No abstract

Cancer rates are increasing dramatically, and there is currently a strong emphasis on identifying biologically active substances with anti-cancer activity from traditional herbs, as these are thought to have less adverse side-effects than conventional chemotherapy. Here, we examined the effects of extracts of Orostachys japonicus A. BERGER (O. japonicus) on cancer cell proliferation and apoptosis, and investigated the underlying signaling pathways. Dried powdered O. japonicus was extracted with 95% ethyl alcohol and fractionated with a series of organic solvents, including n-hexane (hexane), dichloromethane (DCM), ethylacetate (EtOAc), n-butanol (BuOH), and water (H 2 O). These extracts were tested for anti-cancer activity on a range of cancer cells; of all these, the EtOAc soluble fraction showed the highest anti-cancer activity, which was most marked in AGS human gastric cancer cells. The EtOAc fraction inhibited the proliferation of AGS cells in a dose-dependent and time-dependent manner, by inducing apoptosis and cell cycle arrest, as evidenced by 4,6-diamidino-2-phenylindole (DAPI) staining, annexin V-fluorescein isothiocyanate staining, propidium iodide-labeling, and DNA fragmentation assays. Western blot analysis revealed that p53 and cleaved caspase-3 proteins were up-regulated, and B cell lymphoma-2 (bcl-2) protein and pro-caspase-3 were down-regulated, but bcl-2 associated x protein (bax) protein was not regulated, in response to treatment of AGS cells with the EtOAc fraction. However, the changes of pro-caspase-3 and cleaved caspase-3 could be abolished by the pancaspase inhibitor Z-VAD-FMK. These results suggest the EtOAc fraction from O. japonicus has substantial anti-cancer activity in human gastric cancer cells.

This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride (CCl 4 )-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100 mg/kg of CLE or 100 mg/kg of butylated hydroxytoluene (BHT) for 14 days before CCl 4 administration. In addition, the CLE control group was pretreated with 100 mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of CCl 4 (20 mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the CCl 4 -treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the CCl 4 -treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the CCl 4 -treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against CCl 4 -induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.Keywords: Curcuma longa Linn. extract, carbon tetrachloride, hepatotoxicity, antioxidant, phase II detoxifying enzyme, nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) -, H 2 O 2 , and · OH, which damage the liver [27,36]. These ROS are eliminated by antioxidants and phase II detoxifying enzymes such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) [25,39]. Upregulation of many phase II detoxifying and antioxidant enzymes is mediated by antioxidant response elements (ARE). The transcription factor nuclear factorerythroid 2 (NF-E2)-related factor 2 (Nrf2) plays a pivotal role in the activation of ARE-driven antioxidant gene expression [6]. Nrf2 is a member of the "cap 'n' collar"

Orostachys japonicus shows various biological activities. However, the molecular mechanisms remain unknown in LPS-stimulated macrophages. Here, we investigated the anti-oxidizing effect of the dichloromethane (DCM) and hexane fractions from O. japonicus (OJD and OJH) against oxidative stress in RAW 264.7 cells stimulated by LPS. OJD and OJH significantly increased the expression of heme oxygenase-1 (HO-1) in a dose- and time-dependent manner. Additionally, it was found that the expression of HO-1 was stimulated by Nrf2 activated via degradation of Keap1. ERK and p38 inhibitors repressed HO-1 induced by OJD and OJH in LPS-stimulated cells, respectively. In conclusion, these results suggest that OJD and OJH may block oxidative damage stimulated by LPS, via increasing the expression of HO-1 and Nrf2, and MAPK signaling pathway. [BMB Reports 2014; 47(2): 98-103]

No abstract