The role of electroacupuncture in altering lipoic acid metabolism to reduce joint inflammation in rheumatoid arthritis rats

Rheumatoid arthritis (RA) is characterized by severe synovial inflammation and progressive joint destruction. This study evaluated the therapeutic effects of electroacupuncture (EA) in a rat model of RA and explored its potential association with lipoic acid (LA) metabolism. Collagen-induced arthritis (CIA) was established in rats, followed by EA stimulation at ST36 (Zusanli) for 14 d. Hind-paw thickness and arthritis index scores were assessed weekly. On day 28, synovial histopathology was examined by hematoxylin and eosin staining. Serum cytokine levels were measured by ELISA. Synovial tissue metabolomics was performed to identify EA-responsive metabolic pathways, and candidate proteins were validated by Western blotting. Serum copper (Cu2+) levels were also quantified. The results demonstrated that EA alleviated CIA manifestations in an intensity-dependent manner, with low-intensity stimulation (0.5 mA) showing the greatest efficacy. EA reduced joint damage and systemic inflammation, as reflected by increased IL-10 and decreased TNF-α, IL-6, and IL-17 levels. Metabolomic analysis highlighted alterations in LA metabolism. Protein levels of DLAT and LIAS were elevated in CIA rats and were reduced after EA or methotrexate treatment. Serum Cu2+ levels exhibited a similar trend. In conclusion, low-intensity EA attenuates joint inflammation in CIA rats, potentially through modulation of LA metabolism and associated copper homeostasis, providing new metabolic insights into its anti-inflammatory effects in RA.