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Jacob Vaya - One of the best experts on this subject based on the ideXlab platform.

  • Glabridin protects paraoxonase 1 from linoleic acid hydroperoxide inhibition via specific interaction a fluorescence quenching study
    Journal of Agricultural and Food Chemistry, 2012
    Co-Authors: Dana Atrahimovich, Jacob Vaya, Hagai Tavori, Soliman Khatib
    Abstract:

    The enzyme paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and is responsible for many of HDL's antiatherogenic properties. We previously showed that recombinant PON1 is inhibited by linoleic acid hydroperoxide (LA-OOH) present in the lipid fraction of the human carotid plaque (LLE) via oxidation of the enzyme's Cys284 thiol. Here we explore the effect of Glabridin, an isoflavan isolated from licorice root, on preventing LA-OOH's inhibitory effect on rePON1 using the tryptophan-fluorescence-quenching technique and modeling calculations. Glabridin significantly prevented rePON1 inhibition by LLE or oxidized linoleic acid (by 22% and 15%, respectively), whereas ascorbic acid and Trolox, strong antioxidants, had no effect. Glabridin quenched the intrinsic fluorescence of rePON1 in a concentration-dependent manner. Binding parameters and modeling calculations demonstrated a major role for hydrophobic forces in the rePON1-Glabridin interaction, indicating that it is not the antioxidant capacity of Glabridin that protects rePON1 from LA-OOH inhibition, but rather its specific interaction with the enzyme.

  • estrogenic activity of Glabridin and glabrene from licorice roots on human osteoblasts and prepubertal rat skeletal tissues
    The Journal of Steroid Biochemistry and Molecular Biology, 2004
    Co-Authors: Dalia Somjen, Sara Katzburg, Jacob Vaya, Alvin M Kaye, David Hendel, Gary H Posner, Snait Tamir
    Abstract:

    Data from both in vivo and in vitro experiments demonstrated that Glabridin and glabrene are similar to estradiol-17 in their stimulation of the specific activity of creatine kinase, although at higher concentrations, but differ in their extent of action and interaction with other drugs. In pre-menopausal human bone cells, the response to estradiol-17 and Glabridin (at higher concentration) was higher than in post-menopausal cells; whereas, glabrene (at higher concentration) was more effective in post-menopausal cells. At both ages, the response to estradiol-17 and Glabridin was enhanced by pretreatment with the less-calcemic Vitamin D analog CB 1093 (CB) and the demonstrably non-calcemic analog JK 1624 F2-2 (JKF). The response to glabrene was reduced by this pretreatment. Both Glabridin and glabrene stimulated creatine kinase specific activity in diaphyseal bone and epiphyseal cartilage of prepubertal female rats. Daily feeding (3‐14 days) of prepubertal female rats with Glabridin, estradiol-17 or their combination, also stimulated creatine kinase specific activity. Glabridine, similarly to estradiol-17 , also stimulated creatine kinase specific activity in ovariectomized female rats. Raloxifene, in combination with Glabridin or estradiol-17 , demonstrated the phenomenon of mutual annihilation of stimulation of creatine kinase specific activity in both epiphysis and diaphysis. Glabrene activity was not inhibited by raloxifene. Therefore, Glabridin shows greater similarity to estradiol-17 and thus greater potential, with or without Vitamin D, to modulate bone disorders in post-menopausal women. © 2004 Elsevier Ltd. All rights reserved.

  • estrogen like activity of licorice root constituents Glabridin and glabrene in vascular tissues in vitro and in vivo
    The Journal of Steroid Biochemistry and Molecular Biology, 2004
    Co-Authors: Dalia Somjen, Jacob Vaya, Naftali Stern, Esther Knoll, Snait Tamir
    Abstract:

    Post-menopausal women have higher incidence of heart diseases compared to pre-menopausal women, suggesting a protective role for estrogen. The recently Women's Health Initiative (WHI) randomized controlled trial concluded that the overall heart risk exceeded benefits from use of combined estrogen and progestin as hormone replacement therapy for an average of five years among healthy postmenopausal US women. Therefore, there is an urgent need for new agents with tissue-selective activity with no deleterious effects. In the present study, we tested the effects on vascular tissues in vitro and in vivo of two natural compounds derived from licorice root: Glabridin, the major isoflavan, and glabrene, an isoflavene, both demonstrated estrogen-like activities. Similar to estradiol-17beta (E2), Glabridin (gla) stimulated DNA synthesis in human endothelial cells (ECV-304; E304) and had a bi-phasic effect on proliferation of human vascular smooth muscle cells (VSMC). Raloxifene inhibited gla as well as E2 activities. In animal studies, both intact females or after ovariectomy, gla similar to E2 stimulated the specific activity of creatine kinase (CK) in aorta (Ao) and in left ventricle of the heart (Lv). Glabrene (glb), on the other hand, had only the stimulatory effect on DNA synthesis in vascular cells, with no inhibition by raloxifene, suggesting a different mechanism of action. To further elucidate the mechanism of action of glb, cells were pre-incubated with glb and then exposed to either E2 or to gla; the DNA stimulation at low doses was unchanged but there was abolishment of the inhibition of VSMC cell proliferation at high doses as well as inhibition of CK stimulation by both E2 and by gla. We conclude that glb behaved differently than E2 or gla, but similarly to raloxifene, being a partial agonist/antagonist of E2. Glabridin, on the other hand, demonstrated only estrogenic activity. Therefore, we suggest the use of glb with or without E2 as a new agent for modulation of vascular injury and atherogenesis for the prevention of cardiovascular diseases in post-menopausal women.

