Abstract
Myocardial ischemic injury is characterized by impaired energy metabolism and oxidative stress, which contribute to cardiac dysfunction and disease progression. Ganoderma lucidum polysaccharide (GLP), a major bioactive component of Ganoderma lucidum, exhibits various pharmacological activities; however, its protective effects against myocardial ischemic injury and underlying mechanisms remain unclear. This study investigated the effects of GLP against isoproterenol (ISO)-induced myocardial ischemic injury and its involvement in metabolic regulation and oxidative stress. A mouse myocardial ischemic injury model was established by subcutaneous injection of ISO (2 mg/kg/day) for 11days. Mice were randomly divided into normal control, model, GLP treatment groups with GLP administered orally at 50 and 100 mg/kg/day, and at 50 mg/kg/day by intraperitoneal injection. An ISO-induced injury model in vitro was established using AC16 cardiomyocytes, which were pretreated with GLP (0.25 ~ 1.00 µg/mL) followed by ISO exposure (40 µM, 24 h). GLP significantly alleviated ISO-induced myocardial injury, reduced cardiac hypertrophy, improved histopathological alterations, and decreased serum AST and LDH activities in mice. Similar protective effects were observed in AC16 cells. Moreover, GLP restored myocardial energy metabolic homeostasis, by improving ATP, phosphocreatine, creatine, and total adenine nucleotides levels, while reducing cAMP accumulation. GLP also alleviated oxidative stress by decreasing malondialdehyde level and enhancing total superoxide dismutase activity. Furthermore, GLP increased the expression of AMPK-α2, phosphorylated AMPK-α2, PGC-1α, and PPAR-α in myocardial tissue. These findings suggest that GLP protects against ISO-induced myocardial ischemic injury by improving myocardial energy metabolism and reducing oxidative stress, with AMPK/PGC-1α/PPAR-α-related metabolic regulation potentially contributing to its cardioprotective effects.