The therapeutic role of natural compounds mediated through Nrf2 in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent chronic liver diseases in the world, with a current global prevalence estimated to exceed 33.6%. Consequently, the search for safe and effective therapeutic agents for MASLD has gained increasing attention. Nuclear factor erythroid 2-related factor 2 (Nrf2), a well-characterized transcription factor, plays a pivotal role in cellular defense against oxidative stress. Accumulating evidence indicates that activating Nrf2 has emerged as a promising therapeutic strategy for MASLD. Notably, numerous natural compounds have been reported to induce the activation of Nrf2 signaling pathway and thereby ameliorating MASLD progression. These natural Nrf2 activators exert beneficial effects on MASLD by attenuating liver oxidative stress, reducing hepatic steatosis, and alleviating liver inflammation and fibrosis. This review aims to elucidate the critical role of Nrf2 in the development and progression of MASLD, and to explore the therapeutic potential of natural compounds that activate Nrf2 as candidate medicinal agents or dietary supplements for the prevention and treatment of MASLD. By providing updated insights into Nrf2-mediated hepatoprotection, this review not only advances our understanding of Nrf2 as a key therapeutic target for MASLD but also supports the discovery and development of natural Nrf2 activators as novel interventions against MASLD.