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Jueitang Cheng - One of the best experts on this subject based on the ideXlab platform.
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mediation of beta endorphin by Isoferulic Acid to lower plasma glucose in streptozotocin induced diabetic rats
Journal of Pharmacology and Experimental Therapeutics, 2003Co-Authors: Imin Liu, Wangchuan Chen, Jueitang ChengAbstract:We investigated the mechanism(s) by which Isoferulic Acid lowers plasma glucose levels in streptozotocin-induced diabetic rats (STZ-diabetic rats). In STZ-diabetic rats, Isoferulic Acid dose dependently lowered plasma glucose concentrations and increased plasma beta-endorphin-like immunoreactivity (BER). Both of these effects of Isoferulic Acid were abolished by pretreatment of rats with tamsulosin or 2-[2,6-dimethoxyphenoxyethyl]aminomethyl-1,4-benzodioxane hydrochloride (WB 4101) at doses sufficient to block alpha1-adrenoceptors. Also, Isoferulic Acid enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that could be abolished by treatment with alpha1-adrenoceptor antagonists. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of Isoferulic Acid, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Naloxone and naloxonazine inhibited the plasma glucose-lowering activity of Isoferulic Acid at doses sufficient to block opioid mu-receptors. In contrast with the effect in wild-type diabetic mice, Isoferulic Acid failed to lower plasma glucose levels in opioid mu-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with Isoferulic Acid three times in 1 day resulted in an increase in the expression of the glucose transporter subtype 4 form in soleus muscle. This effect was blocked by alpha1-adrenoceptor or opioid mu-receptor antagonists. The reduction of elevated mRNA or protein level of hepatic phosphoenolpyruvate carboxykinase was also impeded in the same groups of STZ-diabetic rats. In conclusion, our results suggest that Isoferulic Acid may activate alpha1-adrenoceptors to enhance the secretion of beta-endorphin, which can stimulate the opioid mu-receptors to increase glucose use or/and reduce hepatic gluconeogenesis, resulting in a decrease of plasma glucose in STZ-diabetic rats.
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Mediation of -Endorphin by Isoferulic Acid to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats
2003Co-Authors: Imin Liu, Wangchuan Chen, Jueitang ChengAbstract:We investigated the mechanism(s) by which Isoferulic Acid lowers plasma glucose levels in streptozotocin-induced dia-betic rats (STZ-diabetic rats). In STZ-diabetic rats, Isoferulic Acid dose dependently lowered plasma glucose concentrations and increased plasma -endorphin-like immunoreactivity (BER). Both of these effects of Isoferulic Acid were abolished by pretreatment of rats with tamsulosin or 2-[2,6-dimethoxyphe-noxyethyl]aminomethyl-1,4-benzodioxane hydrochloride (WB 4101) at doses sufficient to block 1-adrenoceptors. Also, isof-erulic Acid enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that could be abolished by treatment with 1-adrenoceptor antagonists. Moreover, bilateral adrenalectomy in STZ-diabetic rats elimi-nated the activities of Isoferulic Acid, including the plasm
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stimulatory effect of Isoferulic Acid on α1a adrenoceptor to increase glucose uptake into cultured myoblast c2c12 cell of mice
Autonomic Neuroscience: Basic and Clinical, 2001Co-Authors: Imin Liu, Chinchuan Tsai, Tungyuan Lai, Jueitang ChengAbstract:In an attempt to elucidate the effect of Isoferulic Acid on alpha1-adrenoceptor (AR), the myoblast C2C12 cells of mice were employed to investigate the change of glucose uptake in the present study. Isoferulic Acid enhanced the uptake of radioactive glucose into C2C12 cells in a concentration-dependent manner, which were abolished by pretreatment with prazosin. Effect of Isoferulic Acid on alpha1-AR was further characterized using the displacement of [3H]YM617 binding in C2C12 cells. The radioactive glucose uptake increasing action of Isoferulic Acid was abolished by tamsulosin or WB 4101 at concentration sufficient to block alpha1A-adrenoceptor (alpha1A-AR) but it was not modified by chlorethylclonidine (CEC) at the concentration sufficient to abolish alpha1B-AR. An activation of alpha1A-AR by Isoferulic Acid in C2C12 cells can thus be considered. Pharmacological inhibition of phospholipase C (PLC) by U73312 resulted in a concentration-dependent reduction of Isoferulic Acid-stimulated glucose uptake in C2C12 cells. This inhibition by U73112 was specific because the inactive congener, U73343, failed to modify the action of Isoferulic Acid. Also, chelerythrine and GF 109203X diminished the action of Isoferulic Acid at concentration sufficient to inhibit the activity of protein kinase C (PKC). The obtained data suggest that an activation of alpha1A-AR by Isoferulic Acid may increase the glucose uptake via PLC-PKC pathway in C2C12 cells.
