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Melpo Christofidousolomidou - One of the best experts on this subject based on the ideXlab platform.
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synthetic Secoisolariciresinol Diglucoside attenuates established pain oxidative stress and neuroinflammation in a rodent model of painful radiculopathy
Antioxidants, 2020Co-Authors: Sonia Kartha, Ralph A Pietrofesa, Melpo Christofidousolomidou, Christine L Weisshaar, Beth A WinkelsteinAbstract:Painful cervical radiculopathy is characterized by chronic neuroinflammation that lowers endogenous antioxidant responses leading to the development of oxidative stress and pain after neural trauma. Therefore, antioxidants such as Secoisolariciresinol Diglucoside (SDG), that promote antioxidant signaling and reduce oxidative damage may also provide pain relief. This study investigated if repeated systemic administration of synthetic SDG after a painful root compression reduces the established pain, oxidative stress and spinal glial activation that are typically evident. SDG was administered on days 1-3 after compression and the extent of oxidative damage in the dorsal root ganglia (DRG) and spinal cord was measured at day 7 using the oxidative stress markers 8-hydroxguanosine (8-OHG) and nitrotyrosine. Spinal microglial and astrocytic activation were also separately evaluated at day 7 after compression. In addition to reducing pain, SDG treatment reduced both spinal 8-OHG and nitrotyrosine, as well as peripheral 8-OHG in the DRG. Moreover, SDG selectively reduced glial activation by decreasing the extent of astrocytic but not microglial activation. These findings suggest that synthetic SDG may attenuate existing radicular pain by suppressing the oxidative stress and astrocytic activation that develop after painful injury, possibly identifying it as a potent therapeutic for painful radiculopathies.
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synthetic Secoisolariciresinol Diglucoside lgm2605 inhibits libby amphibole fiber induced acute inflammation in mice
Toxicology and Applied Pharmacology, 2019Co-Authors: Melpo Christofidousolomidou, Ralph A Pietrofesa, Steven M Albelda, Kyewon Park, Kinta M Serve, Deborah E Keil, Jean C PfauAbstract:Abstract Background Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived Secoisolariciresinol Diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice. Methods Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry. Results LA exposure induced a significant increase (p Conclusions LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases. Summary Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.
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synthetic Secoisolariciresinol Diglucoside lgm2605 inhibits myeloperoxidase activity in inflammatory cells
Biochimica et Biophysica Acta, 2018Co-Authors: Om P Mishra, Ralph A Pietrofesa, Anatoliy V Popov, Eiko Nakamaruogiso, Mark D Andrake, Melpo ChristofidousolomidouAbstract:Abstract Background Myeloperoxidase (MPO) generates hypochlorous acid (HOCl) during inflammation and infection. We showed that Secoisolariciresinol Diglucoside (SDG) scavenges radiation-induced HOCl in physiological solutions. However, the action of SDG and its synthetic version, LGM2605, on MPO-catalyzed generation of HOCl is unknown. The present study evaluated the effect of LGM2605 on human MPO, and murine MPO from macrophages and neutrophils. Methods MPO activity was determined fluorometrically using hypochlorite-specific 3′-(p-aminophenyl) fluorescein (APF). The effect of LGM2605 on (a) the peroxidase cycle of MPO was determined using Amplex Red while the effect on (b) the chlorination cycle was determined using a taurine chloramine assay. Using electron paramagnetic resonance (EPR) spectroscopy we determined the effect of LGM2605 on the EPR signals of MPO. Finally, computational docking of SDG was used to identify energetically favorable docking poses to enzyme's active site. Results LGM2605 inhibited human and murine MPO activity. MPO inhibition was observed in the absence and presence of Cl−. EPR confirmed that LGM2605 suppressed the formation of Compound I, an oxoiron (IV) intermediate [Fe(IV) O] containing a porphyrin π-radical of MPO's catalytic cycle. Computational docking revealed that SDG can act as an inhibitor by binding to the enzyme's active site. Conclusions We conclude that LGM2605 inhibits MPO activity by suppressing both the peroxidase and chlorination cycles. EPR analysis demonstrated that LGM2605 inhibits MPO by decreasing the formation of the highly oxidative Compound I. This study identifies a novel mechanism of LGM2605 action as an inhibitor of MPO and indicates that LGM2605 may be a promising attenuator of oxidant-dependent inflammatory tissue damage.
