Induction of apoptosis by Moutan Cortex Radicis in human gastric cancer cells through the activation of caspases and the AMPK signaling pathway

Abstract Moutan Cortex Radicis, the root bark of Paeonia × suffruticosa Andrews, Paeoniaceae, has been widely used in traditional medicine therapy. Although it has been shown to possess many pharmacological activities, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated. In the present study, we investigated the pro-apoptotic effects of the ethanol extract of Moutan Cortex Radicis in human gastric cancer AGS cells. Moutan Cortex Radicis treatment inhibited the cell viability of AGS cells in a concentration-dependent manner, which was associated with apoptotic cell death. Moutan Cortex Radicis's induction of apoptosis was connected with the upregulation of death receptor 4, death receptor 5, tumor necrosis factor-related apoptosis-inducing ligand, Fas ligand, and Bax, and the downregulation of Bcl-2 and Bid. Moutan Cortex Radicis treatment also induced the loss of mitochondrial membrane potential (Δψm), the proteolytic activation of caspases (-3, -8, and -9), and the degradation of poly(ADP-ribose) polymerase, an activated caspase-3 substrate protein. However, the pre-treatment of a caspase-3 inhibitor significantly attenuated Moutan Cortex Radicis-induced apoptosis and cell viability reduction. In addition, Moutan Cortex Radicis treatment effectively activated the adenosine monophosphate-activated protein kinase signaling pathway; however, a specific inhibitor of AMPK significantly reduced Moutan Cortex Radicis-induced apoptosis. Overall, the results suggest that the apoptotic activity of Moutan Cortex Radicis may be associated with a caspase-dependent cascade through the activation of both extrinsic and intrinsic signaling pathways connected with adenosine monophosphate-activated protein kinase activation, and Moutan Cortex Radicis as an activator of adenosine monophosphate-activated protein kinase could be a prospective application to treat human cancers.

Inhibitory effects on the production of inflammatory mediators and reactive oxygen species by Mori folium in lipopolysaccharide-stimulated macrophages and zebrafish

ABSTRACT Mori folium, the leaf of Morus alba L. (Moraceae), has been traditionally used for various medicinal purposes from ancient times to the present. In this study, we examined the effects of water extract of Mori folium (WEMF) on the production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. Our data indicated that WEMF significantly suppressed the secretion of NO and PGE2 in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects were accompanied by a marked reduction in their regulatory gene expression at the transcription level. WEMF attenuated LPS-induced intracellular ROS production in RAW 264.7 macrophages. It inhibited the nuclear translocation of the nuclear factor-kappa B p65 subunit and the activation of mitogen-activated protein kinases in LPS-treated RAW 264.7 macrophages. Furthermore, WEMF reduced LPS-induced NO production and ROS accumulation in zebrafish. Although more efforts are needed to fully understand the critical role of WEMF in the inhibition of inflammation, the findings of the present study may provide insights into the approaches for Mori folium as a potential therapeutic agent for inflammatory and antioxidant disorders.

Predicting the presence of an accessory hepatic vein using abdominal computed tomography / Predicción de la presencia de una vena hepática accesoria mediante tomografía computarizada abdominal

The incidence of detection of accessory hepatic vein (AHV) using MRI or CT has been reported. However, previous studies had a small sample size or only reported on the incidence of hepatic vein variants. To the best of our knowledge, there has been no previous report evaluating the factors predictive of the presence of an AHV. To evaluate the incidence and morphology of the accessory hepatic vein (AHV) using multidetector row computed tomography (MDCT) and to investigate the factors which may be helpful in predicting the presence of an AHV. We enrolled 360 patients who underwent abdominal MDCT. We investigated whether the AHV was present and evaluated the frequency of AHVs greater than 5 mm in diameter. We classified the morphology of the AHV entering the inferior vena cava (IVC). We also examined the factors that predicted the presence of an AHV by comparing the diameter of the middle hepatic vein (MHV) and the right hepatic vein (RHV). We identified an AHV in 164 of the 360 patients (45.6 %). Among the 164 AHVs, 56.7 % were larger than 5 mm in diameter. The most common morphologies of the inferior RHV were a single main trunk (58.5 %), followed by two main trunks with a V-shape (19.5 %) and two trunks entering the IVC separately (17.0 %). The possibility that an AHV will be present was significantly higher when the diameter of the RHV was smaller than that of the MHV. MDCT can provide important information regarding AHV incidence and morphology. The possibility of an AHV being present was significantly higher when the diameter of the RHV was smaller than that of the MHV.

