Tanshinone IIA ameliorates diabetic cardiomyopathy by inhibiting Grp78 and CHOP expression in STZ-induced diabetes rats.

Diabetic cardiomyopathy (DCM), one of the common diabetic complications, causes a high rate of mortality in patients with diabetes. Tanshinone IIA (TSIIA), one of the components of Salvia miltiorrhiza (Danshen), has anti-oxidative stress activity and is widely used to treat diabetes-associated diseases. However, its efficacy on DCM remains unclear. The present study aimed to investigate the potential therapeutic function of TSIIA on DCM in an experimental diabetic rat model. Streptozotocin (STZ)-induced diabetic rats were intraperitoneally injected with TSIIA for 6 weeks. The present results indicated that blood glucose concentration was slightly reduced in the low-dose TSIIA treatment group. TSIIA injection was also noted to improve cardiac function, and restore loss of mitochondrial cristae, swollen mitochondrial matrix and disorganized myofibrils in myocardial cells, which are thought to be characteristics of apoptosis. Furthermore, TSIIA injection could increase the activity of superoxide dismutase in STZ-induced diabetic rats, and suppress the endoplasmic reticulum (ER) stress signaling pathway via reducing the expression of glucose-regulated protein 78 and C/EBP homologous protein. These results provide evidence that TSIIA may ameliorate DCM in diabetic rats, possibly via suppressing oxidative stress and ER stress activation.

Baicalein attenuates vinorelbine-induced vascular endothelial cell injury and chemotherapeutic phlebitis in rabbits.

Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1ß, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis.

Antitumor effects and chemical compositions of Eupolyphaga sinensis Walker ethanol extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Eupolyphaga sinensis Walker popularly known as "preferred drug to regulate blood flow" are traditionally used in folk medicine in the treatment of ecchymoma, posttraumatic wound, hepatic fibrosis and tumor. AIM OF THE STUDY: To characterize chemical compositions and to evaluate the antitumor and immunomodulatory of Eupolyphaga sinensis Walker ethanol extract (ESEE) in hepatocarcinoma H(22) bearing mice. MATERIALS AND METHODS: ESEE was obtained by ethanol reflux extraction and analyzed by gas chromatography-mass spectrometry (GC-MS) after methylation. ICR mice were treated with ESEE for 14 consecutive days at doses of 31mg/kg (low-dose), 62mg/kg (mid-dose) and 124mg/kg (high-dose) after H(22) tumor cells were implanted. At the end of the experiments, the tumor weight of each mouse was measured. Levels of serum TNF-α and IFN-γ was assayed by ELISA. Protein expressions of Bax, Bcl-2 and caspases-3 were detected by immunohistochemistry. RESULTS: Chemical analysis revealed the presence of 6 components that account for 97.55% of fatty acids, indicating the occurrence of saturated and polyunsaturated fatty acids. Oral administration of ESEE could inhibit tumor growth, promote Th1 type cytokine productions (TNF-α and IFN-γ) and induce apoptosis of hepatocarcinoma via increase of Bax/Bcl-2 ratio and activation of caspases-3. Oral administration of ESEE in a dosage of 6.2g/kg did not lead to toxic effects in mice. CONCLUSIONS: ESEE was effective in inhibiting tumor growth in vivo and could also serve as immunoadjuvant for tumor therapy.