Vitamin A Ameliorated Irinotecan-Induced Diarrhea in a Piglet Model Involving Enteric Glia Modulation and Immune Cells Infiltration.

Vitamin A (VA) and its metabolite, retinoic acid (RA), play important roles in modulating intestinal mucosal immunity, yet little is known about their regulatory effects on enteric nervous system function. The study aims to explore the protective effects of dietary VA on diarrhea in a piglet model involving enteric glia and immune cell modulation. Twenty-eight weaned piglets were fed either the basal or VA (basal diet supplemented with 18,000 IU/kg VA) diet and with or without irinotecan (CPT-11) injection. CPT-11 induced increased diarrhea incidence, immune infiltration, and reactive enteric gliosis. A diet supplemented with 18,000 IU/kg VA ameliorated the adverse effects of CPT-11 on the gut barrier. VA reduced diarrhea incidence and attenuated enteric glial gliosis, immune cell infiltrations, and inflammatory responses of CPT-induced piglets. An in vitro experiment with 1 nmol/L RA showed direct protective effects on monocultures of enteric glial cells (EGCs) or macrophages in LPS-simulated inflammatory conditions. Furthermore, 1 ng/mL glial-derived neurotropic factors (GDNF) could inhibit M1-macrophage polarization and pro-inflammatory cytokines production. In summary, VA exerted protective effects on the intestinal barrier by modulating enteric glia and immune cells, perhaps enhancing epithelial recovery under CPT-11 challenge. Our study demonstrated that RA signaling might promote the roles of enteric glia in intestinal immunity and tissue repair, which provided a reference for the VA supplementation of patient diets.

Berberine improves intestinal barrier function and reduces inflammation, immunosuppression, and oxidative stress by regulating the NF-κB/MAPK signaling pathway in deoxynivalenol-challenged piglets.

The aim of this study was to evaluate the effect of berberine (BBR) on the intestinal health of piglets exposed to deoxynivalenol (DON). A total of 180 weaned piglets were randomly allotted to 1 of 3 treatment groups with 10 replication pens per treatment and 6 piglets per pen. The treatments were basal diet, basal diet +4 mg/kg DON, and basal diet +4 mg/kg DON +40 mg/kg BBR. The experiment lasted for 21 d. BBR improved the growth performance of DON-challenged piglets. BBR could inhibit DON-induced intestinal injury by increasing the expression of serum antioxidant enzymes and T cell surface antigens and reducing the release of proinflammatory cytokines in the small intestine. BBR significantly increased the protein expression levels of zonula occludens 1 (ZO-1), Occludin and Claudin-1 in the ileal and jejunal mucosa and increased the morphological parameters of the jejunum. Moreover, we found that BBR significantly reduced the DON-induced gene and protein expression levels of ERK, JNK, and NF-κB in the jejunum and ileum. In conclusion, BBR can regulate DON-induced intestinal injury, immunosuppression and oxidative stress by regulating the NF-κB and MAPK signaling pathways and ultimately maintain the intestinal health of piglets.

Eucommia ulmoides Flavones as Potential Alternatives to Antibiotic Growth Promoters in a Low-Protein Diet Improve Growth Performance and Intestinal Health in Weaning Piglets.

Eucommia ulmoides flavones (EUF) have been demonstrated to attenuate the inflammation and oxidative stress of piglets. This study aimed to test whether EUF could be used as an alternative antibiotic growth promoter to support growth performance and maintain intestinal health in weanling piglets. Weaned piglets (n = 480) were assigned into three groups and fed with a low-protein basal diet (NC), or supplementation with antibiotics (PC) or 0.01% EUF (EUF). Blood, intestinal contents, and intestine were collected on days 15 and 35 after weaning. The results showed the PC and EUF supplementations increased (p < 0.05) body weight on day 35, average daily gain and gain: feed ratio from day 15 to day 35 and day 0 to day 35, whereas decreased (p < 0.05) the diarrhea index of weanling piglets. EUF treatment increased (p < 0.05) jejunal villus height: crypt depth ratio, jejunal and ileal villus height, and population of ileal lactic acid bacteria on day 15 but decreased (p < 0.05) the population of ileal coliform bacteria on day 15 and day 35. These findings indicated the EUF, as the potential alternative to in-feed antibiotic growth promoter, could improve growth performance and intestinal morphology, and decrease colonization of coliform bacteria and diarrhea index in weanling piglets.

Baicalin alleviates deoxynivalenol-induced intestinal inflammation and oxidative stress damage by inhibiting NF-κB and increasing mTOR signaling pathways in piglets.

