@article{Wang2026, 
author = {Qihan Wang and Weiyi Shen and Wentao Shao and Zhaoyan Jiang and Gang Zhao and Hai Hu},
title = {Luteolin prevents cholesterol gallstone formation in mice by downregulating NRF2-mediated NPC1L1 expression},
year = {2026},
journal = {Food Science and Human Wellness},
volume = {15},
number = {7},
pages = {9250735},
keywords = {Luteolin, Gallstone, Niemann-Pick C1-like 1, Nuclear factor erythroid 2-related factor 2, Cholesterol},
url = {https://www.sciopen.com/article/10.26599/FSHW.2025.9250735},
doi = {10.26599/FSHW.2025.9250735},
abstract = {Luteolin, a flavonoid that has been developed for commercial use in health supplements and cosmetics, has the potential to treat hypercholesterolemia. Gallstone disease is a common disease worldwide. Inhibiting intestinal cholesterol absorption is considered a promising intervention to prevent gallstone formation. This study investigates the inhibitory effects of luteolin on gallstone formation and elucidates its underlying mechanisms. Eight-week-old male C57BL/6J mice were fed a lithogenic diet with or without added luteolin for 8 weeks. Gallstone incidence was assessed. Bile, liver, serum and feces were collected for biochemical indicators. Liver and intestinal tissues were collected for gene expression analyses. Cecal contents were used for gut microbiota analysis. Caco2 cells and Caco2 cells with nuclear factor erythroid 2-related factor 2 (NRF2) knockdown were treated with luteolin to assess its impact on Niemann-Pick C1-like 1 (NPC1L1) expression and cholesterol absorption. The role of NRF2 in NPC1L1 transcriptional activation was validated using a luciferase reporter assay. The binding of luteolin and NRF2 were analyzed by molecular docking and molecular dynamics simulation. All mice fed with lithogenic diet developed gallstones. Luteolin administration significantly inhibited cholesterol absorption, thereby reducing cholesterol levels in both serum and bile, which ultimately prevented cholesterol gallstone formation. Luteolin markedly suppressed the expression of NPC1L1. NRF2 showed significant correlation with the transcriptional activation of NPC1L1. Furthermore, luteolin significantly suppressed NRF2 mRNA expression and demonstrated potential to bind NRF2 protein, might inhibit its nuclear translocation and transcriptional activation function. Our findings confirm that luteolin can inhibit intestinal cholesterol absorption, thereby preventing cholesterol gallstone formation. This effect is achieved through suppression of the NRF2-mediated NPC1L1 expression.}
}