Protective Mechanism Pathway of Swietenia macrophylla Extract Nanoparticles against Cardiac Cell Damage in Diabetic Rats

Hyperglycemia causes cardiac cell damage through increasing ROS production during diabetic complications. The current study proves the antioxidant activity of Swietenia macrophylla (S. macrophylla) extract nanoparticles as a protector against streptozotocin (STZ)-induced cardiac cell damage. In this research, high-energy ball milling is used to create S. macrophylla extract nanoparticles. The active chemical compounds in the S. macrophylla extract nanoparticles were analyzed through phytochemical screening and GC-MS. Furthermore, we characterized the size of S. macrophylla extract nanoparticles with Dynamic Light Scattering (DLS). Forty male rats were divided randomly into five groups. In the control group, rats received aqua dest orally; in the diabetic group, rats were injected intraperitoneally with STZ; in the S. macrophylla group, rats were injected with STZ and orally given S. macrophylla extract nanoparticles. The results of phytochemical screening showed that S. macrophylla extract nanoparticles contain saponins, flavonoids, alkaloids, phenolics and tannins. Seven chemical compounds in S. macrophylla extract nanoparticles were identified using GC-MS, including phenol, piperidine, imidazole, hexadecene, heptadecanol, dihexylsulfide and heptanol. DLS showed that the S. macrophylla extract nanoparticles’ size was 91.50 ± 23.06 nm. Injection with STZ significantly increased malondialdehyde (MDA) levels in cardiac tissue and creatine kinase–myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels in serum. STZ also significantly reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the level of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in cardiac tissue compared with the control group (p < 0.05). In contrast, the administration of S. macrophylla extract nanoparticles can prevent STZ-induced cardiac cell damage through decreasing the level of CK-MB and LDH in serum and the level of MDA in cardiac tissue. S. macrophylla extract nanoparticles also significantly increased Nrf2 expression as well as SOD and GPx levels in cardiac tissue. These effects are related to the prevention of cardiac histopathological alteration (degeneration and necrosis) in diabetic rats. These results suggest that S. macrophylla nanoparticles contain active compounds such as flavonoids, phenols, piperidine, imidazole and hexadecene and have strong antioxidant activity. These can act as a potential cardioprotective agent against STZ-induced cardiac cell damage due to its antioxidant properties.