2-O-?-d-glucopyranosyl-_l-ascorbic acid, a novel vitamin C derivative from Lycium barbarum, prevents oxidative stress.

ABSTRACT: Reducing agents are crucial for the management of maladaptive inflammation-induced macrophage death and hematopoietic toxicity of chemotherapy. 2-O-?-d-glucopyranosyl-_l-ascorbic acid (AA-2?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?G. AA-2?G protected hydrogen peroxide-induced cell death in murine macrophage RAW264.7?cells. Treatment with AA-2?G eliminated oxidative stress and the ratio of cellular glutathione to glutathione disulfide more effectively than AA and AA-2?G. AA-2?G also significantly reduced the fluorescent intensity of DCFH-DA triggered by chemotherapeutic agent camptotehcin-11 but not fluorouracil. AA, AA-2?G, and AA-2?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?G to enhance the Nrf2-DNA binding affinity was approximately two fold as those of AA and AA-2?G. Sodium ascorbate cotransporters (SVCT) inhibitors, sulfinpyrazone, phloretin, and 3-O-methyglucose, potently abrogated the free radical scavenging activities of AA, AA-2?G, and AA-2?G. The cellular uptake efficacy of AA-2?G and AA-2?G was less than 10% of AA, while the inhibition of SVCT with sulfinpyrazone considerably diminished the uptake efficacy of these compounds. AA-2?G and AA-2?G are more stable in the Fenton reagents than AA. In summary, AA-2?G from L. barbarum with excellent free radical scavenging activity is a promising natural AA derivative for further pharmacological evaluation.

SUBMITTER: Wang SF 

PROVIDER: S-EPMC6430735 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature