Protective effect of Broussonetia papyrifera leaf polysaccharides on intestinal integrity in a rat model of diet-induced oxidative stress.

This study aimed to investigate the effect of Broussonetia papyrifera polysaccharides (BPP) on the jejunal intestinal integrity of rats ingesting oxidized fish oil (OFO) induced oxidative stress. Polysaccharides (Mw 16,956 Da) containing carboxyl groups were extracted from Broussonetia papyrifera leaves. In vitro antioxidant assays showed that this polysaccharide possessed antioxidant capabilities. Thirty-two male weaned rats were allocated into two groups orally infused BPP solution and PBS for 26 days, respectively. From day 9 to day 26, half of the rats in each group were fed food containing OFO, where the lipid peroxidation can induce intestinal oxidative stress. OFO administration resulted in diarrhea, decreased growth performance (p < 0.01), impaired jejunal morphology (p < 0.05) and antioxidant capacity (p < 0.01), increased the levels of ROS and its related products, IL-1ß and IL-17 (p < 0.01) of jejunum, as well as down-regulated Bcl-2/Bax (p < 0.01) and Nrf2 signaling (p < 0.01) of jejunum in rats. BPP gavage effectively alleviated the negative effects of OFO on growth performance, morphology, enterocyte apoptosis, antioxidant capacity and inflammation of jejunum (p < 0.05) in rats. In the oxidative stress model cell assay, the use of receptor inhibitors inhibited the enhancement of antioxidant capacity by BPP. These results suggested that BPP protected intestinal morphology, thus improving growth performance and reducing diarrhea in rats ingesting OFO. This protective effect may be attributed to scavenging free radicals and activating the Nrf2 pathway, which enhances antioxidant capacity, consequently reducing inflammation and mitigating intestinal cell death.

Intestinal inflammation marker calprotectin regulates epithelial intestinal zinc metabolism and proliferation in mouse jejunal organoids.

Calprotectin (CP), a heterodimer of S100A8 and S100A9, is expressed by neutrophils and a number of innate immune cells and is used widely as a marker of inflammation, particularly intestinal inflammation. CP is a ligand for toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE). In addition, CP can act as a microbial modulatory agent via a mechanism termed nutritional immunity, depending on metal binding, most notably Zn2+. The effects on the intestinal epithelium are largely unknown. In this study we aimed to characterize the effect of calprotectin on mouse jejunal organoids as a model epithelium, focusing on Zn2+ metabolism and cell proliferation. CP addition upregulated the expression of the Zn2+ absorptive transporter Slc39a4 and of methallothionein Mt1 in a Zn2+-sensitive manner, while downregulating the expression of the Zn2+ exporter Slc30a2 and of methallothionein 2 (Mt2). These effects were greatly attenuated with a CP variant lacking the metal binding capacity. Globally, these observations indicate adaptation to low Zn2+ levels. CP had antiproliferative effects and reduced the expression of proliferative and stemness genes in jejunal organoids, effects that were largely independent of Zn2+ chelation. In addition, CP induced apoptosis modestly and modulated antimicrobial gene expression. CP had no effect on epithelial differentiation. Overall, CP exerts modulatory effects in murine jejunal organoids that are in part related to Zn2+ sequestration and partially reproduced in vivo, supporting the validity of mouse jejunal organoids as a model for mouse epithelium.

Intestinal secretory mechanisms in Okadaic acid induced diarrhoea.

Okadaic acid (OA) is an important marine lipophilic phycotoxin responsible for diarrhetic shellfish poisoning (DSP). This toxin inhibits protein phosphatases (PPs) like PP2A and PP1, though, this action does not explain OA-induced toxicity and symptoms. Intestinal epithelia comprise the defence barrier against external agents where transport of fluid and electrolytes from and to the lumen is a tightly regulated process. In some intoxications this balance becomes dysregulated appearing diarrhoea. Therefore, we evaluated diarrhoea in orally OA-treated mice as well as in mice pre-treated with several doses of cyproheptadine (CPH) and then treated with OA at different times. We assessed stools electrolytes and ultrastructural alteration of the intestine, particularly evaluating tight and adherens junctions. We detected increased chloride and sodium faecal concentrations in the OA-exposed group, suggesting a secretory diarrhoea. Pre-treatment with CPH maintains chloride concentration in values similar to control mice. Intestinal cytomorphological alterations were observed for OA mice, whereas CPH pre-treatment attenuated OA-induced damage in proximal colon and jejunum at 2 h. Conversely, tight junctions' distance was only affected by OA in jejunum at the moment diarrhoea occurred. In this study we found cellular mechanisms by which OA induced diarrhoea revealing the complex toxicity of this compound.

