Targeting NF-κB/COX-2 signaling by soyasaponin I alleviates diclofenac-induced gastric ulceration in male albino rats.

Gastric ulceration is a prevalent worldwide clinical presentation due to altered gastric defense mechanisms. Nonsteroidal anti-inflammatory drugs are one of the common causes of gastric ulcers mediated by the release of inflammatory mediators. The study aimed to investigate the potential protective effect of soyasaponin I (soya) against diclofenac (DIC)-induced gastric ulcer in rats and to highlight the underlying mechanisms. The experiment was conducted on 40 male Wistar albino rats, equally distributed into five groups: control, DIC-induced ulcer (9 mg/kg/d, orally, twice daily for 3 days), ulcer/soya-, ulcer/ranitidine-, and ulcer/soya/selective nuclear factor kappa B inhibitor (JSH-23)-treated groups. The doses of soya, ranitidine, and JSH were 20, 25, and 5 mg/kg/d, respectively, given orally. Gastric specimens were prepared for gene and histological study and for biochemical analysis of gastric prostaglandin E2 (PGE2), oxidative markers, and inflammatory cytokines. The gastric samples were formalin-fixed, paraffin-embedded, and subjected to hematoxylin and eosin (H&E), PAS staining, and immunohistochemical assay for identification of nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), and proliferation marker (Ki67) expressions. The findings revealed decreased gastric PGE2 and altered inflammatory and oxidative markers in the ulcer model group. The H&E staining showed mucosal injury characterized by mucosal surface defects and inflammatory cell infiltrations. The polymerase chain reaction (PCR) and immunohistochemistry demonstrated an upregulation of NF-κB and COX-2 expression at gene/protein levels; meanwhile, Ki67 downregulation. The soya-treated group showed maintained biochemical, histological, and PCR findings comparable to the ranitidine-treated group. The JSH-23-treated group still showed partial gastric protection with biochemical and immunohistochemical changes. Soyasaponin I ameliorated DIC-induced gastric ulcers by targeting the COX-2 activity through modulation of NF-κB signaling.

Insight into the characterization and digestion of lotus seed starch-tea polyphenol complexes prepared under high hydrostatic pressure.

Complex starch is gaining research attention due to its unique physicochemical and functional properties. In this study, the effects of green tea polyphenols on the properties and digestion of lotus seed starch under high hydrostatic pressure were investigated. The particle size, swelling power, solubility, crystallization, morphology and thermal properties of lotus seed starch were affected by green tea polyphenols. These may be due to the formation of non-inclusive complexes between lotus seed starch and green tea polyphenols. The morphology and green tea polyphenols distribution of the complexes were determined by scanning electron microscopy and confocal laser scanning microscopy. In addition, slow digestion properties of starch were realized under a dynamic in vitro rat stomach-duodenum model and the erosion of granules by amylase gradually decreased by scanning electron microscopy. Furthermore, green tea polyphenols were shown to be able to form V-type inclusion complex with amylose via high hydrostatic pressure.

Dual excitatory and smooth muscle-relaxant effect of ß-phenylethylamine on gastric fundus strips in rats.

ß-Phenylethylamine (ß-PEA) is a trace amine with chemical proximity to biogenic amines and amphetamines. It is an endogenous agonist of trace amine-associated receptors (TAARs) that acts as a neuromodulator of classic neurotransmitters in the central nervous system. At high concentrations, ß-PEA contracts smooth muscle, and a role for TAARs in these responses has been postulated. The high dietary intake of trace amines has been associated with such symptoms as hypertension and migraine, especially after the intake of foods containing such compounds. In gastrointestinal tissues, TAAR expression was reported, although the effect of ß-PEA on gastric contractile behaviour is unknown. Here, isolated strips that were obtained from the rat gastric fundus were stimulated with high micromolar concentrations of ß-PEA. Under resting tonus, ß-PEA induced contractions. In contrast, when the strips were previously contracted with KCl, a relaxant response to ß-PEA was observed. The contractile effect of ß-PEA was inhibited by 5-hydroxytryptamine (5-HT) receptor antagonists (i.e., cyproheptadine and ketanserin) but not by the TAAR1 antagonist EPPTB. In gastric fundus strips that were previously contracted with 80 mmol/L KCl, the relaxant effect of ß-PEA intensified in the presence of 5-HT receptor antagonists, which was inhibited by EPPTB and the adenylyl cyclase inhibitor MDL-12,330A. The guanylyl cyclase inhibitor ODQ did not alter the relaxant effects of ß-PEA. In conclusion, ß-PEA exerted dual contractile and relaxant effects on rat gastric fundus. The contractile effect appeared to involve the recruitment of 5-HT receptors, and the relaxant effect of ß-PEA on KCl-elicited contractions likely involved TAAR1 .

Effects of the gastric juice injection pattern and contraction frequency on the digestibility of casein powder suspensions in an in vitro dynamic rat stomach made with a 3D printed model.

