Jing Shi

Hesperidin (HES) is an abundant and economical dietary bioflavonoid, and it has several pharmacological properties such as antioxidant activity and powerful cardiac protection. However, HES protection against cisplatin (CP)-induced cardiotoxicity and its mechanism have not been fully clarified. The current study was performed to further elucidate the mechanism of HES against CP-induced cardiotoxicity. Mice were orally administered HES (100 or 300 mg kg⁻¹ day⁻¹) for 7 consecutive days and then injected intraperitoneally (i.p.) with CP (5 mg kg⁻¹) on days 3 and 6. On day 8, mice were anaesthetised with sodium pentobarbital (50 mg kg⁻¹, i.p.), and blood and heart samples were collected for analysis. HES treatment reduced CP-induced cardiac pathologic damage and leakage of the myocardial markers cardiac troponin I (cTnI), creatine kinase (CK), and lactate dehydrogenase (LDH). HES treatment reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), which is an oxidative product, and increased antioxidant marker levels including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). HES also reduced the CP-induced release of the inflammatory factors tumour necrosis factor (TNF)-α and interleukin (IL)-6. Additionally, HES treatment up-regulated the expression of anti-apoptotic protein Bcl-2 and down-regulated the expression of pro-apoptotic proteins Bax and Caspase-3. HES treatment also improved the expression of pathway proteins p62 and Nrf2 and inhibited the increase in CP-induced Keap1 expression. Thus, HES may provide protection against CP cardiotoxicity through inhibiting oxidative stress, inflammation, and apoptosis, which may contribute to activation of the p62–Keap1–Nrf2 signalling pathway. These findings suggest that HES may be a promising protective agent against CP cardiotoxicity in future anticancer clinical practice.

Safranal (SFR), an active ingredient extracted from saffron, exhibits a protective effect on the cardiovascular system. However, the mechanism of SFR against hypoxia/reoxygenation (H/R)‑induced cardiomyocyte injury has previously not been investigated in vitro. The aim of the present study was therefore to observe the protective effects of SFR on H/R‑induced cardiomyocyte injury and to explore its mechanisms. A H/R injury model of H9c2 cardiac myoblasts was established by administering 800 µmol/l CoCl2 to H9c2 cells for 24 h and reoxygenating the cells for 4 h to induce hypoxia. H9c2 cardiac myoblasts were pretreated with SFR for 12 h to evaluate the associated protective effects. A Cell Counting Kit‑8 assay was used for cell viability detection, and the expression levels of lactate dehydrogenase (LDH), creatine kinase‑MB (CK‑MB), glutathione peroxidase (GSH‑px), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and caspase‑3, and the intracellular Ca²⁺ concentration were measured using the corresponding commercial kits. Levels of reactive oxygen species (ROS) in the cells were detected using 2,7‑dichlorodihydrofluorescein diacetate. Flow cytometry was used to determine the degree of apoptosis and the level of mitochondrial membrane potential (MMP). Moreover, the expression levels of phosphorylated (p‑)PI3K, AKT, p‑AKT, glycogen synthase kinase 3β (GSK3β), p‑GSK3β, Bcl‑2, Bax, caspase‑3 and cleaved caspase‑3 were measured using western blot analysis. Results of the present study demonstrated that the H9c2 cardiac myoblasts treated with SFR exhibited significantly improved levels of viability and significantly reduced levels of ROS, compared with the H/R group. Furthermore, compared with the H/R group, SFR treatment significantly increased the MMP levels and antioxidant enzyme levels, including CAT, SOD and GSH‑px; whereas the levels of CK‑MB, LDH, MDA and intracellular Ca²⁺ concentration were significantly decreased. Moreover, the results of the present study demonstrated that SFR significantly reduced caspase‑3, cleaved caspase‑3 and Bax protein expression levels, but upregulated the Bcl‑2 protein expression levels. SFR also increased the protein expressions of PI3K/AKT/GSK3β. In summary, the results suggested that SFR may exert a protective effect against H/R‑induced cardiomyocyte injury, which occurs in connection with the inhibition of oxidative stress and apoptosis via regulation of the PI3K/AKT/GSK3β signaling pathway.