This study aimed to explore the protective effect of sulfated Codonopsis polysaccharides (SCP) on acute oxidative stress. SCP was modified by chlorosulfonic acid-pyridine method from Codonopsis polysaccharides (CP), which had 34.48% of sulfate content determined by ultrasonic-acidic barium chromate spectrophotometry. The analysis of Fourier transform-infrared spectroscopy (FT-IR) appeared an absorption peak of SCP at 811.91 cm^-1 , which related to C-O-SO₃ . In vitro test, the antioxidant activities of CP and SCP was induced by H₂ O₂ in RAW264.7 cells, results indicated that SCP and CP could significantly enhance the activity of superoxide dismutase (SOD), glutathione peroxidase (GDH-Px) and catalase (CAT), and nitric oxide (NO) and decrease the level of malondialdehyde (MDA), reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) secreted by RAW264.7 cells compared with modeling group (p < .05). The flow cytometry results also revealed that SCP and CP could markedly inhibit the apoptosis of macrophage induced by acute oxidative stress. In vivo test, 50% ethanol was used to induce mice acute oxidative stress, results indicated that the blood biochemical parameters in mice were restored to normal levels following administration of SCP and CP, and alanine aminotransferase (ALT), aspartate transaminase (AST), total protein (TP), albumin (ALB), glucose (GLU), and creatinine (UREA) had significant differences compared with modeling group (p < .05). Quantitative real-time PCR analysis revealed that SCP and CP could promote the expression of Keap1 and Nrf2. In summary, both SCP and CP had protective effects against acute oxidative stress. PRACTICAL APPLICATIONS: Oxidative stress is a kind of stress injury, which can cause a variety of diseases and accelerate physical aging. Codonopsis has many active components, among which Codonopsis polysaccharide has antioxidant effect. Recent studies have found that Codonopsis polysaccharides could be modified by sulfate molecules to obtain higher antioxidant activity. The modified Codonopsis polysaccharides could significantly promote the production of antioxidant enzymes (SOD, CAT, GDH-Px) and reduce the content of oxidative stress marks (ROS, MDA). Moreover, its antioxidant mechanism may be related to the Keap1 /Nrf2 signaling pathway. Therefore, SCP was an effective antioxidant, and could be used as a potential health food with antioxidant and anti-aging effects.

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