Ginsenoside Rd alleviates lipopolysaccharide-induced myocardial injury via modulating the MAPK and NF-κB pathways in cardiomyocytes and macrophages

Cardiac dysfunction is a common complication of sepsis that manifests as uncontrolled inflammatory responses and myocardial injury. Ginsenoside Rd possesses various biological activities, with neuroprotective effects being most commonly reported. This study aimed to investigate the protective effects of ginsenoside Rd on lipopolysaccharide (LPS)-induced myocardial injury and its underlying mechanisms. Here, the cell counting kit-8 (CCK-8) assay was used to detect the cytotoxicity of ginsenoside Rd on mouse macrophages (RAW264.7) and rat cardiomyocytes (H9C2). Furthermore, the expression of the inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW264.7 cells was detected through enzyme-linked immunosorbent assay (ELISA). LPS was also used to induce damage in H9C2 cells, and CCK-8 assay and Hoechst staining were used to assess cell viability and apoptosis. Cardiac cell injury, oxidative stress, and inflammation were determined by measuring lactate dehydrogenase (LDH), Ca ²⁺ , malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO) levels. Moreover, western blotting was used to detect the expression of normal and phosphorylated forms of the mitogen-activated protein kinase (MAPK)signaling components extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 and the nuclear factor kappa-B (NF-κB) signaling components p65 and phospho-p65 as well as the nuclear translocation of p65 in RAW264.7 and H9C2 cells. Interestingly, the results illustrated that ginsenoside Rd significantly reduced the release of TNF-α, IL-6, and IL-1β in a concentration-dependent manner. Ginsenoside Rd improved the survival rate of myocardial cells, which might be attributable to reduced apoptosis. Ginsenoside Rd decreased the levels of LDH, Ca ²⁺ , ROS, MDA, and NO in myocardial cells. Mechanistically, ginsenoside Rd inhibited the phosphorylation of ERK, JNK, and p38 and the phosphorylation and nuclear translocation of p65 in RAW264.7 cells. Similarly, ginsenoside Rd inhibited the phosphorylation of JNK, p38, and p65 in H9C2 cells. In conclusion, ginsenoside Rd can reduce the inflammatory response in macrophages, increase their survival rate, reduce apoptosis, and suppress oxidative stress and inflammation in cardiomyocytes by inhibiting the MAPK and NF-κB signaling pathways. Overall, the findings of this study indicate that ginsenoside Rd has the potential to be used for the treatment of septic myocardial injury.