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Phytomedicine

Phytomedicine

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Salidroside alleviates bone cancer pain by inhibiting Th17/Treg imbalance through the AMPK/SIRT1 pathway

Published:19 June 2025 DOI: 10.1016/j.phymed.2025.157000
Kesong Zheng , Chengwei Yang , Mingming Han , Fang Kang , Juan Li

Abstract

Background

Bone cancer pain (BCP) remains a significant clinical challenge with poorly understood mechanisms. While Th17 and Treg cells have been implicated in pain pathways, their specific roles in BCP pathogenesis require further investigation. Salidroside (SAL), a natural compound with anti-inflammatory properties, shows potential for pain management but its mechanism in BCP is unclear.

Purpose

This study aimed to investigate SAL's analgesic effects in BCP and elucidate its mechanism of action through the AMPK/SIRT1 pathway and Th17/Treg cell regulation.

Study design

Experimental animal study using a well-established BCP mouse model with pharmacological interventions and cellular/molecular analyses.

Methods

C57BL/6 mice were used to establish a BCP model via tumor cell implantation. Behavioral tests assessed mechanical allodynia and thermal hyperalgesia. Flow cytometry analyzed spinal cord Th17/Treg populations, while Western blotting evaluated AMPK/SIRT1 pathway proteins. Pharmacological interventions included SAL administration, IL-17 neutralization, and AMPK/SIRT1 pathway modulation.

Results

SAL treatment significantly alleviated pain behaviors in BCP mice (p < 0.01). Cellular analyses revealed SAL restored Th17/Treg balance by reducing Th17 markers (IL-17, RORγt, p-STAT3) and increasing Treg markers (FOXP3, p-STAT5). SAL activated the AMPK/SIRT1 pathway, while pathway inhibitors reversed SAL's therapeutic effects, confirming the mechanism.

Conclusion

SAL effectively alleviates BCP by modulating Th17/Treg cell differentiation through AMPK/SIRT1 pathway activation. These findings suggest SAL's potential as a novel immunomodulatory therapy for BCP management.

Substances (14)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Salidroside 10338-51-9 C14H20O7 690 suppliers $5.00-$2053.00
Salidroside 10338-51-9 C14H20O7 690 suppliers $5.00-$2053.00
Salidroside 10338-51-9 C14H20O7 690 suppliers $5.00-$2053.00
Salidroside 10338-51-9 C14H20O7 690 suppliers $5.00-$2053.00
AICAR 2627-69-2 C9H14N4O5 406 suppliers $25.00-$15640.00
AICAR 2627-69-2 C9H14N4O5 406 suppliers $25.00-$15640.00
AICAR 2627-69-2 C9H14N4O5 406 suppliers $25.00-$15640.00
AICAR 2627-69-2 C9H14N4O5 406 suppliers $25.00-$15640.00
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE 49843-98-3 C13H13ClN2O 266 suppliers $20.00-$1949.90
6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE 49843-98-3 C13H13ClN2O 266 suppliers $20.00-$1949.90

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