Tissular Genomic Responses to Oral FB1 Exposure in Pigs.

Fumonisin B1 (FB1) is a widespread mycotoxin produced by fungal Fusarium species-mainly in maize, one of the plants most commonly used for food and feed. Pigs and horses are the animal species most susceptible to this mycotoxin. FB1 exposure can cause highly diverse clinical symptoms, including hepatotoxicity, immunotoxicity, and intestinal barrier function disturbance. Inhibition of ceramide synthetase is a well-understood ubiquitous molecular mechanism of FB1 toxicity, but other more tissue-specific effects remain to be elucidated. To investigate the effects of FB1 in different exposed tissues, we cross-analyzed the transcriptomes of fours organs: liver, jejunum, jejunal Peyer's patches, and spleen. During a four-week study period, pigs were fed a control diet or a FB1-contaminated diet (10 mg/kg feed). In response to oral FB1 exposure, we observed common biological processes in the four organs, including predominant and recurrent processes (extracellular matrix organization, integrin activation, granulocyte chemotaxis, neutrophil migration, and lipid and sterol homeostasis), as well as more tissue-specific processes that appeared to be related to lipid outcomes (cell cycle regulation in jejunum, and gluconeogenesis in liver).

Allicin Improves Intestinal Epithelial Barrier Function and Prevents LPS-Induced Barrier Damages of Intestinal Epithelial Cell Monolayers.

Gut barrier disruption is the initial pathogenesis of various diseases. We previously reported that dietary allicin improves tight junction proteins in the endoplasmic reticulum stressed jejunum. However, whether the allicin benefits the gut barrier within mycotoxin or endotoxin exposure is unknown. In the present study, IPEC-J2 cell monolayers within or without deoxynivalenol (DON) or lipopolysaccharide (LPS) challenges were employed to investigate the effects of allicin on intestinal barrier function and explore the potential mechanisms. Results clarified that allicin at 2 µg/mL increased the viability, whereas the allicin higher than 10 µg/mL lowered the viability of IPEC-J2 cells via inhibiting cell proliferation. Besides, allicin increased trans-epithelial electric resistance (TEER), decreased paracellular permeability, and enhanced ZO-1 integrity of the IPEC-J2 cell monolayers. Finally, allicin supplementation prevented the LPS-induced barrier damages via activating Nrf2/HO-1 pathway-dependent antioxidant system. In conclusion, the present study strongly confirmed allicin as an effective nutrient to improve intestinal barrier function and prevent bacterial endotoxin-induced barrier damages.

Sources and levels of copper affect liver copper profile, intestinal morphology and cecal microbiota population of broiler chickens fed wheat-soybean meal diets.

Super dosing copper (Cu) has long been used as an alternative to antibiotic growth-promoters in broiler chickens' diet to improve gut health. This study was designed to compare nutritional and growth-promoting levels of Cu hydroxychloride (CH) with CuSO4 on gut health bio-markers and liver mineral profile of broiler chickens. Ross 308 chicks (n = 864) were randomly assigned to eight treatments, as basal diet containing no supplemental Cu; the basal diet with 15 or 200 mg/kg Cu as CuSO4; or 15, 50, 100, 150 or 200 mg/kg Cu from CH. The highest liver Cu content was observed in birds fed the diets with 200 mg/kg CuSO4 (P < 0.01). Serum FITC-d concentration as the leaky gut marker, and liver malondialdehyde concentration were not affected. Copper level or source had no effect on cecal short chain fatty acid and the mRNA expression of five jejunal genes involved in gut integrity. Negative linear responses of Cu were observed on Lactobacillus (P = 0.032), Bacteroides (P = 0.033), and Enterobacteriaceae (P = 0.028) counts. The jejunal villus height increased in birds fed CH at 200 and 100 mg/kg (P < 0.05). Increasing Cu levels, linearly and quadratically (P < 0.001), increased Cu excretion.

Regulation of Glucose Insulinotropic Peptide and Intestinal Glucose Transporters in the Diet-Induced Obese Mouse.

