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Naturally occurring compounds are reported as effective candidates for prevention and treatment of various cancers. Breviscapine (BVP) is a mixture of flavonoid glycosides, derived from the Chinese herbs. Previous researches have indicated that BVP has comprehensive pharmacological functions. However, little is known about whether BVP has preventive effects on human prostate cancer. Here, we attempted to explore if BVP inhibits human prostate cancer in vitro and in vivo in a comprehensive manner. We found that BVP triggered cytotoxicity in prostate cancer cell lines dose-dependently. BVP-induced DNA damage caused the cell cycle arrest and apoptosis and further induced cell death. High expression of MCM-7 was reduced in BVP-treated cancer cells and tumor tissues, and also the DNA damage response marker of γH2AX is down-regulated by BVP, associated with MCM-7 expression through regulating retinoblastoma protein (Rb) and checkpoint control proteins expression. Additionally, BVP induced apoptotic response in prostate cancer cells and tumors via activating Caspase-3 and PARP. In vivo studies indicated that BVP impeded tumor growth in xenograft animal models. In conclusion, our data indicates that breviscapine (BVP) can be further explored for its potential, which might be used in human prostate cancer therapeutics. [ABSTRACT FROM AUTHOR]

Polygoni multiflori radix (PM) is a well-known tonic herb. It has been reported that PM could cause idiosyncratic inflammatory liver injury in some individuals. In this study, we investigated the mechanism of PM-induced idiosyncratic inflammatory liver injury in zebrafish and rat models based on pharmacodynamics and pharmacokinetics. The zebrafish were administered with polygoni multiflori radix extract (PME), emodin (EMO), and 2,3,5,4′-tetrahydroxystilbene-2-Ο-β- D -glucoside (TSG) after lipopolysaccharide (LPS) treatment, to establish an idiosyncratic inflammation model. In zebrafish with idiosyncratic inflammation, PME, EMO, and TSG decreased liver area and brightness and increased the number of immune cells around the colliculi. PME+LPS produced hepatocyte damage, aggravated mitochondrial and endoplasmic reticulum damage, and increased AST and ALT activity. RT-PCR showed that PME and EMO up-regulated the expression of IL-6, IL-1β, and INF-γ, and PME down-regulated expression of FXR and SHP. In rats with idiosyncratic inflammation, AST and ALT activities increased significantly, and liver tissues showed pathological damage. An efficient and sensitive LC-MS/MS method was established for the pharmacokinetic study of EMO and TSG in rats with idiosyncratic inflammation. The AUC 0−t was higher for EMO and TSG in the model group compared with the normal group. The MRT 0−t was significantly prolonged in EMO, while CL z/F was significantly reduced. The present results suggested that the absorption of potentially toxic components of PM increased and metabolism slowed down under inflammatory stress, and PM induced idiosyncratic liver injury via the FXR-SHP axis. [Display omitted] • PME induces liver injury under inflammatory stress. • The mechanism of idiosyncratic liver injury by PME may be related to FXR-SHP pathway. • A rapid and reliable UPLC-MS/MS method was established for pharmacokinetics of PME. • The absorption of EMO and TSG increased and metabolism slowed down in idiosyncratic liver injury rats, leading to aggravation of liver injury. [ABSTRACT FROM AUTHOR]

