The impact of alpha-lipoic acid treatment on various mediators of inflammatory and immune responses in a murine arthritis model.
PMID 40960577 | DOI 10.1007/s10787-025-01941-5 · Inflammopharmacology · 2025
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by inflammation in the synovial lining of joints, leading to pain, stiffness, and significant functional limitations. Current treatments focus on managing symptoms and slowing disease progression, but they often have side effects and may not be effective for all patients. This study investigated the effects of alpha-lipoic acid (ALA) on immune response and inflammation in mouse model of arthritis. Adjuvant-induced arthritis (AIA) was established in mice, and ALA was administered to mice at a dose of 75 mg/kg via oral gavage twice daily for 7 consecutive days. ALA administration significantly reduced arthritis severity, as evidenced by decreased paw oedema and arthritis score. ALA treatment led to a significant reduction in plasma levels of IL-17A, TNF-α, and MMP-3, key biomarkers of arthritis disease activity. ALA decreased the number of circulating Th17 and NF-κB p65+ CD4+ T lymphocytes, suggesting its potential to modulate the immune response. ALA downregulated the expression of pro-inflammatory genes (IL17F, TNF) and upregulated the expression of the anti-inflammatory cytokine IL10 gene in the joint tissues. In the joint tissue, ALA modulated the expression of NFKB1, STAT3, GATA3, TBX21, and RORC, all of which are key transcription factors associated with arthritis pathogenesis. Molecular docking results suggest potential binding interactions between ALA and key molecules like GATA-3 and TNF-α, as a potential mechanism for its anti-inflammatory properties. These findings support ALA's potential as a promising therapeutic agent for RA in human patients, as it appears to modulate inflammation, immune responses, and key molecular pathways involved in disease pathogenesis.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | IL17F | “ALA downregulated the expression of pro-inflammatory genes (IL17F, TNF) and upregulated the expression of the anti-inflammatory cytokine IL10 gene in the joint tissues.” | 0.98 | hgnc_dict_v1 |
| gene | TNF | “ALA downregulated the expression of pro-inflammatory genes (IL17F, TNF) and upregulated the expression of the anti-inflammatory cytokine IL10 gene in the joint tissues.” | 0.98 | hgnc_dict_v1 |
| gene | IL10 | “ALA downregulated the expression of pro-inflammatory genes (IL17F, TNF) and upregulated the expression of the anti-inflammatory cytokine IL10 gene in the joint tissues.” | 0.98 | hgnc_dict_v1 |
| gene | NFKB1 | “In the joint tissue, ALA modulated the expression of NFKB1, STAT3, GATA3, TBX21, and RORC, all of which are key transcription factors associated with arthritis pathogenesis.” | 0.98 | hgnc_dict_v1 |
| gene | STAT3 | “In the joint tissue, ALA modulated the expression of NFKB1, STAT3, GATA3, TBX21, and RORC, all of which are key transcription factors associated with arthritis pathogenesis.” | 0.98 | hgnc_dict_v1 |
| gene | GATA3 | “In the joint tissue, ALA modulated the expression of NFKB1, STAT3, GATA3, TBX21, and RORC, all of which are key transcription factors associated with arthritis pathogenesis.” | 0.98 | hgnc_dict_v1 |
| gene | TBX21 | “In the joint tissue, ALA modulated the expression of NFKB1, STAT3, GATA3, TBX21, and RORC, all of which are key transcription factors associated with arthritis pathogenesis.” | 0.98 | hgnc_dict_v1 |
| gene | RORC | “In the joint tissue, ALA modulated the expression of NFKB1, STAT3, GATA3, TBX21, and RORC, all of which are key transcription factors associated with arthritis pathogenesis.” | 0.98 | hgnc_dict_v1 |
| phenotype | rheumatoid arthritis | “Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by inflammation in the synovial lining of joints, leading to pain, stiffness, and significant functional limitations.” | 0.98 | phenotype_alias_lexicon_v2 |