School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi 'an 710021, China.
School of Chemistry and Chemical Engineering, Xi'an University of Science and Technology, Xi'an 710054, China.
Food Funct. 2021 Oct 4;12(19):9054-9065. doi: 10.1039/d1fo01182k.
The inflammatory and antioxidant effects of a novel polysaccharide (SGP-1-1) were investigated in an inflammation-suppressed diabetic nephropathy (DN) mouse model, and the underlying molecular mechanisms of inflammation and oxidative stress in SGP-1-1-treated mouse models were elucidated. The results demonstrated that DN mouse models treated with SGP-1-1 (50, 100, and 200 mg kg d) exhibited good inflammation-modulating activity. In addition, histopathological analysis showed that glomerular atrophy, severe glomerular thylakoid hyperplasia, tubular endothelial detachment, basement membrane exposure, cytoplasmic infiltration with inflammatory cells, and interstitial oedema were all alleviated in DN mice after treatment with SGP-1-1. Metabolomics analysis based on UPLC-Q-TOF/MS revealed that a close relationship between the occurrence of DN and the potential 39 biomarkers, especially, leukotriene E3 and arachidonic acid,of which the main invloved metabolic pathways may beglycerophospholipid metabolism, arachidonic acid metabolism and primary bile acid biosynthesis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis results demonstrated that SGP-1-1 downregulates mRNA and the protein expression of the G protein-coupled cell membrane receptor TLR4 and its downstream protein kinase (NF-κB p65). This, resulted in the inhibition of the TLR4-NF-κB pathway in the peritoneum of DN mice by regulating inflammation, while stimulating the production of superoxide dismutase (SOD) and reducing the production of cytokine (IL-6, TNF-α) and malondialdehyde (MDA).
一种新型多糖（SGP-1-1）的抗炎和抗氧化作用在炎症抑制型糖尿病肾病（DN）小鼠模型中进行了研究，并阐明了 SGP-1-1 处理的小鼠模型中炎症和氧化应激的潜在分子机制。结果表明，SGP-1-1（50、100 和 200 mg kg d）治疗的 DN 小鼠模型表现出良好的炎症调节活性。此外，组织病理学分析表明，SGP-1-1 治疗后，DN 小鼠的肾小球萎缩、严重的肾小球类囊泡增生、管状内皮细胞脱落、基底膜暴露、细胞质浸润炎症细胞和间质水肿均得到缓解。基于 UPLC-Q-TOF/MS 的代谢组学分析表明，DN 的发生与潜在的 39 种生物标志物之间存在密切关系，特别是白细胞三烯 E3 和花生四烯酸，其主要涉及的代谢途径可能是甘油磷脂代谢、花生四烯酸代谢和初级胆汁酸生物合成。定量实时聚合酶链反应（qRT-PCR）和 Western blot 分析结果表明，SGP-1-1 下调 G 蛋白偶联细胞膜受体 TLR4 及其下游蛋白激酶（NF-κB p65）的 mRNA 和蛋白表达。这导致 SGP-1-1 通过调节炎症抑制了 DN 小鼠腹膜中的 TLR4-NF-κB 途径，同时刺激超氧化物歧化酶（SOD）的产生，减少细胞因子（IL-6、TNF-α）和丙二醛（MDA）的产生。