Previously, we have prepared a version of the dynamic in vitro rat stomach system (DIVRS-II or Biomimic Rat II). It was constructed and tested by showing similar digestive behaviors with those occurred in vivo. In the present work, a 3D-printed plastic mold was employed to create highly repeatable silicone rat stomach model. It has been seen to have shortened the time to handcraft a model like that used in DIVRS-II. The maximum mechanical force of the current stomach model generated by rolling extrusion is found to be more stable probably due to the more uniform wall thickness of the new model. Then the effects of the simulated gastric secretion patterns and contraction frequency of the system on the in vitro digestibility of casein powder suspensions were investigated. The results have shown that the location of the gastric secretion injection has an impact on experimental digestibility. The position of rolling-extrusion area, established at the central part of glandular portion (stomach B), displayed the highest digestibility compared to that at the other locations. Furthermore, the extent of digestion was positively correlated with the contraction frequency of the model stomach system, with the maximum frequency of 12cpm giving the highest digestibility. This highest digestibility is almost the same as the average value found in vivo. The better digestive performance produced by optimizing the gastric secretion pattern and contraction frequency may be both resulted from the improved mixing efficiency of the food matrix with digestive juice. This study shows that it is possible to achieve what in vivo in a simulated digestion device, which may be used for future food and nutrition studies in vitro.

Extracellular acidosis selectively inhibits pharmacomechanical coupling induced by carbachol in strips of rat gastric fundus.

NEW FINDINGS: What is the central question of this study? Acute acidosis that results from short-term exercise is involved in delayed gastric emptying in rats and the lower responsiveness of gastric fundus strips to carbachol. Does extracellular acidosis decrease responsiveness to carbachol in tissues of sedentary rats? How? What is the main finding and its importance? Extracellular acidosis inhibits cholinergic signalling in the rat gastric fundus by selectively influencing the Gq/11 protein signalling pathway. Acute acidosis that results from short-term exercise delays gastric emptying in rats and decreases the responsiveness to carbachol in gastric fundus strips. The regulation of cytosolic Ca2+ concentrations appears to be a mechanism of action of acidosis. The present study investigated the way in which acidosis interferes with gastric smooth muscle contractions. Rat gastric fundus isolated strips at pH 6.0 presented a lower magnitude of carbachol-induced contractions compared with preparations at pH 7.4. This lower magnitude was absent in carbachol-stimulated duodenum and KCl-stimulated gastric fundus strips. In Ca2+ -free conditions, repeated contractions that were induced by carbachol progressively decreased, with no influence of extracellular pH. In fundus strips, CaCl2 -induced contractions were lower at pH 6.0 than at pH 7.4 but only when stimulated in the combined presence of carbachol and verapamil. In contrast, verapamil-sensitive contractions that were induced by CaCl2 in the presence of KCl did not change with pH acidification. In Ca2+ store-depleted preparations that were treated with thapsigargin, the contractions that were induced by extracellular Ca2+ restoration were smaller at pH 6.0 than at pH 7.4, but relaxation that was induced by SKF-96365 (an inhibitor of store-operated Ca2+ entry) was unaltered by extracellular acidification. At pH 6.0, the phospholipase C inhibitor U-73122 relaxed carbachol-induced contractions less than at pH 7.4, and this phenomenon was absent in tissue that was treated with the RhoA kinase blocker Y-27632. Thus, extracellular acidosis inhibited pharmacomechanical coupling in gastric fundus by selectively inhibiting the Gq/11 protein signalling pathway, whereas electromechanical coupling remained functionally preserved.

Enhancement of Digestibility of Casein Powder and Raw Rice Particles in an Improved Dynamic Rat Stomach Model Through an Additional Rolling Mechanism.

Previously, a dynamic in vitro rat stomach system (DIVRS-I) designed based on the principles of morphological bionics was reported. The digestibilities of casein powder and raw rice particles were found to be lower than those in vivo due to perhaps the less efficient compression performance and lower mixing efficiency. In this study, a 2nd version of the rat stomach system (DIVRS-II) with an additional rolling extrusion type motility on the wall of the soft-elastic silicone rat stomach model is introduced. The DIVRS-II was then tested by comparing the digestive behaviors of the casein powder suspensions and raw rice particles with those previously published data obtained from the in vivo test on living rats, the DIVRS-I, and the stirred tank reactor at its optimum stirring speed. The results have indicated that although the digestibilities of the casein powder and raw rice particles in the DIVRS-II are still lower than the average results obtained from in vivo, they are significantly improved by about 50% and 32% at the end of digestion compared with that in the DIVRS-I, respectively. The work has demonstrated that the powerful rolling extrusion is highly effective and has contributed to the significant improvement of digestibility as shown here. In addition, the digestibility presented in the DIVRS-II was found already higher than that tested in the STR at its optimum speed, indicating the high potential of the soft-elastic stomach under the influence of the "rolling and squeezing" for more realistic investigation of food digestion.

Advanced spatiotemporal mapping methods give new insights into the coordination of contractile activity in the stomach of the rat.

We used spatiotemporal mapping of strain rate to determine the direction of propagation and amplitudes of the longitudinal and circumferential components of antrocorporal (AC) contractions and fundal contractions in the rat stomach maintained ex vivo and containing a volume of fluid that was within its normal functional capacity. In the region of the greater curvature the longitudinal and circular components of AC contractions propagated synchronously at right angles to the arciform geometric axis of the stomach. However, the configuration of AC contractions was U shaped, neither the circular nor the longitudinal component of contractions being evident in the upper proximal corpus. Similarly, in the distal upper antrum of some preparations, circumferential components propagated more rapidly than longitudinal components. Ongoing "high-frequency, low-amplitude myogenic contractions" were identified in the upper proximal gastric corpus and on the anterior and posterior wall of the fundus. The amplitudes of these contractions were modulated in the occluded stomach by low-frequency pressure waves that occurred spontaneously. Hence the characteristics of phasic contractions vary regionally in the antrum and corpus and a previously undescribed high-frequency contractile component was identified in the proximal corpus and fundus, the latter being modulated in synchrony with cyclic variation in intrafundal pressure in the occluded fundus.