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硫酸化和羧甲基化对青钱柳多糖的影响:理化性质、抗肿瘤活性及对细胞氧化应激的保护作用

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

作者信息

Xie Liuming, Huang Zhibing, Qin Li, Yu Qiang, Chen Yi, Zhu Haibing, Xie Jianhua

机构信息

State Key Laboratory of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang 330047, China.

State Key Laboratory of Food Science and Technology, Nanchang University, No. 235 Nanjing East Road, Nanchang 330047, China; Sino-German Joint Research Institute, Nanchang University, No. 235 Nanjing East Road, Nanchang 330047, China.

出版信息

Int J Biol Macromol. 2022 Apr 15;204:103-115. doi: 10.1016/j.ijbiomac.2022.01.192. Epub 2022 Feb 7.

DOI:10.1016/j.ijbiomac.2022.01.192
PMID:35144010
Abstract

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.

摘要

对青钱柳多糖(CP)进行化学修饰,制备出硫酸化衍生物(S-CP)和羧甲基化衍生物(CM-CP)。随后,对这些衍生物的抗氧化活性、细胞保护作用和抗肿瘤活性进行了研究,以建立其结构与功能活性之间的关系。结果发现,化学修饰导致CP的化学组成和表观结构发生显著变化。葡萄糖含量最高的S-CP具有最强的清除DPPH•和HO•的抗氧化能力,但CM-CP在清除HO•方面低于CP。更重要的是,与CP相比,S-CP和CM-CP通过降低乳酸脱氢酶(LDH)、细胞内活性氧(ROS)和丙二醛(MDA)的分泌,增强吞噬作用和超氧化物歧化酶(SOD)水平,以及抑制异常凋亡,更有效地保护RAW264.7细胞免受HO诱导的损伤。进一步实验表明,S-CP和CM-CP的抗凋亡作用与Caspase-9/3活性的下调以及S期细胞周期阻滞的缓解密切相关。此外,S-CP和CM-CP降低了肿瘤细胞的活力。这些发现表明官能团类型在衍生物的生物学功能中起重要作用,并为新型天然抗氧化剂或低毒抗肿瘤药物的开发提供了理论依据。

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