insulin sensitivity, leading to millions of deaths worldwide each year. T2DM is caused by reduced uptake of glucose facilitated by glucose transporter 4 (GLUT4) in muscle and adipose tissue due to decreased intracellular translocation of GLUT4-containing vesicles to the plasma membrane. To treat T2DM, novel medications are required. Through a fluorescence microscopy-based high-content screen, we tested more than 600 plant extracts for their potential to induce GLUT4 translocation in the absence of insulin. The primary screen in CHO-K1 cells resulted in 30 positive hits, which were further investigated in HeLa and 3T3-L1 cells. In addition, full plasma membrane insertion was examined by immunostaining of the first extracellular loop of GLUT4. The application of appropriate inhibitors identified PI3 kinase as the most important signal transduction target relevant for GLUT4 translocation. Finally, from the most effective hits in vitro, four extracts effectively reduced blood glucose levels in chicken embryos (in ovo), indicating their applicability as antidiabetic pharmaceuticals or nutraceuticals.

Phytogenic actives supplemented in hyperprolific sows: effects on maternal transfer of phytogenic compounds, colostrum and milk features, performance and antioxidant status of sows and their offspring, and piglet intestinal gene expression.

Phytogenic actives (PA) are plant-derived natural bioactive compounds that may promote livestock health and well-being, as well as improve growth performance and production efficiency. The current study aims to evaluate their effects on sows and their offspring. Eighty-one hyperprolific sows (up to parity 7) were assigned to 3 experimental treatments. Control sows were offered a nonsupplemented diet during gestation and lactation, and treated sows were fed the control diet supplemented with 1 g/kg of a blend of PA (BPA) in lactation (L) or during gestation and lactation (GL). An evaluation was made of placental and milk maternal transfer of these BPA and colostrum-milk features, sows and piglets antioxidant status, reproductive performance (litter size), body weight (BW) changes, weaning-estrus interval, and litter performance. Finally, piglet´s jejunum gene expression was measured. The BPA supplementation during gestation (GL) increased the number of piglets born alive (P = 0.020) and reduced (P < 0.05) the newborn piglets BW, while there were no differences among treatments on the suckling (day 20) and weaned (day 7) piglets BW (P > 0.05). Dietary phytogenic volatile compounds reached GL placental fluid, and milk of L and GL sows (P < 0.05). Moreover, colostrum protein in GL and milk fat content in L and GL were increased (P < 0.05). Milk of GL showed inhibitory activity against Bacillus subtilis and Staphylococcus aureus (P < 0.05). Antioxidant status of GL sows showed an enhanced (P < 0.05) of catalase (CAT) and total antioxidant capacity levels at early gestation (day 35), whereas higher levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes at late gestation (day 110). Likewise, GL newborn piglets showed higher CAT levels, whereas both CAT and SOD levels in suckling piglets, as well as CAT, SOD, and GSH-Px in weaned piglets, were increased in L and GL (P < 0.05). Jejunum messenger ribonucleic acid abundance of suckling piglets in L and GL groups showed overexpression of barrier function MUC2, digestive enzyme IDO, and immune response PPARGC-α, TNF-α, TGF-ß1, and IL-10 genes (P < 0.05). In conclusion, dietary BPA supplementation in hyperprolific sows increased the litter size (born alive) and improved the composition and bioactivity of colostrum and milk, besides, modified the antioxidant status of sows and their offspring, as well as the suckling piglets gut health gene expression. Several BPA volatile compounds were prenatal and postnatal maternally transferred (placental fluid and milk).

Possible Molecular Mechanisms by Which an Essential Oil Blend from Star Anise, Rosemary, Thyme, and Oregano and Saponins Increase the Performance and Ileal Protein Digestibility of Growing Broilers.

Phytogenic feed additives represent a potential alternative to antibiotics with attributed health and growth-promoting effects. Chickens supplemented with an essential oil blend, a Quillaja saponin blend, or a combination of both phytogenic preparations showed a comprehensively and significantly improved apparent ileal digestibility of crude protein and amino acids compared to control birds. Accordingly, holistic transcriptomic analyses of jejunum and liver samples indicated alterations of macromolecule transporters and processing pathways likely culminating in an increased uptake and metabolizing of carbohydrates and fatty acids. Complementary analyses in Caco-2 showed a significant increase in transporter recruitment to the membrane (SGLT1 and PEPT1) after addition of essential oils and saponins. Although the penetrance of effects differed for the used phytogenic feed additives, the results indicate for an overlapping mode of action including local effects at the intestinal border and systemic alterations of macronutrient metabolism resulting in an improved performance of broilers.