Multi-omics unveil Seventy Flavors Pearl Pill ameliorates ischemic stroke via regulating oxidative phosphorylation

Ischemic stroke has high mortality and morbidity. Seventy Flavors Pearl Pill (SFPP) is a classic prescription to treat the disease in Tibetan Medicine, but its mechanism remains to be elucidated. Here, we established three animal models in vivo and three cell models in vitro to evaluate the pharmacological effect of SFPP from anti-hypoxia, anti-ischemia and prevention of reperfusion injury. Quantitative proteomic studies on ischemic neuronal cells showed that oxidative phosphorylation (OXPHOS) was the critical to its efficacy. Then, we explored the functional differences of critical proteins in OXPHOS through cysteine-activity-based protein profiling technologies. Furthermore, the results of quantitative metabolomics illustrated that SFPP could played a neuroprotective role by taking OXPHOS as the core to affect energy metabolism. Finally, the inhibitor of OXPHOS will completely eliminate the neuroprotective effect of SFPP. This research offered new strategies for the treatment of ischemic stroke based on Tibetan Medicine via regulating OXPHOS.