Our recent studies have shown that glucose-dependent insulinotropic polypeptide (GIP), but not glucagon-like peptide 1 (GLP-1), augments Na-glucose transporter 1- (SGLT1-) mediated glucose absorption in mouse jejunum. Na-dependent glucose absorption sharply rose and peaked in 3 months of high-fat (i.e., obese) compared to normal (i.e., normal weight) diet fed animals. Previous studies have shown that GIP-augmented SGLT1 and PEPT1 (peptide transporter 1) are regulated by protein kinase A (PKA) signaling in mouse jejunum. Additional studies have indicated that cAMP and PI3 kinase signaling augment PEPT1 through EPAC and AKT activation pathways, respectively, through increased apical PEPT1 trafficking in intestinal epithelial cells. However, little is known about how the signaling glucose transport paradigm is altered over a long period. Early on, increased glucose absorption occurs through SGLT1, but as the obesity and diabetes progress, there is a dramatic shift towards a Na-independent mechanism. Surprisingly, at the peak of glucose absorption during the fifth month of the progression of obesity, the SGLT1 activity was severely depressed, while a Na-independent glucose absorptive process begins to appear. Since glucose transporter 2 (GLUT2) is expressed on the apical membrane of the small intestine in obese patients and animal models of obesity, it was hypothesized to be the new more efficient route. Western blot analyses and biotinylation of the apical membrane revealed that the GIP expression increases in the obese animals and its trafficking to the apical membrane increases with the GIP treatment.

L-Theanine mediates the p38MAPK signaling pathway to alleviate heat-induced oxidative stress and inflammation in mice.

L-Theanine, an active ingredient in the tea plant (Camellia sinensis) associated with calming, is widely used as a functional ingredient and dietary supplement. In this study, a heat stress mouse model was used to evaluate the anti-heat stress effect of L-theanine and its possible mechanism of action. Mice subjected to heat stress (40 °C) that were administered L-theanine at various doses (100, 200, and 400 mg kg-1 d-1) had reduced oxidative stress and inflammatory factors when L-theanine was administered both long-term and as a preventative treatment. Our L-theanine intervention countered the reduction in growth and feed intake of mice under heat stress and reversed liver and jejunum tissue damage. Moreover, L-theanine countered the increase in inflammatory factors TNF-α, IL-6, and IL-1ß and antioxidant enzymes SOD and CAT; it also counteracted GSH-Px inactivation, the upregulation of AST and ALT enzyme activity, and MDA production. The mechanism of action may involve mediation of the P38 signaling pathway, inhibition of MK2 overexpression, and downregulation of p-P65/P65 caused by the overexpression of downstream HSP27. This would inhibit the heat stress-induced imbalance in oxidative stress and inflammatory responses.

Prolonged oral antimicrobial administration prevents doxorubicin-induced loss of active intestinal stem cells.

Acute intestinal mucositis is a common off-target effect of chemotherapy, leading to co-morbidities such as vomiting, diarrhea, sepsis, and death. We previously demonstrated that the presence of enteric bacteria modulates the extent of jejunal epithelial damage induced by doxorubicin (DXR) in mice. Despite conventional thinking of the crypt as a sterile environment, recent evidence suggests that bacterial signaling influences aISC function. In this study, we labeled aISCs using transgenic Lgr5-driven fluorescence or with immunostaining for OLFM4. We examined the effect of DXR in both germ free (GF) mice and mice depleted of microbiota using an established antimicrobial treatment protocol (AMBx). We found differences in DXR-induced loss of aISCs between GF mice and mice treated with AMBx. aISCs were decreased after DXR in GF mice, whereas AMBx mice retained aISC expression after DXR. Neither group of mice exhibited an inflammatory response to DXR, suggesting the difference in aISC retention was not due to differences in local tissue inflammation. Therefore, we suspected that there was a protective microbial signal present in the AMBx mice that was not present in the GF mice. 16S rRNA sequencing of jejunal luminal contents demonstrated that AMBx altered the fecal and jejunal microbiota. In the jejunal contents, AMBx mice had increased abundance of Ureaplasma and Burkholderia. These results suggest pro-survival signaling from microbiota in AMBx-treated mice to the aISCs, and that this signaling maintains aISCs in the face of chemotherapeutic injury. Manipulation of the enteric microbiota presents a therapeutic target for reducing the severity of chemotherapy-associated mucositis.

Selenium exerts protective effects against heat stress-induced barrier disruption and inflammation response in jejunum of growing pigs.

