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Rashi Arora, Sharad Sawney, Vikas Saini, Chris Steffi, Manisha Tiwari, Daman Saluja
BACKGROUND: A handful of studies have exploited antitumor potential of esculetin, a dihydroxy coumarine derivative; the targets to which it binds and the possible downstream mechanism for its cytotoxicity in cancer cells remain to be elucidated. Using pancreatic cancer cell lines as a model system, herein the study was initiated to check the efficacy of esculetin in inhibiting growth of these cancer cells, to decipher mechanism of its action and to predict its direct binding target protein...
October 18, 2016: Molecular Cancer
Sedar Karakurt
Expression of a drug and xenobiotic metabolizing enzymes, cytochrome P450s (CYPs), and antioxidant enzymes can be modulated by various factors. The flavonoid rutin was investigated for its anti-carcinogen and protective effects as well as modulatory action on CYPs and phase II enzymes in human hepatocellular carcinoma cells. Rutin inhibited proliferation of HEPG2 cells in a dose-dependent manner with the IC50 value of 52.7 μmol L-1 and invasion of HEPG2 cells (21.6 %, p = 0.0018) and colony formation of those invaded cells (57...
December 1, 2016: Acta Pharmaceutica
Daniel Hanna, Ariane Emami Riedmaier, Kim S Sugamori, Denis M Grant
The incidence of liver cancer is higher in men than in women. This sex difference is also observed in murine tumor induction models that result in the appearance of liver tumors in adult mice following their exposure on postnatal days 8 and/or 15 to carcinogens such as 4-aminobiphenyl (ABP) or diethylnitrosamine (DEN). Previous studies performed in adult mice showed that acute hepatotoxic and inflammatory responses to high-dose DEN exposure were greater in males than in females, leading to the suggestion that these responses could account for the sex difference in tumor development...
October 13, 2016: Toxicology
Chang-Bum Ahn, Jae-Young Je, Young-Sang Kim, Sun-Joo Park, Boo Il Kim
Chemical modification of chitosan is a promising method for the improvement of biological activity. In this study, chitosan-caffeic acid (CCA) was prepared and its in vitro hepatoprotective ability against hydrogen peroxide-induced hepatic damage in liver cells was evaluated. Treatment with CCA (50-400 µg/mL) did not show cytotoxicity and also significantly (p < 0.05) recovered cell viability against 650 µM hydrogen peroxide-induced hepatotoxicity. CCA treatment attenuated reactive oxygen species generation and lipid peroxidation in addition to increasing cellular glutathione level in cultured hepatocytes...
October 15, 2016: Molecular and Cellular Biochemistry
Zhiying Luo, Xi Li, Mingfeng Zhu, Jie Tang, Zhi Li, Xinming Zhou, Guobao Song, Zhaoqian Liu, Honghao Zhou, Wei Zhang
BACKGROUND: The variation among patients in warfarin response complicated the management of warfarin therapy, improper therapeutic dose usually result in serious adverse events. OBJECTIVE: A two-stage extreme phenotype strategy was conducted to discover novel warfarin dose associated mutations in heart valve replacement (HVR) patients. PATIENTS/METHOD: A total of 1617 warfarin stable dose (WSD) patients were enrolled and divided randomly into two cohorts...
October 14, 2016: Journal of Thrombosis and Haemostasis: JTH
Yeon-Hui Jeong, Jin-Sun Park, Dong-Hyun Kim, Hee-Sun Kim
Lonchocarpine is a phenylpropanoid compound isolated from Abrus precatorius that has anti-bacterial, anti-inflammatory, antiproliferative, and antiepileptic activities. In the present study, we investigated the antioxidant effects of lonchocarpine in brain glial cells and analyzed its molecular mechanisms. We found that lonchocarpine suppressed reactive oxygen species (ROS) production and cell death in hydrogen peroxide-treated primary astrocytes. In addition, lonchocarpine increased the expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and manganese superoxide dismutase (MnSOD), which are all under the control of Nrf2/antioxidant response element (ARE) signaling...
October 17, 2016: Biomolecules & Therapeutics
Hui Ding, Handong Wang, Lin Zhu, Wuting Wei
Previous studies have indicated oxidative stress and inflammatory injury as significant contributors to the secondary damage associated with traumatic brain injury (TBI). Ursolic acid (UA) has been demonstrated to exert anti-oxidative and anti-inflammatory effects on cerebral ischemia by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. However, the effects of UA on TBI remain unclear. The aim of this study is to evaluate the potential roles of UA in the activation of the Nrf2 pathway using an experimental TBI model and the underlying mechanism...
