Ginseng polysaccharide attenuates red blood cells oxidative stress injury by regulating red blood cells glycolysis and liver gluconeogenesis

• Published in: Journal of ethnopharmacology 2023-01, Vol.300, p.115716-115716, Article 115716
• Main Authors: Wang, Siming, Zhao, Yuchu, Yang, Junjie, Liu, Shichao, Ni, Weifeng, Bai, Xueyuan, Yang, Ze, Zhao, Daqing, Liu, Meichen
• Format: Article
• Language: English
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2022.115716

ETHNOPHARMACOLOGICAL RELEVANCEPanax 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 STUDYThis 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 METHODSEstablished 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 μM). All three models were also tested in the presence of different concentrations of GPS. RESULTSThe 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-1α) 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 gluconeo