Alcoholic liver disease (ALD), one of the most common causes of liver-related morbidity and mortality, is induced by chronic alcohol intake. With the increasing alcohol consumption worldwide, the global incidence of alcohol-related hepatic disease has increased in recent years, especially among young people and women (Devarbhavi et al., 2023). Alcohol consumption has become one of the most common causes of end-stage liver disease and was implicated directly or indirectly in 50 % of cirrhosis-related deaths (Mandrekar and Mandal, 2024).

ALD encompasses a spectrum of liver injury, including alcoholic fatty liver, steatohepatitis, hepatic fibrosis, cirrhosis and hepatocellular carcinoma (Seitz et al., 2018). As the early stage of ALD, fatty liver is characterized by excessive deposition of TG-rich lipid droplets (LDs) in hepatocytes, which is mainly derived from the imbalance between fat synthesis and fat degradation in hepatocytes (Valcin et al., 2020). However, despite the tremendous progress in research on ALD, the pathogenesis of this disease remains unclear and there is still no effective therapy up till now.

As the most important detoxification organ of the body, liver is the primary site of alcohol metabolism and is more susceptible to alcohol-induced injury (Massey and Arteel, 2012). Nearly over 90 % of ethanol ingested is metabolized in the liver, with the remaining excreted unchanged in breath, sweat and urine (Hyun et al., 2021). Alcohol-induced liver damage is due not only to nutritional disturbances but also to its metabolic hepatotoxicity (Stickel et al., 2017). Two main enzymes in hepatocyte, cytosolic alcohol dehydrogenase (ADH) and microsomal ethanol-oxidizing system (MEOS) located in endoplasmic reticulum, are responsible for metabolizing ethanol to acetaldehyde, which is then converted to acetate by mitochondrial acetaldehyde dehydrogenase (ALDH) (Lieber, 2004). Both reactions catalyzed by ADH and ALDH use nicotinamide adenine dinucleotide (NAD+) as a hydrogen acceptor and reduce it to NADH, resulting in a decrease in intracellular NAD+ level (Liu et al., 2021). As an important coenzyme, NAD+ level influence the activities of various metabolic enzymes regulating energy metabolism. Decrease in NAD+ levels suppress the activities of a series of NAD+ dependent enzymes implicated in oxidative phosphorylation, tricarboxylic acid (TCA) cycle and fatty acid oxidation (Xiao et al., 2018). SIRT1, a member of the sirtuin family, is also a NAD+ dependent protein deacetylase that plays a pivotal role in maintaining hepatic lipid metabolism balance through regulating the activities of enzymes related to fat synthesis and degradation (Majeed et al., 2021). Previous studies indicated that SIRT1 could promote hepatic lipolysis through upregulating peroxisome proliferator activated receptor γ (PPARγ), which in turn promoted the expression of adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL), the rate-limiting enzymes for triacylglycerol hydrolysis (Wang et al., 2024; Zhao et al., 2022). Besides, SIRT1 could induce AMP-activated protein kinase (AMPK) activation, which then phosphorylated acetyl-CoA carboxylases (ACC), the rate-limiting enzyme in the de novo lipogenesis, and suppressed its activity (Liou et al., 2020). In view of the critical role of NAD+ dependent SIRT1 in maintaining hepatic lipid metabolism, ethanol induced NAD+ depletion and subsequent SIRT1 dysfunction have been recognized as a key pathogenesis of alcoholic hepatic steatosis, while regulation of SIRT1 signaling pathway has been considered a potential target for the treatment of ALD (Ren et al., 2020). In recent years, increasing studies indicated that natural products were able to attenuate ALD through regulating SIRT1 signaling pathway (Jiang et al., 2024; Zhou et al., 2022), providing a new therapeutic strategy for ALD.

Curcumol, a bioactive component extracted from a traditional Chinese medicine Curcuma rhizom, possesses diverse pharmacological activities, including anti-cancer, anti-inflammatory and hepatoprotective effects (Zhai et al., 2024). We have previously demonstrated that curcumol was able to ameliorate non-alcoholic fatty liver disease and alcoholic fatty liver disease through inhibition of hepatocyte senescence (Qi et al., 2021, 2022). Recent studies have revealed that curcumol could induce autophagy and necroptosis in hepatic stellate cells (HSCs) through activation of SIRT1 signaling pathway (Sun et al., 2022). However, whether curcumol can regulate SIRT1 signaling pathway in hepatocytes and contribute to its amelioration of alcoholic fatty liver disease remains unclear. The present study was designed to investigate the effect of curcumol on SIRT1 signaling pathway in hepatocytes and its possible contribution to the amelioration of ALD.