An insight into role of amino acids as antioxidants via NRF2 activation

Amino Acids. 2024 Mar 20;56(1):23. doi: 10.1007/s00726-024-03384-8.

Abstract

Oxidative stress can affect the protein, lipids, and DNA of the cells and thus, play a crucial role in several pathophysiological conditions. It has already been established that oxidative stress has a close association with inflammation via nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Amino acids are notably the building block of proteins and constitute the major class of nitrogen-containing natural products of medicinal importance. They exhibit a broad spectrum of biological activities, including the ability to activate NRF2, a transcription factor that regulates endogenous antioxidant responses. Moreover, amino acids may act as synergistic antioxidants as part of our dietary supplementations. This has aroused research interest in the NRF2-inducing activity of amino acids. Interestingly, amino acids' activation of NRF2-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway exerts therapeutic effects in several diseases. Therefore, the present review will discuss the relationship between different amino acids and activation of NRF2-KEAP1 signaling pathway pinning their anti-inflammatory and antioxidant properties. We also discussed amino acids formulations and their applications as therapeutics. This will broaden the prospect of the therapeutic applications of amino acids in a myriad of inflammation and oxidative stress-related diseases. This will provide an insight for designing and developing new chemical entities as NRF2 activators.

Keywords: Amino acids; Anti-inflammatory; Antioxidant; NRF2-KEAP1 signaling; Oxidative stress.

Publication types

  • Review

MeSH terms

  • Amino Acids / metabolism
  • Antioxidants* / metabolism
  • Humans
  • Inflammation / drug therapy
  • Kelch-Like ECH-Associated Protein 1 / chemistry
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • Kelch-Like ECH-Associated Protein 1
  • Amino Acids