  • inhibition of serotonin re uptake by licorice constituents
    Journal of Molecular Neuroscience, 2003
    Co-Authors: Rivka Ofir, Soliman Khatib, Snait Tamir, Jacob Vaya
    Abstract:

    Ovarian steroid hormones, estrogen and progestin, affect the function of the serotonin neural system by inhibiting serotonin re-uptake through allosteric interaction with the serotonin transporter (SERT) in a nongenomic mechanism. Blocking or reducing serotonin re-uptake at the synapse alleviates depression. The aim of this study was to test the effect of compounds of the isoflavan and isoflavene groups, subclasses of the flavonoids family, on serotonin re-uptake and to compare the results with the effect of other known phytoestrogens like genistein and daidzein to relate the activity of these compounds to their structure. The effect of these compounds on the re-uptake of radioactive serotonin was assayed in HEK-293 cells stably expressed the recombinant human serotonin transporter (hSERT). The results demonstrated that the isoflavans Glabridin and 4′-O-methylGlabridin (4′-OMeG) and the isoflavene glabrene inhibited serotonin re-uptake by 60, 53 and 47%, respectively, at 50 µM, whereas resorcinol, the isoflavan 2′-O-methylGlabridin (2′-OMeG), and the isoflavones genistein and daidzein were inactive. The inhibition of serotonin re-uptake is dose dependant with Glabridin and estradiol. These results emphasize the importance of the lipophilic part of the isoflavans, as well as the hydroxyl at position 2′ on ring B. In conclusion, this study showed that several isoflavans are unique phytoestrogens, which like estradiol, affects the serotonergic system and inhibits serotonin re-uptake and, thus, potentially may be beneficial for mild to moderate depression in pre- and postmenopausal women.

  • estrogen like activity of glabrene and other constituents isolated from licorice root
    The Journal of Steroid Biochemistry and Molecular Biology, 2001
    Co-Authors: Snait Tamir, Dalia Somjen, Mark Eizenberg, Sarit Izrael, Jacob Vaya
    Abstract:

    Licorice root extract and its major isoflavan, Glabridin, exhibited varying degrees of estrogen receptor (ER) agonism in different tissues in vitro and in vivo. Animals fed with licorice extract, compared with estradiol and Glabridin, showed an increase in creatine kinase (CK) activity, a known marker for estrogen responsive genes, which was higher than expected from the levels of Glabridin in the extract. This led us to test for other components that may contribute to this strong estrogen agonist activity. Results indicated that glabrene and isoliquiritigenin, (2',4',4-three hydroxy chalcone) (ILC) in the licorice extract can bind to the human ER with higher affinity (IC50, 1 and 0.5 microM) than Glabridin (IC50, 5 microM). The stimulatory effects of glabrene in vivo were tissue specific and similar to those of estradiol. The effect of increasing concentrations of glabrene and ILC on the growth of breast tumor cell were biphasic. Both showed an ER-dependent growth-promoting effect at low concentrations (10 nM-10 microM), and ER-independent antiproliferative activity at concentrations >15 microM. This is the first study to indicate that glabrene, an isoflavene exerted varying degrees of ER agonism in different tissues.

Snait Tamir - One of the best experts on this subject based on the ideXlab platform.

  • Glabridin an isoflavan from licorice root upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation
    Molecular Nutrition & Food Research, 2016
    Co-Authors: Itamar Yehuda, Zecharia Madar, Alicia Leikinfrenkel, Andrea Szuchmansapir, Faiga Magzal, Gilad Markman, Snait Tamir
    Abstract:

    Scope Hyperglycemia is associated with oxidative stress, which accelerates cardiovascular complications. This study investigates the potential of Glabridin to regulate paraoxonase 2 (PON2) levels, in vivo, and explores the Glabridin protective effect on PON2 through tryptophan-fluorescence quenching and mass spectrometry. Methods and results Adult mouse offspring of saturated fatty acids fed mothers, which developed hyperglycemia after exposure to a high fat diet in their adult life, had lower levels of heart PON2 mRNA and protein expression than did the control mice (64 and 26%, respectively). Glabridin supplementation significantly upregulated PON2 mRNA and protein expression in the liver (2.1-fold and 2.6-fold, respectively) and heart (2.5-fold and 1.6-fold, respectively) in these mice. In vitro studies demonstrated that the fluorescence quenching of PON2 by Glabridin was a result of the formation of a Glabridin–PON2 interaction. The binding constant (7.61 × 105 M−1) and the ΔG (–33.55kJ/mol) indicated that this interaction was driven by a hydrophobic force, which confers protection against CuSO4-induced PON2 oxidation. Conclusion Such results indicate that Glabridin preserves the anti-atherogenic abilities of PON2 by maintaining its levels, in vivo. The Glabridin–PON2 interaction may be the mechanism by which Glabridin protects PON2 from oxidation, thus contributing to the protection of PON2 activity in hyperglycemia.

