Li Ke, Cui Lian-Jie, Cao Yu-Xin, Li Shu-Ying, Shi Li-Xia, Qin Xue-Mei, Du Yu-Guang
Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.
Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
Front Pharmacol. 2020 Dec 15;11:595692. doi: 10.3389/fphar.2020.595692. eCollection 2020.
polysaccharides (APS) have a wide range of biological activities. Most researchers discuss total APS as the main research object. However, because the relative molecular weight of APS has a wide distribution, in-depth studies on the mechanisms of the biological activity of notable molecules are limited. For example, the relationship between the immunomodulatory effect of APS and its relative molecular weight has not been clearly defined. Therefore, in this paper, we separated and obtained APS of different molecular weights by ultrafiltration technology and then constructed a mouse cyclophosphamide-induced immunosuppression model to investigate the immune activity of APS of different molecular weights. The immune enhancement mechanism of APS was explored by examining changes in routine blood indicators, body weight, immune organs, and differential metabolites in mouse serum. Results showed that APS-I (molecular weight, >2,000 kDa), APS-II (molecular weight, 1.02 × 10 Da) and APS-III (molecular weight, 286 Da) could increase the number of immune cells in mouse serum and improve immune organ damage to varying degrees. Among the samples obtained, APS-II showed the best effects. Compared with those in the blank group, 29 metabolites determined by UHPLC Q-Exactive MS in the serum of the model group changed remarkably, and APS-I, APS-II, and APS-III respectively restored 13, 25, and 19 of these metabolites to normal levels. Metabolomics analysis revealed that APS-II is mainly responsible for the immunomodulatory activity of APS. Metabolomics analysis revealed that the mechanisms of this specific molecule may involve the regulation of phenylalanine metabolism, cysteine and methionine metabolism, tricarboxylic acid cycle (TCA cycle) and arginine and proline metabolism.
多糖（APS）具有广泛的生物活性。大多数研究人员将总APS作为主要研究对象。然而，由于APS的相对分子质量分布较宽，对显著分子的生物活性机制的深入研究有限。例如，APS的免疫调节作用与其相对分子质量之间的关系尚未明确界定。因此，在本文中，我们通过超滤技术分离并获得了不同分子量的APS，然后构建了小鼠环磷酰胺诱导的免疫抑制模型，以研究不同分子量APS的免疫活性。通过检测小鼠血清中的常规血液指标、体重、免疫器官和差异代谢产物的变化，探讨了APS的免疫增强机制。结果表明，APS-I（分子量，>2000 kDa）、APS-II（分子量，1.02×10 Da）和APS-III（分子量，286 Da）可不同程度地增加小鼠血清中免疫细胞的数量，并改善免疫器官损伤。在所获得的样品中，APS-II显示出最佳效果。与空白组相比，模型组血清中通过UHPLC Q-Exactive MS测定的29种代谢产物有显著变化，APS-I、APS-II和APS-III分别将其中13、25和19种代谢产物恢复到正常水平。代谢组学分析表明，APS-II主要负责APS的免疫调节活性。代谢组学分析表明，这种特定分子的机制可能涉及苯丙氨酸代谢、半胱氨酸和蛋氨酸代谢、三羧酸循环（TCA循环）以及精氨酸和脯氨酸代谢的调节。
