THE PREVENTIVE EFFECT AND ENHANCE IMMUNITY FUNCTION OF BU-ZHONG-YI-QIWAN ON S180 TUMOR MICE.

Background: To evaluate the preventive effect and enhance immunity functions of Bu-zhong-yi-qi wan in vivo. Materials and Methods: S180 tumor mice model was established by subcutaneous injection a dose of 0.2 ml (1×107/ml) at the right oxter. The inhibitory rates, spleen indexes and thymus indexes were calculated. Splenic lymphocyte proliferative activity assay and phagocytosis activity of peritoneal macrophages were done. Interferon (IFN-γ), interleukin (IL-2) and tumor necrotic factor (TNF-α) in serum were detected. Results: In the S180 tumor-bearing mice, Bu-zhong-yi-qi wan with medium-dose (975 mg/kg, 100 mg/l) had potent preventive effect and anti-tumor effect, macrophage phagocytosis and Con A-stimulated splenocyte proliferation were increased as compared with model control treatment. Bu-zhong-yi-qi wan could take part in the immune response by promoting the proliferation and differentiation of Tcells, increasing the activity of the macrophages, inducing the generation of cell factor IL-2, TNF-α, IFN-γ. Conclusion: It proved that Bu-zhong-yi-qi wan of medium-dose had great preventive effect and could enhance immunity function

Comparative stomach tissue distribution profiles of four major bio-active components of Radix Astragali in normal and gastric ulcer mice

Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-β-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-β-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali

Milk Fat Globule Membrane Supplementation Promotes Neonatal Growth and Alleviates Inflammation in Low-Birth-Weight Mice Treated with Lipopolysaccharide

Impaired intestinal mucosal integrity and immunity are frequently observed in low-birth-weight (LBW) animals, which lead to inadequate growth and high neonatal mortality. However, the mechanisms of intestinal dysfunction in LBW animals are still unclear. Milk fat globule membrane (MFGM), a protein-lipid complex surrounding the fat globules in milk, has many healthful benefits for animals. Therefore, this study was conducted to explore the effect of MFGM supplementation on intestinal injury and inflammation in LBW mouse pups while being challenged with lipopolysaccharide (LPS). C57BL/6J LBW female neonatal mice were fed on breast milk and divided into four groups, including two normal diet groups (ND; CON group and LPS group) and the diet supplemented with two dosages of MFGM, namely, MFGM100 (ND plus MFGM at 100 mg/kg BW) and MFGM200 (ND plus MFGM at 200 mg/kg BW) from postnatal day (PND) 4 to PND 21. At PND21, pups from the LPS group, MFGM100 group, and MFGM200 group were injected intraperitoneally with LPS while the pups from the CON group were injected with equivalent volume of sterile saline. After 4 h of LPS administration, all pups were slaughtered and then the plasma, mid-ileum, and mid-colon tissue samples were collected. Our results showed that MFGM supplementation promoted the body weight from PND16 to PND21 and attenuated intestinal inflammation manifested by reduced histological damage, decreased secretion of TNF-α, IL-6, IFN-γ, and IL-1β, and improved oxidative stress characterized by increased SOD activity and decreased secretion of MDA. Expression of tight junction proteins (ZO-1, occludin, and claudin-1), MUC1, and MUC2 was increased in MFGM presupplemented groups compared to the LPS-challenged mice with normal diet. Meanwhile, the expression of proinflammatory cytokines and TLRs was decreased by MFGM presupplementation. Collectively, MFGM is a critical nutrient with an ability to improve the growth performance of LBW mouse pups, especially during the LPS challenge, by promoting the intestinal epithelial integrity and inhibiting inflammation through activating of TLR2 and TLR4 signals

Glucosamine Supplementation in Premating Drinking Water Improves Within-Litter Birth Weight Uniformity of Rats Partly through Modulating Hormone Metabolism and Genes Involved in Implantation

