Rutaecarpine attenuates high glucose‐induced damage in AC16 cardiomyocytes by suppressing the MAPK pathway

Diabetic cardiomyopathy is a common diabetic complication, resulting in heart failure. Rutaecarpine is an active compound with cardiovascular protective effects. However, the function of rutaecarpine in diabetic cardiomyopathy is largely unknown. The aim of this research was to study the effect and action mechanism of rutaecarpine in high glucose (HG)‐induced cardiomyocyte damage. The overlapping genes of diabetic cardiomyopathy and rutaecarpine were analyzed according to GeneCards, DisGeNet, and SwissTargetPrediction. Cell damage was investigated by determining apoptosis, oxidative stress, and inflammatory response in HG‐stimulated AC16 cells. The expression of proteins involved in the mitogen‐activated protein kinase (MAPK) signaling was measured using Western blotting. Totally seven overlapping genes of diabetic cardiomyopathy and rutaecarpine were screened out and predicted to be associated with the MAPK signaling. Rutaecarpine protected against HG‐induced cardiomyocyte damage by enhancing cell viability and reducing cell apoptosis, caspase‐3 activity, and lactate dehydrogenase (LDH) release. Rutaecarpine mitigated HG‐induced oxidative stress in cardiomyocytes through decreasing reactive oxygen species (ROS) formation and malondialdehyde (MDA) level and elevating superoxide dismutase (SOD) activity and glutathione peroxidase (GSH‐Px) level. Rutaecarpine alleviated HG‐induced inflammatory response via reducing the level of interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α, and IL‐8. Moreover, rutaecarpine inhibited HG‐induced activation of the MAPK pathway. Treatment with MAPK signaling agonist reversed the suppressive effect of rutaecarpine on HG‐induced damage. In conclusion, rutaecarpine alleviated HG‐induced cardiomyocyte damage through decreasing apoptosis, oxidative stress, and inflammatory response by inactivating the MAPK pathway.

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