Zhang Xiaoxuan, Yuan Xinru, Li Xin, Yu Haonan, Wang Tingfang, Zhang Chuan, Wu Jingxiang, You Xingji
School of Medicine, Shanghai University, Shanghai, 200444, China; Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200030, China.
Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200030, China; School of Medical Instrument and Food Engineering USST, University of Shanghai for Science and Technology, Shanghai, 200093, China.
Eur J Pharmacol. 2025 Apr 5;992:177296. doi: 10.1016/j.ejphar.2025.177296. Epub 2025 Feb 1.
The morbidity of bone cancer pain (BCP) is on the rise, yet current treatments have limited analgesic efficacy. Sodium Danshensu (SDSS), or sodium 3-(3,4-dihydroxyphenyl)-DL-lactate, exhibits anti-inflammatory, anti-osteoporotic properties. Current research shows that bone cancer pain is closely related to the development of osteoclasts.
To investigate the analgesic effects of SDSS on BCP in mice and explore the underlying mechanisms.
MATERIALS & METHODS: Nociceptive behaviors in BCP mice were evaluated by paw withdrawal threshold (PWT) and limb using score (LUS). Network pharmacology, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and molecular docking identified potential targets. Histological analyses, Western blot, RT-qPCR, ELISA, and immunofluorescence staining were performed on mice femurs.
SDSS significantly increased PWT and LUS in BCP mice. Forty-three common targets were identified, with the estrogen signaling pathway showing the highest enrichment. Molecular docking analysis suggested a potential binding affinity between SDSS and ESRα. SDSS administration up-regulated ESRα expression and down-regulated RANKL, RANK, NFATc1, c-fos, TRAP, and Cathepsin K (CTSK). In addition, SDSS suppressed the abnormal increase of calcitonin gene-related peptide-positive (CGRP) neural budding and expression in nerve endings, effects which were reversed by ESRa inhibitor ICI-182780.
SDSS relieves bone cancer pain by inhibiting osteoclast activity, providing a potential new drug option for cancer pain patients.
骨癌痛（BCP）的发病率正在上升，但目前的治疗方法镇痛效果有限。丹参素钠（SDSS），即3-(3,4-二羟基苯基)-DL-乳酸钠，具有抗炎、抗骨质疏松特性。目前的研究表明，骨癌痛与破骨细胞的发育密切相关。
研究SDSS对小鼠骨癌痛的镇痛作用，并探讨其潜在机制。
通过爪部缩足阈值（PWT）和肢体使用评分（LUS）评估骨癌痛小鼠的伤害性反应行为。采用网络药理学、基因本体（GO）富集分析、京都基因与基因组百科全书（KEGG）通路注释和分子对接来确定潜在靶点。对小鼠股骨进行组织学分析、蛋白质免疫印迹法、逆转录-定量聚合酶链反应、酶联免疫吸附测定和免疫荧光染色。
SDSS显著提高了骨癌痛小鼠的PWT和LUS。共鉴定出43个共同靶点，其中雌激素信号通路的富集程度最高。分子对接分析表明SDSS与雌激素受体α（ESRα）之间具有潜在的结合亲和力。给予SDSS上调了ESRα的表达，下调了核因子κB受体活化因子配体（RANKL）、核因子κB受体活化因子（RANK）、活化T细胞核因子1（NFATc1）、原癌基因c-fos、抗酒石酸酸性磷酸酶（TRAP）和组织蛋白酶K（CTSK）的表达。此外，SDSS抑制了降钙素基因相关肽阳性（CGRP）神经芽生的异常增加以及神经末梢中CGRP的表达，而雌激素受体α抑制剂ICI-182780可逆转这些作用。
SDSS通过抑制破骨细胞活性缓解骨癌痛，为癌症疼痛患者提供了一种潜在的新药选择。
