Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon, 57922, Republic of Korea.
Arch Biochem Biophys. 2022 Sep 30;727:109326. doi: 10.1016/j.abb.2022.109326. Epub 2022 Jun 18.
We aimed to identify the molecular mechanisms behind curcumin's therapeutic benefits for metabolic syndrome (MetS) and its components.
The Comparative Toxicogenomics Database, MIENTURNET, Metascape, GeneMania, and Cytoscape software were critical analytic tools.
Curcumin may have therapeutic effects on MetS and its components via the following genes: NOS3, IL6, INS, and ADIPOQ, particularly PPARG. Curcumin has higher docking scores than other genes with INS and PPARG (docking scores: -8.3 and -5.8, respectively). Physical interactions (56%) were found to be the most prevalent for dyslipidemia, co-expression for hypertension, obesity, T2DM, and MetS. "Galanin receptor pathway", "lipid particles composition", "IL-18 signaling pathway", "response to extracellular stimulus", and "insulin resistance" were listed in the first of the key pathways for MetS, dyslipidemia, hypertension, obesity, and diabetes, respectively. The protein-protein interaction enrichment analysis study also identified "vitamin B12 metabolism," "folate metabolism," and "selenium micronutrient network" as three major molecular pathways linked to MetS targeted by curcumin. PPARG was the key transcription factor that regulated practically all curcumin-targeted genes linked to MetS and its components. Curcumin targeted hsa-miR-155-5p, which has been linked to T2DM, hypertension, and MetS, as well as hsa-miR-130b-3p and hsa-miR-22-3p, which have been linked to dyslipidemia and obesity, respectively. In silico, sponges that regulated hsa-miR-155-5p were developed and evaluated. Curcumin, MetS, and its components have been found to target adipocytes, cardiac myocytes, smooth muscle, the liver, and pancreas. Curcumin's physicochemical properties and pharmacokinetics are closely connected with its therapeutic advantages in MetS and its components due to its high gastrointestinal absorption, drug-likeness, water solubility, and lipophilic nature. Curcumin is a CYP1A9 and CYP3A4 inhibitor. Although curcumin has a low bioavailability, it can be synthesized and administered to increase its pharmacokinetic features.
Curcumin needs to undergo therapeutic optimization and further study into its pharmacological structure before it can be used to treat MetS and its components.
本研究旨在确定姜黄素治疗代谢综合征（MetS）及其各组分的分子机制。
使用比较毒理学基因组数据库、MIENTURNET、Metascape、GeneMania 和 Cytoscape 软件进行关键分析。
姜黄素可能通过以下基因对 MetS 及其各组分发挥治疗作用：NOS3、IL6、INS 和 ADIPOQ，特别是 PPARG。姜黄素与 INS 和 PPARG 的对接评分更高（对接评分：-8.3 和-5.8）。在血脂异常中发现物理相互作用（56%）最为普遍，在高血压、肥胖、T2DM 和 MetS 中发现共表达。Gal 氨酸受体途径、脂质颗粒组成、IL-18 信号通路、对外界刺激的反应和胰岛素抵抗分别在 MetS、血脂异常、高血压、肥胖和糖尿病的关键途径中排名第一。蛋白质-蛋白质相互作用富集分析研究还确定了维生素 B12 代谢、叶酸代谢和硒微量元素网络作为与姜黄素靶向治疗 MetS 相关的三个主要分子途径。PPARG 是调控姜黄素靶向治疗 MetS 及其各组分的几乎所有基因的关键转录因子。姜黄素靶向 hsa-miR-155-5p，该基因与 T2DM、高血压和 MetS 有关，以及 hsa-miR-130b-3p 和 hsa-miR-22-3p，它们分别与血脂异常和肥胖有关。在计算机模拟中，开发并评估了调节 hsa-miR-155-5p 的海绵体。已经发现姜黄素、MetS 及其各组分靶向脂肪细胞、心肌细胞、平滑肌、肝脏和胰腺。由于姜黄素具有较高的胃肠道吸收、类药性、水溶性和亲脂性，因此其理化性质和药代动力学与在 MetS 及其各组分中的治疗优势密切相关。姜黄素是 CYP1A9 和 CYP3A4 的抑制剂。尽管姜黄素的生物利用度较低，但可以通过合成和给药来增加其药代动力学特征。
在将姜黄素用于治疗 MetS 及其各组分之前，需要对其治疗优化和药理学结构进行进一步研究。