  • Glabridin an isoflavan from licorice root downregulates inos expression and activity under high glucose stress and inflammation
    Molecular Nutrition & Food Research, 2015
    Co-Authors: Itamar Yehuda, Zecharia Madar, Alicia Leikinfrenkel, Snait Tamir
    Abstract:

    cope In females, hyperglycemia abolishes estrogen-vascular protection, leading to inflammation and oxidative stress that are related to diabetes-associated cardiovascular complications. Such knowledge led us to examine the potential of Glabridin, as a replacement of estrogen anti-inflammatory activity under high-glucose conditions. Methods and results In macrophage-like cells, chronic glucose stress (28 and 44 mM) upregulated inducible nitric oxide synthase (iNOS) mRNA expression by 42 and 189%, respectively. Pretreatment with Glabridin, under chronic glucose stress, downregulated the LPS-induced nitric oxide secretion and nitrotyrosine formation, by 39 and 21%, respectively. Pretreatment with estradiol did not prevent the LPS-induced nitrotyrosine formation. Furthermore, Glabridin, brought about a decrease in the LPS-induced iNOS mRNA expression by 48%, as compared to cells pretreated with estradiol. Glabridin decreased protein levels of liver iNOS by 69% in adult mouse offspring which developed hyperglycemia after early fetal exposure to a saturated fatty acid-enriched maternal diet. Glabridin also decreased liver nitrotyrosine levels in offspring of regular diet-fed mothers after further receiving high-fat diet. Conclusion Such results indicate that Glabridin retains anti-inflammatory abilities to regulate the synthesis and activity of iNOS under high-glucose levels, implying that a Glabridin supplement may serve as an anti-inflammatory agent in diabetes-related vascular dysfunction.

  • Glabridin a phytoestrogen from licorice root up regulates manganese superoxide dismutase catalase and paraoxonase 2 under glucose stress
    Phytotherapy Research, 2011
    Co-Authors: Itamar Yehuda, Zecharia Madar, Andrea Szuchmansapir, Snait Tamir
    Abstract:

    The risk of death from cardiovascular diseases (CVDs), which are exacerbated by oxidative stress, is higher in diabetic women. This phenomenon has been attributed to the loss of estradiol-vascular protection. Such knowledge led us to examine the potential of Glabridin, a phytoestrogen, to substitute estradiol up-regulation of antioxidant enzymes under high glucose conditions. Chronic glucose stress was found to down-regulate catalase (CAT) and paraoxonase 2 (PON2) mRNA expression by 20% and 17%, respectively, and to decrease PON2 activity by 83% in macrophages. Inflammatory conditions had an additive effect on PON2 expression in a time-dependent manner. Treatment with Glabridin, under high glucose stress, increased PON2 activity by 60% and up-regulated its mRNA expression by 3.5 fold. Furthermore, Glabridin up-regulated the expression of manganese superoxide dismutase (Mn-SOD) and CAT in monocytes. In conclusion, Glabridin has the potential of strengthening the antioxidant defense mechanism and may serve as an antiatherogenic agent in diabetes.

  • estrogenic activity of Glabridin and glabrene from licorice roots on human osteoblasts and prepubertal rat skeletal tissues
    The Journal of Steroid Biochemistry and Molecular Biology, 2004
    Co-Authors: Dalia Somjen, Sara Katzburg, Jacob Vaya, Alvin M Kaye, David Hendel, Gary H Posner, Snait Tamir
    Abstract:

    Data from both in vivo and in vitro experiments demonstrated that Glabridin and glabrene are similar to estradiol-17 in their stimulation of the specific activity of creatine kinase, although at higher concentrations, but differ in their extent of action and interaction with other drugs. In pre-menopausal human bone cells, the response to estradiol-17 and Glabridin (at higher concentration) was higher than in post-menopausal cells; whereas, glabrene (at higher concentration) was more effective in post-menopausal cells. At both ages, the response to estradiol-17 and Glabridin was enhanced by pretreatment with the less-calcemic Vitamin D analog CB 1093 (CB) and the demonstrably non-calcemic analog JK 1624 F2-2 (JKF). The response to glabrene was reduced by this pretreatment. Both Glabridin and glabrene stimulated creatine kinase specific activity in diaphyseal bone and epiphyseal cartilage of prepubertal female rats. Daily feeding (3‐14 days) of prepubertal female rats with Glabridin, estradiol-17 or their combination, also stimulated creatine kinase specific activity. Glabridine, similarly to estradiol-17 , also stimulated creatine kinase specific activity in ovariectomized female rats. Raloxifene, in combination with Glabridin or estradiol-17 , demonstrated the phenomenon of mutual annihilation of stimulation of creatine kinase specific activity in both epiphysis and diaphysis. Glabrene activity was not inhibited by raloxifene. Therefore, Glabridin shows greater similarity to estradiol-17 and thus greater potential, with or without Vitamin D, to modulate bone disorders in post-menopausal women. © 2004 Elsevier Ltd. All rights reserved.

