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Nrf2 AND pterostilbene

Ramoji Kosuru, Vidya Kandula, Uddipak Rai, Swati Prakash, Zhengyuan Xia, Sanjay Singh
PURPOSE: Oxidative stress has a pivotal role in the pathogenesis of diabetes-associated cardiovascular problems, which has remained a primary cause of the increased morbidity and mortality in diabetic patients. It is of paramount importance to prevent the diabetes-associated cardiac complications by reducing oxidative stress with the help of nutritional or pharmacological agents. Pterostilbene (PT), the primary antioxidant in blueberries, has recently gained attention for its promising health benefits in metabolic and cardiac diseases...
April 2018: Cardiovascular Drugs and Therapy
Zhi-Wei Chen, Hai-Feng Miu, Hui-Ping Wang, Zhi-Niu Wu, Wen-Juan Wang, Yu-Jing Ling, Xiao-Hui Xu, Hai-Jian Sun, Xia Jiang
Chronic kidney disease causes uremia-related endothelial cell dysfunction associated with high risk for cardiovascular diseases. The vascular endothelium is permanently exposed to uraemic toxins including indoxyl sulfate, which provokes endothelial damage in subjects with end-stage renal disease. Pterostilbene (PT) is identified to be homologous derivative of resveratrol and exerts antioxidant and anti-inflammatory actions. However, the effects of PT on uraemic serum-induced endothelial cell damage have not been elucidated...
March 2018: International Urology and Nephrology
Huaping Li, Na Jiang, Bihua Liang, Qing Liu, Erting Zhang, Liqian Peng, Huiyan Deng, Runxiang Li, Zhenjie Li, Huilan Zhu
OBJECTIVE: Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes. METHODS: Human keratinocytes were pretreated with Pter (5 and 10 μM) for 24 h prior to UVB irradiation (300 mJ/cm(2))...
May 22, 2017: Redox Report: Communications in Free Radical Research
En-Xing Xue, Jian-Ping Lin, Yu Zhang, Sun-Ren Sheng, Hai-Xiao Liu, Yu-Long Zhou, Hui Xu
Pterostilbene has been reported as a potential drug to inhibit oxidative stress and inflammation. However, the effect of pterostilbene on chondrocytes and osteoarthritis remains to be elucidated. We sought to investigate whether pterostilbene could protect chondrocytes from inflammation and ROS production through factor erythroid 2-related factor 2 (Nrf2) activation. The pterostilbene toxicity on chondrocytes collected from cartilages of Sprague-Dawley rats was assessed by CCK-8 test. Immunofluorescence and Western blotting explored the nuclear translocation of Nrf2...
June 27, 2017: Oncotarget
Dornadula Sireesh, Munuswamy-Ramanujam Ganesh, Umapathy Dhamodharan, Murugesan Sakthivadivel, Srinivasan Sivasubramanian, Palani Gunasekaran, Kunka Mohanram Ramkumar
Nrf2 (nuclear factor erythroid 2-related factor-2) is a transcription factor that regulates oxidative/xenobiotic stress response and also suppress inflammation. Nrf2 signaling is associated with an increased susceptibility to various kinds of stress. Nrf2 has been shown as a promising therapeutic target in various human diseases including diabetes. Our earlier studies showed Pterostilbene (PTS) as a potent Nrf2 activator, and it protects the pancreatic β-cells against oxidative stress. In this study, we investigated PTS confer protection against cytokine-induced β-cell apoptosis and its role on insulin secretion in streptozotocin (STZ)-induced diabetic mice...
June 2017: Journal of Nutritional Biochemistry
Yang Yang, Chongxi Fan, Bodong Wang, Zhiqiang Ma, Dongjin Wang, Bing Gong, Shouyin Di, Shuai Jiang, Yue Li, Tian Li, Zhi Yang, Erping Luo
In the present study, neuroblastoma (SH-SY5Y) cells were used to investigate the mechanisms mediating the potential protective effects of pterostilbene (PTE) against mitochondrial metabolic impairment and oxidative stress induced by hyperglycemia for mimicking the diabetic encephalopathy. High glucose medium (100mM) decreased cellular viability after 24h incubation which was evidenced by: (i) reduced mitochondrial complex I and III activities; (ii) reduced mitochondrial cytochrome C; (iii) increased reactive oxygen species (ROS) generation; (iv) decreased mitochondrial membrane potential (ΔΨm); and (v) increased lactate dehydrogenase (LDH) levels...
April 2017: Biochimica et Biophysica Acta
Nadine Fischer, Christian Büchter, Karoline Koch, Sabrina Albert, René Csuk, Wim Wätjen
OBJECTIVES: Resveratrol (trans-3,4',5-trihydroxystilbene (1)) was previously shown to extend the lifespan of different model organisms. However, its pharmacological efficiency is controversially discussed. Therefore, the bioactivity of four newly synthesized stilbenes (trans-3,5-dimethoxy-4-fluoro-4'-hydroxystilbene (3), trans-4'-hydroxy-3,4,5-trifluorostilbene (4), trans-2,5-dimethoxy-4'-hydroxystilbene (5), trans-2,4',5-trihydroxystilbene (6)) was compared to (1) and pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene (2)) in the established model organism Caenorhabditis elegans...
