A Bibliometric Review of the Keap1/Nrf2 Pathway and its Related Antioxidant Compounds

Abstract

Nrf2 is a master transcriptional regulator of antioxidant and cytoprotective pathways. Currently in its third decade, research on Nrf2 has expanded to encompass not only basic but also clinical studies. In the present bibliometric review, we employed the VOSviewer tool to describe the existing Nrf2 literature landscape. As of July 2019, 11,931 papers on Nrf2 were listed in the “Web of Science” database, with more than 1000 new papers published each year. As expected, terms related to oxidative stress and antioxidant molecules occur very often in the Nrf2 literature throughout the years. Interestingly, there is also a gradual increase in the occurrence of terms related to diseases or to natural compounds, the most prominent being sulforaphane, curcumin, and resveratrol that modulate the Nrf2 pathway. Going beyond molecular biology/biochemistry and related fields, Nrf2 research has begun to spread into more clinical areas like endocrinology/metabolism, cardiology, and nephrology, likely reflecting an increased interest in clinical applications of Nrf2 pathway activators. China has become the most prolific producer of Nrf2 papers the last five years followed by the USA and Japan, a reverse pattern compared to the past. In conclusion, Nrf2 is the subject of a globally active research field that keeps growing and extends from bench to bedside.

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

“…PPARγ cooperates also with another transcription factor, Nrf2, which controls the expression of genes encoding cytoprotective proteins, particularly antioxidant proteins [28,88]. PPARγ may bind to specific elements in the promoter region of genes it regulates, including Nrf2, catalase (CAT), glutathione S-transferase (GST), heme-oxygenase-1 (HO-1), and manganese-dependent superoxide dismutase (Mn-SOD).…”

Sulforaphane Protects Cells against Lipopolysaccharide-Stimulated Inflammation in Murine Macrophages

“…SFN is extensively studied because of its diverse protective effect and/or activity at the transcriptional level. Former studies described that, in diseased conditions, SFN naturally interacts with the transcription factor NF-E2-related factor 2 (Nrf2), which is suppressed in the cytoplasm by the repressor protein Keap1 (Kelch-like erythroid cell-derived protein with cap 'n' collar homology-associated protein 1) under homeostatic conditions [15,16]. Upon stimulation, there is a conformational change in the cysteine residues within Keap1, and Nrf2 translocates into the nucleus, followed by interact with antioxidant response element (ARE) [17][18][19].…”

<p>The Protective Role of Tanshinone IIA in Silicosis Rat Model via TGF-β1/Smad Signaling Suppression, NOX4 Inhibition and Nrf2/ARE Signaling Activation</p>

“…31 Nuclear factor erythroid 2-like 2 (Nrf2) is a cellular sensor for oxidation reaction, and as the central regulator of antioxidant and detoxifying systems, it protects cells and tissues against oxidative stress through regulation of antioxidant response element (ARE)-mediated induction of antioxidant enzymes and diverse phase II detoxification. 32,33 Nrf2 is principally controlled by the binding of cytosolic protein Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm and subsequent proteasome degradation. In the presence of ROS, Nrf2 was separated from its bound with keap1, transferred to the nucleus and bounds to ARE, a small Maf protein, inducing the expression of a series of antioxidant genes, including heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1).…”