Activator of NRF2
Int Urol Nephrol.2017 Nov 1. doi: 10.1007/s11255-017-1734-4.
Pterostilbene protects against
Chen ZW1, Miu HF1, Wang HP2, Wu ZN2, Wang WJ1, Ling YJ2, Xu XH2, Sun HJ2, Jiang X3.
Abstract
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
KEYWORDS: Chronic kidney disease; Endothelial cell; Nrf2; Pterostilbene; Uremia
PMID: 29094331 DOI: 10.1007/s11255-017-1734-4
Redox Rep.2017 Nov;22(6):501-507. doi: 10.1080/13510002.2017.1329917. Epub 2017 May 22.
Pterostilbene protects against UVB-induced photo-damage through a phosphatidylinositol-3-
Li H1, Jiang N1,2, Liang B1, Liu Q1,3, Zhang E1, Peng L1, Deng H1, Li R1, Li Z1, Zhu H1.
Abstract
OBJECTIVE: Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (
METHODS: Human keratinocytes were pretreated with
RESULTS:
CONCLUSION: The present study indicated that
KEYWORDS: Nrf2; Pterostilbene; antioxidants; photoprotection; ultraviolet
PMID: 28532341 DOI: 10.1080/13510002.2017.1329917
Oncotarget.2017 Jun 27;8(26):41988-42000. doi: 10.18632/oncotarget.16716.
Pterostilbene inhibits inflammation and ROS production in chondrocytes by activating Nrf2 pathway.
Xue EX1, Lin JP2, Zhang Y1, Sheng SR1, Liu HX1, Zhou YL1, Xu H1.
Abstract
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. Nrf2 expression was silenced by siRNA to evaluate the involvement of Nrf2 in the effect of pterostilbene on chondrocytes. Finally, osteoarthritis model was established by the
KEYWORDS: chondrocyte; inflammation; nuclear factor erythroid 2-related factor 2; pterostilbene; reactive oxygen species
PMID: 28410217 PMCID: PMC5522043DOI: 10.18632/oncotarget.16716
J Nutr Biochem.2017 Jun;44:11-21. doi: 10.1016/j.jnutbio.2017.02.015. Epub 2017 Mar 6.
Role of pterostilbene in attenuating
Sireesh D1, Ganesh MR2, Dhamodharan U1, Sakthivadivel M3, Sivasubramanian S3, Gunasekaran P3, Ramkumar KM4.
Abstract
Nrf2 (nuclear factor erythroid 2-related factor-2) is a transcription factor that regulates oxidative/xenobiotic stress response and also
KEYWORDS: Cytokine cocktail; Diabetes; MIN6; Nrf2; Streptozotocin
PMID: 28343084 DOI: 10.1016/j.jnutbio.2017.02.015
Biochim Biophys Acta.2017 Apr;1863(4):827-837. doi: 10.1016/j.bbadis.2017.01.005. Epub 2017 Jan 9.
Pterostilbene attenuates high glucose-induced oxidative injury in hippocampal neuronal cells by activating nuclear factor erythroid 2-related factor 2.
Yang Y1, Fan C2, Wang B3, Ma Z2, Wang D4, Gong B4, Di S2, Jiang S5, Li Y6, Li T6, Yang Z6, Luo E7.
Abstract
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
KEYWORDS: High glucose; Neuroprotection; Nuclear factor erythroid 2-related factor 2 signaling; Oxidative stress; Pterostilbene
PMID: 28089584 DOI: 10.1016/j.bbadis.2017.01.005
J Pharm Pharmacol.2017 Jan;69(1):73-81. doi: 10.1111/jphp.12657. Epub 2016 Nov 23.
The resveratrol derivatives trans-3,5-dimethoxy-4-fluoro-4′-
Fischer N1, Büchter C1, Koch K1, Albert S2, Csuk R2, Wätjen W1.
Abstract
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′-
METHODS: Trolox equivalent antioxidant capacity (TEAC), 2′,7′-dichlorofluorescein (DCF), thermotolerance assays, C.
KEY FINDINGS: All compounds exert a strong in-vitro radical scavenging activity (6 > 1 > 5 > 2 = 3 = 4), but in vivo, only (3) and (6) reduce reactive oxygen species (ROS) accumulation. Furthermore, (3) and (6) increased the mobility of aged nematodes and prolonged their mean lifespans, while these compounds decreased the thermal stress resistance. Using daf-16 (FoxO),
CONCLUSION: In contrast to resveratrol, the synthetic stilbene derivatives (3) and (6) increase the lifespan of C.
© 2016 Royal Pharmaceutical Society.
