benzofurans and pyrazolanthrone

The aim of this study was to evaluate the neuroprotective effects of SalB on high glucose (HG)-induced excessive autophagy and apoptosis in vitro.. The proliferation and apoptosis of RSC96 cells were determined using the MTT assay and flow cytometry, respectively. Western blot analysis was performed to examine the expression of autophagy and apoptosis-related proteins. RT-PCR and flow cytometry were manipulated to examine the level of Bcl-2. The signals of autophagy markers were detected using immunofluorescence methods.. We found that HG significantly reduced RSC96 cell's proliferation and induced apoptosis. What's more, HG increased the level of autophagy and apoptosis-related proteins. However, these effects were reversed by SalB. In addition, we also found that 3-MA decreased the expression of LC3A/B and Beclin1, while the JNK inhibitor SP600125 reduced the levels of phosphorylated JNK, LC3A/B and Beclin1.. High glucose not only induced apoptosis but also caused autophagic cell death by activating the JNK pathway. These effects prevented by SalB in an opposite manner.

Topics: Animals; Anthracenes; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Benzofurans; Cell Line; Cell Proliferation; Diabetic Neuropathies; Glucose; MAP Kinase Signaling System; Peripheral Nervous System Diseases; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Rats; Signal Transduction

Sulfuretin is one of the major flavonoid components in Rhus verniciflua Stokes (Anacardiaceae) isolates. In this study, we investigated the protective effects of sulfuretin against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury. The results indicated that the addition of sulfuretin before t-BHP treatment significantly inhibited cytotoxicity and reactive oxygen species (ROS) production in human liver-derived HepG2 cells. Sulfuretin up-regulated the activity of the antioxidant enzyme heme oxygenase (HO)-1 via nuclear factor E2-related factor 2 (Nrf2) translocation into the nucleus and increased the promoter activity of the antioxidant response element (ARE). Moreover, sulfuretin exposure enhanced the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2), which are members of the mitogen-activated protein kinase (MAPK) family. Furthermore, cell treatment with a JNK inhibitor (SP600125) and ERK inhibitor (PD98059) reduced sulfuretin-induced HO-1 expression and decreased its protective effects. Taken together, these results suggest that the protective effect of sulfuretin against t-BHP-induced oxidative damage in human liver-derived HepG2 cells is attributable to its ability to scavenge ROS and up-regulate the activity of HO-1 through the Nrf2/ARE and JNK/ERK signaling pathways. Therefore, sulfuretin could be advantageous as a bioactive source for the prevention of oxidative injury.

Topics: Anthracenes; Antioxidant Response Elements; Benzofurans; Cell Survival; Flavonoids; Heme Oxygenase-1; Hep G2 Cells; Humans; JNK Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; NF-E2-Related Factor 2; Oxidative Stress; Phosphorylation; Protective Agents; Reactive Oxygen Species; Signal Transduction; tert-Butylhydroperoxide; Up-Regulation

We have recently reported that phlorofucofuroeckol A isolated from Ecklonia stolonifera showed potential antioxidative and anti-inflammatory properties in LPS-stimulated macrophages. This study aims to investigate the cytoprotective effect of phlorofucofuroeckol A and to characterize its molecular mechanisms using tacrine-treated HepG2 cells. Phlorofucofuroeckol A showed a cytoprotective effect against tacrine-treated HepG2 cells in a dose-dependent manner (EC(50): 5.7±0.5 μM). Increased intracellular reactive oxygen species (ROS) by tacrine were decreased by phlorofucofuroeckol A. The cytotoxicity of tacrine to HepG2 cells was associated with upregulations of Fas and JNK phosphorylation resulted in the caspase activations and apoptosis. Phlorofucofuroeckol A inhibited the phosphorylation of JNK and the expression of Fas-mediated apoptotic proteins including Fas ligand, cleaved caspase-8, cleaved caspase-3, and poly (ADP-ribose) polymerase. In addition, treatment of phlorofucofuroeckol A regulated the release of cytochrome c from mitochondria to cytosol in a dose-dependent manner in tacrine-treated HepG2 cells. Furthermore, pretreatment of an inhibitor of JNK, SP600125, downregulated Fas and cleaved caspase-3 without change of ROS productions in tacrine-treated HepG2 cells. In conclusion, our study demonstrated that phlorofucofuroeckol A regulates Fas-mediated apoptosis via inhibition of ROS productions and inhibition of JNK phosphorylation in tacrine-treated HepG2 cells.

Topics: Anthracenes; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Benzofurans; Caspase 3; Caspase 8; Cholinesterase Inhibitors; Cytochromes c; Cytosol; Dioxins; Dose-Response Relationship, Drug; Fas Ligand Protein; fas Receptor; Hep G2 Cells; Humans; JNK Mitogen-Activated Protein Kinases; Mitochondria; Oxidative Stress; Phaeophyceae; Phosphorylation; Plant Extracts; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Tacrine