Immunomodulatory influences of sialylated lactuloses in mice

https://doi.org/10.1016/j.bbrc.2019.04.157Get rights and content

Highlights

  • Some sialylated lactuloses had significantly effects on weight gain rate, thymus index and spleen index of mice.

  • Some sialylated lactuloses showed potent immune modulatory influences in mice.

  • Kdn-α2,3-lactulose is relatively safe and superior to use as a food supplement or potential drug candidate.

Abstract

The aim of this study was to investigate the immune modulatory influences of sialylated lactuloses in mice. The effects of the four sialylated lactuloses by gavage methods on the weight gain rate, organ, serum and spleen immunoglobulin of mice were investigated. Neu5Ac-α2,3-lactulose group and Kdn-α2,3-lactulose group had significantly higher weight gain rate than control group. The weight gain rate, thymus index and spleen index of Kdn-α2,3-lactulose group were significantly higher than control group and lactulose group. Liver and small intestine of Neu5Ac-α2,3-lactulose group, Neu5Ac-α2,6-lactulose group and Kdn-α2,6-lactulose group showed different degree of damage. IgG levels of serum and spleen in Neu5Ac-α2,6-lactulose group and Kdn-α2,6-lactulose group were significantly higher than control group and lactulose group. The contents of IgG in serum and spleen of Kdn-α2,3-lactulose group were significantly lower than that of control group, while the contents of IgA and IgM in serum were significantly higher than those of control group. The IgA level increased by 12.23% and 58.77% comparing with lactulose group and control group, respectively. The IgM level in serum of Kdn-α2,3-lactulose group mice increased by 43.88% and 8.05% comparing with control group and lactulose group, respectively. The IgA level and IgM level in spleen of Kdn-α2,3-lactulose group mice increased by 49.05% and 47.25% comparing with control group. In short, Kdn-α2,3-lactulose is relatively safe and superior to use as a food supplement or potential drug candidate. Our results also indicate that some other sialylated oligosaccharides are potentially harmful to organisms, they may cause some side effects.

Introduction

Oligosaccharides have many biological activity functions, such as stimulating immunity, anti-tumor, anti-cancer, anti-inflammatory, anti-coagulation, hypoglycemia, anti-virus [[1], [2], [3], [4], [5]]. Many studies indicated that oligosaccharides could affect to specific and non-specific immune systems, by acting as an immune modulator to activate the immune system and improve the immune function [[6], [7], [8]]. Oligosaccharides can be used as substrates by intestinal microorganisms for fermentation, thus reducing the pH in the intestinal tract. Studies indicated that they can reduce pathogenic microorganisms, promote the absorption of minerals, intestinal barrier function, nutrient absorption, and immunity [3,6,7]. Intestinal tract is the largest immune organ of the human body, with 70% of the immune cells in the human body. Bifidobacterium and its lysates can stimulate the intestinal tract to produce immune substances and antibodies, enhance cell activity, and thus improve the ability of the immune system to recognize and fight infection [9]. Oligosaccharides can promote the proliferation of intestinal probiotics such as bifidobacterium and lactobacillus [3,6,7].

Sialylated oligosaccharides have key roles in physiological and pathological processes, including cellular recognition, bacterial and viral infection, and tumor cell metastasis, development and differentiation. The oligosaccharides on the cell surface are recognized by a series of carbohydrate-binding proteins [10]. Sialic acids occupy the end of the glycan chain of glycolipids and glycoproteins in many cell membranes, and are the first site of cell information transmission. Therefore, sialylated oligosaccharides play an important role in many physiological and pathological processes [11].

During the infants’ growth and development, the synthesis of their own endogenous sialic acids can’t meet their bodies’ need, which have to be obtained from external food. Sialylated oligosaccharides in human milk can meet the needs of newborn infants, and are considered as the best nutritional condition for infants. However, it is found that, in the brain saliva and immune system of the middle-aged and elderly people, the degree of salivary acidification constantly reduced. The endogenous sialic acids synthesis level is low, which can’t meet the needs of the seniors for sialic acids. The interaction of sialic acids with the immune system highlights the importance of minor structural modifications on the overall physiological responses [12]. Dysregulation of glycan-lectin interactions has been implicated in both autoimmune diseases and cancers [13,14]. Consequently, the glycome and its interacting partners have attracted a great deal of attention as targets for therapeutics, ranging from small molecules to antibodies [15,16].

The aim of this study is to investigate the immune-stimulant influence of sialylated lactuloses in Kunming mice under by gavage methods.

Section snippets

Materials

Lactulose was purchased from Carbosynth Ltd, UK; Hematoxylin H9627 was purchased from Sigma; paraformaldehyde 80096618, eosin Y (water-soluble) 71014544, Ethanol 10009218, dimethylbenzene 10023418, hydrochloric acid 10011018, paraffin 69019361, Neutral gum 10004160 were purchased from China National Pharmaceutical Group Corporation (SINOPHARM), Beijing, China.

Neu5Ac-α2,3-lactulose, Neu5Ac-α2,6-lactulose, Kdn-α2,3-lactulose, Kdn-α2,6-lactulose were prepared previously in our lab [17,18].

Animals

Female

Weight gain rate

Table 1 showed the weight gain rate of mice during feeding. In the process of continuous gavage of four different sialylated lactuloses, there was no death or any abnormal reaction in each group of mice. As shown in Table 1, the weight gain rate of Neu5Ac-α2,3-lactulose group was significantly higher on day 15th and 22nd than that of control group. There was no significant difference between Neu5Ac-α2,6-lactulose group and control group. The weight gain rates of Kdn-α2,3-lactulose group on day

Discussion

Sialic acid and sialylated oligosaccharides have significant health benefits for newborns or infants. They play the role for neonatal resistance to pathogens, intestinal maturation, immune function, enhancing intestine and brain development. The need for sialic acid in the neonatal period is even thought to exceed endogenous synthesis. These structures are important nutrients for newborns. Based on its potential benefits, sialic acid and sialylated oligosaccharides may be interesting components

Conclusion

In summary, the present study shows immunomodulatory influences of different sialylated lactuloses on mice. Neu5Ac-α2,3-lactulose group and Kdn-α2,3-lactulose group showed significantly higher weight gain rate than control group. The Neu5Ac-α2,6-lactulose group had significantly lower spleen index than control group. The results of HE staining showed that there were different degrees of damage in mice liver or small intestine of Neu5Ac-α2,3-lactulose, Neu5Ac-α2,6-lactulose and

Conflicts of interest

No conflict of interest is associated with this work.

Acknowledgements

This work is financially supported by the Program for Innovative Research Talents (in Science and Technology) of the University of Henan Province (grant number 16HASTIT015); the Excellent Youth Foundation of the Henan Scientific Committee (grant number 174100510003); academic talent program of Henan Institute of Science and Technology (grant number 205010617006); and Science and Technology Projects in Henan Province (grant number 19A550007). The funders had no role in study design, data

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