The potential effect of salvianolic acid B against rat ischemic brain injury in combination with mesenchymal stem cells

Mesenchymal stem cells (MSCs) and Salvianolic acid B (SAB) are known to exert potent anti-inflammatory and anti-oxidative properties. But the effect of SAB and MSCs combination treatment on the cerebral ischemia/reperfusion injury (CI/RI) is not clear.After the CI/RI animal model established, rats were administered with MSCs and SAB individually or combination treatment. To evaluate the therapeutic potential, behavioral tests, TTC staining, Hematoxylin-eosin (HE) staining, and immunofluorescence assays were performed to evaluate the neuroprotection and endogenous neurogenesis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the anti-apoptosis and anti-inflammatory effect. Meanwhile, the expression of the TLR4/NF-ĸB/MYD88 signal pathway-related proteins was evaluated by Western blot.MSCs and SAB individually or combination treatment have protective effect in CI/RI rats. More importantly, the rats with the combination treatment showed a better behavioral recovery, neurogenesis and smaller infarct size compared with the rats administered with MSCs or SAB individually. Further research showed that the combination treatment decreased CI/RI induced inflammatory cytokines and oxidative stress, including inhibiting the production of IL-1β, IL-6, TNF-α, decreasing the levels of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD). In addition, the neuroprotection effect of SAB and MSCs combination was achieved through the regulation of TLR4/NF-κB/MyD88 signaling pathway related proteins, including inhibition the protein levels of TLR4, MYD88, p-NF-κB p65, TRAF6-and action of SIRT1 in brain tissues.The present study indicated that the MSCs and SAB combination treatment had better protective effect against rat ischemic brain injury. The combination of SAB and MSCs may provide a potent and promising strategy for the treatment of ischemic stroke and is worthy for further development.