  • estrogen like activity of licorice root constituents Glabridin and glabrene in vascular tissues in vitro and in vivo
    The Journal of Steroid Biochemistry and Molecular Biology, 2004
    Co-Authors: Dalia Somjen, Jacob Vaya, Naftali Stern, Esther Knoll, Snait Tamir
    Abstract:

    Post-menopausal women have higher incidence of heart diseases compared to pre-menopausal women, suggesting a protective role for estrogen. The recently Women's Health Initiative (WHI) randomized controlled trial concluded that the overall heart risk exceeded benefits from use of combined estrogen and progestin as hormone replacement therapy for an average of five years among healthy postmenopausal US women. Therefore, there is an urgent need for new agents with tissue-selective activity with no deleterious effects. In the present study, we tested the effects on vascular tissues in vitro and in vivo of two natural compounds derived from licorice root: Glabridin, the major isoflavan, and glabrene, an isoflavene, both demonstrated estrogen-like activities. Similar to estradiol-17beta (E2), Glabridin (gla) stimulated DNA synthesis in human endothelial cells (ECV-304; E304) and had a bi-phasic effect on proliferation of human vascular smooth muscle cells (VSMC). Raloxifene inhibited gla as well as E2 activities. In animal studies, both intact females or after ovariectomy, gla similar to E2 stimulated the specific activity of creatine kinase (CK) in aorta (Ao) and in left ventricle of the heart (Lv). Glabrene (glb), on the other hand, had only the stimulatory effect on DNA synthesis in vascular cells, with no inhibition by raloxifene, suggesting a different mechanism of action. To further elucidate the mechanism of action of glb, cells were pre-incubated with glb and then exposed to either E2 or to gla; the DNA stimulation at low doses was unchanged but there was abolishment of the inhibition of VSMC cell proliferation at high doses as well as inhibition of CK stimulation by both E2 and by gla. We conclude that glb behaved differently than E2 or gla, but similarly to raloxifene, being a partial agonist/antagonist of E2. Glabridin, on the other hand, demonstrated only estrogenic activity. Therefore, we suggest the use of glb with or without E2 as a new agent for modulation of vascular injury and atherogenesis for the prevention of cardiovascular diseases in post-menopausal women.

Michael Aviram - One of the best experts on this subject based on the ideXlab platform.

  • the licorice root derived isoflavan Glabridin inhibits the activities of human cytochrome p450s 3a4 2b6 and 2c9
    Drug Metabolism and Disposition, 2002
    Co-Authors: Ute M Kent, Michael Aviram, Mira Rosenblat, Paul F Hollenberg
    Abstract:

    The potent antioxidants licorice root extract and Glabridin, an isoflavan purified from licorice root extract, were tested for their ability to modulate the activities of several cytochrome P450 (P450) enzymes. P450 3A4, the major human drug metabolizing P450 enzyme, was inactivated by licorice root extract and by Glabridin in a time-and concentration-dependent manner. The inactivation was NADPH-dependent and was not reversible by extensive dialysis. Further analysis showed that the loss in enzymatic activity correlated with a loss in the P450-reduced CO spectrum and with a loss of the intact heme moiety. In contrast, incubations of P450 3A4 with similar concentrations of 2,4-dimethylGlabridin and NADPH did not lead to inactivation of P450 3A4. P450 2B6 was also inactivated by Glabridin in a time- and concentration-dependent manner. The majority of the Glabridin-inactivated P450 2B6 was able to form a reduced CO spectrum suggesting that the heme was not modified with this isoform. High-performance liquid chromatography analysis of the P450 heme confirmed that incubations with Glabridin and NADPH did not result in the destruction of the heme moiety. The activity of P450 2C9 was competitively inhibited by Glabridin, whereas P450 2D6 and P450 2E1 were virtually unaffected. The data show that Glabridin can serve as a substrate for at least three human P450 enzymes and that depending on the isoform, metabolism of Glabridin can lead to mechanism-based inactivation or inhibition of the P450. Heme and reduced CO spectral analysis also indicated that Glabridin inactivated P450s 2B6 and 3A4 by different mechanisms.

  • macrophage enrichment with the isoflavan Glabridin inhibits nadph oxidase induced cell mediated oxidation of low density lipoprotein a possible role for protein kinase c
    Journal of Biological Chemistry, 1999
    Co-Authors: Mira Rosenblat, Jacob Vaya, Paula Belinky, Rachel Levy, Tony Hayek, Raymond Coleman, Shoshana Merchav, Michael Aviram
    Abstract:

    Macrophage-mediated oxidation of low density lipoprotein (LDL) is considered to be of major importance in early atherogenesis; therefore, intervention means to inhibit this process are being extensively studied. In the present study, we questioned the ability of the isoflavan Glabridin (from licorice) to accumulate in macrophages and to affect cell-mediated oxidation of LDL. We first performed in vitro studies, using mouse peritoneal macrophages (MPMs) and the J-774 A.1 macrophage-like cell line. Both cells accumulated up to 1.5 micrograms of Glabridin/mg of cell protein after 2 h of incubation, and this process was time- and Glabridin dose-dependent. In parallel, in Glabridin-enriched cells, macrophage-mediated oxidation of LDL was inhibited by up to 80% in comparison with control cells. Glabridin inhibited superoxide release from MPMs in response to phorbol 12-myristate 13-acetate, or to LDL when added together with copper ions, by up to 60%. Translocation of P-47, a cytosolic component of NADPH oxidase to the plasma membrane was substantially inhibited. In Glabridin-enriched macrophages, protein kinase C activity reduced by approximately 70%. All of the above effects of Glabridin required the presence of the two hydroxyl groups on the flavonoid's B phenol ring. In order to assess the physiological significance of these results, we next performed in vivo studies, using the atherosclerotic apolipoprotein E-deficient (E0) mice. MPMs harvested from Glabridin-treated E0 mice (20 micrograms/mouse/day for a period of 6 weeks) demonstrated reduced capability to oxidize LDL by 80% in comparison with placebo-treated mice. This latter phenomenon was associated with a reduction in the lesion oxysterols and a 50% reduction in the aortic lesion size. We thus conclude that Glabridin accumulation in macrophages is associated with reduced cell-mediated oxidation of LDL and decreased activation of the NADPH oxidase system. These phenomena could be responsible for the attenuation of atherosclerosis in E0 mice, induced by Glabridin.

