scholarly journals Protective Effects of Yinchenhao Decoction on Cholesterol Gallstone in Mice Fed a Lithogenic Diet by Regulating LXR, CYP7A1, CYP7B1, and HMGCR Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yong Meng ◽  
Ke Meng ◽  
Xin Zhao ◽  
Donghua Li ◽  
Qiaoying Gao ◽  
...  
Keyword(s):  
Cholesterol Gallstone ◽  
Saturation Index ◽  
Gallstone Formation ◽  
Intragastric Administration ◽  
Protective Effects ◽  
Biochemical Tests ◽  
Lithogenic Diet ◽  
Preventive Drug ◽  
Cholesterol Saturation Index ◽  
Bile Cholesterol

The study attempted to elucidate whether lipid genes are closely associated with lipid metabolic abnormalities during the lithogenic time and how Yinchenhao Decoction (YCHD) works on the transcriptions of lipid genes against cholesterol gallstone model. C57BL/6J mice fed on lithogenic diet (LD) were used for model establishment and randomized into 5 groups. All groups received LD for different weeks with isometrically intragastric administration of YCHD or NS. Biochemical tests were measured and liver tissues were harvested for histological and genetic detection. It was found that all groups with increasing LD showed a following tendency of gallstone incidence, bile cholesterol, phospholipids, total bile acid, and cholesterol saturation index (CSI). Conversely, YCHD could significantly normalize the levels of gallstone incidence, bile lipids, and CSI (CSI<1). As lithogenic time progressed, ABCG5, ABCG8, PPAR-α, and ABCB4 were upregulated, and SREBP2, CYP7A1, and CYP7B1 were downregulated, while CYP7A1, CYP7B1, LXR, and HMGCR mRNA were increased 3-fold under the administration of YCHD. It was concluded that abnormal expressions of the mentioned genes may eventually progress to cholesterol gallstone. CYP7A1, CYP7B1, LXR, and HMGCR mRNA may be efficient targets of YCHD, which may be a preventive drug to reverse liver injury, normalize bile lipids, facilitate gallstone dissolution, and attenuate gallstone formation.

Fenugreek seeds reduce atherogenic diet-induced cholesterol gallstone formation in experimental mice

2009 ◽  
Vol 87 (11) ◽  
pp. 933-943 ◽  
Author(s):  
R.L.R. Reddy ◽  
K. Srinivasan
Keyword(s):  
Cholesterol Metabolism ◽  
Cholesterol Gallstone ◽  
Saturation Index ◽  
Gallstone Formation ◽  
Atherogenic Diet ◽  
High Cholesterol ◽  
Cholesterol Gallstones ◽  
Lithogenic Diet ◽  
Fenugreek Seed ◽  
Cholesterol Saturation Index

Dietary hypocholesterolemic adjuncts may have a beneficial role in the prevention and treatment of cholesterol gallstones (CGS). In this investigation, fenugreek (Trigonella foenum-graecum) seed was evaluated for this potential on the experimental induction of CGS in laboratory mice. CGS was induced by maintaining mice on a lithogenic diet (0.5% cholesterol) for 10 weeks. Fenugreek seed powder was included at 5%, 10%, and 15% of this lithogenic diet. Dietary fenugreek significantly lowered the incidence of CGS in these mice; the incidence was 63%, 40%, and 10% in the 5%, 10%, and 15% fenugreek groups, respectively, compared with 100% in the lithogenic control. The antilithogenic influence of fenugreek is attributable to its hypocholesterolemic effect. Serum cholesterol level was decreased by 26%–31% by dietary fenugreek, while hepatic cholesterol was lowered by 47%–64% in these high cholesterol-fed animals. Biliary cholesterol was 8.73–11.2 mmol/L as a result of dietary fenugreek, compared with 33.6 mmol/L in high-cholesterol feeding without fenugreek. Cholesterol saturation index in bile was reduced to 0.77–0.99 in fenugreek treatments compared with 2.57 in the high-cholesterol group. Thus, fenugreek seed offers health-beneficial antilithogenic potential by virtue of its favourable influence on cholesterol metabolism.

