Xinnaotongluo liquid protects H9c2 cells against hypoxic damage through IRF2/HIF-1α-mediated oxidation, inflammation, and apoptosis.

Abstract

Myocardial ischemia is the primary reason for ischemic heart disease. Xinnaotongluo liquid has been reported to have an improving effect on cardiovascular diseases. In our study, we detected the effects of Xinnaotongluo liquid on H9c2 cell oxidation, inflammation, and apoptosis induced by hypoxia stimulation. H9c2 cells were exposed to hypoxia and/or Xinnaotongluo liquid stimulation. Cell viability, oxidation, inflammation, and apoptosis, along with HIF-1α expression were measured. Subsequently, si-HIF-1α was transfected into H9c2 cells to detect whether HIF-1α depletion was involved in the effect of Xinnaotongluo liquid on H9c2 cells stimulated by hypoxia. Then, the regulatory effect of IRF2 on HIF-1α was detected. Hypoxia exposure induced H9c2 cell viability reduction, oxidation, inflammation, and apoptosis. Xinnaotongluo liquid alleviated the H9c2 cell viability reduction, oxidation, inflammation, and apoptosis induced by hypoxia. HIF-1α was activated in hypoxia-exposed H9c2 cells, and the knockdown of HIF-1α strengthened the effects of Xinnaotongluo liquid on hypoxia-exposed H9c2 cells. Additionally, HIF-1α was transcriptionally regulated by IRF2, and IRF2 was associated with the upregulation of HIF-1α in hypoxia-exposed H9c2 cells. Xinnaotongluo liquid alleviated H9c2 cell apoptosis and inflammation induced by hypoxia, which might be achieved by regulating IRF2/HIF-1α expression.