To investigate the protective effects and mechanisms of norwogonin against acute hypobaric hypoxia (HH) induced heart injury in mice,78 male BALB/c mice were randomly divided into control group,model group,rutin group,low,medium,and high-dose norwogonin groups.Except for the control group,the mice in other groups were exposed to a simulated altitude of 8 000 m for 24 h.Then the mice were killed,and the serum and heart were taken.The pathological changes of heart tissues were assessed by HE staining.Commercial kits were used to detect the levels of hydrogen peroxide (H₂O₂),malondialdehyde (MDA),superoxide dismutase (SOD) and glutathione (GSH) in heart tissues to assess the state of oxidative stress.The levels of interleukin-1 beta (IL-1β),tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and heart tissues was detected by ELISA for assessing the inflammatory response.The expressions of related proteins were measured by Western blot.Norwogonin significantly reduced HH induced histopathological changes in heart tissues,markedly increased the levels of SOD and GSH,and decreased the levels of H₂O₂ and MDA,as well as the expressions of hypoxia related proteins (HIF-1α and VEGF) in heart tissues.Moreover,norwogonin was also able to reduce the levels of inflammatory factors (IL-1β,TNF-α,and IL-6) in serum and heart tissues as well as the expression of inflammation-related proteins ［nuclear factor kappa-B (NF-κB) and TNF-α］ in heart tissues.In addition,norwogonin modulated the expression of anti-oxidative stress related proteins ［nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1)］ and apoptosis related proteins ［B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cleaved Caspase-3］ in heart tissues.These results suggested that norwogonin could alleviates HH induced acute heart injury in mice by inhibiting oxidative stress,inflammatory response and apoptosis via activation of Nrf2/HO-1 signaling pathway.