{"title":"Timosaponin AⅢ inhibits ectopic lipid deposition and enhances the browning of white adipose tissue.","authors":"Wenjun Zhao, Xiaoying Wang, Yun Liu, Lu Lu, Yue Ding, Tong Zhang","doi":"10.1016/j.ejphar.2025.177506","DOIUrl":null,"url":null,"abstract":"<p><p>Timosaponin AⅢ(TAⅢ), derived from the Chinese medicinal herb Anemarrhena asphodeloides Bunge, has been reported to have a range of pharmacological effects including improvement of learning and memory deficits, anti-tumor, hypoglycemic effect and anti-hypertension. This study explored the therapeutic effects and preliminary mechanisms of TAⅢ in improving insulin resistance in ob/ob mice. We found that treatment with 10 mg·kg<sup>-1</sup>·d<sup>-1</sup> of TAⅢ reduced the expression of SREBPs and alleviated ectopic lipid deposition by decreasing DAG accumulation in liver. The decrease of DAG further inhibited the membrane translocation of PKC-ε, releasing its inhibition of phosphorylation at Ser307 of IRS1, and ultimately enhancing the AKT signaling response to insulin stimulation. In addition, TAⅢ promoted the browning of iWAT by activating the PGC1α-UCP1 axis on ob/ob mice, thereby enhancing fatty acid oxidation and increasing energy consumption, thus reducing its interference with insulin signaling. TAⅢ worked by enhancing the function of adipose tissue and inhibited lipid synthesis. These actions collectively ameliorated metabolic disturbances associated with insulin resistance. Therefore, we preliminarily concluded that TAⅢ improved metabolic disturbances related to insulin resistance. However, further research is needed,additional studies are necessary to validate these potential mechanisms.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177506"},"PeriodicalIF":4.2000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ejphar.2025.177506","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Timosaponin AⅢ(TAⅢ), derived from the Chinese medicinal herb Anemarrhena asphodeloides Bunge, has been reported to have a range of pharmacological effects including improvement of learning and memory deficits, anti-tumor, hypoglycemic effect and anti-hypertension. This study explored the therapeutic effects and preliminary mechanisms of TAⅢ in improving insulin resistance in ob/ob mice. We found that treatment with 10 mg·kg-1·d-1 of TAⅢ reduced the expression of SREBPs and alleviated ectopic lipid deposition by decreasing DAG accumulation in liver. The decrease of DAG further inhibited the membrane translocation of PKC-ε, releasing its inhibition of phosphorylation at Ser307 of IRS1, and ultimately enhancing the AKT signaling response to insulin stimulation. In addition, TAⅢ promoted the browning of iWAT by activating the PGC1α-UCP1 axis on ob/ob mice, thereby enhancing fatty acid oxidation and increasing energy consumption, thus reducing its interference with insulin signaling. TAⅢ worked by enhancing the function of adipose tissue and inhibited lipid synthesis. These actions collectively ameliorated metabolic disturbances associated with insulin resistance. Therefore, we preliminarily concluded that TAⅢ improved metabolic disturbances related to insulin resistance. However, further research is needed,additional studies are necessary to validate these potential mechanisms.
期刊介绍:
The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems.
The scope includes:
Behavioural pharmacology
Neuropharmacology and analgesia
Cardiovascular pharmacology
Pulmonary, gastrointestinal and urogenital pharmacology
Endocrine pharmacology
Immunopharmacology and inflammation
Molecular and cellular pharmacology
Regenerative pharmacology
Biologicals and biotherapeutics
Translational pharmacology
Nutriceutical pharmacology.