High-resolution Tandem Mass Spectrometry for Studying Chemical Constituents of Gynura bicolor DC.

The separation and analysis of the desired chemical components are important subjects for the fundamental research of traditional Chinese medicine (TCM). Ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) has gradually become a leading technology for the identification of TCM ingredients. Gynura bicolor DC. (BFH), a perennial stemless herb used for medicine and food in China has medicinal effects such as clearing heat, moistening the lung, relieving cough, dispersing stasis, and relieving swelling. Polyphenols and flavonoids contain numerous isomers, which hinder the identification of the complex compounds in BFH. This paper presents a systematic protocol for studying chemical constituents of BFH based on solvent extraction and integrated data via UPLC-Q-TOF-MS. The method described here includes systematic protocols for sample pretreatment, MS calibration, MS acquisition, data processing, and analysis of results. Sample pretreatment includes collection, cleaning, drying, crushing, and extraction. MS calibration consists of multipoint and single-point correction. Data processing includes data importing, method establishment, analysis processing, and result presentation. Representative results of the typical fragmentation pattern of phenolic acids, esters, and glycosides in Gynura bicolor DC. (BFH) are presented in this paper. In addition, organic solvent selection, extraction, data integration, collision energy selection, and method improvement are discussed in detail. This universal protocol can be widely used to identify complex compounds in TCM.

Taurine alleviates high-fat-high-glucose-induced pancreatic islet ß-cell oxidative stress and apoptosis in rat.

The effect of taurine (TAU) as a specific regulatory mediator on pancreatic function in obese rats induced by a high-fat-high-glucose (HFHG) diet was investigated. We fed male Sprague-Dawley rats under different conditions, namely the control, HFHG, TAU, and HFHG + TAU treatment groups for 4 months. Compared with the HFHG group, TAU supplementation significantly reduced malondialdehyde levels and increased superoxide dismutase, total antioxidant capacity, and glutathione levels in the rat pancreas. In addition, TAU significantly decreased the level of reactive oxygen species, and markedly increased the activity of heme oxygenase 1 (HO-1), Kelch-like ECH-associated protein 1 (KEAP-1), and nuclear factor erythrocyte-2-related factor 2 (Nrf2) in the rat pancreas. Notably, HFHG diet could induce pancreatic injury in the rats through the Nrf2/HO-1 signaling pathway and activate the mitochondrial channel-mediated apoptotic signaling pathway. The addition of TAU significantly improved the pancreatic tissue injury induced by the HFHG diet in the rats and reduced the protein expression of Caspase-3, Cleaved-caspase-3, Caspase-9 and Bcl-2 associated protein X (BAX), and increased the protein expression of B-cell lymphoma-2 (Bcl-2). In conclusion, this experiment confirmed that TAU could alleviate the oxidative stress and apoptosis induced by the HFHG diet in rat pancreatic ß-cells.

Parisfargosides A-E, five new cholestane glycosides from the rhizomes of Paris fargesii.

Five new cholestane glycosides, named parisfargosides A-E (1-5), were isolated from the rhizomes of Paris fargesii. Their structures were elucidated on the basis of UV, HR-ESI-MS, 1D and 2D NMR data as well as chemical methods. The structures of all compounds contained α, ß-unsaturated ketone unit. Compounds 3-5 possessed a 16,23-cyclocholest skeleton with 6/6/6/5/5 condensed ring, and the absolute configurations of C-16 and C-23 were confirmed according to ROESY spectra with pyridine­d5 and DMSO­d6 as solvents. In addition, the platelet aggregation activity and cytotoxic activity against five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480) of compounds 1-5 were evaluated.

Isobavachalcone isolated from Psoralea corylifolia inhibits cell proliferation and induces apoptosis via inhibiting the AKT/GSK-3ß/ß-catenin pathway in colorectal cancer cells.

