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Astragalosides were the main active components from a native Chinese herb Astragalus membranaceus. Recent studies have shown that Astragalosides have a protective effect on myocardial injury in rats. The present study was designed to investigate the effect of Astragalosides on intracellular calcium overload and sarcoplasmic reticulum calcium load (SR Ca²⁺ load) in cultured cardiac myocytes from neonatal rats. Astragalosides (100 μg/ml) were incubated in the presence of isoproterenol (ISO) (10^-5 M) for 72 hours in cardiomyocytes. Metoprorol (10^-6 M), a β₁-selective antagonist, was cultured in the same condition as Astragalosides. The result showed that intracellular calcium concentration ([Ca²⁺]_i) and SR Ca²⁺ load increased in ISO-treated cardiac myocytes as compared to control (P<0.01). Astragalosides prevented ISO-induced increase in [Ca²⁺]_i and SR Ca²⁺ load. Metoprolol also inhibited those increase. The mRNA expression and activity of sarcoplasmic reticulum Ca²⁺ ATPase (SERCA) were enhanced following ISO treatment in cardiac myocytes, and these increases were inhibited by Astragalosides or metoprolol (P<0.05). The decrease of superoxide dismutase (SOD) activity and the elevation of intracellular maleic dialdehyde (MDA) were observed after ISO treatment in cardiac myocytes. Both Astragalosides and metoprolol restored the SOD activity and reduced the level of MDA. We conclude that Astragalosides have the effects on reducing [Ca²⁺]_i and SR Ca²⁺ load, enhancing free radical removal and decreasing lipid peroxidation in ISO-treated cardiomyocytes, which might account for their protective effect on myocardial injury.

We have extracted and roughly purified astragalosides (AS) from Astragalus membranaceus, a natural herb used as a traditional Chinese medicine, regarded to have pharmacodynamic benefits of protecting injured myocardium. We hypothesized that the astragalosides might exert beneficial effect in myocardial lesion by preserving both energy metabolism and Ca²⁺ homeostasis. Sprague-Dauley (SD) rats were injected with isoproterenol (ISO) subcutaneous (s.c.) at a dose of 5 mg/kg/day consecutively for two days as models and were treated with astragalosides and trimetazidine intraperitoneally (i.p.) respectively, at a dose of 5 mg/kg/day one day prior to isoproterenol for 8 days. The histological changes were alleviated in isoproterenol-injected SD rats treated with astragalosides. Compared with isoproterenol-injected rats, the concentration of myocardial intracellular [Ca²⁺]i was decreased, L-type Ca²⁺ current density and sarcoplasmic reticulum (SR) Ca²⁺ load were recovered, the concentration of myocardial ATP was increased and phosphocreatine (PCr) was decreased in rats treated with astragalosides. In conclusion, the efficacious treatment of astragalosides for myocardial injury might be through regulating intracellular Ca²⁺ homeostasis and energy metabolism.

Heart disease (HD) is associated with estrogen and therefore gender and menopausal status. In addition, clinical evidence shows that increased serum norepinephrine is found in patients with HD. Therefore, this study aimed to investigate the cardio-protective effect of genistein, a selective estrogen receptor modulator (SERM) from soy bean extract, in H9c2 cardiomyoblast cells treated with isoproterenol (ISO), a norepinephrine analog. In this in vitro model, image data and results from western blotting shown that ISO treatment was capable of inducing cellular apoptosis, especially the mitochondrial dependent pathway. Treatment of genistein could suppress the expression of mitochondrial pro-apoptotic proteins including Bad, caspase-8, caspase-9, and caspase-3 in H9c2 treated with ISO. By contrast, several survival proteins were expressed in H9c2 treated with genistein, such as phosphor (p)-Akt, p-Bad, and p-Erk1/2. Furthermore, we confirmed that the protective role of genistein was partially mediated through the expression of Erk1/2, Akt, and NFκB proteins by adding several pathway inhibitors. These in vitro data suggest that genistein may be a safe and natural SERM alternative to hormone therapy in cardio-protection.

This study investigates the cardio-protective effect of Nos. 1 and 5 extracts from Taiwan Mingjian Oolong Tea on H9c2 cardiomyoblast cells treated with isoproterenol (ISO). Treatment with Nos. 1 and 5 extracts increased cell viability and blocked apoptosis in ISO exposed H9c2 cells. Moreover, Nos. 1 and 5 extracts blocked hypertrophy markers like G$\alpha$s, calcineurin, NFATc3, and BNP, thereby increasing cell proliferation markers -PI3K and AKT in a dose dependent manner. In contrast, apoptotic proteins, such as caspase-3 and cytochrome c were decreased in H9c2 cells treated with Nos. 1 and 5 extracts. We confirmed that the protective effect of No. 1 extract was partially mediated through the expression of ERK and p38, however, the No. 5 extract showed a protective effect via the ERK, JNK, and p38 pathways. This evidence provides new insights into the pharmacological role and therapeutic mechanism of Taiwan Mingjian Oolong Tea in heart diseases.

Isoproterenol (ISO) is widely used to treat bronchial asthma, cardiogenic or septic shock, complete atrioventricular block, and cardiac arrest. However, it can also cause myocardial damage owing to infarct-like necrosis. Curdione, an extract of the Chinese herb Rhizoma Curcumae, has a variety of pharmacological activities, including cardioprotective effects. In this study, we investigated the protective effects of curdione and its underlying mechanisms in an ISO-induced myocardial injury model. Our results showed that curdione attenuated ISO-induced H9c2 cell proliferation inhibition and lactic dehydrogenase (LDH) release. Curdione ameliorated morphological damage and reduced the ISO-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB) and LDH. Furthermore, curdione inhibited ISO-induced cell apoptosis, modulated the expression of Bcl-2 and Bax proteins, repealed the accumulation of ISO-induced reactive oxygen species (ROS), prevented mitochondrial dysfunction, and activated the Nrf2/SOD1/HO-1 signaling pathway. The above results show that curdione exerts a protective effect against ISO-induced myocardial damage by inhibiting apoptosis and oxidative stress, suggesting that curdione is a potential therapeutic strategy to prevent ISO-induced myocardial damage.