October 12, 2016: Neurochemical Research
Winifred Broekman, Helene Roelofs, Maria C Zarcone, Christian Taube, Jan Stolk, Pieter S Hiemstra
Autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) are evaluated for clinical use in chronic obstructive pulmonary disease (COPD) patients, but it is unclear whether COPD affects BM-MSCs. To investigate this, BM-MSCs from nine COPD patients and nine non-COPD age-matched controls were compared with regard to immunophenotype, growth and differentiation potential, and migration capacity. Other functional assays included the response to pro-inflammatory stimuli and inducers of the nuclear factor (erythroid derived 2)-like 2 antioxidant response element (Nrf2-ARE) pathway, and effects on NCI-H292 airway epithelial cells...
April 2016: ERJ Open Research
Shu-Hua Yang, Miao Long, Li-Hui Yu, Lin Li, Peng Li, Yi Zhang, Yang Guo, Feng Gao, Ming-Da Liu, Jian-Bin He
Sulforaphane (SFN) is a natural and highly effective antioxidant. Studies suggest that SFN protects cells and tissues against cadmium (Cd) toxicity. This study investigated the protective effect of SFN against oxidative damage in the testes of Kunming mice exposed to cadmium, and explored the possible molecular mechanisms involved. Cadmium greatly reduced the serum testosterone levels in mice, reduced sperm motility, total sperm count, and increased the sperm deformity rate. Cadmium also reduces superoxide dismutase (T-SOD) and glutathione (GSH) levels and increases malondialdehyde (MDA) concentrations...
October 11, 2016: International Journal of Molecular Sciences
Ananddeep Patel, Shaojie Zhang, Amrit Kumar Shrestha, Paramahamsa Maturu, Bhagavatula Moorthy, Binoy Shivanna
Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC...
October 8, 2016: Toxicology and Applied Pharmacology
Qianying Zhang, Zhike Li, Shuangchan Wu, Xiaofei Li, Ying Sang, Jian Li, Yunhui Niu, Hong Ding
Multiple sclerosis (MS) is a demyelinating disease occurring in the central nervous system. In the present study, we evaluated the function of myricetin on the alleviation of behavioral dysfunction and myelin protection in the cuprizone-induced demyelination model. Mice were daily fed with fodder including 0.2% cuprizone and were administrated myricetin (100 mg kg(-1)) by gavage administration for 5 weeks. The treatment of myricetin ameliorated hyper-locomotion and behavior impairment induced by cuprizone toxicity...
October 12, 2016: Food & Function
Shinhee Park, Sunny Lihua Cheng, Julia Yue Cui
Intestine is responsible for the biotransformation of many orally-exposed chemicals. The constitutive androstane receptor (CAR/Nr1i3) is known to up-regulate many genes encoding drug-metabolizing enzymes and transporters (drug-processing genes/DPGs) in liver, but less is known regarding its effect in intestine. Sixty-day-old wild-type and Car(-/-) mice were administered the CAR-ligand TCPOBOP or vehicle once daily for 4 days. In wild-type mice, Car mRNA was down-regulated by TCPOBOP in liver and duodenum. Car(-/-) mice had altered basal intestinal expression of many DPGs in a section-specific manner...
September 2016: Acta Pharmaceutica Sinica. B
Hwa-Kyung Kim, Tae Gen Son, Dong-Gyu Jo, Dong Chung Kim, Dong-Hoon Hyun
Lipid-soluble ginseng extracts (LSGE) is known to inhibit many types of cancer cells through arresting cell cycle and inducing apoptosis. Usually, normal cells are can also be damaged by anti-tumor reagents. The plasma membrane redox system (PMRS) is enhanced to compensate mitochondrial dysfunction and impaired energy metabolism. NADH-quinone oxidoreductase 1 (NQO1), a plasma membrane redox enzyme, is known to be induced by panaxytriol, one of components of lipid-soluble ginseng extracts (LSGE). The objective of this study was determine the mechanisms of NQO1 involved in neuroprotection in response to cytotoxicity induced by LSGE...
October 2016: Archives of Pharmacal Research
I S Haslam, L Jadkauskaite, Imre Lőrinc Szabó, S Staege, J Hesebeck-Brinckmann, G Jenkins, R Bhogal, F L Lim, N Farjo, B Farjo, T Bíró, M Schäfer, R Paus
The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of Nrf2, the "master regulator" of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ, human scalp hair follicles (HFs)...
October 1, 2016: Journal of Investigative Dermatology
Seon Yeong Chae, Sun Young Park, Jin Oh Park, Kyu Jin Lee, Geuntae Park
This study reports a green approach for synthesis of gold nanoparticles using Gardenia jasminoides extract, and specifically, can potentially enhance anti senescence activity. Biological synthesis of gold nanoparticles is ecofriendly and effective for the development of environmentally sustainable nanoparticles compared with existing methods. Here, we developed a simple, fast, efficient, and ecofriendly approach to the synthesis of gold nanoparticles by means of a Gardenia jasminoides extract. These G. jasminoides extract-capped gold nanoparticles (GJ-GNPs) were characterized by UV-vis, high resolution transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), and Furrier transform infrared spectroscopy (FT-IR)...
