The NRF-2/HO-1 Signaling Pathway: A Promising Therapeutic Target for Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder with a rising prevalence. It begins with lipid accumulation in hepatocytes and gradually progresses to Metabolic-associated steatohepatitis (MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). The pathophysiology of MASLD is complex and involves multiple factors, with oxidative stress playing a crucial role. Oxidative stress drives the progression of MASLD by causing cellular damage, inflammatory responses, and fibrosis, making it a key pathogenic mechanism. The Nuclear Factor Erythroid 2-Related Factor 2 / Heme Oxygenase-1 (Nrf2/HO-1) signaling axis provides robust multi-organ protection against a spectrum of endogenous and exogenous insults, particularly oxidative stress. It plays a pivotal role in mediating antioxidant, anti-inflammatory, and antiapoptotic responses. Many studies indicate that activating the Nrf2/HO-1 signaling pathway can significantly mitigate the progression of MASLD. This article examines the role of the Nrf2/HO-1 signaling pathway in MASLD and highlights natural compounds that protect against MASLD by targeting Nrf2/HO-1 activation. The findings indicate that the Nrf2/HO-1 signaling pathway holds great promise as a therapeutic target for MASLD.