2-O-β-d-glucopyranosyl-l-ascorbic acid, a novel vitamin C derivative from Lycium barbarum, prevents oxidative stress

Reducing agents are crucial for the management of maladaptive inflammation-induced macrophage death and hematopoietic toxicity of chemotherapy. 2- O - β - d -glucopyranosyl- l -ascorbic acid (AA-2 β G), a unique AA (or vitamin C) derivative identified in Lycium barbarum , exhibited enhanced free radical scavenging activity compared with AA and its synthetic derivative AA-2 α G. AA-2 β G protected hydrogen peroxide-induced cell death in murine macrophage RAW264.7 cells. Treatment with AA-2 β G eliminated oxidative stress and the ratio of cellular glutathione to glutathione disulfide more effectively than AA and AA-2 α G. AA-2 β G also significantly reduced the fluorescent intensity of DCFH-DA triggered by chemotherapeutic agent camptotehcin-11 but not fluorouracil. AA, AA-2 α G, and AA-2 β G significantly decreased Keap-1expression, and increased the expression levels of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1. All compounds triggered the nuclear translocation of Nrf2, while the ability of AA-2 β G to enhance the Nrf2-DNA binding affinity was approximately two fold as those of AA and AA-2 α G. Sodium ascorbate cotransporters (SVCT) inhibitors, sulfinpyrazone, phloretin, and 3- O -methyglucose, potently abrogated the free radical scavenging activities of AA, AA-2 α G, and AA-2 β G. The cellular uptake efficacy of AA-2 α G and AA-2 β G was less than 10% of AA, while the inhibition of SVCT with sulfinpyrazone considerably diminished the uptake efficacy of these compounds. AA-2 α G and AA-2 β G are more stable in the Fenton reagents than AA. In summary, AA-2 β G from L. barbarum with excellent free radical scavenging activity is a promising natural AA derivative for further pharmacological evaluation.