Center for Clinical Medicine Research, The First People's Hospital of Yunnan Province (Affiliated Hospital of Kunming University of Science and Technology), Kunming, 650032, China.
Medical School, Kunming University of Science and Technology, Kunming, 650500, China.
Sci Rep. 2024 May 2;14(1):10114. doi: 10.1038/s41598-024-60859-0.
Wogonin is a natural flavone compound from the plant Scutellaria baicalensis, which has a variety of pharmacological activities such as anti-cancer, anti-virus, anti-inflammatory, and immune regulation. However, the potential mechanism of wogonin remains unknown. This study was to confirm the molecular mechanism of wogonin for acute monocytic leukemia treatment, known as AML-M5. The potential action targets between wogonin and acute monocytic leukemia were predicted from databases. The compound-target-pathway network and protein-protein interaction network (PPI) were constructed. The enrichment analysis of related targets and molecular docking were performed. The network pharmacological results of wogonin for AML-M5 treatment were verified using the THP-1 cell line. 71 target genes of wogonin associated with AML-M5 were found. The key genes TP53, SRC, AKT1, RELA, HSP90AA1, JUN, PIK3R1, and CCND1 were preliminarily found to be the potential central targets of wogonin for AML-M5 treatment. The PPI network analysis, GO analysis and KEGG pathway enrichment analysis demonstrated that the PI3K/AKT signaling pathway was the significant pathway in the wogonin for AML-M5 treatment. The antiproliferative effects of wogonin on THP-1 cells of AML-M5 presented a dose-dependent and time-dependent manner, inducing apoptosis, blocking the cell cycle at the G2/M phase, decreasing the expressions of CCND1, CDK2, and CyclinA2 mRNA, as well as AKT and p-AKT proteins. The mechanisms of wogonin on AML-M5 treatment may be associated with inhibiting cell proliferation and regulating the cell cycle via the PI3K/AKT signaling pathway.
汉黄芩素是一种天然黄酮类化合物，来源于植物黄芩，具有多种药理活性，如抗癌、抗病毒、抗炎和免疫调节。然而，汉黄芩素的潜在机制尚不清楚。本研究旨在确认汉黄芩素治疗急性单核细胞白血病（AML-M5）的分子机制。从数据库中预测汉黄芩素与急性单核细胞白血病之间的潜在作用靶点。构建化合物-靶标-通路网络和蛋白质-蛋白质相互作用网络（PPI）。对相关靶点进行富集分析和分子对接。采用 THP-1 细胞系验证汉黄芩素治疗 AML-M5 的网络药理学结果。发现了与 AML-M5 相关的汉黄芩素 71 个靶基因。初步发现 TP53、SRC、AKT1、RELA、HSP90AA1、JUN、PIK3R1 和 CCND1 等关键基因可能是汉黄芩素治疗 AML-M5 的潜在核心靶标。PPI 网络分析、GO 分析和 KEGG 通路富集分析表明，PI3K/AKT 信号通路是汉黄芩素治疗 AML-M5 的重要通路。汉黄芩素对 AML-M5 的 THP-1 细胞的增殖抑制作用呈剂量依赖性和时间依赖性，诱导细胞凋亡，将细胞周期阻滞在 G2/M 期，降低 CCND1、CDK2 和 CyclinA2 mRNA 以及 AKT 和 p-AKT 蛋白的表达。汉黄芩素治疗 AML-M5 的机制可能与通过 PI3K/AKT 信号通路抑制细胞增殖和调节细胞周期有关。