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synthetic lignan Secoisolariciresinol Diglucoside lgm2605 reduces asbestos induced cytotoxicity in an nrf2 dependent and independent manner
Antioxidants, 2018Co-Authors: Ralph A Pietrofesa, Evguenia Arguiri, Steven M Albelda, Shampa Chatterjee, Kyewon Park, Melpo ChristofidousolomidouAbstract:Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan Secoisolariciresinol Diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2−/−) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm2) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2−/− macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.
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synthetic lignan Secoisolariciresinol Diglucoside lgm2605 reduces asbestos induced cytotoxicity in an nrf2 dependent and independent manner
Antioxidants, 2018Co-Authors: Ralph A Pietrofesa, Evguenia Arguiri, Steven M Albelda, Shampa Chatterjee, Kyewon Park, Melpo ChristofidousolomidouAbstract:Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan Secoisolariciresinol Diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2−/−) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm2) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2−/− macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.
Massimo Bambagiottialberti - One of the best experts on this subject based on the ideXlab platform.
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validation of a reversed phase high performance thin layer chromatographic densitometric method for Secoisolariciresinol Diglucoside determination in flaxseed
Journal of Chromatography A, 2008Co-Authors: Silvia A. Coran, Gianluca Bartolucci, Massimo BambagiottialbertiAbstract:The validation of a HPTLC-densitometric method for the determination of Secoisolariciresinol Diglucoside (SDG) in flaxseed was performed improving the reproducibility of a previously reported HPTLC densitometric procedure by the use of fully wettable reversed phase plates (silica gel 60 RP18W F(254S), 10cmx10cm) with MeOH:HCOOH 0.1% (40:60, v/v) mobile phase. The analysis required only the alkaline hydrolysis in aqueous medium of undefatted samples and densitometry at 282nm of HPTLC runs. The method was validated following the protocol proposed by the Societe Francaise des Sciences et Techniques Pharmaceutiques (SFSTP) giving rise to a dependable and high throughput procedure well suited to routine application. SDG was quantified in the range of 321-1071ng with RSD of repeatability and intermediate precision not exceeding 3.61% and accuracy inside the acceptance limits. Flaxseed of five cultivars of different origin was elected as test-bed.
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high performance thin layer chromatographic densitometric determination of Secoisolariciresinol Diglucoside in flaxseed
International Symposium on Pharmaceutical and Biomedical Analysis, 2004Co-Authors: Silvia A. Coran, Valerio Giannellini, Massimo BambagiottialbertiAbstract:A HPTLC-densitometric method, based on an external standard approach, was developed in order to obtain a novel procedure for routine analysis of Secoisolariciresinol Diglucoside (SDG) in flaxseed with a minimum of sample pre-treatment. Optimization of TLC conditions for the densitometric scanning was reached by eluting HPTLC silica gel plates in a horizontal developing chamber. Quantitation of SDG was performed in single beam reflectance mode by using a computer-controlled densitometric scanner and applying a five-point calibration in the 1.00-10.00 μg/spot range. As no sample preparation was required, the proposed HPTLC-densitometric procedure demonstrated to be reliable, yet using an external standard approach. The proposed method is precise, reproducible and accurate and can be employed profitably in place of HPLC for the determination of SDG in complex matrices.