• Paris saponins I, II, Ⅵ and Ⅶ are the major bioactive compounds in Rhizoma Paris. • HUVEC cells was used for the first time to explore the anti-angiogenic activity of four saponins. • Paris saponins can inhibit endothelial cell proliferation, migration and invasion. • Paris saponins blocks cell cycle and induce endothelial cell apoptosis. • VEGF2, PI3K/AKT/mTOR, SRC/eNOS, P38, PLCγ/ERK/MERK, and JAK2-STAT3 pathways. Rhizoma Paris is a popular Chinese medicine in clinics. It contains four main saponins which are its major bioactive compounds. These saponins are Paris saponin I, II, VI and VII (PSI, PSII, PSVI and PSVII, respectively). Up to now, the research using HUVEC cells to evaluate the anti-angiogenic activity of four saponins is blank. The purpose of this study was to evaluate the anti-angiogenic properties (also known as angiotoxicity) of the four saponins in Rhizoma Paris on vascular endothelial cells-HUVEC cells, and to investigate the underlying mechanism, which has not been studied before. In this study, MTT assay, Lactate dehydrogenase (LDH) assay, wound healing experiments, transwell cell invasion assay, tubule formation experiment, DAPI staining, AV-PI double staining, and cell cycle analysis were used to determine the effects of Paris saponins. The results showed that, with increases in concentrations of PSI, PSII, PSVI and PSVII, the viability of HUVEC cells decreased significantly. In addition, four saponins dose-dependent enhanced LDH release and inhibited HUVEC cell migration, invasion, and angiogenesis. In terms of mechanism, PSI significantly inhibited protein expression in multiple signaling pathways. In particular, with the VEGF2 as the target, it activate the downstream PI3K / AKT / mTOR, SRC / eNOS, P38, PLCγ / ERK / MERK and JAK2/STAT3 signaling pathways. In conclusion, PSI, PSII, PSVI and PSVII can inhibit endothelial cell proliferation, migration and invasion, block endothelial cell cycle, induce endothelial cell apoptosis, act on protein expression in several anti-angiogenic signaling pathways, and finally inhibit angiogenesis in vitro. This study provides further data support for the clinical application of Paris saponins as antiangiogenic drugs. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common cancers with the highest morbidity and mortality. It is necessary to develop new anti-liver cancer drugs. Itraconazole is a popular systemic anti-fungal drug with a strong anti-tumor effect. However, so far, it is not clear whether itraconazole has specific anti-tumor effect on liver cancer. The purpose of this study was to investigate itraconazole resistant effect of liver cancer and to explore its potential anti-cancer mechanism. The effect of itraconazole on the proliferation of liver cancer cells was studied with MTT assay. Flow cytometry was used to determine the effect of itraconazole on apoptosis, cell cycle distribution, changes in intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). In addition, after DAPI staining, nuclear morphological changes were observed under the fluorescent microscope, and the release of lactate dehydrogenase (LDH) was measured using the microplate reader. Finally, the expressions of proteins related to the anti-tumor signaling pathway were determined by Western blotting. The results showed that itraconazole significantly inhibited the proliferation of HepG2 and Bel-7405 cells. In addition, the data showed that itraconazole induced apoptosis in HepG2 cells, increased the production of ROS, blocked cell cycle, and decreased MMP. Furthermore, itraconazole inhibited HCC cell growth and promoted apoptosis through the Hh, Wnt/catenin, AKT/mTOR/S6K, ROS and death receptor pathways. Finally, we come to the conclusion that itraconazole exerts anti-liver cancer effect, and has potential for use as a new drug for liver cancer in clinic. [ABSTRACT FROM AUTHOR]

• Xiaosheng prescription comes from clinic with definite curative effect. • Efficacy data combined with component data to reduce experimental workload. • Potential effective ingredients for early treatment of dry eye disease. Xiaosheng prescription (XSP) has been used for dry eye disease (DED) for more than 10 years in Eye Hospital of China Academy of Chinese Medicine Sciences. However, the effective ingredients involved have remained unclear, which was investigated in this study by the correlation of ingredient and therapeutic activity. Human corneal epithelial cells (HCEC) cultured with 110 mM NaCl solution in vitro and C57BL/6 mice injected subcutaneously with scopolamine hydrobromide were used to establish dry eye models, and the therapeutic effect of XSP extract 1 was better than that of XSP extract 2 significantly. Then, UPLC-Q-TOF/MS and data analysis program Progenesis QI and Makerlynx XS were used to analyze the potential effective ingredients of XSP, and 4 compounds were speculated and identified, in which Schisandrin and 1 μM of Schisantherin A could obviously increase the cell survival rate of injured cells on the cell model. It can be indicated that Schisandrin and Schisantherin A are probably the potential effective ingredients in XSP for DED. [ABSTRACT FROM AUTHOR]

To better understand the hepatotoxicity of anthraquinone glycosides, the hepatotoxicity of six anthraquinone glycosides was evaluated. The results show that chrysophanol-8- O -glucoside(C8G) has strong hepatotoxicity and can lead to increased LDH leakage and ROS, decreased GSH and MMP in L-02 hepatocytes. The results of C8G hepatotoxicity proteomics shows that, a total of 773 differentially expressed proteins were screened and analyzed using GO analysis and Pathway enrichment analysis. Our results show that C8G can lead to abnormal oxidative phosphorylation by inhibiting the function of mitochondrial complexes, resulting in decreased mitochondrial membrane potential (MMP), increased reactive oxygen species (ROS), and eventually resulting in mitochondrial damage and apoptosis. Western blot results verified the accuracy of quantitative proteomic results, and also evaluated the expression of Bax, caspase-3, -8, -9, Bcl-2, Cyt C in the mitochondria and cytosolic. The mitochondrial respiratory chain complexes activity assay result also confirmed that C8G could inhibit the activity of all mitochondrial complexes. The results of this study indicate that the hepatotoxicity mechanism of C8G is related to mitochondrial dysfunction, especially the mitochondrial complex function. [ABSTRACT FROM AUTHOR]