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stimulatory effect of Isoferulic Acid on a adrenoceptor to increase
2001Co-Authors: Imin Liu, Chinchuan Tsai, Tungyuan Lai, Jueitang ChengAbstract:Ž. In an attempt to elucidate the effect of Isoferulic Acid on a -adrenoceptor AR , the myoblast C C cells of mice were employed to 12 12 investigate the change of glucose uptake in the present study. Isoferulic Acid enhanced the uptake of radioactive glucose into C C cells 21 2 in a concentration-dependent manner, which were abolished by pretreatment with prazosin. Effect of Isoferulic Acid on a -AR was further 1 w 3 x characterized using the displacement of H YM617 binding in C C cells. The radioactive glucose uptake increasing action of Isoferulic 21 2
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antihyperglycemic action of Isoferulic Acid in streptozotocin induced diabetic rats
British Journal of Pharmacology, 2000Co-Authors: Imin Liu, Fenglin Hsu, Chiehfu Chen, Jueitang ChengAbstract:Wistar rats with streptozotocin-induced diabetes (STZ-diabetic rats), which is similar to human insulin-dependent diabetic mellitus (IDDM), were employed to investigate the antihyperglycemic action of Isoferulic Acid. A single intravenous injection of Isoferulic Acid decreased the plasma glucose in a dose-dependent manner in the STZ-diabetic rats. Repeated intravenous administration of STZ-diabetic rats with Isoferulic Acid (5.0 mg kg(-1)) also resulted in the lowering of plasma glucose after one day. Stimulatory effects of Isoferulic Acid on the glucose uptake and glycogen synthesis in soleus muscles isolated from STZ-diabetic rats were also obtained indicating an increase of glucose utilization following Isoferulic Acid treatment which was not dependent on insulin. The mRNA level of glucose transporter subtype 4 form (GLUT4) in soleus muscle was raised by Isoferulic Acid after repeated treatment for 1 day in STZ-diabetic rats. Similar repeated treatment with Isoferulic Acid reversed the elevated mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) in liver of STZ-diabetic rats to the normal level. However, expression of GLUT4 and PEPCK genes in nondiabetic rats were not influenced by similar treatment with Isoferulic Acid. These results suggest that Isoferulic Acid can inhibit hepatic gluconeogenesis and/or increase the glucose utilization in peripheral tissue to lower plasma glucose in diabetic rats lacking insulin.
Sirichai Adisakwattana - One of the best experts on this subject based on the ideXlab platform.
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Isoferulic Acid attenuates methylglyoxal induced apoptosis in ins 1 rat pancreatic β cell through mitochondrial survival pathways and increasing glyoxalase 1 activity
Biomedicine & Pharmacotherapy, 2018Co-Authors: Aramsri Meeprom, Weerachat Sompong, Catherine B Chan, Sirichai AdisakwattanaAbstract:Abstract Methylglyoxal (MG) is a reactive precursor to advanced glycation end-products (AGEs), which exert deleterious effects on cells and tissues. MG also causes pancreatic β-cell dysfunction and apoptosis. Isoferulic Acid (IFA), a naturally occurring cinnamic Acid derivative, is considered to be an antiglycating agent. However, the effect of IFA on MG-induced pancreatic β-cell dysfunction remains unknown. The objective of this study was to determine the protective effect of IFA against MG-induced mitochrondrial dysfunction and apoptosis in INS-1 pancreatic β-cells. The results showed that pretreatment of INS-1 cells with 100 μM IFA for 48 h prevented MG-induced decrease in cell viability and impairment of glucose-stimulated insulin secretion (GSIS). In addition, 100 μM IFA pretreatment also decreased MG-induced generation of reactive oxygen species (ROS) and upregulation of mitochondrial uncoupling protein 2 (Ucp2) mRNA expression. Furthermore, IFA pretreatment reduced MG-induced increase in caspase-3 activity, suggesting a reduction of apoptotic cell death. IFA (50–100 μM) itself markedly increased the activity of glyoxalase 1 (GLO1), a major enzyme for the detoxification of MG. The results showed that 100 μM IFA protected MG-induced loss of GLO1 activity in INS-1 cells. These findings suggest that IFA pretreatment attentuates MG-induced dysfunction and apoptosis in INS-1 pancreatic β-cells through mitochondrial survival pathway and increasing GLO1 activity.
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Isoferulic Acid prevents methylglyoxal induced protein glycation and dna damage by free radical scavenging activity
BMC Complementary and Alternative Medicine, 2015Co-Authors: Aramsri Meeprom, Weerachat Sompong, Catherine B Chan, Tanyawan Suantawee, Thavaree Thilavech, Sirichai AdisakwattanaAbstract:Isoferulic Acid (IFA), a naturally occurring cinnamic Acid derivative, is a main active ingredient of the rhizoma of Cimicifuga dahurica. It has been shown various pharmacological activities. The aim of the study was to investigate the effect of IFA against MG-induced protein glycation and oxidative DNA damage. Free radical scavenging activity and the MGO-trapping abilities of IFA were also investigated. The fluorescent MG-derived AGEs and non-fluorescent Ne-(carboxymethyl) lysine (Ne-CML) was measured using a spectrofluorometer and an enzyme linked immunosorbant assay (ELISA). Protein carbonyl content was used to detect protein oxidation. Gel electrophoresis was used to determine DNA damage. Superoxide anion radicals and hydroxyl radicals were determined using cytochrome c reduction assay and thiobarbituric Acid reactive 2-deoxy-D-ribose oxidation products, respectively. The MG-trapping capacity was performed by HPLC. IFA (1.25–5 mM) inhibited the formation of fluorescent MG-derived AGEs, and Ne-CML, and protein carbonyl in bovine serum albumin. In addition, IFA (0.1–1 mM) also prevented MG/lysine-mediated oxidative DNA damage in the presence and absence of copper ion. The protective ability of IFA was directly correlated to inhibition of hydroxyl and superoxide anion radical generation during the reaction of MG and lysine. Most notably, IFA had no the directly trapping ability to MG. The present results highlighted that free radical scavenging activity, but not the MG-trapping ability, is the mechanism of IFA for preventing MG-induced protein glycation and DNA damage.
