Epigallocatechin-3-Gallate Pretreatment Improves Autologous Adipose-derived Stem Cells Against Rheumatoid Arthritis-induced Neuroinflammation in the Brain of Collagen-induced Rats

Adipose tissue-derived mesenchymal stem cells (ADSC) exert neuroprotective and anti-inflammatory effects. ADSCs are considered potential therapeutics for rheumatoid arthritis (RA), an inflammatory, multisystemic autoimmune disease. Epigallocatechin-3-gallate (EGCG), the major polyphenolic compound in green tea, has strong anti-inflammatory and antioxidant properties. This study aimed to investigate whether EGCG has a synergistic effect on the neuroprotective effects of ADSCs to protect the RA-damaged brain. Wistar rats were classified into four groups: sham, RA, RA + ADSCs (1 x 10(6) cells per rat), and RA + EGCG (10 mu M)-pretreated ADSCs. After 2 months of treatment, the brain tissues from the rats were collected and investigated. The brains of RA rats had higher inflammation and apoptosis. ADSC treatment ameliorated these negative effects significantly; however, the neuroprotective abilities of EGCG-pretreated ADSCs were significantly higher than ADSCs. Furthermore, the RA-induced repression of the PI3K/Akt survival pathway was reactivated by EGCG-pretreated ADSCs. Collectively, this study provides evidence that EGCG synergistically enhances the neuroprotective ability of ADSCs to repress the negative effects of RA on the brain. These findings could help develop new therapeutic strategies against RA or other neurodegenerative diseases after clinical validation in the future.