BACKGROUND: Heat stress (HS) has a negative impact on the intestinal barrier and immune function of pigs. Selenium (Se) may improve intestinal health through affecting selenoproteins. Thus we investigate the protective effect of new organic Se (2-hydroxy-4-methylselenobutanoic acid, HMSeBA) on jejunal damage in growing pigs upon HS and integrate potential roles of corresponding selenoproteins. RESULTS: HS decreased the villus height and increased (P < 0.05) the protein abundance of HSP70, and downregulated (P < 0.05) protein levels of tight junction-related proteins (CLDN-1 and OCLD). HS-induced jejunal damage was associated with the upregulation of four inflammation-related genes and ten selenoprotein-encoding genes, downregulation (P < 0.05) of four selenoprotein-encoding genes and decreased (P < 0.05) the protein abundance of GPX4 and SELENOS. Compared with the HS group, HMSeBA supplementation not only elevated the villus height and the ratio of V/C (P < 0:05), but also reduced (P < 0.05) the protein abundance of HSP70 and MDA content, and increased (P < 0.05) the protein abundance of OCLD. HMSeBA supplementation downregulated the expression of seven inflammation-related genes, changed the expression of 12 selenoprotein-encoding genes in jejunum mucosa affected by HS, and increased the protein abundance of GPX4, TXNRD1 and SELENOS. CONCLUSION: Organic Se supplementation beyond nutritional requirement alleviates the negative effect of HS on the jejunum of growing pigs, and its protective effect is related to the response of corresponding selenoproteins. © 2021 Society of Chemical Industry.

FumDSB Can Reduce the Toxic Effects of Fumonisin B1 by Regulating Several Brain-Gut Peptides in Both the Hypothalamus and Jejunum of Growing Pigs.

Fumonisin B1 (FB1) is the most common food-borne mycotoxin produced by the Fusarium species, posing a potential threat to human and animal health. Pigs are more sensitive to FB1 ingested from feed compared to other farmed livestock. Enzymatic degradation is an ideal detoxification method that has attracted much attention. This study aimed to explore the functional characteristics of the carboxylesterase FumDSB in growing pigs from the perspective of brain-gut regulation. A total of 24 growing pigs were divided into three groups. The control group was fed a basal diet, the FB1 group was supplemented with FB1 at 5 mg/kg feed, and the FumDSB group received added FumDSB based on the diet of the FB1 group. After 35 days of animal trials, samples from the hypothalamus and jejunum were analyzed through HE staining, qRT-PCR and immunohistochemistry. The results demonstrated that the ingestion of FB1 can reduce the feed intake and weight gain of growing pigs, indicating that several appetite-related brain-gut peptides (including NPY, PYY, ghrelin and obestatin, etc.) play important roles in the anorexia response induced by FB1. After adding FumDSB as detoxifying enzymes, however, the anorexia effects of FB1 were alleviated, and the expression and distribution of the corresponding brain-gut peptides exhibited a certain degree of regulation. In conclusion, the addition of FumDSB can reduce the anorexia effects of FB1 by regulating several brain-gut peptides in both the hypothalamus and the jejunum of growing pigs.

Moxifloxacin and gemifloxacin mediates its antispasmodic profile via ATP-sensitive potassium channels: An in-vitro bioassay study.

Moxifloxacin and gemifloxacin were tested on isolated rabbits' jejunal preparations as little is known about its effects on gastrointestinal tissues. Moxifloxacin and gemifloxacin were tested in concentrations 0.01-10µg/mL for possible effect(s) on isolated rabbits' jejunal preparations. The drugs were applied on spontaneous, on low K+ (20mM)-induced contractions and on high K+ (80mM)-induced contractions. Response was plotted as % of its respective controls. EC50 for Moxifloxacin and Gemifloxacin on spontaneous (without Glibenclamide) contractions are 2.83±0.5µg/mL and 1.11±0.2µg/mL, respectively. Moxifloxacin and Gemifloxacin relaxed the low K+ (20mM) -induced contractions, which were inhibited in presence of Glibenclamide (3µM). Our result indicates that the relaxant activity of Moxifloxacin and Gemifloxacin is mediated possibly through activation of ATP-sensitive potassium channels (KATP). The relaxant effect of Moxifloxacin and Gemifloxacin is predominantly mediated by activation of ATP-Sensitive potassium channels (KATP), which could be cause of one of relaxing mechanisms.

Microcirculatory Function during Endotoxemia-A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation.