This study was conducted to evaluate the intestinal protective effects of baicalin (BAI) in deoxynivalenol (DON)-treated piglets. A total of 320 weaned piglets were randomly allotted to 1 of 4 treatments with 8 replication pens per treatment and 10 piglets per pen. The treatments were basal diet (NC), basal diet + 0.1% baicalin (BAI), basal diet + 4 mg/kg DON (DON), and basal diet + 4 mg/kg DON + 0.1% BAI (DON + BAI). The experiment was conducted for 14 days. BAI supplementation alleviated the impairment of growth performance and the disorder of serum biochemical parameters in DON-challenged piglets. BAI supplementation also alleviated DON-induced negative effects, decreasing protein and gene expression levels of pro-inflammatory cytokines in the serum and intestinal tissue and increasing antioxidant capacity in the serum. BAI increased villus height and villus height/crypt depth but decreased the protein expression levels of nuclear factor kappa B (NF-κB), as determined by immunohistochemical analysis, in the ileum and jejunum. Moreover, we found that BAI inhibited NF-κB and increased mTOR protein and gene expression levels in the serum and intestinal tissues. Collectively, BAI alleviates intestinal inflammatory and oxidative damage by inhibiting NF-κB and increasing mTOR signaling to modulate downstream inflammatory and oxidative responses after DON challenge.

The Evaluation of the Antioxidant and Intestinal Protective Effects of Baicalin-Copper in Deoxynivalenol-Challenged Piglets.

The present study was performed to evaluate the antioxidant and intestinal protective effects of baicalin-copper on deoxynivalenol-challenged piglets. Forty weaned piglets were randomly divided into four groups and assigned to different diets: (1) basal diet (Con), (2) 4 mg/kg deoxynivalenol of basal diet (DON), (3) 5 g/kg baicalin-copper of basal diet (BCU); and (4) 4 mg/kg deoxynivalenol + 5 g/kg baicalin-copper of basal diet (DBCU). The results showed that the ADFI and ADG of piglets in the DON group were markedly lower than those in the Con group, but the ADFI and ADG of the DBCU group were not significantly different from those of the Con group. In piglets fed a DON-contaminated diet, dietary supplementation with BCU significantly decreased the mRNA levels of P70S6K, 4E-BP1, and HSP70 in the liver, the protein expression of HO-1 in the jejunum, and the expression of p-Nrf2 and p-NF-κB in the ileum but increased Mn-SOD activity in serum. Dietary supplementation with BCU increased jejunal maltase, ZIP4 and MT mRNA levels, and serum concentrations of Arg, Val, Ile, Leu, Lys, and Tyr in DON-contaminated piglets. In summary, BCU can alleviate the growth impairment induced by DON and enhance antioxidant capacity and nutrition absorption in piglets fed DON-contaminated diets.

The Role of Nrf2 Signaling Pathway in Eucommia ulmoides Flavones Regulating Oxidative Stress in the Intestine of Piglets.

Eucommia ulmoides flavones (EUF) have been demonstrated to alleviate oxidative stress and intestinal damage in piglets, but their effect target is still poorly understood. NF-E2-related factor 2 (Nrf2) pathway plays a very important role in the defense mechanism. This study was designed to investigate the regulation of EUF on the Nrf2 pathway and inhibition of Nrf2 on oxidative stress in the intestine of piglets. An in vivo study was conducted in weaned piglets treated with basal diet, basal diet+diquat, and 100 mg/kg EUF diet+diquat for 14 d to determine Nrf2 and Keap1 protein expressions, as well as downstream antioxidant gene mRNA expression. An in vitro study was performed in a porcine jejunal epithelial cell line to investigate the effect of inhibiting Nrf2 on cell growth and intracellular oxidative stress parameters. The results showed that the supplementation of EUF decreased the oxidized glutathione (GSSG) concentration and the ratio of GSSG to glutathione (GSH) but increased the protein expressions of nuclear Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) as well as mRNA expression of heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1), and glutamate cysteine ligase catalytic subunit (GCLC) in the small intestinal mucosa of diquat-challenged piglets. When Nrf2 was inhibited by using ML385, cell viability, cellular antioxidant activities, expressions of nuclear Nrf2 and Keap1 protein, and downstream antioxidant enzyme (HO-1, NQO-1, and GCLC) mRNA were decreased in paraquat-treated enterocytes. These results showed that the Nrf2 signaling pathway played an important role in EUF-regulating oxidative stress in the intestine of piglets.

PGC-1α activation: a therapeutic target for type 2 diabetes?