  • structural aspects of the inhibitory effect of Glabridin on ldl oxidation
    Free Radical Biology and Medicine, 1998
    Co-Authors: Paula Belinky, Michael Aviram, S Mahmood, Jacob Vaya
    Abstract:

    The inhibitory effects of Glabridin, an isoflavan isolated from licorice (Glycyrrhiza glabra) root, and its derivatives on the oxidation of LDL induced by copper ions or mediated by macrophages were studied, in order to evaluate the contribution of the different parts of the isoflavan molecule to its antioxidant activity. The peak potential (E1/2) of the isoflavan derivatives, their radical scavenging capacity toward 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and their ability to chelate heavy metals were also analyzed and compared to their inhibitory activity on LDL oxidation. In copper ion-induced LDL oxidation, Glabridin (1), 4'-O-methylGlabridin (2), hispaGlabridin A (3), and hispaGlabridin B (4), which have two hydroxyl groups at positions 2' and 4' or one hydroxyl at position 2' on ring B, successfully inhibited the formation of conjugated dienes, thiobarbituric acid reactive substances (TBARS) and lipid peroxides, and inhibited the electrophoretic mobility of LDL under oxidation. Compounds 1-3 exhibited similar activities, whereas compound 4 was less active. In macrophage-mediated LDL oxidation, the TBARS formation was also inhibited by these isoflavans (1-4) at a similar order of activity to that obtained in copper ion-induced LDL oxidation. On the other hand, 2'-O-methylGlabridin (5), a synthesized compound, whose hydroxyl at 2'-position is protected and the hydroxyl at 4'-position is free, showed only minor inhibitory activity in both LDL oxidation systems. 2',4'-O-DimethylGlabridin (6), whose hydroxyls at 2'- and 4'-positions are both protected, was inactive. Resorcinol (7), which is identical to the phenolic B ring in Glabridin, presented low activity in these oxidation systems. The isoflavene glabrene (8), which contains an additional double bond in the heterocyclic C ring, was the most active compound of the flavonoid derivatives tested in both oxidation systems. The peak potential of compounds 1-5 (300 microM), tested at pH 7.4, was similar (425-530 mV), and that for compound 6 and 8 was 1078 and 80 mV, respectively. Within 30 min of incubation, compounds 1, 2, 3, 4, 8 scavenged 31%, 16%, 74%, 51%, 86%, respectively, of DPPH radical, whereas compounds 5 and 6, which almost did not inhibit LDL oxidation, also failed to scavenge DPPH. None of the isoflavan derivatives nor the isoflavene compound were able to chelate iron, or copper ions. These results suggest that the antioxidant effect of Glabridin on LDL oxidation appears to reside mainly in the 2' hydroxyl, and that the hydrophobic moiety of the isoflavan is essential to obtain this effect. It was also shown that the position of the hydroxyl group at B ring significantly affected the inhibitory efficiency of the isoflavan derivatives on LDL oxidation, but did not influence their ability to donate an electron to DPPH or their peak potential values.

  • the antioxidative effects of the isoflavan Glabridin on endogenous constituents of ldl during its oxidation
    Atherosclerosis, 1998
    Co-Authors: Paula Belinky, Mira Rosenblat, Michael Aviram, Bianca Fuhrman, Jacob Vaya
    Abstract:

    The effect of the consumption of Glabridin, an isoflavan isolated from Glycyrrhiza glabra (licorice) root, on the susceptibility of low density lipoprotein (LDL) to oxidation was studied in atherosclerotic apolipoprotein E deficient (E[o] mice) and was compared with that of the known flavonoids, quercetin and catechin. Glabridin inhibitory activity on in vitro oxidation of human LDL was also investigated by determining the formation of lipid peroxides and oxysterols and the consumption of LDL-associated lipophilic antioxidants. Determination of the extent of LDL oxidation by measuring the formation of thiobabituric acid reactive substances (TBARS) after 2 h of LDL incubation with CuSO4 (10 microM) or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) (5 mM), revealed that Glabridin or quercetin consumption resulted in a 53 and 54% reduction in copper ion induced oxidation, respectively, and a 95 and 83% reduction in AAPH induced LDL oxidation, respectively. No inhibition was obtained with consumption of catechin. About 80% of Glabridin was found to bind to the LDL human particle. In the in vitro oxidation of LDL induced by AAPH (5 mM), Glabridin inhibited the formation of TBARS, lipid peroxides and cholesteryl linoleate hydroperoxide (CLOOH) at all the concentrations tested (5-60 microM), while in oxidation induced by copper ions (10 microM), Glabridin exhibited a pro-oxidant activity at concentrations lower than 20 microM, and a clear antioxidant activity at concentrations greater than 20 microM. Glabridin (30 microM) inhibited the formation of cholest-5-ene-3,7-diol (7-hydroxycholesterol), cholest-5-ene-3-ol-7-one (7-ketocholesterol) and cholestan-5,6-epoxy-3-ol (5,6-epoxycholesterol) after 6 h of AAPH induced LDL oxidation, by 55, 80 and 40%, respectively, and after 6 h of copper ion induced LDL oxidation, by 73, 94 and 52%, respectively. Glabridin also inhibited the consumption of beta-carotene and lycopene by 38 and 52%, respectively, after 0.5 h of LDL oxidation with AAPH, but failed to protect vitamin E. The in vivo and in vitro reduction of the susceptibility of LDL to oxidation obtained with Glabridin, may be related to the absorption or binding of Glabridin to the LDL particle and subsequent protection of LDL from oxidation by inhibiting the formation of lipid peroxides and oxysterols, and by protecting LDL associated carotenoids.

