Toddalia asiatica (L.) Lam. induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes by modulating the PI3K/AKT/NF-κB pathway
Year: 2026
Type: article
Abstract: BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease. Although current pharmacological treatments can alleviate symptoms, they are often associated with significant adverse reactions and fail to halt disease progression. Therefore, there is an urgent need to develop novel therapies derived from natural resources that have broad immunomodulatory effects with minimal side effects. The root of Toddalia asiatica (L.) Lam. (TA), a traditional remedy used by the Tujia and Miao ethnic groups for rheumatism, represents a promising natural candidate for RA treatment. However, its specific mechanism of action in RA is not fully elucidated. METHODS: Collagen-induced arthritis (CIA) rat models and interleukin-1β (IL-1β)-stimulated fibroblast-like synoviocyte (FLS) models were established to assess the therapeutic effects of TA on RA. Network pharmacology analysis was performed to identify potential therapeutic targets and associated pathways. Cellular functions were assessed through CCK-8, wound healing, and transwell migration assays. Apoptosis was evaluated using TUNEL staining and flow cytometry analysis. mRNA and protein expression levels were determined by qPCR, Western blotting, immunofluorescence, and immunohistochemical staining. RESULTS: TA alleviated joint swelling in CIA rats by reducing serum levels of pro-inflammatory cytokines and reactive oxygen species (ROS). It also modulated the Bax/Bcl-2 ratio and induced synovial cell apoptosis. Network pharmacology analysis revealed that common targets between TA and RA were enriched in the PI3K/AKT/NF-κB pathway. In vitro studies showed that TA inhibited the proliferation, migration, and invasion of MH7A cells, decreased the secretion of pro-inflammatory cytokines and ROS production, and promoted apoptosis. Mechanistically, TA suppressed the phosphorylation of key proteins in the PI3K-AKT and NF-κB pathways and reduced the nuclear translocation of NF-κB. CONCLUSIONS: TA exerts anti-RA effects by inhibiting the PI3K/AKT/NF-κB pathways and modulating the apoptosis balance of synovial fibroblasts. These findings provide a theoretical foundation for the clinical application of TA in RA treatment.
Source: Molecular Immunology
Authors: Jianjun Niu, Chaocao Yan, Fanyong Zeng, Huanzhen Wang, Zhiliang Fan, Yihui Chai, Chunyan Liu
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,340
OpenAlex ID: W7125970685