Anti-cholelithogenic effect of dietary tender cluster beans (Cyamopsis tetragonoloba) on the formation of cholesterol gallstones in mice

2014 ◽  
Vol 39 (2) ◽  
pp. 152-157 ◽  
Author(s):  
Chikkanna K. Raghavendra ◽  
Krihnapura Srinivasan
Keyword(s):  
Cholesterol Gallstone ◽  
Saturation Index ◽  
Liver Cholesterol ◽  
Cyamopsis Tetragonoloba ◽  
Cholesterol Gallstones ◽  
Lithogenic Diet ◽  
Cholesterol Saturation ◽  
Freeze Dried ◽  
Phospholipid Ratio ◽  
Cholesterol Saturation Index

Providing a lithogenic diet that contains 0.5% cholesterol to experimental mice for 10 weeks resulted in cholesterol supersaturation in gallbladder bile, which induced the formation of cholesterol gallstones. In this study, to evaluate the anti-cholelithogenic potential of dietary tender cluster bean, a freeze-dried powder of the test legume was included in the lithogenic diet at 5%, 10%, and 15%. Dietary cluster beans reduced the cholesterol gallstone incidence by 43%, 46%, and 58% at the respective doses. Dietary cluster beans markedly reduced biliary cholesterol and, hence, the cholesterol saturation index. This was corroborated by the beneficial modification of the cholesterol/phospholipid ratio and the cholesterol/bile acid ratio in the bile. Dietary cluster beans countered the alterations in serum and liver cholesterol and lipid profiles caused by the lithogenic diet. Thus, dietary tender cluster beans exerted an anti-cholelithogenic influence by decreasing cholesterol hypersecretion into bile and, hence, the cholesterol saturation index, decreasing the formation of lithogenic bile in experimental mice.

scholarly journals Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice

2000 ◽  
Vol 4 (1) ◽  
pp. 59-65 ◽  
Author(s):  
BEVERLY PAIGEN ◽  
NICHOLAS J. SCHORK ◽  
KAREN L. SVENSON ◽  
YIN-CHAI CHEAH ◽  
JIAN-LONG MU ◽  
...  
Keyword(s):  
Quantitative Trait ◽  
Congenic Strain ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Gallstone Formation ◽  
Quantitative Trait Loci Mapping ◽  
Cholesterol Gallstones ◽  
Lithogenic Diet ◽  
The Difference ◽  
Trait Locus

Quantitative trait locus (QTL) mapping was used to locate genes that determine the difference in cholesterol gallstone disease between the gallstone-susceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallstone weight was determined in 231 male (AKR × C57L) F1× AKR backcross mice fed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at ∼20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit56 and was confirmed by constructing a congenic strain, AK.L- Lith1s. Another locus, Lith2, mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L- Lith2s. Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation.

scholarly journals Molecular Mechanisms Underlying the Link between Nuclear Receptor Function and Cholesterol Gallstone Formation

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mary Carmen Vázquez ◽  
Attilio Rigotti ◽  
Silvana Zanlungo
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Gallstone Formation ◽  
Receptor Function ◽  
Prevalent Disease ◽  
Bile Cholesterol

Cholesterol gallstone disease is highly prevalent in western countries, particularly in women and some specific ethnic groups. The formation of water-insoluble cholesterol crystals is due to a misbalance between the three major lipids present in the bile: cholesterol, bile salts, and phospholipids. Many proteins implicated in biliary lipid secretion in the liver are regulated by several transcription factors, including nuclear receptors LXR and FXR. Human and murine genetic, physiological, pathophysiological, and pharmacological evidence is consistent with the relevance of these nuclear receptors in gallstone formation. In addition, there is emerging data that also suggests a role for estrogen receptor ESR1 in abnormal cholesterol metabolism leading to gallstone disease. A better comprehension of the role of nuclear receptor function in gallstone formation may help to design new and more effective therapeutic strategies for this highly prevalent disease condition.

scholarly journals Gallstone Formation Follows a Different Trajectory in Bariatric Patients Compared to Nonbariatric Patients

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 682
Author(s):  
Sylke Haal ◽  
Maimoena S. S. Guman ◽  
Yair I. Z. Acherman ◽  
Johannes P. G. Jansen ◽  
Michel van Weeghel ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Saturation Index ◽  
Gallstone Formation ◽  
Gallbladder Bile ◽  
Gallbladder Emptying ◽  
Cholesterol Gallstones ◽  
Interesting Pattern ◽  
Lipid Species ◽  
Cholesterol Saturation Index ◽  
Bariatric Patients