Competition for the amino acid arginine by endothelial nitric-oxide synthase (NOS3) and (pro-)inflammatory NO-synthase (NOS2) during endotoxemia appears essential in the derangement of the microcirculatory flow. This study investigated the role of NOS2 and NOS3 combined with/without citrulline supplementation on the NO-production and microcirculation during endotoxemia. Wildtype (C57BL6/N background; control; n = 36), Nos2-deficient, (n = 40), Nos3-deficient (n = 39) and Nos2/Nos3-deficient mice (n = 42) received a continuous intravenous LPS infusion alone (200 µg total, 18 h) or combined with L-citrulline (37.5 mg, last 6 h). The intestinal microcirculatory flow was measured by side-stream dark field (SDF)-imaging. The jejunal intracellular NO production was quantified by in vivo NO-spin trapping combined with electron spin-resonance (ESR) spectrometry. Amino-acid concentrations were measured by high-performance liquid chromatography (HPLC). LPS infusion decreased plasma arginine concentration in control and Nos3-/- compared to Nos2-/- mice. Jejunal NO production and the microcirculation were significantly decreased in control and Nos2-/- mice after LPS infusion. No beneficial effects of L-citrulline supplementation on microcirculatory flow were found in Nos3-/- or Nos2-/-/Nos3-/- mice. This study confirms that L-citrulline supplementation enhances de novo arginine synthesis and NO production in mice during endotoxemia with a functional NOS3-enzyme (control and Nos2-/- mice), as this beneficial effect was absent in Nos3-/- or Nos2-/-/Nos3-/- mice.

MicroRNA Expression Profiling in Porcine Liver, Jejunum and Serum upon Dietary DON Exposure Reveals Candidate Toxicity Biomarkers.

Deoxynivalenol (DON), a frequent mycotoxin worldwide, impairs human and animal health. The response of microRNAs, small non-coding RNAs, to DON has been scarcely investigated, but holds remarkable potential for biomarker applications. Hence, we aimed to investigate DON-induced changes in the microRNA expression in porcine liver, jejunum and serum by combining targeted and untargeted analyses. Piglets received uncontaminated feed or feed containing 900 µg/kg and 2500 µg/kg DON for four weeks, followed by a wash-out period. In tissue, only slight changes in microRNA expression were detected, with ssc-miR-10b being downregulated in liver of DON-exposed piglets. In serum, several microRNAs were differentially expressed upon DON exposure, four of which were validated by qPCR (ssc-miR-16, ssc-miR-128, ssc-miR-451, ssc-miR-205). The serum microRNA response to DON increased over time and declined after removal of contaminated diets. Receiver operating curve analyses for individual microRNAs were significant, and a combination of the four microRNAs increased the predictive capacity for DON exposure. Predicted microRNA target genes showed enrichment of several pathways including PIK3-AKT, Wnt/ß-catenin, and adherens junctions. This study gives, for the first time, a comprehensive view of the porcine microRNA response to DON, providing a basis for future research on microRNAs as biomarkers for mycotoxins.

Calcium-sensing receptor (CaSR) agonist R568 inhibits small intestinal motility of mice through neural and non-neural mechanisms.

Gastrointestinal motility (GI) disorder causes symptoms such as dyspepsia, abdominal distention, and constipation and severely affects quality of life. The calcium (Ca2+)-sensing receptor (CaSR) expressed in the digestive tract can be activated by amino acids and participates in GI motility regulation. This study is designed to explore the effect and underlying mechanism of CaSR agonist R568 on the small intestine motility of mice in vivo and ex vivo. R568 was given to male C57BL/6 mice by gavage or incubated with isolated jejunum and ileum segments to observe its effects on GI motility and the involved neurons, neurotransmitters and hormones were detected by fluorescence immunohistochemistry and enzyme-linked immunosorbent assays. The in vivo results showed that the intestinal propulsive rate reduced in response to oral intake of R568. R568 treatment increased the numbers of nitric oxide synthase-positive neurons and nitric oxide release but decreased the choline acetyl transferase-positive neurons and acetylcholine release in the myenteric plexuses. R568 increased the secretion of cholecystokinin in the intestinal tissues and serum but had no effect on the secretion of glucagon like peptide-1. Ex vivo results showed that R568 inhibited the contractility of intestinal strips from the jejunum and ileum. Nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (L-NAME), M-receptor antagonist-atropine, and tetrodotoxin (TTX) failed to block the effect of R568. CaSR co-expressed with interstitial cells of Cajal (ICCs) in the myenteric plexus suggests the possibility that ICCs mediated the effect of R568. Our findings demonstrate that CaSR activation inhibited intestinal motility, and both the enteric nervous system and non-neural mechanism are involved in this process.