September 28, 2016: Journal of Photochemistry and Photobiology. B, Biology
Fuguo Shi, Xiaobing Li, Hong Pan, Li Ding
Rifampicin (RIF) is used in regimens for infections caused by Mycobacteria accompanied by serious adverse reactions. Rifampicin-quinone (RIF-Q) is a major autoxidation product of RIF. It is not clear whether RIF-Q plays a role in RIF induced adverse reactions. Investigation of the systemic exposure of RIF-Q is helpful to better understand the role of RIF-Q in RIF induced adverse reactions. In this study, a simple and reproducible high performance liquid chromatography-mass spectrometry (LC-MS) method involving a procedure to prevent the RIF from oxidation for simultaneous quantification of RIF and RIF-Q in rat plasma has been developed and validated, and applied to elucidate the systemic exposure of RIF-Q in rats...
September 26, 2016: Journal of Pharmaceutical and Biomedical Analysis
Nicholas O Thomas, Kate P Shay, Amanda R Kelley, Judy A Butler, Tory M Hagen
Isolated hepatocytes from young (4-6mo) and old (24-26mo) F344 rats were exposed to increasing concentrations of menadione, a vitamin K derivative and redox cycling agent, to determine whether the age-related decline in Nrf2-mediated detoxification defenses resulted in heightened susceptibility to xenobiotic insult. An LC50 for each age group was established, which showed that aging resulted in a nearly 2-fold increase in susceptibility to menadione (LC50 for young: 405μM; LC50 for old: 275μM). Examination of the known Nrf2-regulated pathways associated with menadione detoxification revealed, surprisingly, that NAD(P)H: quinone oxido-reductase 1 (NQO1) protein levels and activity were induced 9-fold and 4-fold with age, respectively (p=0...
September 22, 2016: Redox Biology
Xiaohui Su, Qingchun Huang, Jianyu Chen, Maojie Wang, Hudan Pan, Rui Wang, Hua Zhou, Zhanqing Zhou, Juan Liu, Fen Yang, Ting Li, Liang Liu
The activation of synovial fibroblasts (SFs) and the subsequent production and expression of pro-inflammatory cytokines play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). In the current study, rheumatoid arthritis synovial fibroblasts (RASFs) isolated from the joint of the patients were used to evaluate the suppressive effects of calycosin (CAL), a compound derived from the Chinese medicinal herb Radix Astragali, on the expression of pro-inflammatory cytokines in RASFs. The results demonstrated that increased mRNA expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-25 (IL-25), interleukin-33(IL-33) were significantly inhibited by CAL...
September 24, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Christoph Bisig, Michèle Roth, Loretta Müller, Pierre Comte, Norbert Heeb, Andreas Mayer, Jan Czerwinski, Alke Petri-Fink, Barbara Rothen-Rutishauser
Ethanol can be produced from biomass and as such is renewable, unlike petroleum-based fuel. Almost all gasoline cars can drive with fuel containing 10% ethanol (E10), flex-fuel cars can even use 85% ethanol (E85). Brazil and the USA already include 10-27% ethanol in their standard fuel by law. Most health effect studies on car emissions are however performed with diesel exhausts, and only few data exists for other fuels. In this work we investigated possible toxic effects of exhaust aerosols from ethanol-gasoline blends using a multi-cellular model of the human lung...
September 23, 2016: Environmental Research
Wenli Wang, Ning Li, Jian Wang, Gang Chen, Renbin Huang, Weihong Zhao, Jiayuan Li, Yingying Si
Five chalcanes ((α'R)-2, α'-dimethoxy-furano-[4″, 5'': 3', 4'] chalcane, (α'R, βR)-2', α', β-trimethoxy-furano-[4″, 5'': 3', 4'] chalcane, (α'S, βR)-2', α', β-trimethoxy-furano-[4″, 5'': 3', 4'] chalcane, (α'R, βR)-2', β-dimethoxy-α'-hydroxyethoxy-furano-[4″, 5'': 3', 4'] chalcane, (α'S, βR)-2', β-dimethoxy-α'-hydroxyethoxy-furano-[4″, 5'': 3', 4'] chalcane) and a flavonoid glycoside (3', 7-dihydroxy-6-methoxy-4', 5'-methylenedioxyisoflavone 6-O-β-D- glucopyranoside), together with 15 known components, were isolated from the leaves of Millettia pulchra (Benth) Kurzvar-laxior (Dunn) Z...
November 2016: Phytochemistry
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