通过调节由CYP7B1介导的替代胆酸合成途径,塞拉斯可以改善与脂肪肝相关的代谢功能障碍
Meifen Hu1, Jingtao Yang1, Yuxuan Chen1
1Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
概括
通过恢复胆汁酸 (BA) 代谢,塞拉斯 (CEL) 有效地治疗与代谢功能失调相关的脂肪肝炎 (MASH). 这种天然化合物通过FXR/LXR-CYP7B1轴重新激活了替代的BA合成途径,为MASH提供了一种新的治疗方法.
科学领域:
- 肝病学
- 代谢疾病
- 药理学
背景情况:
- 代谢功能障碍相关的脂肪肝炎 (MASH) 是一种进展性肝病,其特征是脂肪炎,炎症和纤维化.
- 天然化合物塞拉斯特罗尔 (CEL) 对MASH具有前临床的前景,但其在胆酸 (BA) 代谢中的机制尚不清楚.
研究的目的:
- 研究CEL对MASH的治疗效果.
- 阐明CEL的作用机制,重点关注替代BA合成途径.
主要方法:
- 使用西方和高脂肪饮食建立了MASH小鼠模型.
- 通过肝功能,组织病理学,脂质水平,蛋白质学和代谢学来评估CEL的疗效.
- 网络药理学,转录学和分子对接确定并验证了CEL在HepG2细胞中的分子点.
主要成果:
- 在MASH模型中,CEL改善了肝脏形态,使脂质代谢正常化,并减少了肝脏损伤.
- 通过增加12α-化与非12-OH-BA的比率,CEL纠正了破坏BA的平衡.
- 通过激活FXR/ LXR信号,CEL重新激活了替代的BA合成途径,并对CYP7B1进行上调.
结论:
- 塞拉斯托尔是一种新的MASH治疗方法.
- CEL针对FXR/LXR-CYP7B1轴恢复替代BA合成和新陈代谢平衡.
- 这项研究为CEL在MASH干预中的使用提供了机制基础.
相关概念视频
Hepatic Drug Excretion: Enterohepatic Cycling
1.7K
Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
1.7K
Chronic Pancreatitis II: Collaborative Care
128
The management of chronic pancreatitis is multifaceted, involving a comprehensive approach that includes thorough assessment, diagnostic testing, and a variety of management strategies.
Assessment:
Assessment:
128
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
869
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
869
Hepatic Drug Excretion: Influencing Factors
216
The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
216
Lipid Catabolism
165
Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
165
Overview of Fatty Acid Metabolism
31.7K
Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
31.7K


