Polysaccharides from Hemp Seed Protect against Cyclophosphamide-Induced Intestinal Oxidative Damage via Nrf2-Keap1 Signaling Pathway in Mice.

Hemp seed has been used as a traditional oriental medicine and health food in China for centuries. Polysaccharides from hemp seed (HSP) exhibit important properties of intestinal protection, but there are limited data on the specific underlying mechanism. The primary objective of this study was to investigate the protective effect of HSP on intestinal oxidative damage induced by cyclophosphamide (Cy) in mice. The results showed that pretreatment with HSP significantly increased the average daily gain, thymus index, spleen index, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity in serum and ileal homogenate and significantly reduced malondialdehyde (MDA) content in ileal homogenate. In addition, the expression levels of SOD, GSH-Px, Nrf2, heme oxidase-1 (HO-1), and quinoneoxidoreductase-1 (NQO1) mRNA in ileal homogenate were significantly increased. Western blot results showed that HSP significantly upregulated the expression of Nrf2 protein and downregulated the expression of Keap1 protein in the ileum. Collectively, our findings indicated that HSP had protective effects on intestinal oxidative damage induced by Cy in mice, and its mechanism might be related to the activation of Nrf2-Keap1 signaling pathway.

Protective effect of seleno-amino-oligosaccharide on oxidative damage of IPEC-1 cells by activating Keap1/Nrf2 signaling pathway.

The aim of the study was to investigate the antioxidant effect of seleno-amino-oligosaccharide (Se-AOS) on intestinal porcine epithelial cells (IPEC-1). MTT assay showed that Se-AOS had no effect on the viability of IPEC-1 cells up to a concentration of 9200 µg/L and Se-AOS significantly increased the viability of IPEC-1 cells compared to cells exposed to H2O2 alone. Se-AOS significantly increased the level of superoxide Dismutase (SOD) and decreased the levels of malonic dialdehyde (MDA) and lactate dehydrogenase (LDH) in IPEC-1 cells. The gene expression levels of different antioxidant enzymes dramatically increased by the pretreatment of Se-AOS compared to H2O2 treatment. In addition, the results indicated that Se-AOS up-regulated the intracellular Nrf2 and down-regulated the level of Keap1 by western blot. Taken together, these findings suggested that Se-AOS can protect IPEC-1 cells from oxidative damage through activating the Keap1/Nrf2 signaling pathway.

Low Molecular Seleno-Aminopolysaccharides Protect the Intestinal Mucosal Barrier of Rats under Weaning Stress.

Low molecular seleno-aminopolysaccharide (LSA) was synthesized with sodium selenite and low molecular aminopolysaccharide (LA), which is an organic selenium compound. This study is aimed to investigate the protective effect of LSA on the intestinal mucosal barrier in weaning stress rats by detecting the intestinal tissue morphology and function, mucosal thickness and permeability, the structure of MUC2, antioxidant index, the expression level of intracellular transcription factor NF-E2-related factor 2 (Nrf2), and its related factors. The results showed that LSA significantly increased the height of intestinal villi (p < 0.05) and increased the thickness of intestinal mucosa and the number of goblet cells, which indicated that LSA has a protective effect on the intestinal mucosal barrier that is damaged by weaning. Moreover, LSA significantly reduced the level of DAO, D-LA, and LPS compared with the weaning group (p < 0.05), which indicated that LSA reduced the intestinal damage and permeability of weaning rats. In addition, LSA could increase the number and length of glycans chains and the abundance of acid glycans structures in the MUC2 structure, which indicated that LSA alleviated the changes of intestinal mucus protein structure. LSA significantly increased the levels of GSH-Px, SOD, LDH, and CAT, while it decreased the level of MDA in serum and intestinal tissue, which suggested that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress of weaning rats. RT-PCR results showed that LSA significantly increased the expression level of antioxidant genes (GSH-Px, SOD, Nrf2, HO-1), glycosyltransferase genes (GalNT1, GalNT3, GalNT7) and mucin gene (MUC2) in intestinal mucosa (p < 0.05). The results of western blot showed that the LSA activated the Nrf2 signaling pathway by down-regulating the expression of Keap1and up-regulating the expression of Nrf2, and protected the intestinal mucosa from oxidative stress. Overall, LSA could play a protective role in intestinal mucosal barrier of weaning rats by activating the Nrf2 pathway and alleviating the alnormal change of mucin MUC2.

Salidroside Delays Cellular Senescence by Stimulating Mitochondrial Biogenesis Partly through a miR-22/SIRT-1 Pathway.

Calorie restriction (CR) is a nongenetic intervention with a robust effect on delaying aging in mammals and other organisms. A mild stimulation on mitochondrial biogenesis induced by CR seems to be an important action mode for its benefits. Here, we reported that a component isolated from Rhodiola rosea L., salidroside, delays replicative senescence in human fibroblasts, which is related to its stimulation on mitochondrial biogenesis by activating SIRT1 partly resulted from inhibition on miR-22. Salidroside increased the mitochondrial mass that accompanied an increment of the key regulators of mitochondrial biogenesis including PGC-1α, NRF-1, and TFAM and reversed the mitochondrial dysfunction in presenescent 50PD cells, showing a comparable effect to that of resveratrol. SIRT1 is involved in the inducement of mitochondrial biogenesis by salidroside. The declined expression of SIRT1 in 50PD cells compared with the young 30PD cells was prevented upon salidroside treatment. In addition, pretreatment of EX-527, a selective SIRT1 inhibitor, could block the increased mitochondrial mass and decreased ROS production induced by salidroside in 50PD cells, resulting in an accelerated cellular senescence. We further found that salidroside reversed the elevated miR-22 expression in presenescent cells according to a miRNA array analysis and a subsequent qPCR validation. Enforced miR-22 expression by using a Pre-miR-22 lentiviral construct induced the young fibroblasts (30PD) into a senescence state, accompanied with increased senescence-related molecules including p53, p21, p16, and decreased SIRT1 expression, a known target of miR-22. However, salidroside could partly impede the senescence progression induced by lenti-Pre-miR-22. Taken together, our data suggest that salidroside delays replicative senescence by stimulating mitochondrial biogenesis partly through a miR22/SIRT1 pathway, which enriches our current knowledge of a salidroside-mediated postpone senility effect and provides a new perspective on the antidecrepitude function of this naturally occurring compound in animals and humans.

Physicochemical properties and inhibition effect on iron deficiency anemia of a novel polysaccharide-iron complex (LPPC).

Porphyran (P) was extracted from red algae Porphyra by boiling water. A novel polysaccharide-iron complex (LPPC) was prepared under the alkaline condition by adding a ferric chloride solution to the low molecular weight porphyran (LP) solution. Physicochemical properties and inhibition effect on iron deficiency anemia of this complex were studied. The content of iron(III) in the complex is 21.57% determined with iodometry. The results indicate that LPPC was product required. The complex can increase red blood cell count (RBC), hemoglobin (Hb), Serum iron (SI), spleen index, spleen mass and mass of mice with iron deficiency anemia (IDA). Although the structure and deeper mechanisms on hemolytic anemia of LPPC should be further studied, LPPC is hoped to be developed as a late-model iron supplement which has a synergism on anemia.