Role of Baicalin and Liver X Receptor Alpha in the Formation of Cholesterol Gallstones in Mice

This study was aimed at investigating the effect of baicalin on experimental cholesterol gallstones in mice. The mouse gallstone model was induced by feeding with a lithogenic diet, and cholesterol stones were found in the gallbladder. The lithogenic diet caused elevation of triglycerides, cholesterol, and low-density lipoprotein concentrations and descent of high-density lipoprotein concentration in serum. Hyperplasia and inflammatory infiltration were observed in the gallbladder wall of lithogenic diet-fed mice. We also found the increase of cholesterol content and the decrease of bile acid in bile. Real-time PCR and western blot results demonstrated that the expression levels of two enzymes (cholesterol 7α-hydroxylase (CYP7a1) and sterol 12α-hydroxylase (CYP8b1)) to catalyze the synthesis of bile acid from cholesterol were decreased and that two cholesterol transporters (ATP-binding cassette transporter G5/G8 (ABCG5/8)) were increased in the liver of lithogenic diet-fed mice. The lithogenic diet also led to enhanced activity of alanine aminotransferase and aspartate aminotransferase in serum; increased concentrations of tumor necrosis factor-α, interleukin- (IL-) 1β, IL-6, and malondialdehyde; and decreased superoxide dismutase activity in the liver, suggesting inflammatory and oxidative stress. In addition, liver X receptor alpha (LXRα) was increased in the liver. After gavage of baicalin, the lithogenic diet-induced gallstones, hyperlipidemia, gallbladder hyperplasia, inflammation, and oxidative stress in liver and cholesterol metabolism disorders were all alleviated to some degree. The expression of LXRα in the liver was inhibited by baicalin. In addition, the LXRα agonist T0901317 aggravated lithogenic diet-induced harmful symptoms in mice, including the increase of gallstone formation, hyperlipidemia, hepatic injury, inflammation, and oxidative stress. In conclusion, we demonstrated that baicalin played a protective role in a lithogenic diet-induced gallstone mouse model, which may be mediated by inhibition of LXRα activity. These findings may provide novel insights for prevention and therapy of gallstones in the clinic.

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Identification of human low-density lipoprotein receptor as a novel target gene regulated by liver X receptor alpha

FEBS Letters ◽

10.1016/j.febslet.2006.08.010 ◽

2006 ◽

Vol 580 (20) ◽

pp. 4929-4933 ◽

Cited By ~ 26

Author(s):

Kenji Ishimoto ◽

Keisuke Tachibana ◽

Mikako Sumitomo ◽

Shiho Omote ◽

Ikuko Hanano ◽

...

Keyword(s):

Target Gene ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Liver X Receptor ◽

Low Density ◽

Lipoprotein Receptor ◽

Receptor Alpha ◽

Density Lipoprotein Receptor ◽

Novel Target ◽

Liver X Receptor Alpha

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The liver X-receptor alpha controls hepatic expression of the human bile acid-glucuronidating UGT1A3 enzyme in human cells and transgenic mice

Hepatology ◽

10.1002/hep.21259 ◽

2006 ◽

Vol 44 (2) ◽

pp. 368-378 ◽

Cited By ~ 46

Author(s):

Mélanie Verreault ◽

Kathy Senekeo-Effenberger ◽

Jocelyn Trottier ◽

Jessica A. Bonzo ◽

Julie Bélanger ◽

...

Keyword(s):

Bile Acid ◽

Transgenic Mice ◽

Liver X Receptor ◽

Human Cells ◽

Human Bile ◽

Receptor Alpha ◽

Hepatic Expression ◽

Liver X Receptor Alpha

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Lactobacillus delbrueckii Interfere With Bile Acid Enterohepatic Circulation to Regulate Cholesterol Metabolism of Growing–Finishing Pigs via Its Bile Salt Hydrolase Activity

Frontiers in Nutrition ◽

10.3389/fnut.2020.617676 ◽

2020 ◽

Vol 7 ◽

Author(s):

Gaifeng Hou ◽

Wei Peng ◽

Liangkai Wei ◽

Rui Li ◽

Yong Yuan ◽

...