  • licorice extract and its major polyphenol Glabridin protect low density lipoprotein against lipid peroxidation in vitro and ex vivo studies in humans and in atherosclerotic apolipoprotein e deficient mice
    The American Journal of Clinical Nutrition, 1997
    Co-Authors: Bianca Fuhrman, Jacob Vaya, Paula Belinky, Tony Hayek, Raymond Coleman, S Buch, Michael Aviram
    Abstract:

    Polyphenolic flavonoids are powerful antioxidants. In the present study we investigated the antioxidative activity against low-density-lipoprotein (LDL) oxidation of a not yet studied subclass of polyphenols, the isoflavans, which are present in licorice alcoholic extract. The study was performed in humans as well as in atherosclerotic apolipoprotein E-deficient mice (E zero), because their LDL is highly susceptible to oxidation. LDL oxidation was induced by incubating it with copper ions as well as with the aqueous or lipid-soluble free radical generators 2,2'-azobis'2-amidino propane hydrochloride (AAPH) and 2,2'-azobis 2,4-dimethylvaleronitrile (AMVN), respectively. The extent of LDL oxidation was determined by measuring the formation of conjugated dienes, thiobarbituric acid reactive-substances (TBARS), and lipid peroxides. By all methods in human studies, licorice ethanolic extract as well as a pure material, which was identified by gas chromatography-mass spectroscopy as the isoflavan Glabridin, were shown to inhibit LDL oxidation by a mechanism involving scavenging of free radicals. In an ex vivo study, LDL isolated from the plasma of 10 normolipidemic subjects who were orally supplemented for 2 wk with 100 mg licorice/d was more resistant to oxidation than was LDL isolated before licorice supplementation. Dietary supplementation of each E zero mouse with licorice (200 micrograms/d) or pure Glabridin (20 micrograms/d) for 6 wk resulted in a substantial reduction in the susceptibility of their LDL to oxidation along with a reduction in the atherosclerotic lesion area. These results could be related to the absorption and binding of Glabridin to the LDL particle and subsequent protection of the LDL from oxidation by multiple modes as shown in humans and in E zero mice.

Eun Mi Choi - One of the best experts on this subject based on the ideXlab platform.

  • Glabridin alleviates the toxic effects of methylglyoxal on osteoblastic mc3t3 e1 cells by increasing expression of the glyoxalase system and nrf2 ho 1 signaling and protecting mitochondrial function
    Journal of Agricultural and Food Chemistry, 2016
    Co-Authors: Eun Mi Choi, Soo Min Hong, So Yong Park, Suk Chon
    Abstract:

    Methylglyoxal (MG) contributes to the pathogenesis of age- and diabetes-associated complications. The present study investigated the effects of Glabridin on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. MC3T3-E1 cells were treated with Glabridin in the presence of MG, and markers of mitochondrial function and oxidative damage were examined. Pretreatment of MC3T3-E1 osteoblastic cells with Glabridin prevented MG-induced cell death, the production of intracellular reactive oxygen species and mitochondrial superoxides, cardiolipin peroxidation, and the production of inflammatory cytokines. The soluble form of receptor for advanced glycation end products (sRAGEs)/RAGE ratio increased upon MG treatment, but less so after pretreatment with Glabridin, which also increased the level of reduced glutathione and the activities of glyoxalase I and heme oxygenase-1, all of which were reduced by MG. In addition, Glabridin elevated the level of nuclear factor erythroid 2-related factor 2. These findings sugges...

  • Glabridin protects osteoblastic mc3t3 e1 cells against antimycin a induced cytotoxicity
    Chemico-Biological Interactions, 2011
    Co-Authors: Eun Mi Choi
    Abstract:

    Mitochondrial dysfunction, particularly respiratory chain disruption, is often responsible for aging-related bone diseases. In this study, the protective effects of Glabridin, an isoflavan isolated from licorice root, against pharmacological inhibition of the respiratory chain were studied using osteoblastic MC3T3-E1 cells treated with antimycin A, which inhibits complex III of the electron transport system. Glabridin restored mitochondrial membrane potential dissipation, ATP loss, inactivation of complex IV, intracellular calcium elevation, and cytochrome c release that was induced by antimycin A treatment. This compound also prevented cell death. These results imply that Glabridin protects osteoblasts from antimycin A-induced cell death via improved mitochondrial function. Glabridin scavenged ROS and mitochondrial superoxide anions generated by antimycin A. In addition, Glabridin prevented antimycin A-induced nitrotyrosine increase and thioredoxin reductase inactivation, suggesting that Glabridin may be useful for protecting mitochondria against a burst of oxidative stress. Since phosphoinositide 3-kinase (PI3K) and cAMP-response element-binding protein (CREB) signaling is known to be pro-survival, we determined whether PI3K and CREB activation is associated with the cytoprotective effects of Glabridin in the MC3T3-E1 cells. Glabridin restored antimycin A-induced inactivation of PI3K and CREB, suggesting that PI3K and CREB-dependent pathways may be involved in Glabridin-induced cytoprotective responses. Our study demonstrates that Glabridin reduces mitochondrial dysfunction induced during aging, and could significantly prevent osteoblast damage in osteoporotic patients.

