{"title":"Calycosin improves insulin resistance by regulating the hsa-miR-324-3p/AKT pathway to inhibit FOXO3a nuclear transfer.","authors":"Junling Zhu, Rilian Lai, Qin Zheng, Shuying Huang, Shenghua Hu, Zhangfei Xu, Huixia Sun","doi":"10.1080/00498254.2025.2558648","DOIUrl":null,"url":null,"abstract":"<p><p>1. To study the effects of calycosin on palmitic acid-induced HepG2 cells, as well as the potential mechanisms of action.</p><p><p>2. Potential targets of calycosin for the alleviation of insulin resistance were predicted by network pharmacology. Glucose concentration in the culture medium was determined by the GOD-POD method. The model of insulin resistance was established by palmitic acid-induced HepG2 cells. Effects of palmitic acid and calycosin on HepG2 cell activity were determined using an MTT assay kit. The expression levels of AKT1 and FOXO3a were detected by western blot. The expression level of hsa-miR-324-3p was detected by RT-qPCR. Dual luciferase reporter assay to detect targeting of AKT1 by hsa-miR-324-3p.</p><p><p>3. AKT1 was predicted and validated as a potential target of calycosin for treatment of insulin resistance. The model of insulin resistance was successfully established by palmitic acid-induced HepG2 cells. Up-regulation of AKT1 expression inhibits FOXO3a entry into the nucleus. Calycosian was demonstrated to concentration-dependently increase the sensitivity of insulin resistance cells to insulin. The hsa-miR-324-3p was proven to exist in insulin-resistant cells. Hsa-miR-324-3p was found to target AKT1 involved in the alleviation of insulin resistance.</p><p><p>4. Calycosin inhibits FOXO3a nuclear translocation by regulating the hsa-miR-324-3p/AKT pathway, thus alleviating insulin resistance.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.2000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Xenobiotica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00498254.2025.2558648","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
1. To study the effects of calycosin on palmitic acid-induced HepG2 cells, as well as the potential mechanisms of action.
2. Potential targets of calycosin for the alleviation of insulin resistance were predicted by network pharmacology. Glucose concentration in the culture medium was determined by the GOD-POD method. The model of insulin resistance was established by palmitic acid-induced HepG2 cells. Effects of palmitic acid and calycosin on HepG2 cell activity were determined using an MTT assay kit. The expression levels of AKT1 and FOXO3a were detected by western blot. The expression level of hsa-miR-324-3p was detected by RT-qPCR. Dual luciferase reporter assay to detect targeting of AKT1 by hsa-miR-324-3p.
3. AKT1 was predicted and validated as a potential target of calycosin for treatment of insulin resistance. The model of insulin resistance was successfully established by palmitic acid-induced HepG2 cells. Up-regulation of AKT1 expression inhibits FOXO3a entry into the nucleus. Calycosian was demonstrated to concentration-dependently increase the sensitivity of insulin resistance cells to insulin. The hsa-miR-324-3p was proven to exist in insulin-resistant cells. Hsa-miR-324-3p was found to target AKT1 involved in the alleviation of insulin resistance.
4. Calycosin inhibits FOXO3a nuclear translocation by regulating the hsa-miR-324-3p/AKT pathway, thus alleviating insulin resistance.
1. 目的：研究毛蕊异黄酮对棕榈酸诱导的HepG2细胞的影响及其可能的作用机制。利用网络药理学方法预测毛蕊异黄酮对胰岛素抵抗的潜在作用靶点。采用GOD-POD法测定培养基中葡萄糖浓度。采用棕榈酸诱导HepG2细胞建立胰岛素抵抗模型。采用MTT法检测棕榈酸和毛蕊异黄酮对HepG2细胞活性的影响。western blot检测AKT1和FOXO3a的表达水平。RT-qPCR检测hsa-miR-324-3p的表达水平。双荧光素酶报告基因检测检测hsa- mir -324-3p靶向AKT1。AKT1被预测并证实是毛蕊异黄酮治疗胰岛素抵抗的潜在靶点。用棕榈酸诱导HepG2细胞成功建立胰岛素抵抗模型。上调AKT1表达抑制FOXO3a进入细胞核。花萼花素被证明可以浓度依赖性地增加胰岛素抵抗细胞对胰岛素的敏感性。hsa-miR-324-3p被证实存在于胰岛素抵抗细胞中。发现Hsa-miR-324-3p靶向AKT1参与胰岛素抵抗的缓解。毛蕊异黄酮通过调控hsa-miR-324-3p/AKT通路抑制FOXO3a核易位，从而减轻胰岛素抵抗。
期刊介绍：
Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
