Ginseng polysaccharide attenuates red blood cells oxidative stress injury by regulating red blood cells glycolysis and liver gluconeogenesis
Ginseng polysaccharide attenuates red blood cells oxidative stress injury by regulating red blood cells glycolysis and liver gluconeogenesis
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DOI：
10.1016/j.jep.2022.115716
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发表时间：
2022-09-19
影响因子：
5.4
通讯作者：
Liu, Meichen
中科院分区：
文献类型：
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作者：
Wang, Siming;Zhao, Yuchu;Liu, Meichen
民族药理学相关性：人参甘草以“益气”功效著称，其药用历史已有2000多年。现代药理学研究证实，PG的“益气”作用可能与其抗氧化、降血脂、治疗心血管疾病等药理学特性密切相关。红细胞作为最早受到氧化应激影响的细胞之一，广泛应用于疾病的诊断。人参多糖（Ginseng polysaccharide，GPS）是人参多糖的主要活性成分之一，具有抗氧化应激、影响能量代谢等作用。然而，从红细胞氧化损伤角度解释GPS“益气”作用的分子机制尚未见报道。研究目的：本研究旨在通过体外和体内模型研究GPS对氧化损伤的红细胞的保护作用，并从糖酵解和糖异生途径的角度探讨其分子机制。材料与方法：建立了三种不同的体内外研究模型：红细胞暴露于过氧化氢（H2 O2）（40 mM）的体外模型、大鼠红细胞暴露于力竭游泳的体内模型和BRL-3A细胞暴露于H2 O2（25 μ M）的体外模型。所有三个模型也测试了在不同浓度的GPS的存在下。结果：结果表明，GPS是最有效的拮抗剂H2 O2诱导的红细胞溶血和氧化还原失衡。GPS可改善力竭运动大鼠RBVs溶血，包括降低全血粘度、改善变形能力、提高携氧和释氧能力，这与其增强抗氧化能力有关。GPS通过恢复糖酵解相关酶的活性和增加带3蛋白的表达，促进力竭运动大鼠红细胞糖酵解，从而调节氧化应激引起的能量代谢失衡。此外，我们证明，GPS改善抗氧化防御系统，增强能量代谢，并通过激活过氧化物酶体增殖物激活物γ共激活因子1 α（PGC-1 α）途径在H2 O2暴露的BRL-3A细胞调节胚胎发生。GPS促进糖酵解、保护红细胞免受氧化损伤的机制部分依赖于调节红细胞新生，二甲双胍（metformin，Met）抑制红细胞新生可减弱GPS对力竭运动大鼠抗氧化酶和糖酵解关键酶的调节。结论：GPS通过促进红细胞糖酵解和肝脏新生途径保护红细胞免受氧化应激损伤。这些结果可能有助于研究新的红细胞治疗方法，以提高抗氧化能力和保护红细胞免受氧化应激。
Ethnopharmacological relevance: Panax ginseng C.A. Mey (PG) is famous for "Qi-tonifying" effect, which has a medicinal history of more than 2 millennia. Modern pharmacology has confirmed that the "Qi-tonifying" effect of PG may be closely related to its pharmacological properties such as anti-oxidation, antineoplastic and treatment of cardiovascular disease. As one of the earliest cells affected by oxidative stress, RBCs are widely used in the diagnosis of diseases. Ginseng polysaccharide (GPS), is one of the major active components of PG, which plays an important role in resisting oxidative stress, affecting energy metabolism and other effects. However, the molecular mechanism explaining the "Qi-tonifying" effect of GPS from the perspective of RBCs oxidative damage has not been reported.Aim of the study: This study aimed to investigate the protective effect of GPS on oxidatively damaged RBCs using in vitro and in vivo models and explore the molecular mechanisms from the perspective of glycolysis and gluconeogenesis pathways. To provides a theoretical basis for the future research of antioxidant drugs.Materials and methods: Established three different in vitro and in vivo research models: an in vitro model of RBCs exposed to hydrogen peroxide (H2O2) (40 mM), an in vivo model of RBCs from rats subjected to exhaustive swimming, and an in vitro model of BRL-3A cells exposed to H2O2 (25 mu M). All three models were also tested in the presence of different concentrations of GPS.Results: The findings showed that GPS was the most potent antagonist of H2O2-induced hemolysis and redox inbalance in RBCs. In exhaustive exercise rats, GPS ameliorated RBVs hemolysis, including reducing whole-blood viscosity (WBV), improving deformability, oxygen-carrying and -releasing capacities, which was related to the enhancing of antioxidant capacity. Moreover, GPS promoted RBCs glycolysis in rats with exhaustive exercise by recovering the activities of glycolysis-related enzymes and increasing band 3 protein expression, thereby regulating the imbalance of energy metabolism caused by oxidative stress. Furthermore, we demonstrated that GPS improved antioxidant defense system, enhanced energy metabolism, and regulated gluconeogenesis via activating PPAR gamma co-activator 1 alpha (PGC-1 alpha) pathway in H2O2-exposed BRL-3A cells. Mechanistically, GPS promoted glycolysis and protected RBCs from oxidative injury was partly dependent on the regulation of gluconeogenesis, as inhibition of gluconeogenesis by metformin (Met) attenuates the regulation of antioxidant enzymes and key enzymes of glycolytic by GPS in exhaustive exercise rats.Conclusion: This study demonstrates that GPS protects RBCs from oxidative stress damage by promoting RBCs glycolysis and liver gluconeogenesis pathways. These results may contribute to the study of new RBCs treatments to boost antioxidant capacity and protect RBCs against oxidative stress.