KEYWORDS: Nrf2; ageing; insulin-signalling; oxidative stress; secondary plant compounds
PMID: 27882602 DOI: 10.1111/jphp.12657
Eur J Pharmacol.2016 Oct 15;789:229-243. doi: 10.1016/j.ejphar.2016.07.046. Epub 2016 Jul 27.
Promising therapeutic potential of pterostilbene and its mechanistic insight based on preclinical evidence.
Kosuru R1, Rai U1, Prakash S1, Singh A2, Singh S3.
Abstract
Pterostilbene (PS) is a well-recognized antioxidant that primarily exists in blueberries, grapevines
KEYWORDS: AMPK; Cardiovascular disease; HO-1; NF-κB; Nrf2; Pterostilbene
PMID: 27475678 DOI: 10.1016/j.ejphar.2016.07.046
Bioorg Med Chem.2016 Aug 15;24(16):3378-86. doi: 10.1016/j.bmc.2016.05.011. Epub 2016 May 11.
Pterostilbene-mediated Nrf2 activation: Mechanistic insights on Keap1:Nrf2 interface.
Bhakkiyalakshmi E1, Dineshkumar K2, Karthik S1, Sireesh D3, Hopper W2, Paulmurugan R4, Ramkumar KM5.
Abstract
The discovery of Keap1-Nrf2 protein-protein interaction (PPI) inhibitors
KEYWORDS: ARE; Keap1; Molecular docking; Molecular dynamic simulation; Nrf2; Pterostilbene
PMID: 27312421 DOI: 10.1016/j.bmc.2016.05.011
Brain Res.2016 Jul 15;1643:70-9. doi: 10.1016/j.brainres.2016.04.048. Epub 2016 Apr 21.
Neuroprotective effects of pterostilbene against oxidative stress injury: Involvement of nuclear factor erythroid 2-related factor 2 pathway.
Wang B1, Liu H1, Yue L1, Li X1, Zhao L1, Yang X1, Wang X1, Yang Y2, Qu Y3.
Abstract
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. PTE was nontoxic and induced the nuclear translocation of Nrf2 when HT22 cell cultures were incubated with different concentrations of PTE. Further, PTE displayed a dose-dependent neuroprotective effect, as indicated by increased cell viability and a reduction in lactate dehydrogenase (LDH) release after glutamate treatment. Nrf2 siRNA treatment inhibited PTE-induced neuroprotective effects. Moreover, the levels of nuclear Nrf2 and downstream heme oxygenase-1 (HO-1) and
NAD(P)H: quinone oxidoreductase 1 (NQO1) were elevated after PTE treatment. The PTE-induced elevation of nuclear Nrf2, as well as the increases in HO-1 and NQO1 levels, was abolished by Nrf2 siRNA. PTE treatment reduced the production of reactive oxygen species (ROS) and significantly enhanced the activities of the cellular anti-oxidants glutathione (GSH) and superoxide dismutase (SOD), indicating an attenuation of glutamate-induced oxidative stress. These changes in ROS and GSH and SOD activity were reversed by Nrf2 siRNA. Our results indicate that PTE treatment attenuates glutamate-induced oxidative stress injury in neuronal cells via the Nrf2 signaling pathway.
Copyright © 2016 Elsevier B.V. All rights reserved.
KEYWORDS: Glutamate; Neuroprotection; Nuclear factor erythroid 2 (NF-E2)-related factor 2 signaling; Oxidative stress; Pterostilbene
PMID: 27107941 DOI: 10.1016/j.brainres.2016.04.048
Drug Chem Toxicol.2017 Jan;40(1):36-46. doi: 10.3109/01480545.2016.1169542. Epub 2016 Apr 14.
A comparative assessment of the cytotoxicity and nitric oxide reducing
Abstract
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
KEYWORDS: Nrf2; Resveratrol; anti-inflammatory effect of stilbenes; macrophages; piceatannol; pterostilbene; stilbenoids
PMID: 27079867 DOI: 10.3109/01480545.2016.1169542
Eur J Pharmacol.2016 Apr 15;777:9-16. doi: 10.1016/j.ejphar.2016.02.054. Epub 2016 Feb 24.
Anti-hyperlipidemic and anti-peroxidative role of pterostilbene via Nrf2 signaling in experimental diabetes.
Bhakkiyalakshmi E1, Sireesh D1, Sakthivadivel M2, Sivasubramanian S2, Gunasekaran P2, Ramkumar KM3.
