Myocardial ischemia-reperfusion (IR) causes widespread cardiomyocyte dysfunction, including apoptosis and necrosis. The present study aimed to investigate the possible cardioprotective effects of p-nitro caffeic acid phenethyl ester (CAPE-NO) on myocardial IR-induced injury . To generate a rat model of myocardial IR, the left anterior descending coronary artery was occluded for 30 min, followed by reperfusion for 2 h. The rats were administered either the sham treatment (the sham and IR control groups) or the therapeutic agents [the caffeic acid phenethyl ester (CAPE) and CAPE-NO groups] 10 min prior to the occlusion. Myocardial IR-induced injury is characterized by: A significant increase in the levels of myocardial enzymes, including creatine kinase, lactate dehydrogenase and aspartate transaminase; a marked increase in intercellular adhesion molecule 1 expression levels, lipid peroxidation products and inflammatory mediators; and a significant decrease in myocardial antioxidants, including catalase, total superoxide dismutase and glutathione peroxidase. In the present study, pretreatment with CAPE-NO significantly ameliorated these changes, and decreased the infarct size, as compared with the IR control group (10.32±3.8 vs. 35.65±5.4%). Furthermore, western blotting demonstrated that pretreatment with CAPE-NO downregulated the myocardial IR-induced protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), cleaved caspase-3, P38 and the Bax/Bcl-2 ratio. CAPE-NO also upregulated the myocardial IR-induced expression levels of Bcl-2, phosphoinositide-3-kinase, phosphorylated Akt and mammalian target of rapamycin. In conclusion, the results of the present study indicated that CAPE-NO demonstrated improved cardioprotective effects, as compared with CAPE; therefore, CAPE-NO may represent a novel approach to pharmacological cardioprotection.

The medical properties of baicalin have been well known for many years. However, the discovery that baicalin in the presence of metal ions is more effective than baicalin alone changed the course of drug research. The present study was designed to investigate the effect and possible mechanism of apoptosis induced by baicalin-copper in a human hepatoblastoma cancer cell line (HepG2) and in vivo. This study demonstrated that baicalin-copper suppresses the proliferation of HepG2 cells in a dose-dependent manner. Intraperitoneal injection of baicalin-copper resulted in a significant decrease in tumor growth in xenografts in nude mice. Acridine orange staining and flow cytometry analysis demonstrated that baicalin-copper induced apoptosis in HepG2 cells and caused cells to arrest in G2-M phase of the cell cycle. Furthermore, baicalin-copper treatment significantly increased the Bax/Bcl-2 ratio and p38 levels, as well as decreased the expression of caspase-3, p-PI3K, p-Akt and p-mTOR (P < 0.01). All of the evidences above indicate that baicalin-copper induces apoptosis in HepG2 cells by down-regulating the PI3K/Akt/mTOR signaling pathway.

Tupistra chinensis Baker has been used as a folk remedy in China, and it has been shown to exhibit anti-inflammation, expectorant and anti-bacterial effects. In this study, we report the cytotoxic activity of the total saponins of Tupistra chinensis Baker (TST) against several carcinoma cell lines, including A549, MCF-7 and HeLa cells with the IC50 values of 4.11 μg/ml, 6.47 μg/ml and 7.78 μg/ml respectively. Treatment of A549 cells with TST resulted in growth inhibition and induction of apoptosis in a time-dependent manners determined by cell viability, chromatin condensation, DNA fragmentation and flow cytometry analysis. The activities of caspase-3, 9 were significantly increased following TST treatment. Real-time PCR analysis showed that the mRNA expression levels of pro-apoptosis related genes including Bax, P21, P27 and P53 were markedly increased in the cells treated with TST but anti-apoptosis related gene Bcl-2 was slightly decreased. TST also leads to a loss of mitochondrial membrane potential in a time-dependent manner the release of cytochrome C from mitochondria into the cytosol. Thus, these results suggest that TST may play an important role in tumor growth suppression by inducing apoptosis in human A549 cells via mitochondria-dependent apoptotic pathways and the TST would be promising to treat human lung adenocarcinoma.

Context: Caffeic acid phenethyl ester (CAPE), isolated from honeybee propolis, has pharmacological applications. A synthesized CAPE derivative, p-nitro-caffeic acid phenethyl ester (CAPE-NO 2 ), showed similar activities with CAPE. The pharmacological activities of CAPE and CAPE-NO 2 are related to their absorption properties. Objective: To understand the pharmacokinetic profiles of CAPE and CAPE-NO 2 in rats and investigate the absorption mechanisms and effects on P-glycoprotein in Caco-2 cells. Materials and methods: The pharmacokinetic profiles of CAPE and CAPE-NO 2 were obtained after oral administration (10 mg/kg) to rats. Transport studies of CAPE and CAPE-NO 2 (5, 10, 20 lM) were performed in Caco-2 cell model. P-gp activities were assayed by rhodamine 123 cellular retention. Expression of P-gp was determined after the cells were administrated with CAPE and CAPE-NO 2 (5, 20 lM) for 48 and 72 h. Results: The AUC (0Àt) of CAPE-NO 2 (3239.9 ± 352 ng  h/mL) was two-time greater than CAPE (1659.6 ± 152 ng  h/mL) in rats. The P app values of CAPE and CAPE-NO 2 were (4.86 ± 0.90)  10 À6

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