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complete assignment of the 1h and 13c nmr spectra of Secoisolariciresinol Diglucoside a mammalian lignan precursor isolated from linum usitatissimum
Magnetic Resonance in Chemistry, 1999Co-Authors: Stefano Chimichi, Massimo Bambagiottialberti, Valerio Giannellini, Silvia A. Coran, Boris BiddauAbstract:A convenient isolation and purification protocol for Secoisolariciresinol Diglucoside (1), a precursor of the biologically active mammalian lignans enterolactone and enterodiol, from flax seed is reported together with an extensive 1D- and 2D-NMR study (GE-HSQC, GE-HMBC and NOESY) leading to its definitive characterization as 2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]-1,4-butanediyl bis-[R-(R*,R*)]-β-D-glucopyranoside. Copyright © 1999 John Wiley & Sons, Ltd.
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investigation of mammalian lignan precursors in flax seed first evidence of Secoisolariciresinol Diglucoside in two isomeric forms by liquid chromatography mass spectrometry
Rapid Communications in Mass Spectrometry, 1994Co-Authors: Massimo Bambagiottialberti, Caterina Ghiara, Andrea Raffaelli, Silvia A Coron, Gloriano Moneti, Pietro TraldiAbstract:A strong research effort has been devoted in recent years to the mammalian lignans enterolactone and enterodiol because of their claimed protective effects against breast and colon cancer. Some plant lignans appear to be precursors of these molecules. This paper reports a novel identification procedure for one of these precursors, the Secoisolariciresinol Diglucoside, in the extracts of defatted flax-seed meal. The procedure is based on high-performance liquid chromatography coupled with either ionspray or continuous-flow fast-atom bombardment mass spectrometry. The application of these techniques allowed the identification in flax seed of two isomeric forms of this precursor for the first time. The isomers are reasonable the two diastereoisomers, due to the two equivalent stereogenic centers present in the molecule.
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revealing the mammalian lignan precursor Secoisolariciresinol Diglucoside in flax seed by ionspray mass spectrometry
Rapid Communications in Mass Spectrometry, 1994Co-Authors: Massimo Bambagiottialberti, Caterina Ghiara, Valerio Giannellini, Andrea Raffaelli, Silvia A. Coran, Pietro TraldiAbstract:Ionspray mass spectrometry allowed the rapid detection and unambiguous identification of Secoisolariciresinol Diglucoside, an important mammalian lignan precursor occurring in flax seed. It was observed that this compound is embedded in a complex form, probably a complex glucoside of still undisclosed structure, among the polar solvent extractables of flax seed from which it could not be released as such without the intervention of alkaline methanolysis. Comparison of ionspray mass spectra of untreated and methanolysed flax-seed extracts confirmed methanolysis as the crucial step in setting up any further analytical or preparative procedure concerned with Secoisolariciresinol Diglucoside.
Markus Dachtler - One of the best experts on this subject based on the ideXlab platform.
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on line liquid chromatography nuclear magnetic resonance spectroscopy mass spectrometry coupling for the separation and characterization of Secoisolariciresinol Diglucoside isomers in flaxseed
Journal of Chromatography A, 2002Co-Authors: Jan Fritsche, R Angoelal, Markus DachtlerAbstract:Abstract Two Secoisolariciresinol Diglucoside (SDG) diastereomers were extracted from flaxseed and liberated through alkaline hydrolysis. Anion-exchange and reversed-phase chromatography were successfully employed to purify the hydrolyzed flaxseed extract. On-line LC–NMR–MS analyses revealed the structure of the isolated and purified SDG diastereomers, [2 R ,2′ R ]-2,3-bis[(4-hydroxy-3-methoxyphenyl)-methyl]-1,4-butanediyl-bis-β-glucopyranoside the predominant flaxseed lignan and [2 R ,2′ S ]-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]-1,4-butanediyl-bis-β-glucopyranoside, a previously incompletely characterized minor flaxseed lignan. Circular dichroism (CD) analyses confirmed the presence of two distinguished optically active compounds present in the flaxseed extract.
