Zeng Shifan, Liu Benjuan, Ge Rui, Yuan Zhilong, Yang Yunyun, Zhu Weiqiang, Wang Zhuo
Department of Pharmacy, Shanghai Changhai Hospital, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, PR China; College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, PR China.
Department of Pharmacy, Shanghai Changhai Hospital, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, PR China.
Phytomedicine. 2025 Sep;145:157051. doi: 10.1016/j.phymed.2025.157051. Epub 2025 Jul 6.
Lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is a major contributor to poor prognosis. Prunella vulgaris (P. vulgaris), a traditional medicinal herb, has shown potential in inhibiting PTC metastasis, but its molecular mechanism remains unclear.
This study aimed to elucidate the molecular mechanisms by which P. vulgaris exerts its anti-metastatic effects on PTC, focusing on identifying key active compounds and their target genes.
RNA sequencing was used to identify differentially expressed genes (DEGs) between PTC and LNM tissues. Active compounds and targets of P. vulgaris were obtained from TCMSP and BATMAN-TCM and integrated with DEGs to construct a compound-target network. Machine-learning algorithms were applied to identify hub genes related to β-sitosterol (BS). The effects of BS and ADRB2 on cell viability, proliferation, migration, invasion, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were examined in vitro.
696 DEGs and 195 P vulgaris targets were identified, with 91 overlapping genes intersecting DEGs and P. vulgaris targets. Within this network, 17 target genes were associated with BS, and five machine-learning algorithms consistently identified ADRB2 as a central hub. ADRB2 expression was significantly elevated in LNM tissues and closely correlated with clinicopathological features. BS treatment inhibited PTC cell growth and metastasis-related behaviors, which were reversed by ADRB2 overexpression.
BS, an active component of P. vulgaris, inhibits key processes associated with PTC metastasis by targeting ADRB2 and inducing mitochondrial dysfunction. These findings not only provide the first experimental evidence linking BS to ADRB2-mediated anti-metastatic activity in PTC, but also offer a novel integrated approach for identifying therapeutic compounds from traditional herbs.
甲状腺乳头状癌（PTC）中的淋巴结转移（LNM）是导致预后不良的主要因素。夏枯草，一种传统草药，已显示出抑制PTC转移的潜力，但其分子机制仍不清楚。
本研究旨在阐明夏枯草对PTC发挥抗转移作用的分子机制，重点是确定关键活性化合物及其靶基因。
采用RNA测序鉴定PTC组织和LNM组织之间的差异表达基因（DEG）。从中药系统药理学数据库与分析平台（TCMSP）和中药系统生物学数据库（BATMAN-TCM）获取夏枯草的活性化合物和靶点，并与DEG整合以构建化合物-靶标网络。应用机器学习算法鉴定与β-谷甾醇（BS）相关的枢纽基因。在体外检测BS和肾上腺素能受体β2（ADRB2）对细胞活力、增殖、迁移、侵袭、线粒体膜电位（MMP）和活性氧（ROS）的影响。
鉴定出696个DEG和195个夏枯草靶点，其中91个重叠基因同时存在于DEG和夏枯草靶点中。在该网络中，17个靶基因与BS相关，五种机器学习算法一致将ADRB2鉴定为中心枢纽。ADRB2表达在LNM组织中显著升高，且与临床病理特征密切相关。BS处理抑制PTC细胞生长和转移相关行为，而ADRB2过表达可逆转这些作用。
BS是夏枯草的一种活性成分，通过靶向ADRB2并诱导线粒体功能障碍来抑制与PTC转移相关的关键过程。这些发现不仅提供了首个将BS与PTC中ADRB2介导的抗转移活性联系起来的实验证据，还为从传统草药中鉴定治疗性化合物提供了一种新的综合方法。