Abstract
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. PTS administration to diabetic mice for 5 weeks significantly regulated blood glucose levels through the elevation of insulin secretion. The circulatory and liver lipid profiles of total cholesterol (TC), triglycerides (TG) and non-esterified fatty acids (NEFA) were maintained to normal levels upon PTS treatment. Moreover, PTS administration also normalized the circulatory levels of very low-, low- and
KEYWORDS: Diabetes; Dyslipidemia; Lipids; Nrf2; Pterostilbene; Streptozotocin
PMID: 26921755 DOI: 10.1016/j.ejphar.2016.02.054
Chem Res Toxicol.2016 Jan 19;29(1):47-57. doi: 10.1021/acs.chemrestox.5b00378. Epub 2016 Jan 7.
Pterostilbene Ameliorates Streptozotocin-Induced Diabetes through Enhancing Antioxidant Signaling Pathways Mediated by Nrf2.
Elango B, Dornadula S, Paulmurugan R1, Ramkumar KM.
Abstract
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. In STZ-induced diabetic mice, PTS administration significantly decreased blood glucose levels through the improvement of insulin secretion. In addition, we also observed insulin-positive cells with recovered islet architecture in the pancreas of STZ-induced diabetic mice after treatment with PTS. The activation of Nrf2 and expression of its downstream target genes were observed upon PTS treatment, thereby reducing oxidative damage to
PMID: 26700463 DOI: 10.1021/acs.chemrestox.5b00378
Antioxid Redox Signal.2016 Jun 10;24(17):974-90. doi: 10.1089/ars.2015.6437. Epub 2016 Mar 15.
Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo: A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism.
Benlloch M1, Obrador E2, Valles SL2, Rodriguez ML2, Sirerol JA2, Alcácer J3, Pellicer JA2, Salvador R2, Cerdá C4, Sáez GT4,5, Estrela JM2.
Abstract
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 (
RESULTS: Intravenous administration of
INNOVATION: Although bioavailability-related limitations may preclude direct anticancer effects in vivo, natural polyphenols may also interfere with the growth and defense of cancer cells by downregulating the pituitary gland-dependent ACTH synthesis.
CONCLUSIONS:
PMID: 26651028 PMCID: PMC4921902DOI: 10.1089/ars.2015.6437
Free Radic Biol Med.2015 Aug;85:1-11. doi: 10.1016/j.freeradbiomed.2015.03.027. Epub 2015 Apr 4.
Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcinogenesis.
Sirerol JA1, Feddi F2, Mena S1, Rodriguez ML1, Sirera P1, Aupí M1, Pérez S1, Asensi M3, Ortega A3, Estrela JM4.
Abstract
The aim of our study was to investigate in the SKH-1 hairless mouse model the effect of pterostilbene (
KEYWORDS: Free radicals; Oxidative stress; Photocarcinogenesis; Phytochemicals; Polyphenols; Pterostilbene; Resveratrol; Skin damage; Stilbenes; UV radiation
PMID: 25845487 DOI: 10.1016/j.freeradbiomed.2015.03.027
Pharmacol Res.2015 Jan;91:104-14. doi: 10.1016/j.phrs.2014.10.004. Epub 2014 Oct 29.
The emerging role of redox-sensitive Nrf2-Keap1 pathway in diabetes.
Bhakkiyalakshmi E1, Sireesh D2, Rajaguru P3, Paulmurugan R4, Ramkumar KM5.
Abstract
The pathogenic processes involving in the development of diabetes range from autoimmune destruction of pancreatic β-cells with consequent insulin deficiency to abnormalities that result in resistance to insulin action. The major contributing factor for excessive β-cell death includes oxidative stress-mediated mitochondrial damage, which creates an imbalance in redox homeostasis. Yet, β-cells have evolved adaptive mechanisms to endure a wide range of stress conditions to safeguard
KEYWORDS: Antioxidants; Bardoxolone methyl (PubChem CID: 400769); Cinnamaldehyde (PubChem CID: 637511); Curcumin (PubChem CID: 969516); Diabetes; Epigallocatechin gallate (PubChem CID: 65064); MG-132 (PubChem CID: 462382); Magnesium Lithospermate B (PubChem CID: 6438135); Nrf2 activators; Nrf2–Keap1 pathway; Oxidative stress; Pterostilbene (PubChem CID: 5281727); Resveratrol (PubChem CID: 445154); Sulforaphane (PubChem CID: 5350); tert-Butylhydroquinone (PubChem CID: 16043)
PMID: 25447793 DOI: 10.1016/j.phrs.2014.10.004
J Pharmacol Sci.2014;126(3):216-29. Epub 2014 Oct 21.
Involvement of the Nrf2 pathway in the regulation of pterostilbene-induced apoptosis in HeLa cells via ER stress.
Zhang B1, Wang XQ, Chen HY, Liu BH
Abstract
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. During drug exposure, alterations in the intracellular redox homeostasis that favor oxidation
PMID: 25341683
Food Chem Toxicol.2014 Oct;72:303-11. doi: 10.1016/j.fct.2014.07.038. Epub 2014 Aug 8.
