Scutellarein-containing novel formula attenuates hypoxia through inhibiting apoptosis

Background High-altitude hypoxia limits human performance, and existing interventions face limitations in efficacy, safety, or personalization. Our team developed a novel formula to enhance hypoxic tolerance. Methods Anti-hypoxia effects were evaluated using normobaric and acute hypoxia models. Blood bioactive components were profiled via LC–MS non-targeted metabolomics. Network pharmacology and molecular docking identified potential targets and pathways, with cellular experiments validating the effects of the key component. Results The formula significantly prolonged survival time under normobaric hypoxia and increased survival rate dose-dependently in acute hypoxia. Twenty-three prototype blood components were identified, with scutellarein as the primary constituent. Network analysis revealed 88 potential targets, primarily involving the PI3K-Akt pathway. Scutellarein showed strong binding to Hsp90 (docking score: –9.560 kcal/mol). Cellular assays confirmed its dose-dependent anti-hypoxic effect via reduced LDH release and apoptosis. Conclusion The novel formula may alleviate acute mountain sickness by improving hypoxic tolerance, likely through flavonoid-mediated inhibition of neuronal apoptosis.