  • the licorice root derived isoflavan Glabridin increases the function of osteoblastic mc3t3 e1 cells
    Biochemical Pharmacology, 2005
    Co-Authors: Eun Mi Choi
    Abstract:

    Glabridin, an isoflavan purified from licorice root, exhibits diverse biological activities, including estrogen-like activity. To investigate the bioactivities of Glabridin, which act on bone metabolism, the effects of Glabridin on the function of mouse osteoblastic cell line (MC3T3-E1) and the production of local factors in osteoblasts were studied. Glabridin (1-10microM) significantly increased the growth of MC3T3-E1 cells and caused a significant elevation of alkaline phosphatase (ALP) activity, collagen content and osteocalcin secretion in the cells (P<0.05). The effect of Glabridin (10microM) in increasing ALP activity and collagen content was completely prevented by the presence of 10(-6)M cycloheximide and 10(-6)M tamoxifen, suggesting that Glabridin's effect results from a newly synthesized protein component and might be partly involved in estrogen action. Then, the effects of Glabridin on the TNF-alpha-induced apoptosis and production of prostaglandin E2 (PGE2) and nitric oxide (NO) in osteoblasts were examined. Treatment with Glabridin (1-10microM) prevented apoptosis induced by TNF-alpha (10(-10)M) in osteoblastic cells. Moreover, Glabridin (50microM) decreased the 10(-10)M TNF-alpha-induced production of PGE2 and NO in osteoblasts. Our data indicate that the enhancement of osteoblast function by Glabridin may result in the prevention for osteoporosis and inflammatory bone diseases.

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  • cardiovascular protective effect of Glabridin implications in ldl oxidation and inflammation
    International Immunopharmacology, 2015
    Co-Authors: Moo Rim Kang, Chang Woo Lee, Sang-bae Han, Ki Hwan Park, Jieun Yun, Myeong Youl Lee, Jong Soon Kang
    Abstract:

    Atherosclerosis is one of the most common causes of death in Western countries and now considered as a chronic inflammatory disease in broad outline. Glaridin, a flavonoid isolated from licorice root, has been shown to exert a variety of biological activities, including antimicrobial, antioxidant, anti-inflammatory and cardiovascular protective effects. Among these, the most extensive research area in the past two decades was a cardiovascular protection-related activity of Glabridin. The protective effect of Glabridin on LDL oxidation, which is one of the important processes involved in the development of atherosclerosis, was demonstrated in vitro and in vivo and the mechanisms involved in this process were established well. Structure-activity relationship of Glabridin derivatives on LDL oxidation was also reported. In addition, the inhibitory effects of Glabridin on early inflammatory processes, including the expression of adhesion molecules on endothelial cells and the activation of macrophages and dendritic cells, were also demonstrated previously. In this review, we summarized the cardiovascular protection-related activities of Glabridin and the mechanism of action involved in these activities. Collectively, it is hoped that Glabridin or Glabridin derivatives might be used as a therapeutic agent for the treatment of cardiovascular diseases in the future.

  • inhibition of bone marrow derived dendritic cell maturation by Glabridin
    International Immunopharmacology, 2010
    Co-Authors: Jee Youn Kim, Jong Soon Kang, Hwan Mook Kim, Hwa Sun Ryu, Hyung Sook Kim, Hong Kyung Lee, Yeon Jin Kim, Jin Tae Hong, Youngsoo Kim, Sang-bae Han
    Abstract:

    Glabridin has multiple pharmacological activities including anti-microbial, anti-atherosclerotic, anti-nephritic, anti-inflammatory and cardiovascular protective activities. In this study, we investigated the effect of Glabridin on dendritic cells, which play an essential role in innate and adaptive immune responses. Glabridin inhibited lipopolysaccharide-, poly (I:C)-, or zymosan-induced phenotypic maturation of dendritic cells (DCs), as proven by the decreased expression of CD40, CD80, CD86, MHC-I, and MHC-II. Glabridin decreased the functional maturation of DCs, in that Glabridin attenuated pro-inflammatory cytokine production of IL-12, IL-1β, TNF-α, and IFN-α/β, enhanced antigen capture capacity, inhibited migration to SDF-1α and MIP-3β, and impaired induction of allogenic T cell activation. We also showed that Glabridin inhibited zymosan-induced inflammation in mice. As a mode of action, we showed that Glabridin inhibited degradation of IκΒα/β, nuclear translocation of NF-κB p65/p50, and phosphorylation of ERK, JNK, and p38 MAPKs. Taken together, the present results show that Glabridin inhibits dendritic cell maturation by blocking NF-κB and MAPK signalings.