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) has gained popularity as a very attractive target for diabetic therapies due to its role in lipid and glucose metabolism. Pharmacological activation of PGC-1α is thought to elicit health benefits. However, this notion has been questioned by increasing evidence, which suggests that insulin resistant is exacerbated when PGC-1α expression is far beyond normal physiological limits and is prevented under the condition of PGC-1α deficiency. This narrative review suggests that PGC-1α, as a master metabolic regulator, exerts roles in insulin sensitivity in a tissue-specific manner and in a physical activity/age-dependent fashion. When using PGC-1α as a target for therapeutic strategies against insulin resistance and T2DM, we should take these factors into consideration.Level of evidence: Level V, narrative review.

Key factors involved in obesity development.

Obesity has been considered to be a chronic disease that requires medical prevention and treatment. Intriguingly, many factors, including adipose tissue dysfunction, mitochondrial dysfunction, alterations in the muscle fiber phenotype and in the gut microbiota composition, have been identified to be involved in the development of obesity and its associated metabolic disorders (in particular type 2 diabetes mellitus). In this narrative review, we will discuss our current understanding of the relationships of these factors and obesity development, and provide a summary of potential treatments to manage obesity. Level of Evidence Level V, narrative review.

The Evaluation of Antioxidant and Anti-Inflammatory Effects of Eucommia ulmoides Flavones Using Diquat-Challenged Piglet Models.

This study was designed to evaluate the antioxidant and anti-inflammatory effects of Eucommia ulmoides flavones (EUF) using diquat-challenged piglet models. A total of 96 weaned piglets were randomly allotted to 1 of 3 treatments with 8 replication pens per treatment and 4 piglets per pen. The treatments were basal diet, basal diet + diquat, and 100 mg/kg EUF diet + diquat. On day 7 after the initiation of treatment, the piglets were injected intraperitoneally with diquat at 8 mg/kg BW or the same amount of sterilized saline. The experiment was conducted for 21 days. EUF supplementation improved the growth performance of diquat-treated piglets from day 14 to 21. Diquat also induced oxidative stress and inflammatory responses and then impaired intestinal morphology. But EUF addition alleviated these negative effects induced by diquat that showed decreasing serum concentrations of proinflammatory cytokines but increasing antioxidant indexes and anti-inflammatory cytokines on day 14. Supplementation of EUF also increased villi height and villous height, crypt depth, but decreased the histopathological score and MPO activity compared with those of diquat-challenged pigs fed with the basal diet on day 14. Results indicated that EUF attenuated the inflammation and oxidative stress of piglets caused by diquat injection.

[Effects of total favonoids of Ecommia umoides on atioxidant aility of imune ogans in lead poisoning mice].

OBJECTIVE: To explore the effects of total flavonoids of Eucommia ulmoides on antioxidant ability of immune organs in lead poisoning mice. METHODS: Fifty male mice were randomly divided into 5 groups, normal control group, lead group, positive control group, the total flavonoids of Eucommia ulmoides groups( 200, 50 mg / kg). The lead poisoning model was established by peritoneally injecting mice with 70 mg / kg lead acetate every day for 8 days. After the total flavonoids of Eucommia ulmoides was gavaged for 14 days, mice were sacrificed and immediately subjected to necropsy. The concentration of lead in blood, spleen and thymus were determined. The spleen and thymus index and the content of T-SOD、GSH-Px、T-AOC and MDA of spleen and thymus in mice were assayed. RESULTS: Intraperitoneal injection of 70 mg / kg lead acetate for 8 consecutive days could cause an immunity decline in lead poisoning mice, the total flavonoids of Eucommiaulmoides could significantly improve the immunity of lead poisoning mice. After the total flavonoids of Eucommia ulmoides was gavaged for 14 days, the viscera index in mice induced by lead acetate was significantly improve( P < 0. 01). Compared with lead group, the total flavonoids of Eucommia ulmoides( 200 mg / kg) could significantly reduce the lead contents in blood, spleen and thymus and improve the activities of T-SOD、GSH-Px、TAOC and reduce the content of MDA of mouse spleen and thymus( P < 0. 01), while there were no significant changes in concentrations of the lead contents in blood, spleen and thymus in the total flavonoids of Eucommia ulmoides( 50 mg / kg) treatment group. But the total flavonoids of Eucommia ulmoides( 50 mg / kg) could increase the activities of T-SOD、GSH-Px、T-AOC and reduce the content of MDA of mouse spleen and thymus in different degree. CONCLUSION: The total flavonoids of Eucommia ulmoides can effectively improve the antioxidant ability of immune organs in mice induced by lead acetate.