2. Academic Validation
  3. Sodium Danshensu alleviates bone cancer pain by inhibiting the osteoclast differentiation and CGRP expression

Sodium Danshensu alleviates bone cancer pain by inhibiting the osteoclast differentiation and CGRP expression

  • Eur J Pharmacol. 2025 Apr 5:992:177296. doi: 10.1016/j.ejphar.2025.177296.
Xiaoxuan Zhang 1,  Xinru Yuan 1,  Xin Li 2,  Haonan Yu 3,  Tingfang Wang 3,  Chuan Zhang 3,  Jingxiang Wu 4,  Xingji You 5
Affiliations

Affiliations

  • 1 School of Medicine, Shanghai University, Shanghai, 200444, China; Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200030, China.
  • 2 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.
  • 3 School of Medicine, Shanghai University, Shanghai, 200444, China.
  • 4 Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200030, China. Electronic address: wjx1132@163.com.
  • 5 School of Medicine, Shanghai University, Shanghai, 200444, China. Electronic address: yoyo1976@shu.edu.cn.
PMID: 39900329 DOI: 10.1016/j.ejphar.2025.177296
Abstract

Context: 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.

Objective: 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.

Results: 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.

Conclusions: SDSS relieves bone Cancer pain by inhibiting osteoclast activity, providing a potential new drug option for Cancer pain patients.

Keywords

Bone cancer pain; ESR1; Network pharmacology; Osteoclast; Sodium Danshensu.

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