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

Shen-Fei Wang,Xin Liu,Mo-Yu Ding,Shuangcheng Ma,Jing Zhao,Ying Wang,Shaoping Li

doi:10.1016/j.redox.2019.101173

Abstract

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

Highlights

Imbalance between the oxidant and antioxidant system results in excess amounts of free radicals and oxidative stress (ROS), which is considered as a two-edged weapon
Phosphate-buffered saline (PBS), Dulbecco's modified Eagle medium (DMEM), fetal bovine serum (FBS), and 100 × penicillin and streptomycin were purchased from Gibco-Invitrogen (Paisley, Scotland, UK)
We reported the excellent antioxidant activity of AA-2βG, which is a unique natural AA derivative identified in L. barbarum

Summary

Introduction

Imbalance between the oxidant and antioxidant system results in excess amounts of free radicals and oxidative stress (ROS), which is considered as a two-edged weapon. The accumulation of free radicals is associated with maladaptive inflammation-induced macrophage death that leads to the subsequent necrotic death of plaque cells [1]. Chronic elevated ROS is responsible for hematopoietic toxicity of chemotherapeutic agents [2] and the development of many types of diseases, including various types of cancer [3] and neurodegenerative diseases [4]. Exclusive generation of intracellular free radicals, such as hydrogen peroxide (H2O2) and superoxide (O2−), through the oxidation of antioxidants induces apoptotic cell death in KRAS and BRAF mutant colorectal cancer [5,6]. The pharmacological but not physiology dose of AA increases the risk of kidney stone, and renal and metabolic toxicity [8]. Stable AA derivative with fast and long-lasting free radical scavenging activity and reduced therapeutic dose is urgently needed

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