Background: Colorectal cancer (CRC) is a common form of cancer associated with a high mortality rate and poor prognosis. Given the limited efficacy of current therapies for CRC, interest in novel therapeutic agents isolated from natural sources has increased. We studied the anticancer properties of isobavachalcone (IBC), a flavonoid isolated from the herb Psoralea corylifolia, which is used in traditional Chinese medicine, in an in vitro model of CRC. Materials and methods: Cell viability and growth of CRC cells were determined by Cell Counting Kit-8 and colony formation assays following treatment with varying concentrations of IBC, respectively. Apoptosis was examined by 4',6-diamidino-2-phenylindole staining and flow cytometry with Annexin V/propidium iodide double staining. Western blot analysis was used to analyze expression of apoptosis-associated protein pathway and the AKT/GSK-3ß/ß-catenin signaling pathway. Results: Initial experiments showed that IBC inhibited proliferation and colony formation of human CRC cell lines in dose- and time-dependent manners. The antiproliferative effect of IBC resulted from induction of apoptosis, as evidenced by morphological changes in the nucleus, flow cytometry analysis, upregulation of cleaved caspase-3 and cleaved PARP, changes in the ratio of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax, translocation of Bax from the cytosol to the mitochondria, and decreased expression of two inhibitors of apoptosis family proteins, XIAP, and survivin. Western blot analysis of signaling pathway proteins demonstrated that IBC downregulated Wnt/ß-catenin signaling, which has previously been associated with CRC, by inhibiting the AKT/GSK-3ß signaling pathway. Conclusion: This study demonstrated that IBC inhibited cell proliferation and induced apoptosis through inhibition of the AKT/GSK-3ß/ß-catenin pathway in CRC. These results suggest the potential of IBC as a novel therapeutic agent for the treatment of CRC.

IR780-loaded folate-targeted nanoparticles for near-infrared fluorescence image-guided surgery and photothermal therapy in ovarian cancer.

Background and purpose: Surgery is regarded as the gold standard for patients with advanced ovarian cancer. However, complete surgical removal of tumors remains extremely challenging; fewer than 40% of patients are cured. Here, we developed a new modality of theranostics for ovarian cancer based on a near-infrared light-triggered nanoparticle. Methods: Nanoparticles loading IR780 iodide on base of folate modified liposomes were prepared and used for theranostics of ovarian cancer. Tumor targeting of FA-IR780-NP was evaluated in vitro and in an ovarian xenograft tumor model. A fluorescence stereomicroscope was applied to evaluate the tumor recognition of FA-IR780-NP during surgery. FA-IR780-NP mediated photothermal therapy effect was compared with other treatments in vivo. Results: FA-IR780-NP was demonstrated to specifically accumulate in tumors. IR780 iodide selectively accumulated in tumors; the enhanced permeability and retention effect of the nanoparticles and the active targeting of folate contributed to the excellent tumor targeting of FA-IR780-NP. With the aid of tumor targeting, FA-IR780-NP could be used as an indicator for the real-time delineation of tumor margins during surgery. Furthermore, photothermal therapy mediated by FA-IR780-NP effectively eradicated ovarian cancer tumors compared with other groups. Conclusion: In this study, we present a potential, effective approach for ovarian cancer treatment through near-infrared fluorescence image-guided resection and photothermal therapy to eliminate malignant tissue.

Effects of in utero meso-2,3-dimercaptosuccinic acid with calcium and ascorbic acid on lead-induced fetal development.

To examine the effects of meso-2,3-dimercaptosuccinic acid (DMSA) on developmental toxicity resulting from exposure to lead in utero, female albino mice were exposed to lead by drinking water contaminated with lead acetate for 4 weeks. After the cessation of lead exposure, female mice were supplemented by gavage with saline solution, DMSA, or DMSA and calcium as well as ascorbic acid from the fourth day of gestation until parturition, respectively. Lead levels (blood, liver, and bone) were measured at birth. Pups were then tested about neural development including surface righting reflex, cliff avoidance and air righting reflex. The markers of physical maturation, such as body weight, pinna unfolding, incisor eruption, and eye opening were also recorded. DMSA treatment decreased blood lead levels of pregnant mice, however, increased lead levels in both liver and bone of fetus, and delayed the early physical and neural development of offspring. Calcium and ascorbic acid reduced the transfer of lead to fetus. In conclusion, DMSA treatment during pregnancy enhances lead-induced fetal developmental toxicity.