Zhao Menglu, Xie Boya, Li Yuxuan, Dong Haiqing, Jiang Sijia, Zhu Tiantian, Wu Xiaolong, Xu Chengchen, Zhang Jian, Sun Shiyi, Li Rui, Xie Yinghai
School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China.
Anhui Shendong Biotechnology Development Co., Ltd., Huainan, China.
Front Pharmacol. 2025 Mar 17;16:1543865. doi: 10.3389/fphar.2025.1543865. eCollection 2025.
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.
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.
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.
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.
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.
随着生活水平的逐步提高，胆结石的发病率越来越高，其中胆固醇结石（CG）是最常见的亚型。因此，我们迫切需要一种更好的治疗胆结石的方法。
本研究旨在评估白藜芦醇（Res）对胆固醇结石形成的影响，并探讨其潜在机制，重点关注其对肝脏过氧化物酶体增殖物激活受体γ（PPAR-γ）表达、胆汁胆固醇饱和度和肝脏胆固醇代谢的调节作用。
将32只雄性C57BL/6小鼠随机分为四组：对照组、模型组、熊去氧胆酸（UDCA）组和Res组。通过灌胃给予Res（100mg/kg/天）和UDCA（100mg/kg/天），持续5周。收集胆囊胆汁、肝脏和胆囊组织，进行胆汁胆固醇晶体分析、胆汁脂质谱分析和组织病理学检查。采用蛋白质免疫印迹法和免疫组织化学法分析PPARγ和B类I型清道夫受体（SR-BI）的蛋白表达水平。
高脂饮食喂养的小鼠胆囊增大（长径和宽径约为对照组的2倍）并形成CG，而白藜芦醇治疗显著减少了结石形成，改善了胆囊扩张，并减轻了胆汁淤积症状。Res通过下调晚期糖基化终产物受体（RAGE）的表达和抑制促炎因子的合成来抑制肝脏炎症。Res减轻了肝脏脂质沉积。它还增强了PPARγ和SR-BI的表达，促进胆固醇外流并降低胆固醇水平，从而预防小鼠CG的形成。
白藜芦醇通过调节肝脏胆固醇代谢、降低胆汁胆固醇饱和度和减轻肝脏炎症，显示出作为预防和治疗胆固醇结石病（CGD）治疗药物的巨大潜力。有必要进一步研究其在人类中的临床适用性。
