## 5 Structural Modification of _Astragalus_ Polsaccharides  
Pharmacological activities of polysaccharides are closely related to their structures. Several studies have shown that structural modification of polysaccharides can change their pharmacological activities. Structural modification is usually performed using chemical, physical, enzymatic, and other effective methods for the improvement of nutraceutical and therapeutic functions of polysaccharides. Currently, studies on the modification of APS mainly employ chemical methods, including sulfation, phosphorylation, selenation, and carboxymethylation.  
Sulfation of APS is a commonly used chemical modification method. It involves the reaction of polysaccharides, dissolved in a specific solvent, with corresponding sulfating reagents under certain conditions, leading to the introduction of sulfate groups into hydroxyl groups of side chains of polysaccharides (Figure 2). Sulfated polysaccharides can be obtained using the chlorosulfonic acid-pyridine (CSA-Pyr), sulfuric acid, and sulfur trioxide-dimethylacetamide or pyridine methods [43; 44; 45]. The CSA-Pyr method is the most popular, owing to its convenience, high yield, and high degree of sulfation. The sulfated APS obtained by the CSA-Pyr method had a better anti-inflammatory activity than did unmodified APS, in vitro and in vivo [46; 47]. Sulfation of APS by the CSA-Pyr method also enhanced its antiviral effect [48]. [PERSON] et al. [49] have found that compared with non-sulfated APS, sulfated APS could significantly increase the antibody titer and promote lymphocyte proliferation. Therefore, sulfated APS can be a candidate for a new immune adjuvant [50; 51].  
Phosphorylation is a covalent modification of hydroxyl groups in side chains of polysaccharides with phosphate groups. Studies have shown that phosphorylation of polysaccharides can enhance their bioactivities. Phosphorylation of APS using the sodium tripolymphosphate-sodium trimetaphosphate method enhanced its antiviral effect against duck viral hepatitis [52]. Reaction with polyphosphoric acid under alkaline conditions resulted in a good antiviral activity of APS against porcine reproductive and respiratory syndrome virus [53].  
Natural Se-containing polysaccharides have been found in several animals, plants, and microorganisms. As organic Se compounds, polysaccharides modified with Se can exhibit the physiological activities of both Se and polysaccharides. Moreover, the bioavailability of Se and its physiological functions as an essential trace element are effectively improved, while its toxicity and side effects are considerably lower than those of inorganic Se. [PERSON] et al. [54] have reacted APS with a SeOCl\({}_{2}\) reagent and obtained a Se-containing APS, with a Se content of 16.820 mg/g. It has been reported that the inhibitory rate of tumor growth was 51.14% in the Se-APS group compared with 23.66% in the water control group, suggesting that combining APS with Se might enhance not only the tumor inhibitory effects of APS but also the antioxidant effect of Se [55; 56]. It has been reported that a high Se content in Se-modified APS increases the antioxidant effect of APS [57].  
Carboxymethyl groups are introduced into polysaccharide chains for complete carboxymethylation of polysaccharides. Carboxymethylation increases the negative charge of polysaccharide chains and their solubility in water. In addition, carboxymethylation has a strong effect on the bioactivity of polysaccharides. [PERSON] et al. [58] prepared carboxymethyl-modified APS in the reaction with NaOH and C\({}_{2}\)H\({}_{3}\)ClO\({}_{2}\). The optimum reaction conditions were as follows: the reaction temperature, 65 \({}^{\circ}\)C; NaOH/C\({}_{2}\)H\({}_{3}\)ClO\({}_{2}\) ratio, 16:1; and reaction time, 3.5 h. The results showed  
Figure 2: The reaction of APS sulfate by the chlorosulfonic acid–pyridine (CSA–Pyr) method.  
that the carboxymethyl-modified APS had the highest growth-promotion for microwave and immunological activities.