2. Academic Validation
  3. Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1

Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1

  • Cytokine. 2024 May 14:180:156635. doi: 10.1016/j.cyto.2024.156635.
Bo Xu 1,  Yue Xu 2,  Jian Kong 1,  Yujiang Liu 1,  Long Zhang 1,  Fan Shen 1,  Jiangping Wang 1,  Xiaofeng Shen 3,  Hua Chen 4
Affiliations

Affiliations

  • 1 Department of Orthopedics and Traumatology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215000, Jiangsu Province, PR China.
  • 2 Department of Orthopedics and Traumatology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu 215500, Jiangsu Province, PR China.
  • 3 Department of Orthopedics and Traumatology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215000, Jiangsu Province, PR China. Electronic address: 29240818@qq.com.
  • 4 Department of Orthopedics and Traumatology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215000, Jiangsu Province, PR China. Electronic address: chen20168@sina.com.
PMID: 38749277 DOI: 10.1016/j.cyto.2024.156635
Abstract

Background: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA.

Methods: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 μg/mL chrysin. The cell viability and macrophage Pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot.

Results: Chrysin alleviated macrophage Pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/Akt pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/Akt pathway, hence reducing KOA damage and peripheral sensitization.

Conclusion: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/Akt pathway modulated by HMGB1.

Keywords

Chrysin; HMGB1/RAGE pathway; Knee osteoarthritis; PI3K/AKT pathway.

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