Natural phenolic compounds potentiate hypoglycemia via inhibition of Dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DPP IV) is a surface glycoprotein that can degrade glucagon like pepetide-1 (GLP-1) by decreasing blood sugar. Herbal medicines for diabetic therapy are widely used with acceptable efficacy but unsatisfied in advances. DPP IV was chosen as a template to employ molecular docking via Discovery Studio to search for natural phenolic compounds whether they have the inhibitory function of DPP IV. Then, docking candidates were validated and further performed signal pathway via Caco-2, C2C12, and AR42J cells. Lastly, a diet-induced diabetes in mice were applied to examine the efficacy and toxicity of hit natural phenolic products in long-term use (in vivo). After screening, curcumin, syringic acid, and resveratrol were found in high affinity with DPP IV enzymes. In enzymatic tests, curcumin and resveratrol showed potential inhibition of DPP IV. In vitro assays, curcumin inhibited of DPP IV activity in Caco-2 cells and ERK phosphorylation in C2C12 cells. Additionally, curcumin attenuated blood sugar in S961-treated C57BL/6 mice and in diet-induced diabetic ICR mice and long-term regulate HbA1c in diabetic mice. Curcumin targeted to DPP IV for reducing blood glucose, it possesses potential and alternative substitution of synthetic clinical drugs for the medication of diabetes.

Hypoglycemic Efficacy of Docking Selected Natural Compounds against α-Glucosidase and α-Amylase.

The inhibition of α-glucosidase and α-amylase is a clinical strategy for the treatment of type II diabetes, and herbal medicines have been reported to credibly alleviate hyperglycemia. Our previous study has reported some constituents from plant or herbal sources targeted to α-glucosidase and α-amylase via molecular docking and enzymatic measurement, but the hypoglycemic potencies in cell system and mice have not been validated yet. This study was aimed to elucidate the hypoglycemic efficacy of docking selected compounds in cell assay and oral glucose and starch tolerance tests of mice. All test compounds showed the inhibition of α-glucosidase activity in Caco-2 cells. The decrease of blood sugar levels of test compounds in 30 min and 60 min of mice after OGTT and OSTT, respectively and the decreased glucose levels of test compounds were significantly varied in acarbose. Taken altogether, in vitro and in vivo experiments suggest that selected natural compounds (curcumin, antroquinonol, HCD, docosanol, tetracosanol, rutin, and actinodaphnine) via molecular docking were confirmed as potential candidates of α-glucosidase and α-amylase inhibitors for treating diabetes.

Acute osmotic stress affects Tilapia (Oreochromis mossambicus) innate immune responses.

Most of the tilapia studies are focused on its osmoregulatory mechanism. Meanwhile, less information is available about its innate immune response on fish faced with hyperosmolality. In the present study, in vivo analyses were carried out to investigate the innate immune response of Oreochromis mossambicus, transferred from freshwater to 25 ppt seawater (SW). In vivo, lysozyme activities of plasma and head kidney (HK) were increased at 1h and at 24h after transfer to SW but decreased at 8h after SW transfer. Surprisingly, the alternative complement pathway in plasma increased 8h after SW transfer. The phagocytic capacity of spleen and HK immune cells increased modestly at 1h and at 4h, after SW transfer, but the respiratory burst activity of immune cells in both HK and spleen shows an increase in superoxide release at 8h after SW transfer. Our results reveal that the transfer of fish from conditions of hypoosmolarity to hyperosmolality significantly enhances plasma lysozyme, ACP activity, and both phagocytic and respiratory burst activity. Taken together, the results indicate that exposure of tilapia to hyperosmotic conditions has immunostimulatory effects on its cellular immune reactions (phagocytosis and respiratory burst activity) and humoral reactions (lysozyme activity and complement activity).

Temperature and humidity alter prolactin receptor expression in the skin of toad (Bufo bankorensis and Bufo melanostictus).

Bufo bankorensis and Bufo melanostictus, the only two species of Bufonidae genus in Taiwan, live in habitats that differ in altitude and humidity. This study tested the hypothesis that prolactin receptor (PRLR) expression responds to environmental change. Western blot analysis showed that the PRLR protein was widely distributed in brain, lung, liver, kidney, dorsal skin and ventral skin of toads. The level PRLR protein was elevated in the dorsal skin of the two toad species treated with dry or wet conditions for 14 days. The increase in PRLR of dorsal skin in B. bankorensis was higher than that in B. melanostictus. This experimental result suggests that B. bankorensis secretes more mucus to reduce water evaporation from its thinner cuticle than B. melanostictus. The expression of PRLR protein was increased in the lung of B. bankorensis and decreased in the lung of B. melanostictus. Moreover, PRLR protein levels were increased in the kidneys in the two species toad, likely due to reduction in water lost through lung and urine. The two toad species were subjected to varying temperatures (25 degrees C, 15 degrees C and 10 degrees C) for 14 days. The lowest PRLR protein expression was observed at 10 degrees C. Comparison of the decreasing trend in PRLR protein levels demonstrated that the variation in B. bankorensis was significantly higher than that in B. melanostictus. Comparisons of variation in PRLR protein expression in the two species under different environments suggest that B. bankorensis is more adaptable to different environments than B. melanostictus.

Expression of porcine epidermal growth factor in Pichia pastoris and its biology activity in early-weaned piglets.

Early-weaned piglets often have abnormalities in intestinal morphology and function. Epidermal growth factor (EGF) is critical in the development and in the repair of the gastrointestinal tract in pigs. This study investigated the effects of dietary EGF supplementation on growth performance and small intestinal morphology of early-weaned piglets. The functional domain of porcine EGF (pEGF) was cloned after RT-PCR amplification. The recombinant protein was expression by the Pichia pastoris expression system and the construct pPIC9K-pEGF was transformed into host GS115. The secretary recombinant protein in the supernatants was analyzed by SDS-PAGE. The gel indicated that the extra band at 6 kDa in the transformant, which corresponds to the standard hEGF, were both reactive to anti-pEGF antibody by Western blotting. The expression level of pEGF in the culture supernatant was 870 microg/mL. An animal feeding test was conducted to identify the effects of pEGF supplementation on growth performance and the development of digestive tracts of 14-day weaned piglets. The dietary treatment was a corn-soybean meal basal diet either with or without 1.5 mg/kg recombinant pEGF from the transformant fermentative supernatant. Dietary treatments enhanced the daily gain during 0-7 days postweaning (p < 0.05), but did not affect the performance throughout the entire test period. Dietary supplemental pEGF significantly increased serum IgA levels on day 18 postweaning, and increased the mucosa IgA levels and crypt depth at jejunum on day 28 postweaning (p < 0.05). The experimental results showed that the recombinant pEGF could be secreted by P. pastoris. The trophic effects of pEGF on growth performance, immune response, and small intestine development were determined by feeding recombinant pEGF to early-weaned piglets.