Since obese patients form cholesterol gallstones very rapidly after bariatric surgery, in patients who did not form gallstones during preceding years, we hypothesized that gallstone formation follows a different trajectory in bariatric patients compared to nonbariatric patients. We therefore analyzed the lipid composition of gallbladder bile derived from 18 bariatric gallstone patients and 17 nonbariatric gallstone patients (median (IQR) age, 46.0 (28.0–54.0) years; 33 (94%) female) during laparoscopic cholecystectomy using an enzymatic and lipidomics approach. We observed a higher concentration of total lipids (9.9 vs. 5.8 g/dL), bile acids (157.7 vs. 81.5 mM), cholesterol (10.6 vs. 5.4 mM), and phospholipids (30.4 vs. 21.8 mM) in bariatric gallstone patients compared to nonbariatric gallstone patients. The cholesterol saturation index did not significantly differ between the two groups. Lipidomics analysis revealed an interesting pattern. Enhanced amounts of a number of lipid species were found in the gallbladder bile of nonbariatric gallstone patients. Most striking was a fivefold higher amount of triglyceride. A concomitant ninefold increase of apolipoprotein B was found, suggesting secretion of triglyceride-rich lipoproteins (TRLs) at the canalicular pole of the hepatocyte in livers from nonbariatric gallstone patients. These findings suggest that gallstone formation follows a different trajectory in bariatric patients compared to nonbariatric patients. Impaired gallbladder emptying might explain the rapid gallstone formation after bariatric surgery, while biliary TRL secretion might contribute to gallstone formation in nonbariatric patients.

scholarly journals Sterol carrier protein 2 participates in hypersecretion of biliary cholesterol during gallstone formation in genetically gallstone-susceptible mice

1998 ◽  
Vol 336 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Michael FUCHS ◽  
Frank LAMMERT ◽  
David Q.-H. WANG ◽  
Beverly PAIGEN ◽  
Martin C. CAREY ◽  
...  
Keyword(s):  
Steady State ◽  
Cholesterol Gallstone ◽  
Gallstone Formation ◽  
Carrier Protein ◽  
Mrna Levels ◽  
Sterol Carrier Protein ◽  
Biliary Cholesterol ◽  
Lithogenic Diet ◽  
Sterol Carrier Protein 2 ◽  
Akr Mice

In inbred mice, susceptibility to cholesterol gallstone disease is conferred by Lith genes, which in part promote hypersecretion of cholesterol into bile in response to a high-fat/cholesterol/cholic acid (lithogenic) diet. Because cytosolic sterol carrier protein 2 (SCP2) is believed to participate in cellular cholesterol trafficking and is elevated in the liver cytosol of cholesterol gallstone patients, we defined the hepatic expression of SCP2 during cholesterol gallstone formation in gallstone-susceptible C57L and gallstone-resistant AKR mice fed the lithogenic diet. Steady-state cytosolic SCP2 levels in C57L, but not AKR mice increased as a function of time and were correlated positively with biliary cholesterol hypersecretion, cholesterol saturation indices of gall-bladder biles and the appearance of liquid and solid cholesterol crystals leading to gallstone formation. Steady-state mRNA levels increased co-ordinately, consistent with regulation of SCP2 expression at the transcriptional level. Our results suggest that overexpression of SCP2 contributes to biliary cholesterol hypersecretion and the pathogenesis of gallstones in genetically susceptible mice. Because of the different chromosomal localizations of the Lith and Scp2 genes, we postulate that Lith genes control SCP2 expression indirectly.

Gallbladder prostaglandins and lysophospholipids as mediators of mucin secretion during cholelithiasis

1986 ◽  
Vol 251 (5) ◽  
pp. G701-G709 ◽  
Author(s):  
W. W. LaMorte ◽  
J. T. LaMont ◽  
W. Hale ◽  
M. L. Booker ◽  
T. E. Scott ◽  
...  
Keyword(s):  
Cholesterol Gallstone ◽  
Early Stage ◽  
Gallstone Formation ◽  
Prairie Dogs ◽  
Crystal Formation ◽  
Cholesterol Feeding ◽  
Culture Studies ◽  
Gallbladder Mucosa ◽  
Lithogenic Diet ◽  
Dose Dependent

