College of Light Industry and Food, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, Guangdong, China; Guangdong Provincial Key Laboratory of Lingnan Specialty Food Science and Technology, Guangzhou, Guangdong, China.
Guangdong Provincial Water Environment and Aquatic Products Security Engineering Technology Research Center, Guangzhou Key Laboratory of Aquatic Animal Diseases and Waterfowl Breeding, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong 510225, China.
Int J Biol Macromol. 2021 Dec 15;193(Pt A):814-822. doi: 10.1016/j.ijbiomac.2021.10.185. Epub 2021 Nov 2.
PCS-2A is a 34,023-Da acidic polysaccharide purified from chestnut shell consisting of rhamnose, arabinose, galactose, glucose, ribose, and galacturonic acid subunits at a molar ratio of 0.019:0.044:0.059:0.052:0.197:0.628. FTIR, methylation, and NMR analyses suggest the following backbone, (→4)-α-d-GalAp-(1 → 2,4)-α-l-Rha-(1→), with the branch chain composed of arabinose on O-2 with 2,4)-α-l-Rha-(1→). CCK-8 assay indicated PCS-2A treatment offset the reduction in cell viability inflicted by HO. Furthermore, histological signs of recovery in hepatocytes and liver tissue and a decreased level of AST and ALT occurred following administration of PCS-2A, indicating anti-liver lesion capability. In addition, we found that PCS-2A effectively alleviated HO-induced oxidative stress via activation of the NRF2 signaling pathway, evidenced by the downregulation of ROS content and upregulation of Nrf2 expression, as well as its corresponding antioxidant enzymes. The antioxidative effect elicited by PCS-2A further ameliorated NF-κB-mediated inflammation, as evidenced by lower mRNA levels of inflammatory cytokines, higher IκB in vitro, and reduced gene expression and activities of proinflammatory cytokines in vivo. Furthermore, in vitro apoptosis-related indicators revealed that P53-mediated apoptosis was alleviated via oxidative stress modulation. In summary, these results suggest that PCS-2A may elicit a protective effect against HO-induced liver injury via upregulation of the NRF2 signaling pathway.
PCS-2A 是一种从板栗壳中提取的 34023Da 酸性多糖，由鼠李糖、阿拉伯糖、半乳糖、葡萄糖、核糖和半乳糖醛酸亚基组成，摩尔比为 0.019:0.044:0.059:0.052:0.197:0.628。FTIR、甲基化和 NMR 分析表明，其主链为（→4）-α-d-GalAp-（1→2,4）-α-l-Rha-（1→），支链由阿拉伯糖在 O-2 上与 2,4）-α-l-Rha-（1→）组成。CCK-8 测定表明，PCS-2A 处理可抵消 HO 引起的细胞活力降低。此外，PCS-2A 给药后肝细胞和肝组织的组织学恢复迹象以及 AST 和 ALT 水平降低，表明其具有抗肝损伤能力。此外，我们发现 PCS-2A 通过激活 NRF2 信号通路有效缓解了 HO 诱导的氧化应激，这表现在 ROS 含量下调和 Nrf2 表达上调以及其相应的抗氧化酶活性增加。PCS-2A 产生的抗氧化作用进一步改善了 NF-κB 介导的炎症，这表现在炎症细胞因子的 mRNA 水平降低，体外 IκB 增加以及体内促炎细胞因子的基因表达和活性降低。此外，体外凋亡相关指标表明，通过氧化应激调节缓解了 P53 介导的细胞凋亡。总之，这些结果表明，PCS-2A 可能通过上调 NRF2 信号通路对 HO 诱导的肝损伤发挥保护作用。
