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钩藤碱通过调节炎症级联反应和抑制3-羟基-3-甲基戊二酰辅酶A还原酶来逆转高脂饮食诱导的肥胖大鼠的肥胖状态。

Rhynchophylline Reverses Obesity in High-Fat Diet-Induced Obese Rats by Regulating the Inflammatory Cascade and Blocking 3‑hydroxy-3-methylglutaryl Coenzyme A Reductase.

作者信息

Bai Feng, Tan Jun, Sun Daqing, Liu Wenshu, Tripathi Alok Shiomurti

机构信息

Department of Children's Healthcare, Northwest Women's and Children's Hospital, Xi'an 710061, China.

Healthcare Clinic, Qingdao Municipal Hospital, Qingdao 266071, China.

出版信息

ACS Omega. 2025 Jul 2;10(27):28721-28727. doi: 10.1021/acsomega.4c09379. eCollection 2025 Jul 15.

Abstract

Obesity is a metabolic disorder that could be the reason for the development of several disorders, and its management is necessary. The investigation evaluated the beneficial effect of rhynchophylline on high-fat diet (HFD)-induced obese rats. Obesity was induced with the HFD for 4 weeks, and rhynchophylline at 50 and 100 mg/kg was administered intraperitoneally (i.p.) for the next 4 weeks in the respective groups. Blood glucose and lipid profiles were estimated in rhynchophylline-treated HFD-induced obese rats. Levels of cytokines, reactive oxygen species (ROS), and oxidative stress parameters were estimated in the liver tissue and blood of all the groups of rats. The weight of adipose tissue and other organs, such as the liver and pancreas, was measured in the rats. The binding affinity of rhynchophylline with 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, ) was estimated through a docking study. Treatment with rhynchophylline ameliorated the altered levels of glucose and lipid profiles in the serum of the obese rats. The weight of adipose tissue isolated from different regions of the body was reduced in the rhynchophylline-treated group compared to that in the obese group. There was a significant reduction of oxidative stress in the rhynchophylline-treated group compared with the obese group of rats. The in silico study showed that rhynchophylline binds with HMG-CoA reductase with a binding energy of -8.37 kcal/mol. In conclusion, data from the report reveal that rhynchophylline reduces obesity by promoting the conversion of white adipose tissue (WAT) to brown adipose tissue (BAT), as it interacts with HMG-CoA reductase in HFD-induced obese rats.

摘要

肥胖是一种代谢紊乱疾病,可能是多种疾病发生的原因,因此对其进行管理很有必要。该研究评估了钩藤碱对高脂饮食(HFD)诱导的肥胖大鼠的有益作用。用高脂饮食诱导肥胖4周,随后在接下来的4周内,分别对相应组的大鼠腹腔注射(i.p.)50和100mg/kg的钩藤碱。对钩藤碱治疗的高脂饮食诱导肥胖大鼠的血糖和血脂水平进行了评估。对所有大鼠组的肝脏组织和血液中的细胞因子、活性氧(ROS)和氧化应激参数水平进行了评估。测量了大鼠脂肪组织以及肝脏和胰腺等其他器官的重量。通过对接研究评估了钩藤碱与3-羟基-3-甲基戊二酰辅酶A还原酶(HMG-CoA还原酶)的结合亲和力。钩藤碱治疗改善了肥胖大鼠血清中葡萄糖和脂质水平的改变。与肥胖组相比,钩藤碱治疗组从身体不同部位分离出的脂肪组织重量减轻。与肥胖大鼠组相比,钩藤碱治疗组的氧化应激显著降低。计算机模拟研究表明,钩藤碱与HMG-CoA还原酶结合,结合能为-8.37 kcal/mol。总之,该报告的数据显示,在高脂饮食诱导的肥胖大鼠中,钩藤碱通过促进白色脂肪组织(WAT)向棕色脂肪组织(BAT)的转化来减轻肥胖,因为它与HMG-CoA还原酶相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af2/12268723/1adc5e67c615/ao4c09379_0001.jpg

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