Within-litter birth weight variation in multiparous animals has become a big issue due to high incidence of low birth weight neonates, which gives rise to high preweaning mortality and morbidity. Foetus with various birth weights is the outcome of diverse embryos competence which is affected by oocyte quality. Glucosamine (GlcN) has been reported to be involved in oocyte maturation; however, its effect on pregnant outcomes remains unknown. The present study was conducted to investigate the effects of premating GlcN supplementation via drinking water on within-litter birth weight variation and its underlying mechanism. Fifty eight Sprague-Dawley female rats were randomly assigned to one of two groups with normal drinking water or drinking water supplemented with 0.5 mM GlcN from six to eight weeks old. Variation of within-litter birth weight in the GlcN group was 5.55%, significantly lower compared with 8.17% in the control group. Birth weight was significantly increased in the GlcN group (2.27 ± 0.06) compared with the control group (2.08 ± 0.04). Both absolute and relative weights of the ovary at the end of GlcN treatment were higher in the GlcN group than in the control group (P<0.05). In the GlcN group, there were more successfully implanted blastocysts (13.38 ± 0.63 and 15.75 ± 0.59 in the control and treatment group, respectively) with more uniform distribution along the two uterine horns compared with the control group. Besides, gene expressions of Alk3 and Bmp2 were increased in the implantation sites, while IGF-1 and Mucin-1 were decreased significantly in rats administrated with GlcN. Maternal progesterone, estradiol, and IGF-1 concentrations on D 19.5 were significantly increased, while insulin and total cholesterol levels were significantly decreased in contrast with control dams. In summary, the administration of 0.5 mM GlcN solution before mating reduced within-litter birth weight variation, accompanied with increased fetal weight. Further investigation indicated that the improved outcome of pregnancy results at least partly from the increased ovary weights of the rats, the homogeneous embryo developmental competence, the enhanced receptivity of the uterine environment, and the adjusted maternal hormone levels

The Role of a Selective P2Y6 Receptor Antagonist, MRS2578, on the Formation of Angiotensin II-Induced Abdominal Aortic Aneurysms

Objective. The P2Y6 receptor has been shown to be involved in many cardiovascular diseases, including hypertension and atherosclerosis. The study is aimed at exploring the role of the P2Y6 receptor in Ang II-induced abdominal aortic aneurysm (AAA) formation in apolipoprotein E-deficient (apoE-/-) mice by using its selective antagonist. Methods. Male apoE-/- mice were fed with high-fat diet and infused with angiotensin (Ang) II (1000 ng/kg/min) for 4 weeks to induce AAA or saline as controls. Mice were divided into four groups: normal saline (NS, placebo control) group (n=8), Ang II+vehicle (Ang II) group (n=14), Ang II-low dose MRS2578 (Ang II+MRS-16 mg) group (n=14), and Ang II-high dose MRS2578 (Ang II+MRS-32 mg) group (n=14). Daily intraperitoneal injection with vehicle or MRS2578 was pretreated one week before Ang II infusion. On postoperative day 10, aorta imaging of each group was taken by ultrasonography. After 4 weeks of Ang II infusion, the excised aortas were processed for diameter measurement and quantification of aneurysm severity and tissue characteristics; the blood samples were collected for measurement of the lipid profile and levels of cytokines. Verhoeff’s Van Gieson (EVG) staining and immunochemistry staining were performed to evaluate disruption of the extracellular matrix (ECM) and infiltration of macrophages. Expression and activity of matrix metalloproteinases (MMPs) was measured by gelatin zymography. Results. Treatment with MRS2578 made no significant difference in AAA formation, and maximal aortic diameter yet caused higher AAA rupture-induced mortality from 7% (Ang II) to 21.4% (Ang II+MRS-16 mg) or 42.9% (Ang II+MRS-32 mg), respectively (p<0.05). Consistently, the severity of aneurysm tended to be more deteriorated in MRS2578-treated groups, especially the high-dosage group. The ratios of type III and IV aneurysm were much higher in the MRS2578-coadministered groups (p<0.05). Furthermore, histological analyses showed that administration of MRS2578 significantly increased infiltration of macrophages, expression of monocyte chemotactic protein 1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1), and activities of MMP-2 and MMP-9 followed by aggravating degradation elastin in vivo (p<0.05). However, the multiple effects of MRS2578 on the development of AAA are independent of changes in systolic blood pressure and lipid profiles. Conclusions. The present study demonstrated that administration of MRS2578 exacerbated the progression and rupture of experimental AAA through promoting proinflammatory response and MMP expression and activity, which indicated a crucial role of the P2Y6 receptor in AAA development. Clinical Relevance. Purinergic P2Y receptors have attracted much attention since the P2Y12 receptor antagonist had been successfully applied in clinical practice. Elucidating the underlying mechanisms of AAA and exploring potential therapeutic strategies are essential to prevent its progression and reduce the mortality rate