Se ha informado de la incidencia de la detección de la vena hepática accesoria (VHA) mediante RM o TC. Sin embargo, estudios previos tenían un tamaño muestral pequeño o solo informaban sobre la incidencia de variantes de las venas hepáticas. Hasta donde sabemos, no ha habido ningún informe previo que evalúe los factores predictivos de la presencia de una VHA. El objetivo del estudio fue evaluar la incidencia y morfología de la vena hepática accesoria (VHA) mediante tomografía computarizada multidetector (TCMD) e investigar los factores que pueden ser útiles para predecir la presencia de un VHA. Se evaluaron 360 pacientes que se sometieron a TCMD abdominal. Se investigó si la VHA estaba presente y se evaluó la frecuencia de VHA mayores de 5 mm de diámetro. Se clasificó la morfología del VHA que drenaba en la vena cava inferior (VCI). Además, se examinaron los factores que predijeron la presencia de una VHA mediante la comparación del diámetro de la vena hepática media (VHM) y la vena hepática derecha (VHD). Se identificó un VHA en 164 de los 360 pacientes (45,6%). Entre las 164 VHA, el 56,7% tenía más de 5 mm de diámetro. Las morfologías más frecuentes del VHD inferior fueron un tronco principal único (58,5%), seguido por dos troncos principales con forma de V (19,5%) y dos troncos que drenaban en la VCI por separado (17,0%). La posibilidad de que una VHA esté presente fue significativamente mayor cuando el diámetro de la VHD era menor que la de la VHM. La MDCT puede proporcionar información importante sobre la incidencia de la VHA y su morfología. La posibilidad de que un VHA estuviera presente era significativamente mayor cuando el diámetro del VHD era menor que la VHM.

Ethanol extract of Prunus mume fruit attenuates hydrogen peroxide-induced oxidative stress and apoptosis involving Nrf2/HO-1 activation in C2C12 myoblasts

ABSTRACT The fruit of the Prunus mume (Siebold) Siebold & Zucc., Rosaceae (Korean name: Maesil) has long been used as a health food or valuable medicinal material in traditional herb medicine in Southeast Asian countries. In this study, we determined the potential therapeutic efficacy of the ethanol extract of P. mume fruits (EEPM) against H2O2-induced oxidative stress and apoptosis in the murine skeletal muscle myoblast cell line C2C12, and sought to understand the associated molecular mechanisms. The results indicated that exposure of C2C12 cells to H2O2 caused a reduction in cell viability by increasing the generation of intracellular reactive oxygen species and by disrupting mitochondrial membrane permeability, leading to DNA damage and apoptosis. However, pretreatment of the cells with EEPM before H2O2 exposure effectively attenuated these changes, suggesting that EEPM prevented H2O2-induced mitochondria-dependent apoptosis. Furthermore, the increased ex-pression and phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulation of heme oxygenase-1 (HO-1), a phase II antioxidant enzyme, were detected in EEPM-treated C2C12 cells. We also found that zinc protoporphyrin IX, an HO-1 inhibitor, attenuated the protective effects of EEPM against H2O2-induced reactive oxygen species accumulation and cytotoxicity. Therefore, these results indicate that the activation of the Nrf2/HO-1 pathway might be involved in the protection of EEPM against H2O2-induced cellular oxidative damage. In conclusion, these results show that EEPM contributes to the prevention of oxidative damage and could be used as a nutritional agent for oxidative stress-related diseases.