January 2017: Journal of Pharmacy and Pharmacology
Elango Bhakkiyalakshmi, Kesavan Dineshkumar, Suresh Karthik, Dornadula Sireesh, Waheeta Hopper, Ramasamy Paulmurugan, Kunka Mohanram Ramkumar
The discovery of Keap1-Nrf2 protein-protein interaction (PPI) inhibitors has become a promising strategy to develop novel lead molecules against variety of stress. Hence, Keap1-Nrf2 system plays an important role in oxidative/electrophilic stress associated disorders. Our earlier studies identified pterostilbene (PTS), a natural analogue of resveratrol, as a potent Nrf2 activator and Keap1-Nrf2 PPI inhibitor as assessed by luciferase complementation assay. In this study, we further identified the potential of PTS in Nrf2 activation and ARE-driven downstream target genes expression by nuclear translocation experiments and ARE-luciferase reporter assay, respectively...
August 15, 2016: Bioorganic & Medicinal Chemistry
Bodong Wang, Haixiao Liu, Liang Yue, Xia Li, Lei Zhao, Xiangmin Yang, Xinchuan Wang, Yang Yang, Yan Qu
UNLABELLED: Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) regulates multiple anti-oxidative enzymes and has neuroprotective effects. Pterostilbene (PTE) is a natural anti-oxidant found in blueberries. Its non-metabolized form exhibits high distribution in the brain after dietary administration. In this study, we aimed to explore the potential of PTE in protecting murine hippocampal neuronal HT22 cells against glutamate-induced oxidative stress injury and possible underlying mechanisms...
July 15, 2016: Brain Research
Christelle A Adiabouah Achy-Brou, Blase Billack
The present study investigated the pharmacological effects of three stilbenoids, resveratrol (RES), pterostilbene (PTR) and piceatannol (PIC), in transformed and normal macrophages. Our first aim was to comparatively assess the cytotoxicity of RES, PTR and PIC in unstimulated transformed mouse macrophages (RAW 264.7 cells) and primary peritoneal macrophages (PMs) harvested from both wild type and Nrf2 (nuclear factor erythroid 2-related factor 2)-deficient female mice. Our second aim was to investigate whether the inhibitory effect of RES, PTR and PIC on nitric oxide (NO) release from stimulated PMs depends on the status of the transcription factor Nrf2...
January 2017: Drug and Chemical Toxicology
Elango Bhakkiyalakshmi, Dornadula Sireesh, Murugesan Sakthivadivel, Srinivasan Sivasubramanian, Palani Gunasekaran, Kunka Mohanram Ramkumar
Nuclear factor erythroid 2-related factor (Nrf2), a key transcription factor triggers the expression of antioxidant and detoxification genes thereby providing cellular protective functions against oxidative stress-mediated disorders. Recent research has identified that pharmacological activation of Nrf2 also regulates the largest cluster of genes associated with lipid metabolism. With this background, this paper highlights the anti-hyperlipidemic and anti-peroxidative role of pterostilbene (PTS), an Nrf2 activator, in streptozotocin (STZ)-induced diabetic model...
April 15, 2016: European Journal of Pharmacology
Bhakkiyalakshmi Elango, Sireesh Dornadula, Ramasamy Paulmurugan, Kunka Mohanram Ramkumar
Nuclear factor erythroid 2-related factor 2 (Nrf2) remains a master regulator of cytoprotective and antioxidant genes. In this study, we investigated the antidiabetic role of pterostilbene (PTS) in streptozotocin (STZ)-induced diabetic model through Nrf2-mediated antioxidant mechanisms. The ability of PTS to activate Nrf2 in MIN6 cells was assessed by dissociation of the Nrf2-Keap1 complex at different time points and by expression of ARE-driven downstream target genes of Nrf2. Immunoblot experiments examining Nrf2 activation and phosphorylation indicated that it conferred cytoprotection against STZ-induced cellular damage...
January 19, 2016: Chemical Research in Toxicology
María Benlloch, Elena Obrador, Soraya L Valles, María L Rodriguez, J Antoni Sirerol, Javier Alcácer, José A Pellicer, Rosario Salvador, Concha Cerdá, Guillermo T Sáez, José M Estrela
AIMS: Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies, lack of correlation with the bioavailable concentrations is a critical issue. Some reports had suggested that these molecules downregulate the stress response, which may affect growth and the antioxidant protection of malignant cells. Initially, we studied this potential underlying mechanism using different human melanomas (with genetic backgrounds correlating with most melanomas), growing in nude mice as xenografts, and pterostilbene (Pter, a natural dimethoxylated analog of resveratrol)...
