Modulating JAK2/STAT3 signaling by quercetin in Qiling Baitouweng Tang: a potential therapeutic approach for diffuse large B-cell lymphoma

IF 4.3 2区化学 Q2 CHEMISTRY, APPLIED Molecular Diversity Pub Date : 2024-10-05 DOI:10.1007/s11030-024-10999-2

Xin-Zhuo Zhan, Tian-Hua Wei, Chen Huang, Hui Yu, Xiao-Li Chen, Xiang-Tu Kong, Zhi-Hao Shang, Shan-Liang Sun, Meng-Yi Lu, Hai-Wen Ni

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Abstract

Qiling Baitouweng Tang (QLBTWT) is a traditional clinical formula for treating diffuse large B-cell lymphoma (DLBCL), but its molecular action is not fully understood. This research is utilized in silico analysis and liquid chromatography tandem mass spectrometry (LC‒MS/MS) to identify the active constituents of QLBTWT with anti-DLBCL properties and their targets. The study identified 14 compounds, including quercetin, naringenin, and astilbin, as potentially effective against DLBCL. Molecular modeling highlighted the favorable interaction of quercetin with the JAK2 protein. In vitro studies confirmed the ability of quercetin to inhibit DLBCL cell growth and migration while inducing apoptosis and causing G2/M phase cell cycle arrest. Molecular dynamics simulations revealed that quercetin binds to JAK2 as a type II inhibitor. In vivo studies in U2932 xenograft models demonstrated that QLBTWT inhibited tumor growth in a dose-dependent manner, which was associated with the JAK2/STAT3 signaling pathway. Overall, this study elucidates the therapeutic effect of QLBTWT on DLBCL through quercetin-mediated suppression of the JAK2/STAT3 pathway, offering novel therapeutic insights for DLBCL.

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祁苓白头翁汤中的槲皮素可调节 JAK2/STAT3 信号：弥漫大 B 细胞淋巴瘤的潜在治疗方法。

祁苓白头翁汤（QLBTWT）是治疗弥漫性大 B 细胞淋巴瘤（DLBCL）的传统临床方剂，但其分子作用尚不完全清楚。本研究利用硅学分析和液相色谱串联质谱法（LC-MS/MS）鉴定了 QLBTWT 中具有抗 DLBCL 特性的活性成分及其靶点。研究确定了 14 种化合物，包括槲皮素、柚皮苷和芪苈强心素，这些化合物对 DLBCL 具有潜在疗效。分子建模强调了槲皮素与 JAK2 蛋白的良好相互作用。体外研究证实，槲皮素能够抑制 DLBCL 细胞的生长和迁移，同时诱导细胞凋亡并导致 G2/M 期细胞周期停滞。分子动力学模拟显示，槲皮素作为一种 II 型抑制剂与 JAK2 结合。在 U2932 异种移植模型中进行的体内研究表明，QLBTWT 能以剂量依赖的方式抑制肿瘤生长，这与 JAK2/STAT3 信号通路有关。总之，这项研究阐明了QLBTWT通过槲皮素介导的JAK2/STAT3通路抑制对DLBCL的治疗作用，为DLBCL的治疗提供了新的思路。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;