Prooxidative inhibition against NF-κB-mediated inflammation by pharmacological vitamin C

Yu-Ting Du; Ying Long; Wei Tang; Xue-Feng Liu; Fang Dai; Bo Zhou

doi:10.1016/j.freeradbiomed.2022.01.007

Prooxidative inhibition against NF-κB-mediated inflammation by pharmacological vitamin C

Free Radic Biol Med. 2022 Feb 20:180:85-94. doi: 10.1016/j.freeradbiomed.2022.01.007. Epub 2022 Jan 14.

Authors

Yu-Ting Du¹, Ying Long², Wei Tang², Xue-Feng Liu³, Fang Dai², Bo Zhou⁴

Affiliations

¹ State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China; Department of Chemistry, Xinzhou Teachers University, Xinzhou, Shanxi, 034000, China.
² State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China.
³ State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China; School of Pharmacy, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China.
⁴ State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China. Electronic address: bozhou@lzu.edu.cn.

PMID: 35038551
DOI: 10.1016/j.freeradbiomed.2022.01.007

Abstract

Vitamin C (VC), widely found in vegetables and fruits, operates as an electron donor to perform various biological functions including anti-inflammatory activity. However, the mechanisms by which VC inhibits inflammation remain insufficiently understood. Accordingly, we performed a detail mechanistic study on anti-inflammatory activity of VC at millimolar (pharmacological) concentrations in lipopolysaccharides-stimulated RAW264.7 cells. It was found that VC and its two-electron oxidative product, dehydroascorbate (DHA) constructs an efficient redox cycle with the aid of intracellular glutathione and copper ions, thereby facilitating the generation of reactive oxygen species (ROS) and the ROS-dependent inhibition against the NF-κB-mediated inflammation.

Keywords: Dehydroascorbate; Inflammation; NF-κB; Reactive oxygen species; Vitamin C.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use
Ascorbic Acid* / pharmacology
Ascorbic Acid* / therapeutic use
Inflammation / drug therapy
Lipopolysaccharides / pharmacology
Mice
NF-kappa B* / genetics
RAW 264.7 Cells
Reactive Oxygen Species

Substances

Anti-Inflammatory Agents
Lipopolysaccharides
NF-kappa B
Reactive Oxygen Species
Ascorbic Acid