June 10, 2016: Antioxidants & Redox Signaling
J Antoni Sirerol, Fatima Feddi, Salvador Mena, María L Rodriguez, Paula Sirera, Miguel Aupí, Salvador Pérez, Miguel Asensi, Angel Ortega, José M Estrela
The aim of our study was to investigate in the SKH-1 hairless mouse model the effect of pterostilbene (Pter), a natural dimethoxy analog of resveratrol (Resv), against procarcinogenic ultraviolet B radiation (UVB)-induced skin damage. Pter prevented acute UVB (360 mJ/cm(2))-induced increase in skin fold, thickness, and redness, as well as photoaging-associated skin wrinkling and hyperplasia. Pter, but not Resv, effectively prevented chronic UVB (180 mJ/cm(2), three doses/week for 6 months)-induced skin carcinogenesis (90% of Pter-treated mice did not develop skin carcinomas, whereas a large number of tumors were observed in all controls)...
August 2015: Free Radical Biology & Medicine
Bo Zhang, Xiao-Qin Wang, Han-Yin Chen, Bin-Hua Liu
Among the various cancer cell lines, HeLa cells were found to be sensitive to pterostilbene (Pte), a compound that is enriched in small fruits such as grapes and berries. However, the mechanism involved in the cytotoxicity of Pte has not been fully characterized. Using biochemical and free radical biological experiments in vitro, we identified the pro-apoptotic profiles of Pte and evaluated the level of redox stress-triggered ER stress during HeLa cell apoptosis. The data showed a strong dose-response relationship between Pte exposure and the characteristics of HeLa apoptosis in terms of changes in apoptotic morphology, DNA fragmentation, and activated caspases in the intrinsic apoptotic pathway...
2014: Journal of Pharmacological Sciences
Constance Lay Lay Saw, Yue Guo, Anne Yuqing Yang, Ximena Paredes-Gonzalez, Christina Ramirez, Douglas Pung, Ah-Ng Tony Kong
Quercetin, kaempferol, and pterostilbene are abundant in berries. The anti-oxidative properties of these constituents may contribute to cancer chemoprevention. However, their precise mechanisms of action and their combinatorial effects are not completely understood. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates anti-oxidative stress enzymes and Phase II drug metabolizing/detoxifying enzymes by binding to antioxidant response element (ARE). This study aimed to investigate the anti-oxidative stress activities of quercetin, kaempferol, and pterostilbene individually and in combination, as well as the involvement of the Nrf2-ARE signaling pathway...
October 2014: Food and Chemical Toxicology
Elango Bhakkiyalakshmi, Devibalan Shalini, Thillai Veerapazham Sekar, Palanisamy Rajaguru, Ramasamy Paulmurugan, Kunka Mohanram Ramkumar
BACKGROUND AND PURPOSE: Nuclear factor erythroid 2-related factor 2 (Nrf2) is considered to be a 'master regulator' of the antioxidant response as it regulates the expression of several genes including phase II metabolic and antioxidant enzymes and thus plays an important role in preventing oxidative stress-mediated disorders, including diabetes. In this study, for the first time, we investigated the protective properties of a naturally available antioxidant, pterostilbene (PTS), against pancreatic beta-cell apoptosis and the involvement of Nrf2 in its mechanism of action...
April 2014: British Journal of Pharmacology
Kunka Mohanram Ramkumar, Thillai Veerapazham Sekar, Kira Foygel, Bhakkiyalakshmi Elango, Ramasamy Paulmurugan
NF-E2-related factor-2 (Nrf2) activators promote cellular defense mechanism and facilitate disease prevention associated with oxidative stress. In the present study, Nrf2 activators were identified using cell-based luciferase enzyme fragment complementation (EFC) assay, and the mechanism of Nrf2 activation was studied by molecular imaging. Among the various Nrf2 activators tested, pterostilbene (PTS) showed effective Nrf2 activation, as seen by luminometric screening, and validation in a high throughput-intact cell-imaging platform...
August 6, 2013: Analytical Chemistry
Yi-Siou Chiou, Mei-Ling Tsai, Kalyanam Nagabhushanam, Yin-Jen Wang, Chih-Hsiung Wu, Chi-Tang Ho, Min-Hsiung Pan
Inflammatory bowel diseases have been a risk factor of colorectal cancer (CRC). The reactive oxygen species (ROS) generated by inflammatory cells create oxidative stress and contribute to neoplastic transformation, proliferation, and even metastasis. Previously, resveratrol (RS) and pterostilbene (PS) had been reported to prevent chemical-induced colon carcinogenesis by anti-inflammatory and pro-apoptotic properties. In this study, we investigated whether RS and PS could prevent the azoxymethane (AOM)-induced colon tumorigenesis via antioxidant action and to explore possible molecular mechanisms...
March 23, 2011: Journal of Agricultural and Food Chemistry
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