Background : This study was done to obtain comprehensive data on changes in the structural components of the enteric nervous system in pediatric patients with intestinal pseudo-obstruction (IPO). We evaluated routinely processed, in formalin-fixed tissues by quantitative morphometric analysis. In addition, we used formalin-fixed tissue to explore the possibility of using previously proposed diagnostic criteria to evaluate frozen serial sections for intestinal neuronal dysplasia (IND) type B and hypoganglionosis. Methods : We analyzed data for 19 IPO cases. Morphometric analysis for quantification of ganglia and ganglion cells (GCs) was done for the myentric and the submucous plexus. In addition, we determined the presence of immature GCs and the distribution of nerve fibers and interstitial cells of Cajal (ICC). Results : Nine patients showed combined hypoganglionosis, IND, and decreased ICC; others showed various combinations of these. Several morphometric factors were significantly different between patient groups as well as being different than the control group. Conclusions : Our pediatric IPO cases showed extensive overlapping of pathological findings. And the findings suggest the utility of using previously proposed morphometrically measured factors in multiple frozen sections as diagnostic criteria for IND type B and hypoganglionosis in formalin-fixed tissue.
Superhongmi is a new rice variety, which was developed for the enrichment of bioactive compounds through crossbreeding three varieties of rice breeds in Korea. The high-performance liquid chromatography coupled with a photodiode array detector quadrupole and tandem time-of-flight mass spectrometry (HPLC/PDA/QTOF-MS) analysis has revealed that superhongmi bran extract contained four taxifolin derivatives as well as cyanidin 3-glucoside. The high-performance countercurrent chromatography (CCC) and reversed-phase HPLC led to the isolation of aforementioned five compounds, and spectroscopic analysis identified cyanidin 3-glucoside (1), along with (2R,3R)-taxifolin 3-O-β-D-glucopyranoside (2), (2R,3R)-4′-O-methyltaxifolin 3-O-β-D-glucopyranoside (a novel compound) (3), (2R,3R)-taxifolin (4), and (2R,3R)-4′-O-methyltaxifolin (5). Compound 2 had the highest rat small intestinal sucrase inhibitory activity (0.54 mM) relevant for potentially managing postprandial hyperglycemia, followed by compound 1 (0.97 mM) and compound 4 (1.74 mM, IC 50 ). The anti-hyperglycemic effect of compound 4 (taxifolin), a main peak in HPLC analysis was investigated using a Sprague-Dawley (SD) rat model. Compared to a control, taxifolin treatment (p < 0.001) reduced significantly after sucrose loading the observed postprandial blood glucose and the maximum blood glucose (C max ) by 15% (203.60 ± 15.86 to 172.30 ± 12.74). These results indicate that taxifolin derivatives that inhibit the activity of carbohydratehydrolyzing enzymes resulting in reduced dietary carbohydrate absorption can potentially be used as a strategy to manage diabetes.
Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.
Hypertension is a major risk factor for the development of cardiovascular diseases. This study aimed to elucidate whether the natural product mixture No-ap (NA) containing Pine densiflora, Annona muricate, and Monordica charantia, or its single components have inhibitory effects on hypertension-related molecules in Angiotensin II (Ang II)-stimulated H9C2 cells. Individual functional components were isolated and purified from NA using various columns and solvents, and then their structures were analyzed using ESI–MS, 1H-NMR, and 13H-NMR spectra. H9C2 cells were stimulated with 300 nM Ang II for 7 h. NA, telmisartan, ginsenoside, roseoside (Roseo), icariside E4 (IE4), or a combination of two components (Roseo and IE4) were administered to the cells 1 h before Ang II stimulation. The expression and activity of hypertension-related molecules or oxidative molecules were determined using RT-PCR, western blot, and ELISA. Ang II stimulation increased the expression of Ang II receptor 1 (AT1), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), tumor growth factor-β (TGF-β) mRNA, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and the levels of hydrogen peroxide (H2O2) and superoxide anion (•O2−) and reduced anti-oxidant enzyme activity. NA significantly improved the expression or activities of all hypertension-related molecules altered in Ang II-stimulated cells. Roseo or IE4 pretreatment either decreased or increased the expression or activities of all hypertension-related molecules similar to NA, but to a lesser extent. The pretreatment with a combination of Roseo and IE4 (1:1) either decreased or increased the expression of all hypertension-related molecules, compared to each single component, revealing a synergistic action of the two compounds. Thus, the combination of single components could exert promising anti-hypertensive effects similar to NA, which should be examined in future animal and clinical studies.
Onion (Allium cepa L.) is widely consumed as food or medicinal plant due to its well-defined health benefits. The antioxidant and antihyperlipidemic effects of onion and its extracts have been reported well. However, very limited information on anti-hyperglycemic effect is available in processed onion extracts. In our previous study, we reported that Amadori rearrangement compounds (ARCs) produced by heat-processing in Korean ginseng can reduce carbohydrate absorption by inhibiting intestinal carbohydrate hydrolyzing enzymes in both in vitro and in vivo animal models. To prove the enhancement of anti-hyperglycemic effect and ARCs content by heat-processing in onion extract, a correlation between the anti-hyperglycemic activity and the total content of ARCs of heat-processed onion extract (ONI) was investigated. ONI has a high content of ARCs and had high rat small intestinal sucrase inhibitory activity (0.34 ± 0.03 mg/mL, IC50) relevant for the potential management of postprandial hyperglycemia. The effect of ONI on the postprandial blood glucose increase was investigated in Sprague Dawley (SD) rats fed on sucrose or starch meals. The maximum blood glucose levels (Cmax) of heat-processed onion extract were significantly decreased by about 8.7% (from 188.60 ± 5.37 to 172.27 ± 3.96, p < 0.001) and 14.2% (from 204.04 ± 8.73 to 175.13 ± 14.09, p < 0.01) in sucrose and starch loading tests, respectively. These results indicate that ARCs in onion extract produced by heat-processing have anti-diabetic effect by suppressing carbohydrate absorption via inhibition of intestinal sucrase, thereby reducing the postprandial increase of blood glucose. Therefore, enhancement of ARCs in onion by heat-processing might be a good strategy for the development of the new product on the management of hyperglycemia.
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