  • Glabridin inhibits lipopolysaccharide induced activation of a microglial cell line bv 2 by blocking nf κb and ap 1 142 3
    Journal of Immunology, 2010
    Co-Authors: Ki Hoon Lee, Sun Hong Park, Jong Soon Kang, Kiho Lee, Sang-bae Han, Song Kyu Park, Hwan Mook Kim
    Abstract:

    Glabridin, a flavonoid present in licorice root, is known to have anti-inflammatory and cardiovascular protective activities. In the present study, we report an inhibitory effect of Glabridin on microglial activation. Glabridin dose-dependently attenuated lipopolysaccharide (LPS)-induced production of inflammatory mediators, including nitric oxide, tumor necrosis factor-α and interleukin-1β, in BV-2 cells, a murine microglia cell line. Moreover, mRNA expression of these inflammatory mediators was also suppressed by Glabridin in LPS-stimulated BV-2 cells. Further study demonstrated that Glabridin inhibited LPS-induced DNA binding activity of NF-κB and AP-1 in BV-2 cells. Collectively, the results presented in this report demonstrate that Glabridin inhibits the production of inflammatory mediators in BV-2 cells and this is mediated, at least in part, by blocking NF-κB and AP-1 activation. Our results suggest that Glabridin might be a potential therapeutic agent for the treatment of neuroinflammatory and neurodegenerative diseases.

  • Glabridin inhibits lipopolysaccharide-induced activation of a microglial cell line, BV-2, by blocking NF-κB and AP-1
    Phytotherapy Research, 2009
    Co-Authors: Sun Hong Park, Jong Soon Kang, Yeo Dae Yoon, Kiho Lee, Kang-jeon Kim, Ki Hoon Lee, Chang Woo Lee, Eun-yi Moon, Sang-bae Han, Bong Hee Kim
    Abstract:

    Glabridin, a flavonoid present in licorice root, is known to have antiinflammatory and cardiovascular protective activities. The present study reports an inhibitory effect of Glabridin on microglial activation. Glabridin dose-dependently attenuated lipopolysaccharide (LPS)-induced production of inflammatory mediators, including nitric oxide, tumor necrosis factor-alpha and interleukin-1beta, in BV-2 cells, a murine microglia cell line. Moreover, mRNA expression of these inflammatory mediators was also suppressed by Glabridin in LPS-stimulated BV-2 cells. Further study demonstrated that Glabridin inhibited LPS-induced DNA binding activity of NF-kappaB and AP-1 in BV-2 cells. Collectively, the results presented in this report demonstrate that Glabridin inhibits the production of inflammatory mediators in BV-2 cells and this is mediated, at least in part, by blocking NF-kappaB and AP-1 activation. The results suggest that Glabridin might be a potential therapeutic agent for the treatment of neuroinflammatory and neurodegenerative diseases.

  • Glabridin suppresses intercellular adhesion molecule 1 expression in tumor necrosis factor α stimulated human umbilical vein endothelial cells by blocking sphingosine kinase pathway implications of akt extracellular signal regulated kinase and nuclea
    Molecular Pharmacology, 2006
    Co-Authors: Jong Soon Kang, Yeo Dae Yoon, Kiho Lee, Ki Hoon Lee, Sang-bae Han, Mi Hwa Han, Song Kyu Park, Hwan Mook Kim
    Abstract:

    ( R )-4-(3,4-Dihydro-8,8-dimethyl)-2 H ,8 H -benzo[1,2- b :3,4- b ′] dipyran-3yl)-1,3-benzenediol (Glabridin) is known to have anti-inflammatory, antimicrobial, and cardiovascular protective activities. In the present study, we report the inhibitory effect of Glabridin on intercellular adhesion molecule-1 (ICAM-1) expression in tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). Glabridin inhibited THP-1 cell adhesion to HUVECs stimulated by TNF-α and cell surface expression of ICAM-1 in TNF-α-stimulated HUVECs. The mRNA expression of adhesion molecules, including ICAM-1, vascular cell adhesion molecule-1, and E-selectin, was also suppressed by Glabridin. Further study demonstrated the inhibitory effect of Glabridin on nuclear factor (NF)-κB/Rel DNA binding, inhibitory factor-κBα (IκBα), and IκBβ degradation, IκB kinase activation, and p65 nuclear translocation in TNF-α-stimulated HUVECs. Treatment of a variety of cell lines with Glabridin revealed that inhibitory effect of Glabridin on NF-κB/Rel activation is not cell type-specific, and both inducible and constitutive NF-κB/Rel activation was suppressed by Glabridin treatment. Moreover, TNF-α-induced phosphorylation of Akt and extracellular signal-regulated kinase (ERK) was blocked by Glabridin treatment in HUVECs. Glabridin also suppressed sphingosine-1-phosphate (S1P)-induced cell surface expression and mRNA expression of ICAM-1. Further study demonstrated that TNF-α-induced sphingosine kinase activity was inhibited by Glabridin, and the inhibitory effect of Glabridin on TNF-α-induced ICAM-1 expression was reversed by addition of exogenous S1P. Together, our results indicate that the inhibitory effect of Glabridin on ICAM-1 expression might be mediated, at least in part, by inhibiting sphingosine kinase pathway and subsequent inhibition of signaling pathways, including Akt, ERK, and NF-κB/Rel signaling pathway.