The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species: involvement of the Nrf2-ARE signaling pathway.
Saw CL1, Guo Y2, Yang AY2, Paredes-Gonzalez X2, Ramirez C3, Pung D4, Kong AN5.
Abstract
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. Quercetin, kaempferol, and pterostilbene all exhibited strong free-radical scavenging activity in the DPPH assay. The MTS assay revealed that low concentration combinations we tested were relatively non-toxic to HepG2-C8 cells. The results of the DCFH-DA assay and combination index (CI) indicated that quercetin, kaempferol, and pterostilbene attenuated intracellular reactive oxygen species (ROS) levels when pretreated individually and had synergistic effects when used in combination. In addition, the combination treatment significantly induced ARE and increased the mRNA and protein expression of Nrf2-regulated genes. Collectively, our study demonstrated that the berry constituents quercetin, kaempferol, and pterostilbene activated the Nrf2-ARE signaling pathway and exhibited synergistic anti-oxidative stress activity at appropriate concentrations.
KEYWORDS: Antioxidant response element (ARE); Kaempferol; Nuclear factor (erythroid-derived 2)-like 2 (Nrf2); Pterostilbene; Quercetin; Reactive oxygen species
PMID: 25111660 DOI: 10.1016/j.fct.2014.07.038
Br J Pharmacol.2014 Apr;171(7):1747-57. doi: 10.1111/bph.12577.
Therapeutic potential of pterostilbene against pancreatic beta-cell apoptosis mediated through Nrf2.
Bhakkiyalakshmi E1, Shalini D, Sekar TV, Rajaguru P, Paulmurugan R, Ramkumar KM.
Abstract
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.
EXPERIMENTAL APPROACH: Immunoblotting and quantitative reverse transcriptase (qRT)-PCR analysis were performed to identify PTS-mediated nuclear translocation of Nrf2 protein and the following activation of target gene expression, respectively, in INS-1E cells. In addition, an annexin-V binding assay was carried out to identify the apoptotic status of PTS-treated INS-1E cells, while confirming the anti-apoptotic potential of Nrf2 by qRT-PCR analysis of the expressions of both pro- and anti-apoptotic genes.
KEY RESULTS: PTS induced significant activation of Nrf2, in
CONCLUSION AND IMPLICATIONS: Collectively, our findings indicate the therapeutic potential of Nrf2 activation by PTS as a promising approach to safeguard pancreatic beta-cells against oxidative damage in diabetes.
© 2014 The British Pharmacological Society.
KEYWORDS: Nrf2; apoptosis; diabetes; pancreatic beta cells; pterostilbene; streptozotocin
PMID: 24417315 PMCID: PMC3966753DOI: 10.1111/bph.12577
Anal Chem.2013 Aug 6;85(15):7542-9. doi: 10.1021/ac401569j. Epub 2013 Jul 23.
Reporter protein complementation imaging assay to screen and study Nrf2 activators in cells and living animals.
Ramkumar KM1, Sekar TV, Foygel K, Elango B, Paulmurugan R.
Abstract
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. Further, PTS increased the expression of Nrf2 downstream target genes, which was confirmed using
PMID: 23826874 PMCID: PMC3759980DOI: 10.1021/ac401569j
J Agric Food Chem.2011 Mar 23;59(6):2725-33. doi: 10.1021/jf2000103. Epub 2011 Feb 28.
Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway.
Chiou YS1, Tsai ML, Nagabhushanam K, Wang YJ, Wu CH, Ho CT, Pan MH.
Abstract
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. Male BALB/c mice were injected with AOM (5 mg/kg of body weight) with or without RS or PS, and at the end of the protocol, all of the mice were euthanized and colons were analyzed. Administrations of PS can be more effective than RS in reducing AOM-induced formation of aberrant crypt foci (ACF), lymphoid nodules (LNs), and tumors. We also find that PS is functioning more effectively than RS to reduce nuclear factor-κB (NF-κB) activation by inhibiting the phosphorylation of protein kinase C-β2 (PKC-β2) and decreasing downstream target gene expression, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and aldose reductase (AR) in mouse colon stimulated by AOM. Moreover, administration of RS and PS for 6 weeks significantly enhanced expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1) and glutathione reductase (GR), via activation of NF-E2-related factor 2 (Nrf2) signaling. When the above findings are taken together, they suggest that both stilbenes block cellular inflammation and oxidative stress through induction of HO-1 and GR, thereby preventing AOM-induced colon carcinogenesis. In comparison, PS was a more potent chemopreventive agent than RS for the prevention of colon cancer. This is also the first study to demonstrate that PS is
PMID: 21355597 DOI: 10.1021/jf2000103