Abstract: Hyperglycemia caused cardiac cell damage by increasing ROS production in diabetic complications. The current study will prove 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 make S. macrophylla extract nanoparticle. Furthermore, characterize the size of S. macrophylla extract nanoparticles with Dynamic Light Scattering (DLS). Forty male rats were divided randomly into five groups. Control group: rats received orally aqua dest; Diabetic group: rats were injected STZ intraperitoneally; S. macrophylla group: rats were injected STZ and given orally with S. macrophylla extract nanoparticles. The DLS showed that the S. macrophylla extract nanoparticles size was 91.50 ± 23.06 nm. Injected with STZ significantly increased cardiac tissue of MDA levels, serum of CK-MB and LDH levels. STZ also significantly reduced expression of Nrf2, level of SOD and GPx in cardiac tissue compared with control group (p<0.05). In contrast, administration of S. macrophylla extract nanoparticles can prevent STZ-induced cardiac cell damage by decreasing level of CK-MB and LDH in serum, and level of MDA in cardiac tissue. S. macrophylla extract nanoparticles also significantly increments Nrf2 expression, 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 might be a potential cardioprotective agent against STZ-induced cardiac cell damage due to its antioxidant properties

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis in insulin-secreting beta-cells is essential. Several pathophysiological conditions and pharmacological agents disrupt the ER homeostasis, thereby causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways whenever the ER stress persists. ER stress has been linked to several diseases, such as cancers, obesity, and diabetes. Thus, the regulation of ER stress may provide possible therapeutic targets for many diseases. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, resulting in irreversible UPR activation and cells death. Despite much progress in understanding the pathophysiology of UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provided up-to-date information regarding the current status of UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.