Resveratrol prevents gallstones in mice fed on a high fat diet via regulating PPAR-γ and SR-BI.
Study Goal
The researchers aimed to evaluate resveratrol's effects on cholesterol gallstone formation and its underlying mechanisms, focusing on PPAR-γ expression, bile cholesterol saturation, and hepatic cholesterol metabolism.
Results Summary
Resveratrol significantly reduced gallstone formation, improved gallbladder dilatation, reduced cholestasis symptoms, suppressed hepatic inflammation, alleviated liver lipid deposition, and enhanced PPARγ and SR-BI expression, promoting cholesterol efflux.
Population
Male C57BL/6 mice fed a high-fat diet.
Effective Dosage
100 mg/kg/day administered via gavage.
Duration
5 weeks.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
high fat diet | increase | gallbladder size | male C57BL/6 mice | about 2 times in both long and width diameters compared to control group | resulted in larger gallbladder | #1 |
high fat diet | increase | cholesterol gallstone (CG) formation | male C57BL/6 mice | - | resulted in | #2 |
resveratrol (Res) | decrease | gallstone formation | male C57BL/6 mice | - | significantly reduced | #3 |
resveratrol (Res) | decrease | gallbladder dilatation | male C57BL/6 mice | - | improved | #4 |
resveratrol (Res) | decrease | cholestasis symptoms | male C57BL/6 mice | - | declined | #5 |
resveratrol (Res) | decrease | hepatic inflammation | male C57BL/6 mice | - | suppressed | #6 |
resveratrol (Res) | decrease | receptor for advanced glycation end products (RAGE) expression | male C57BL/6 mice | - | downregulating | #7 |
resveratrol (Res) | decrease | synthesis of proinflammatory factors | male C57BL/6 mice | - | inhibiting | #8 |
resveratrol (Res) | decrease | liver lipid deposition | male C57BL/6 mice | - | alleviated | #9 |
resveratrol (Res) | increase | PPARγ expression | male C57BL/6 mice | - | enhanced | #10 |
resveratrol (Res) | increase | SR-BI expression | male C57BL/6 mice | - | enhanced | #11 |
resveratrol (Res) | increase | cholesterol efflux | male C57BL/6 mice | - | promoting | #12 |
resveratrol (Res) | decrease | cholesterol levels | male C57BL/6 mice | - | lowering | #13 |
resveratrol (Res) | decrease | CG formation | male C57BL/6 mice | - | preventing | #14 |
BACKGROUND: With the gradual improvement of living standards, the incidence of gallstones is getting higher and higher, and cholesterol gallstones (CG) are the most prevalent subtype. Therefore, we urgently need a better way to treat gallstones. OBJECTIVE: This study aimed to evaluate the effects of resveratrol (Res) on cholesterol gallstone formation and explore its underlying mechanisms, focusing on its modulation of hepatic peroxisome proliferator-activated receptor γ (PPAR-γ) expression, bile cholesterol saturation, and hepatic cholesterol metabolism. METHODS: Thirty-two male C57BL/6 mice were randomly divided into four groups: control, model, ursodeoxycholic acid (UDCA), and Res groups. Res (100 mg/kg/day) and UDCA (100 mg/kg/day) were administered via gavage for 5 weeks. Gallbladder bile, liver, and gallbladder tissues were collected for bile cholesterol crystal analysis, bile lipid profiling, and histopathological examination. Protein expression levels of PPARγ and scavenger receptor class B type I (SR-BI) were analyzed using Western blotting and immunohistochemistry. RESULTS: Mice fed on a high fat diet resulted in larger gallbladder (about 2 times in both long and width diameters compared to control group) and CG formation, while resveratrol treatment significantly reduced gallstone formation, improved gallbladder dilatation, and declined cholestasis symptoms. Res suppressed hepatic inflammation by downregulating the receptor for advanced glycation end products (RAGE) expression and inhibiting the synthesis of proinflammatory factors. Res alleviated liver lipid deposition. It also enhanced PPARγ and SR-BI expression, promoting cholesterol efflux and lowering cholesterol levels, thereby preventing CG formation in mice. CONCLUSION: Resveratrol demonstrates significant potential as a therapeutic agent for the prevention and treatment of cholesterol gallstone disease (CGD) by modulating hepatic cholesterol metabolism, reducing bile cholesterol saturation, and alleviating hepatic inflammation. Further studies are warranted to explore its clinical applicability in humans.