Curcumin attenuates ethanol‐induced hepatic steatosis through modulating Nrf2/FXR signaling in hepatocytes

Abstract

Alcoholic liver disease (ALD) is a common health problem worldwide, characterized by aberrant accumulation of lipid in hepatocytes. Inhibition of lipid accumulation has been well recognized as a promising strategy for ALD. Previous studies showed that curcumin has potential effect on ALD by regulating oxidative stress and ethanol metabolism. However, the effects of curcumin on lipid accumulation and its mechanism remain unclear. Recent researches have indicated that farnesoid X receptor (FXR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) have excellent effects on reducing lipid deposition. This study demonstrated that curcumin alleviated ethanol-induced liver injury by ameliorating activities of serum marker enzymes and inflammation. Moreover, curcumin alleviated the symptom of hyperlipidemia and hepatic steatosis via modulating the expression of sterol regulatory elementbinding protein-1c, fatty acid synthase, and peroxisome proliferator-activated receptor-alpha as well as the activity of carnitine palmitoyltransferase 1. Additionally, curcumin induced the expression of Nrf2 and FXR in liver, strongly implying close relationship between inhibitory effect of curcumin on hepatic steatosis and the above two genes. The following in vitro experiments further verified the protective effects of curcumin against hepatotoxicity and lipid accumulation in hepatocytes induced by ethanol. Gain-or loss-of-function analyses revealed Nrf2 and FXR mediated the effect of curcumin on lipid deposition in hepatocytes, and curcumin modulated Additional Supporting Information may be found in the online version of this article.Abbreviations: ALD, alcoholic liver disease; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPT1, carnitine palmitoyltransferase 1; DMEM, Dulbecco's modified eagle medium; DMSO, dimethylsulfoxide; FAS, fatty acid synthase; FBS, fetal bovine serum; FXR, farnesoid X receptor; GAPDH, glyceraldehyde phosphate dehydrogenase; H&E, haematoxylin-eosin; HDL-C, high-density lipoprotein-cholesterol; LDH, lactate dehydrogenase; LDL-C, low-density lipoprotein-cholesterol; MTT, 3-(4,5-dimethylthiazol-2-yl)22,5-diphenyltetrazolium bromide; NF-jB, nuclear factor-kappa B; Nrf2, nuclear factor (erythroid-derived 2)-like 2; PPAR-a, peroxisome proliferator-activated receptor-alpha; SREBP-1c, sterol regulatory element-binding protein-1c; TC, total cholesterol; TG, triglyceride; TNF-a, tumor necrosis factor-alpha. 645the expression of FXR mediated by Nrf2. Collectively, we drew a conclusion that curcumin attenuated ALD by modulating lipid deposition in hepatocytes via a Nrf2/FXR activationdependent mechanism. The findings make curcumin a potential agent for ALD and broaden the horizon of the molecular mechanism involved. V C 2015 IUBMB Life, 67(8):645-658, 2015

Blockade of hedgehog pathway is required for the protective effects of magnesium isoglycyrrhizinate against ethanol‐induced hepatocyte steatosis and apoptosis

“…By taking advantage of the variation in fluorescence colors, Nile Red can be utilized as a selective dye to detect intracellular lipid droplets in living cells by fluorescence microscopy. Results showed that ethanol stimulation obviously increased the number of lipid droplets in hepatocytes, which supported our previous conclusion . Clearly, MgIG diminished lipid deposition in ethanol‐treated hepatocytes, which was consistent with that in in vitro model of nonalcoholic liver diseases .…”

“…For years, LO2 cells were widely used in considerable studies including ours as an in vitro model of hepatic tissue for investigating the pathophysiology of hepatocytes including hepatotoxicity (22). Herein, according to our Disruption of hedgehog signaling is a prerequisite for MgIG to limit oxidative stress and mitochondrial dysfunction in ethanol- previous studies, an in vitro model mimicking human ALD was successfully established by administrating LO2 hepatocytes with ethanol at the concentration of 100 mM for 24 h (18,23).…”

“…3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT) Assay MTT assay was performed as we previously descripted to evaluate the viability of LO2 cells (18). The absorbance values were recorded by a SPECTRAmax TM microplate spectrophotometer (Molecular Devices, Sunnyvale, CA).…”

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Postprandial Responses of Serum Bile Acids in Healthy Humans after Ingestion of Turmeric before Medium/High‐Fat Breakfasts

“…In humans, turmeric‐based beverage (TUR) has been shown to reduce early incremental blood glucose levels, to lower “prospective consumption” and “desired to eat” statements, while peptide tyrosine–tyrosine levels seem to increase compared to a control containing white wheat bread with 50 g available carbohydrate . Interestingly, several studies also reported that curcumin, an extract of turmeric, has the ability to increase the expression of FXR in the liver . Furthermore, turmeric may potentially act as a prebiotic …”