Therapeutic Effects of Natural Products in the Treatment of Chronic Diseases: The Role in Regulating KEAP1–NRF2 Pathway

Oxidative stress represents a pivotal mechanism in the pathogenesis of numerous chronic diseases. The Kelch-like ECH-associated protein 1–transcription factor NF-E2 p45-related factor 2 (KEAP1–NRF2) pathway plays a crucial role in maintaining redox homeostasis and regulating a multitude of biological processes such as inflammation, protein homeostasis, and metabolic homeostasis. In this paper, we present the findings of recent studies on the KEAP1–NRF2 pathway, which have revealed that it is aberrantly regulated and induces oxidative stress injury in a variety of diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, respiratory diseases, digestive diseases, and cancer. Given this evidence, targeting KEAP1–NRF2 represents a highly promising avenue for developing therapeutic strategies for chronic diseases, and thus the development of appropriate therapeutic strategies based on the targeting of the NRF2 pathway has emerged as a significant area of research interest. This paper highlights an overview of current strategies to modulate KEAP1–NRF2, as well as recent advances in the use of natural compounds and traditional Chinese medicine, with a view to providing meaningful guidelines for drug discovery and development targeting KEAP1–NRF2. Additionally, it discusses the challenges associated with harnessing NRF2 as a therapeutic target.