ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
A Curcumin-Borneol Prodrug Delayed Rheumatoid Arthritis Progression by Inhibiting the Activation of the MAPK/AP-1-MMP9 Inflammatory Axis
Tianyi Xu 1
Qilei Yang 2
Yue Peng 1
Congcong Xie 2
Huimin YU 3,4
Xiuhua Zhao 2
1. Harbin Medical University, Harbin, China
2. Northeast Forestry University College of Chemistry and Chemical Engineering and Resource Utilization, Harbin, China
3. 浙江大学医学院附属第二医院, 杭州市, China
4. Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Abstract
Rheumatoid arthritis (RA) therapy demands agents that are both effective and safe, yet many natural products with promising bioactivity, such as curcumin, face major translational challenges due to poor solubility and bioavailability. To overcome these limitations, we designed and synthesized a series of dual-functional curcumin-borneol prodrugs via a succinate ester linkage, including the parent ester (CBS), its water-soluble sodium salt (CBS-Na), and a disubstituted analog (DCBS), to enhance delivery and synergize therapeutic action. These derivatives markedly improved cellular uptake and nuclear localization, potently scavenged reactive oxygen species, and effectively suppressed the MAPK/AP-1 signaling axis by inhibiting ERK and p38 phosphorylation and c-Fos expression, leading to downregulation of matrix metalloproteinase MMP-9 and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). In a collagen-induced arthritis rat model, the derivatives demonstrated superior efficacy over native curcumin in alleviating joint inflammation and destruction, while exhibiting an excellent safety profile, thereby thus representing a novel and promising therapeutic strategy for RA.
Summary
Keywords
Borneol, Curcumin, MAPK/AP-1 signaling, matrix metalloproteinase-9 (MMP9), Rheumatoid arthritis
Received
26 December 2025
Accepted
19 February 2026
Copyright
© 2026 Xu, Yang, Peng, Xie, YU and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Huimin YU; Xiuhua Zhao
Disclaimer
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