Toxic effects of copper on the jejunum and colon of pigs: mechanisms related to gut barrier dysfunction and inflammation influenced by the gut microbiota.

Copper (Cu) is an essential trace mineral, but its excessive intake can lead to potentially toxic effects on host physiology. The mammalian intestine harbors various microorganisms that are associated with intestinal barrier function and inflammation. In this study, the influences of Cu on barrier function, microbiota, and its metabolites were examined in the jejunum and colon of pigs. Here, we identified that the physical and chemical barrier functions were impaired both in the jejunum and colon, as evidenced by the decreased expression of tight junction proteins (ZO-1, Occludin, Claudin-1, and JAM-1) and mucous secretion-related genes, positive rate of Muc2, and secretion of SIgA and SIgG. Additionally, inflammatory cytokines were overexpressed in the jejunum and colon. Furthermore, Cu might increase the abundances of Mycoplasma, Actinobacillus and unidentified_Enterobacteriaceae in the jejunum, which significantly affected pentose and glucoronate interconversions, histidine metabolism, folate biosynthesis, porphyrin metabolism, and purine metabolism. Meanwhile, the abundances of Lactobacillus and Methanobrevibacter were remarkably decreased and Streptococcus, unidentified_Enterobacteriaceae, and unidentified_Muribaculaceae were significantly increased in the colon, with an evident impact on glycerophospholipid metabolism, retinol metabolism, and steroid hormone biosynthesis. These findings revealed that excess Cu had significant effects on the microbiota and metabolites in the jejunum and colon, which were involved in intestinal barrier dysfunction and inflammation.

Melatonin-Activated Receptor Signaling Pathways Mediate Protective Effects on Surfactant-Induced Increase in Jejunal Mucosal Permeability in Rats.

A well-functional intestinal mucosal barrier can be compromised as a result of various diseases, chemotherapy, radiation, and chemical exposures including surfactants. Currently, there are no approved drugs targeting a dysfunctional intestinal barrier, which emphasizes a significant medical need. One candidate drug reported to regulate intestinal mucosal permeability is melatonin. However, it is still unclear if its effect is primarily receptor mediated or antioxidative, and if it is associated with enteric neural pathways. The aim of this rat intestinal perfusion study was to investigate the mechanisms of melatonin and nicotinic acetylcholine receptors on the increase in intestinal mucosal clearance of 51Cr-labeled ethylenediaminetetraacetate induced by 15 min luminal exposure to the anionic surfactant, sodium dodecyl sulfate. Our results show that melatonin abolished the surfactant-induced increase in intestinal permeability and that this effect was inhibited by luzindole, a melatonin receptor antagonist. In addition, mecamylamine, an antagonist of nicotinic acetylcholine receptors, reduced the surfactant-induced increase in mucosal permeability, using a signaling pathway not influenced by melatonin receptor activation. In conclusion, our results support melatonin as a potentially potent candidate for the oral treatment of a compromised intestinal mucosal barrier, and that its protective effect is primarily receptor-mediated.

Salvianolic acid B attenuates oxidative stress-induced injuries in enterocytes by activating Akt/GSK3ß signaling and preserving mitochondrial function.

The cellular and tissue damage induced by oxidative stress (OS) contribute to a variety of human diseases, which include gastrointestinal diseases. Salvianolic acid B (Sal B), which is a natural polyphenolic acid in Salvia miltiorrhiza, exhibits prominent antioxidant properties. However, its precise function and molecular mechanisms in protecting normal intestine epithelium from OS-induced damage are still poorly defined. In this study, we tried to clarify this relationship. Here, we found Sal B addiction in the rat intestinal epithelial cell, IEC-6, prevented H2O2-induced cell viability decrease and apoptosis induction, ameliorated H2O2-induced intestinal epithelial barrier dysfunction and mitochondrial dysfunction, and suppressed H2O2-induced production of ROS to varying degrees, ranging from 10% to 30%. Moreover, by employing an ischemia reperfusion model of rats, we also discovered that Sal B treatment reversed ischemia and a reperfusion-caused decrease in villus height and crypt depth, decreased proliferation of enterocytes, and increased the apoptotic index in the jejunum and ileum. Mechanistically, Sal B treatment up-regulated the phosphorylated level of Akt and GSK3ß in enterocytes in vitro and in vivo, and PI3K inhibitor LY294002 treatment abrogated the protective effects of Sal B. Meanwhile, the inactivation of GSK3ß reversed the oxidative stress-induced apoptosis and mitochondrial dysfunction in IEC-6 cells. Together, our results demonstrated that the damage of intestinal epithelial cells in in vitro and in vivo models were both attenuated by Sal B treatment, and such antioxidant activity might very possibly be attributed to the activation of Akt/GSK3ß signaling.

