Effects of sulfation and carboxymethylation on Cyclocarya paliurus polysaccharides: Physicochemical properties, antitumor activities and protection against cellular oxidative stress.

The Cyclocarya paliurus polysaccharide (CP) was chemically modified to produce sulfated derivatives (S-CP) and carboxymethylated derivatives (CM-CP). Subsequently, the antioxidant activity, cytoprotective effect and antitumor activity of these derivatives were investigated to establish the relationship between their structure and functional activity. The results found that chemical modifications resulted in remarkable variations in the chemical compositions and apparent structures of CP. S-CP with the highest amount of glucose had the strongest antioxidant capacity to scavenge DPPH• and HO•, but CM-CP was lower than CP in terms of HO• scavenging. More importantly, S-CP and CM-CP more effectively protected RAW264.7 from HO-induced damage compared to CP by reducing the secretion of lactate dehydrogenase (LDH), intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), enhancing phagocytosis and superoxide dismutase (SOD) levels, and suppressing abnormal apoptosis. Further experiments showed that the anti-apoptotic effect of S-CP and CM-CP was in intimate association with down-regulation of Caspase-9/3 activities and alleviation of cell cycle arrest in the S phase. In addition, S-CP and CM-CP decreased the cell viability of tumor cells. These findings suggest that the type of functional group plays important roles in the biological function of the derivatives and provide a theoretical basis for the development of novel natural anti-oxidants or low-toxicity anti-tumor drugs.