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on line liquid chromatography nuclear magnetic resonance spectroscopy mass spectrometry coupling for the separation and characterization of Secoisolariciresinol Diglucoside isomers in flaxseed
Journal of Chromatography A, 2002Co-Authors: Jan Fritsche, R Angoelal, Markus DachtlerAbstract:Two Secoisolariciresinol Diglucoside (SDG) diastereomers were extracted from flaxseed and liberated through alkaline hydrolysis. Anion-exchange and reversed-phase chromatography were successfully employed to purify the hydrolyzed flaxseed extract. On-line LC-NMR-MS analyses revealed the structure of the isolated and purified SDG diastereomers, [2R,2'R]-2,3-bis[(4-hydroxy-3-methoxyphenyl)-methyl]-1,4-butanediyl-bis-beta-glucopyranoside the predominant flaxseed lignan and [2R,2'S]-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]-1,4-butanediyl-bis-beta-glucopyranoside, a previously incompletely characterized minor flaxseed lignan. Circular dichroism (CD) analyses confirmed the presence of two distinguished optically active compounds present in the flaxseed extract.
Ralph A Pietrofesa - One of the best experts on this subject based on the ideXlab platform.
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synthetic Secoisolariciresinol Diglucoside attenuates established pain oxidative stress and neuroinflammation in a rodent model of painful radiculopathy
Antioxidants, 2020Co-Authors: Sonia Kartha, Ralph A Pietrofesa, Melpo Christofidousolomidou, Christine L Weisshaar, Beth A WinkelsteinAbstract:Painful cervical radiculopathy is characterized by chronic neuroinflammation that lowers endogenous antioxidant responses leading to the development of oxidative stress and pain after neural trauma. Therefore, antioxidants such as Secoisolariciresinol Diglucoside (SDG), that promote antioxidant signaling and reduce oxidative damage may also provide pain relief. This study investigated if repeated systemic administration of synthetic SDG after a painful root compression reduces the established pain, oxidative stress and spinal glial activation that are typically evident. SDG was administered on days 1-3 after compression and the extent of oxidative damage in the dorsal root ganglia (DRG) and spinal cord was measured at day 7 using the oxidative stress markers 8-hydroxguanosine (8-OHG) and nitrotyrosine. Spinal microglial and astrocytic activation were also separately evaluated at day 7 after compression. In addition to reducing pain, SDG treatment reduced both spinal 8-OHG and nitrotyrosine, as well as peripheral 8-OHG in the DRG. Moreover, SDG selectively reduced glial activation by decreasing the extent of astrocytic but not microglial activation. These findings suggest that synthetic SDG may attenuate existing radicular pain by suppressing the oxidative stress and astrocytic activation that develop after painful injury, possibly identifying it as a potent therapeutic for painful radiculopathies.
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synthetic Secoisolariciresinol Diglucoside lgm2605 inhibits libby amphibole fiber induced acute inflammation in mice
Toxicology and Applied Pharmacology, 2019Co-Authors: Melpo Christofidousolomidou, Ralph A Pietrofesa, Steven M Albelda, Kyewon Park, Kinta M Serve, Deborah E Keil, Jean C PfauAbstract:Abstract Background Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived Secoisolariciresinol Diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice. Methods Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry. Results LA exposure induced a significant increase (p Conclusions LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases. Summary Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.
