Epigallocatechin-3-gallate preconditioned Adipose-derived Stem Cells confer Neuroprotection in aging rat brain

Aging is the most important current issue and is usually accompanied by complications, such as cardiovascular disorders and neurodegenerative diseases, which are the leading causes of death worldwide and the second major cause of death in Taiwan. In this study, we have investigated the protective effect of adipose-derived mesenchymal stem cells (ADSCs) and the role of epigallocatechin gallate (EGCG) in enhancing this effect in aging cerebral cortex of rats. Further, we attempted to elucidate the molecular mechanism through which EGCG influences the protective effects of ADSC. ADSCs, co-cultured with EGCG, were injected into 20-month-old Wistar rats. Hematoxylin and eosin staining of the cerebral cortex revealed noticeable neurogenic activity and visible improvements in the integrity of the pre-frontal cortex tissue, compared to that in rats treated with ADSCs alone. Western blot analysis confirmed that ADSC, co-cultured with EGCG, enhanced cell survival via the p-Akt pathway and improved mitochondrial biogenesis via the SIRT-1 pathway. Moreover, it increased the available brain-derived neurotrophic factor to a higher degree than that in the ADSC group. Furthermore, western blotting showed that EGCG improved the antioxidant activity of the ADSCs in the cortex tissues via the Nrf-2 and HO-1 pathway. Based on these findings, we propose that this variation in stem cell treatment may facilitate functional recovery and enhanced neuroprotection in aged brains.