Work

Triptolide and Celastrol for Rheumatoid Arthritis: Mechanism-Guided Nanoarchitectonics for Delivery Strategies to Enhance Efficacy and Reduce Toxicity

Year: 2026

Type: review

Abstract: Background: Rheumatoid arthritis remains a leading cause of irreversible joint disability worldwide. Triptolide and celastrol, major bioactive compounds derived from Tripterygium wilfordii Hook F. (TwHF) , have substantial therapeutic potential for rheumatoid arthritis. However, poor solubility, low oral bioavailability, narrow therapeutic windows, and dose-limiting systemic toxicity limit their clinical translation. Objective: This review integrates the anti-rheumatoid arthritis mechanisms of triptolide and celastrol with recent advances in nanodelivery systems to establish a mechanism-guided framework for nanocarrier design and clinical translation. Results: Triptolide and celastrol exert multifaceted anti-rheumatoid arthritis effects by inhibiting inflammatory signaling pathways, regulating macrophage polarization and T-cell homeostasis, suppressing fibroblast-like synoviocyte proliferation, and protecting bone and cartilage. Diverse nanodelivery platforms—including lipid-based, polymeric, inorganic, biomimetic, carrier-free, and hybrid systems—have substantially improved the bioavailability and lesion-targeting capability of triptolide and celastrol, achieving superior anti-inflammatory and joint-protective efficacy while minimizing systemic toxicity. Conclusion: Mechanism-guided nanodelivery may help translate triptolide and celastrol into safer, targeted rheumatoid arthritis therapies. Realizing this potential requires a shift from material-centric research toward application-oriented development supported by rigorous validation. Keywords: rheumatoid arthritis, mechanism-guided delivery, triptolide, celastrol, nanomedicine

Source: International Journal of Nanomedicine

DOI: 10.2147/ijn.s646722

Authors: Peidan Yang, Gangzhong Zhang, Liqun Wu, Chunfeng Xie, Qiang Xu

Institutions: Jinan University, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine

Language: English

Topic: Natural Compounds in Disease Treatment

Subfield: Complementary and alternative medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836