Resveratrol protects intestinal integrity, alleviates intestinal inflammation and oxidative stress by modulating AhR/Nrf2 pathways in weaned piglets challenged with diquat.

This study investigated the effects of resveratrol (RES) on intestinal morphology, antioxidant capacity, intestinal inflammation, and barrier function in weaned piglets challenged with diquat (DIQ). Thirty weaned piglets were randomly assigned to 5 treatments: non-challenged group (CON), DIQ-challenged group (DIQ), and DIQ-challenged group with 10, 30, or 90 mg/kg of RES, respectively. The trail lasted 21 days, and piglets were intraperitoneally injected with DIQ or the same amount of saline on day 15. The results showed that supplementation with 90 mg/kg RES increased (P < 0.05) jejunal villus height and villus height: crypt depth ratio, and decreased (P < 0.05) crypt depth, plasma D-lactate and diamine oxidase (DAO) compared with the DIQ group. Piglets fed with 30 or 90 mg/kg RES prevented the diquat-induced decrease (P < 0.05) of mRNA expression of occludin, claudin-1, ZO-1, and IL-10, and increase (P < 0.05) of TNF-α mRNA expression. Moreover, addition of 90 mg/kg RES increased (P < 0.05) the activities of SOD, GSH-Px, and CAT and decreased (P < 0.05) the MDA levels in jejunal mucosa compared with the DIQ group. Finally, addition of 90 mg/kg RES enhanced (P < 0.05) the mRNA expression of SOD1, SOD2, CAT, GPx1, and HO-1, and increased (P < 0.05) mRNA and protein expression of Nrf2, NQO1, aryl hydrocarbon receptor (AhR), and cytochrome P450 family 1 member A1 (CYP1A1). These data indicated that supplementation with 90 mg/kg RES was effective in protecting the intestinal integrity, alleviating intestinal inflammation and oxidative stress by activating AhR/Nrf2 pathways in diquat-challenged piglets.

Analysis of jejunum microbiota of HFD/STZ diabetic rats.

Currently, several studies propose that the dominant intestinal bacteria are core flora. Besides keeping the homeostasis of the intestinal environment, the intestinal microflora also plays a role in body metabolism, production of some vitamins, and control of barrier function. The study aimed to investigate the jejunum microbiota in diabetic rats as well as it's the relationship with Ceftriaxone sodium-mediated gut dysbiosis, diabetic parameters, and intestinal permeability. Thirty-two Wistar rats (Male) were enrolled and divided into four groups (A, B, C, and D; N = 8). Subsequently, T2DM was induced in C and D groups by HFD/STZ model and then gut dysbiosis in B and D groups via intragastric administration of Ceftriaxone sodium for two weeks. The food-water intake, body weight, fasting blood glucose, plasma insulin, HOMA-IR, intestinal permeability, and jejunum microbiota and it's histology were investigated. In this study, T2DM was associated with a significant decrease in the richness and diversity of jejunum microbiota, elevation in the intestinal permeability, and higher abundance of some opportunistic pathogens. Ceftriaxone sodium-induced gut dysbiosis declined food-water intake, damagedthe villi of jejunum tissue, increased intestinal permeability, and affected the diversity of jejunum microbiota. In diabetic rats, Ceftriaxone sodium-mediated gut dysbiosis also declined the abundance of someSCFAs bacteria and raised the abundant of some opportunistic bacteria such as Staphylococcus_sciuri. Interestingly, we found that several bacteria were negatively correlated with HOMA-IR, fasting blood glucose, body weight, and intestinal permeability. Overall, the study highlighted the jejunum microflora alterations in HFD/STZ diabetic rats and assessed the effect of Ceftriaxone sodium-induced gut dysbiosis on diabetic parameters, jejunum microbiota and histology, and intestinal permeability, which are of potential for further studies.