Mucin hypersecretion from the gallbladder epithelium contributes to cholesterol gallstone formation by accelerating the nucleation of cholesterol-supersaturated bile. Prostaglandins (PGs) and lysophosphatidylcholine (LPC) have both been implicated as potential mediators of mucin hypersecretion, but their roles are unclear. We fed prairie dogs a lithogenic diet (0.34% cholesterol), and after 1, 2, 4, or 6 wk of cholesterol feeding, we measured glycoprotein and LPC concentrations in bile and PG synthesis in gallbladder and liver slices. Hypercholesterolemia and cholesterol supersaturation of bile occurred after 1 wk of cholesterol feeding, but marked crystal formation was delayed until 4 wk, when glycoprotein concentrations became markedly elevated. Glycoprotein hypersecretion was preceded by increased synthesis of PGF2 alpha (P less than 0.002), PGE2 (P less than 0.001), prostacyclin (P less than 0.05), and thromboxane (P = 0.07) in the gallbladder after only 2 wk of cholesterol feeding, but PG synthesis in the liver remained unchanged (P greater than 0.14). LPC concentrations in gallbladder bile also increased at 2 wk (P less than 0.02), but LPC in hepatic bile was unchanged (P = 0.35). In organ culture studies, LPC caused a dose-dependent stimulation of [3H]glycoprotein release from guinea pig gallbladder mucosa that could not be explained solely by LPC's detergent properties. We conclude that gallbladder PG synthesis and LPC production are increased at an early stage of cholesterol gallstone formation in the prairie dog model. These changes probably play a significant role in gallstone pathogenesis, since they mediate hypersecretion of gallbladder mucin and thus favor the nucleation of cholesterol-supersaturated bile.

scholarly journals Alleviation of Cholesterol Gallstones by Lactobacillus Targeting the Gut Microbiota Depends on Global Farnesoid X Receptor-Mediated Bile Acid Metabolism

2020 ◽  
Author(s):  
Xinjian Wan ◽  
Xin Ye ◽  
Qian Zhuang ◽  
Zhixia Dong ◽  
Xiaoxin Wang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Lactobacillus Reuteri ◽  
Cholesterol Gallstone ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Protective Effects ◽  
Lithogenic Diet ◽  
Cytochrome P450 Family

Abstract Background Cholesterol gallstone (CGS) disease is characterized by an imbalance in bile acid (BA) metabolism and is closely associated with gut microbiota disorders. However, the role and mechanism by which probiotics targeting the gut microbiota attenuate CGS are still unknown. In this study, Lactobacillus reuteri CGMCC 17942 (LR) and L. plantarum CGMCC 14407 (LP) were individually administered to lithogenic diet (LD)-fed mice at a dosage of 109 CFU/day for 8 weeks. Results Both Lactobacillus strains significantly reduced LD-induced gallstones, hepatic steatosis, and hyperlipidemia. These strains modulated serum BA profiles, with significantly decreased conjugated primary BA taurine-β-muricholic acid (T-β-MCA), an FXR antagonist. At the molecular level, LR and LP increased Farnesoid X Receptor (FXR) expression in the liver but not in the ileum, increased the levels of ileum and liver fibroblast growth factor 15 (FGF15) and liver FGFR4, small heterodimer partner (SHP), and subsequently reduced cholesterol 7α-hydroxylase (CYP7A1) and cytochrome P450 family 7 subfamily B polypeptide 1 (CYP7B1) to inhibit BA synthesis in the liver. At the same time, the two strains enhanced BA transport by increasing the levels of multidrug-resistance-associated protein homologs (MRP) 3/4, multidrug-resistance-associated protein homologs (MRP) 3/4, hepatic multidrug resistance protein (MDR2) and bile salt export pump (BSEP) mRNA in the liver. In addition, both LR and LP reduced LD-associated gut microbiota dysbiosis. LR increased the relative abundance of Muribaculaceae, while LP increased that of Akkermansia. The changed gut microbiota was significantly negatively correlated with the grade and incidence of gallstones, hyperlipidemia, the level of T-β-MCA in serum, or the gene expression levels of Fxr in liver. Furthermore, the protective effects of the two strains were abolished by a global but not intestinal-specific FXR antagonist. Conclusions Taken together, our results suggested that Lactobacillus might relieve gallstones through FXR-dependent regulation of BA synthesis and transport.

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