Keyword(s):

Bile Acid ◽

Enterohepatic Circulation ◽

Cholesterol Metabolism ◽

Binding Protein ◽

Density Lipoprotein ◽

Lactobacillus Delbrueckii ◽

Farnesoid X Receptor ◽

Bile Salt Hydrolase ◽

Lipoprotein Receptor ◽

Density Lipoprotein Receptor

Microbiota-targeted therapies for hypercholesterolemia get more and more attention and are recognized as an effective strategy for preventing and treating cardiovascular disease. The experiment was conducted to investigate the cholesterol-lowering mechanism of Lactobacillus delbrueckii in a pig model. Twelve barrows (38.70 ± 5.33 kg) were randomly allocated to two groups and fed corn–soybean meal diets with either 0% (Con) or 0.1% Lactobacillus delbrueckii (Con + LD) for 28 days. L. delbrueckii–fed pigs had lower serum contents of total cholesterol (TC), total bile acids (TBAs), and triglyceride, but higher fecal TC and TBA excretion. L. delbrueckii treatment increased ileal Lactobacillus abundance and bile acid (BA) deconjugation and affected serum and hepatic BA composition. Dietary L. delbrueckii downregulated the gene expression of ileal apical sodium-dependent bile acid transporter (ASBT) and ileal bile acid binding protein (IBABP), and hepatic farnesoid X receptor (FXR), fibroblast growth factor (FGF19), and small heterodimer partner (SHP), but upregulated hepatic high-density lipoprotein receptor (HDLR), low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein-2 (SREBP-2), and cholesterol-7α hydroxylase (CYP7A1) expression. Our results provided in vivo evidence that L. delbrueckii promote ileal BA deconjugation with subsequent fecal TC and TBA extraction by modifying ileal microbiota composition and induce hepatic BA neosynthesis via regulating gut–liver FXR–FGF19 axis.

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Genetic Variation in Liver X Receptor Alpha and Risk of Ischemic Vascular Disease in the General Population

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.111.223867 ◽

2011 ◽

Vol 31 (12) ◽

pp. 2990-2996 ◽

Cited By ~ 3

Author(s):

Stefan Stender ◽

Ruth Frikke-Schmidt ◽

Aristomenis Anestis ◽

Dimitris Kardassis ◽

Amar A. Sethi ◽

...

Keyword(s):

Genetic Variation ◽

General Population ◽

Vascular Disease ◽

Liver X Receptor ◽

Receptor Alpha ◽

Liver X Receptor Alpha

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Relationship between atherogenic index and oxidative stress among patients presented with coronary artery disease in a tertiary care hospital

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl4.4560 ◽

2020 ◽

Vol 11 (SPL4) ◽

pp. 2807-2813

Author(s):

Resmi C R ◽

Kedari G S R ◽

Deepa P K

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

Vitamin C ◽

Density Lipoprotein ◽

Atherogenic Index ◽

Enzymatic Antioxidants ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Lipid Parameters ◽

And Oxidative Stress

CAD is recognized as a multifactorial disease that is influenced by environmental and genetic factors. This study aimed to evaluate the levels of lipid parameters, oxidative stress and antioxidant markers in subjects with CAD compared to their age & sex matched controls and to analyze the relationship between atherogenic Index and oxidative stress among them 62 clinically proved CAD patients and 62 healthy age and sex matched subjects without CAD were selected for this study. 5 ml of fasting venous blood was collected from all the subjects and investigations such as FPG, lipid profile, oxidative markers Malondialdehyde (MDA), F2 isoprostanes (F2iso) and antioxidants glutathione S-transferase (GST), superoxide dismutase (SOD), vitamin-C, vitamin-E were performed. This study showed that levels of lipid parameters total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c) and AI were significantly higher whereas high density lipoprotein cholesterol (HDL-c) were significantly low in CAD patients compared to normal controls. Oxidative stress markers MDA and F2 Isoprostanes level were significantly high, whereas enzymatic antioxidants GST and SOD and non-enzymatic antioxidants Vitamin-C and Vitamin-E levels were significantly low in CAD patients. Oxidative stress markers were found to significantly influence the AI. Results of this study showed that oxidative stress markers F2iso and MDA and antioxidants GST, VIT-C and VIT-E are found to influence the atherogenic index significantly.

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