Na Li,1,2 Liyuan Hao,1,2 Shenghao Li,1,2 Jiali Deng,1,2 Fei Yu,1,2 Junli Zhang,3 Aiyu Nie,1,2 Xiaoyu Hu2 

1Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, People’s Republic of China

Correspondence: Xiaoyu Hu, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-Er-Qiao Road, Chengdu, Sichuan Province, 610075, People’s Republic of China, Email TCMxiaoyuhu@aliyun.com

Abstract: 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 anti-apoptotic 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.

Keywords: the NRF-2/HO-1 signaling pathway, antioxidants, anti-inflammatory, natural compounds, non-alcoholic fatty liver disease