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synthetic Secoisolariciresinol Diglucoside lgm2605 inhibits myeloperoxidase activity in inflammatory cells
Biochimica et Biophysica Acta, 2018Co-Authors: Om P Mishra, Ralph A Pietrofesa, Anatoliy V Popov, Eiko Nakamaruogiso, Mark D Andrake, Melpo ChristofidousolomidouAbstract:Abstract Background Myeloperoxidase (MPO) generates hypochlorous acid (HOCl) during inflammation and infection. We showed that Secoisolariciresinol Diglucoside (SDG) scavenges radiation-induced HOCl in physiological solutions. However, the action of SDG and its synthetic version, LGM2605, on MPO-catalyzed generation of HOCl is unknown. The present study evaluated the effect of LGM2605 on human MPO, and murine MPO from macrophages and neutrophils. Methods MPO activity was determined fluorometrically using hypochlorite-specific 3′-(p-aminophenyl) fluorescein (APF). The effect of LGM2605 on (a) the peroxidase cycle of MPO was determined using Amplex Red while the effect on (b) the chlorination cycle was determined using a taurine chloramine assay. Using electron paramagnetic resonance (EPR) spectroscopy we determined the effect of LGM2605 on the EPR signals of MPO. Finally, computational docking of SDG was used to identify energetically favorable docking poses to enzyme's active site. Results LGM2605 inhibited human and murine MPO activity. MPO inhibition was observed in the absence and presence of Cl−. EPR confirmed that LGM2605 suppressed the formation of Compound I, an oxoiron (IV) intermediate [Fe(IV) O] containing a porphyrin π-radical of MPO's catalytic cycle. Computational docking revealed that SDG can act as an inhibitor by binding to the enzyme's active site. Conclusions We conclude that LGM2605 inhibits MPO activity by suppressing both the peroxidase and chlorination cycles. EPR analysis demonstrated that LGM2605 inhibits MPO by decreasing the formation of the highly oxidative Compound I. This study identifies a novel mechanism of LGM2605 action as an inhibitor of MPO and indicates that LGM2605 may be a promising attenuator of oxidant-dependent inflammatory tissue damage.
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synthetic lignan Secoisolariciresinol Diglucoside lgm2605 reduces asbestos induced cytotoxicity in an nrf2 dependent and independent manner
Antioxidants, 2018Co-Authors: Ralph A Pietrofesa, Evguenia Arguiri, Steven M Albelda, Shampa Chatterjee, Kyewon Park, Melpo ChristofidousolomidouAbstract:Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan Secoisolariciresinol Diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2−/−) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm2) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2−/− macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.
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synthetic lignan Secoisolariciresinol Diglucoside lgm2605 reduces asbestos induced cytotoxicity in an nrf2 dependent and independent manner
Antioxidants, 2018Co-Authors: Ralph A Pietrofesa, Evguenia Arguiri, Steven M Albelda, Shampa Chatterjee, Kyewon Park, Melpo ChristofidousolomidouAbstract:Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan Secoisolariciresinol Diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2−/−) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm2) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2−/− macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.
Kaushik Ghose - One of the best experts on this subject based on the ideXlab platform.
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flaxseed lignan Secoisolariciresinol Diglucoside improves insulin sensitivity through upregulation of glut4 expression in diet induced obese mice
Journal of Functional Foods, 2015Co-Authors: Yanwen Wang, Kaushik Ghose, Bourlaye Fofana, Marvasweeney Nixon, Sandhya Nair, Gregoire NyombaAbstract:Abstract The efficacy and mechanism of flaxseed lignan Secoisolariciresinol Diglucoside (SDG) on glucose hemostasis in obese mice were examined. Male C57BL/6J mice fed on a high-fat diet (60 kcal% fat) for 15 weeks were divided into four groups and treated by oral gavage with 0, 10, 100, or 1000 mg/kg/d of SDG dissolved in water for 6 weeks. Age-matched mice fed with a low-fat diet (10% kcal fat) were used as the normal control. SDG lowered fasting blood glucose, insulin, and free fatty acid levels and improved oral glucose tolerance, insulin response, and homeostatic model assessment-estimated insulin resistance index in mice fed the high-fat diet. Flaxseed SDG also increased GLUT4 expression and tended to increase phosphorylated AKT to total AKT ratio in the muscle tissue. The data demonstrated that flaxseed SDG improved glycaemic control, at least in part, by enhancing insulin signalling and sensitivity in diet-induced obese mice.
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Flaxseed lignan Secoisolariciresinol Diglucoside improves insulin sensitivity through upregulating GLUT4 expression in diet-induced obese mice (829.25)
The FASEB Journal, 2014Co-Authors: Yanwen Wang, Bourlaye Fofana, Kaushik GhoseAbstract:Flaxseed Lignan Secoisolariciresinol Diglucoside Improves Insulin Sensitivity through Upregulating GLUT4 Expression in Diet-Induced Obese Mice Yanwen Wang1, Bourlaye Fofana2, Moumita Roy1, and Kaus...