Vitexin alleviates lipid metabolism disorders and hepatic injury in obese mice through the PI3K/AKT/mTOR/SREBP-1c pathway

IF 5.9 2区 医学 Q1 CHEMISTRY, MEDICINAL European Journal of Medicinal Chemistry Pub Date : 2025-04-05 Epub Date: 2025-02-07 DOI:10.1016/j.ejmech.2025.117379
Bo Liu , Ziqing Yao , Lin Song , Chen Sun , Changhong Shen , Fang Cheng , Zefang Cheng , Ruoqi Zhang , Rong Liu
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Abstract

Obesity is recognized as a metabolic disorder, and its treatment and management pose ongoing challenges worldwide. Hawthorn, a traditional Chinese herb used to alleviate digestive issues and reduce blood lipid levels, has unclear mechanisms of action regarding its active components in the treatment of obesity. This study investigated the anti-obesity effects of vitexin, a major flavonoid compound found in hawthorn, in high-fat diet (HFD)-induced C57BL/6 mice. The results demonstrated that vitexin significantly reduced body weight, liver weight, blood lipid levels, and inflammatory markers in obese mice, while also inhibiting hepatic lipid accumulation. Mechanistic studies revealed that vitexin likely suppresses adipogenesis by modulating the PI3K-AKT signaling pathway, as evidenced by reduced expression of PI3K, phosphorylated AKT, phosphorylated mTOR, and SREBP-1c in the livers of vitexin-treated obese mice. Additionally, vitexin inhibited NFκB expression by regulating IκBα phosphorylation, thereby alleviating obesity-induced liver injury. These findings suggest that vitexin may be the primary active component in hawthorn responsible for reducing blood lipid levels, highlighting its potential in the treatment of obesity and its associated metabolic disorders.

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牡荆素通过PI3K/AKT/mTOR/SREBP-1c通路缓解肥胖小鼠脂质代谢紊乱和肝损伤。
肥胖被认为是一种代谢紊乱,其治疗和管理在世界范围内构成了持续的挑战。山楂是一种用于缓解消化问题和降低血脂水平的传统中药,其有效成分治疗肥胖的作用机制尚不清楚。研究了山楂中黄酮类化合物牡荆素对高脂饮食(HFD)诱导的C57BL/6小鼠的抗肥胖作用。结果表明,牡荆素显著降低肥胖小鼠的体重、肝脏重量、血脂水平和炎症标志物,同时抑制肝脏脂质积累。机制研究表明,牡荆素可能通过调节PI3K-AKT信号通路抑制脂肪形成,这可以通过降低牡荆素治疗的肥胖小鼠肝脏中PI3K、磷酸化AKT、磷酸化mTOR和SREBP-1c的表达来证明。此外,牡荆素通过调节i - κ b α磷酸化抑制NFκB的表达,从而减轻肥胖引起的肝损伤。这些发现表明,牡荆素可能是山楂中负责降低血脂水平的主要活性成分,突出了其在治疗肥胖及其相关代谢紊乱方面的潜力。
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来源期刊
CiteScore
11.70
自引率
9.00%
发文量
863
审稿时长
29 days
期刊介绍: The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.
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