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Isoferulic Acid a new anti glycation agent inhibits fructose and glucose mediated protein glycation in vitro
Molecules, 2013Co-Authors: Aramsri Meeprom, Weerachat Sompong, Catherine B Chan, Sirichai AdisakwattanaAbstract:The inhibitory activity of Isoferulic Acid (IFA) on fructose- and glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA) was investigated. Our data showed that IFA (1.25–5 mM) inhibited the formation of fluorescent advanced glycation end products (AGEs) and non-fluorescent AGE [Ne-(carboxymethyl) lysine: CML], as well as the level of fructosamine. IFA also prevented protein oxidation of BSA indicated by decreasing protein carbonyl formation and protein thiol modification. Furthermore, IFA suppressed the formation of β-cross amyloid structures of BSA. Therefore, IFA might be a new promising anti-glycation agent for the prevention of diabetic complications via inhibition of AGEs formation and oxidation-dependent protein damage.
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Isoferulic Acid, a New Anti-Glycation Agent, Inhibits Fructose- and Glucose-Mediated Protein Glycation in Vitro
MDPI AG, 2013Co-Authors: Sirichai Adisakwattana, Aramsri Meeprom, Catherine B Chan, Weerachat SompongAbstract:The inhibitory activity of Isoferulic Acid (IFA) on fructose- and glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA) was investigated. Our data showed that IFA (1.25–5 mM) inhibited the formation of fluorescent advanced glycation end products (AGEs) and non-fluorescent AGE [Nε-(carboxymethyl) lysine: CML], as well as the level of fructosamine. IFA also prevented protein oxidation of BSA indicated by decreasing protein carbonyl formation and protein thiol modification. Furthermore, IFA suppressed the formation of β-cross amyloid structures of BSA. Therefore, IFA might be a new promising anti-glycation agent for the prevention of diabetic complications via inhibition of AGEs formation and oxidation-dependent protein damage
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a series of cinnamic Acid derivatives and their inhibitory activity on intestinal alpha glucosidase
Journal of Enzyme Inhibition and Medicinal Chemistry, 2009Co-Authors: Sirichai Adisakwattana, Praew Chantarasinlapin, Haruthai Thammarat, Sirintorn YibchokanunAbstract:Inhibition of alpha-glucosidase and alpha-amylase delays the digestion of starch and disaccharides to absorbable monosaccharides, resulting in a reduction of postprandial hyperglycemia. Finding effective mammalian alpha-glucosidase inhibitors from natural sources can be beneficial in the prevention and treatment of diabetes mellitus. We investigated the inhibitory activity of cinnamic Acid derivatives against rat intestinal alpha-glucosidase and porcine pancreatic alpha-amylase in vitro. Among 11 cinnamic Acid derivatives, caffeic Acid, ferulic Acid, and Isoferulic Acid were the most potent inhibitors against intestinal maltase with IC(50) values of 0.74 +/- 0.01, 0.79 +/- 0.04, and 0.76 +/- 0.03 mM, respectively, whereas ferulic Acid (IC(50) = 0.45 +/- 0.01 mM) and Isoferulic Acid (IC(50) = 0.45 +/- 0.01 mM) were effective intestinal sucrase inhibitors. However, all cinnamic Acid derivatives were found to be inactive in pancreatic alpha-amylase inhibition. Kinetic analysis revealed that intestinal maltase was inhibited by caffeic Acid, ferulic Acid, and Isoferulic Acid in a mixed-inhibition manner. In addition, ferulic Acid and Isoferulic Acid inhibited intestinal sucrase in a mixed type manner, whereas caffeic Acid was a non-competitive inhibitor. The combination of Isoferulic Acid and acarbose showed an additive inhibition on intestinal sucrase. This study could provide a new insight into naturally occurring intestinal alpha-glucosidase inhibitors that could be useful for treatment of diabetes and its complications.
Julie Anne Lovegrove - One of the best experts on this subject based on the ideXlab platform.
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moderate champagne consumption promotes an acute improvement in acute endothelial independent vascular function in healthy human volunteers
British Journal of Nutrition, 2009Co-Authors: David Vauzour, Emily J Houseman, Christelle Sellier, Trevor George, Orla B. Kennedy, Philippe Gillery, Roselyne Garnotel, Kim G. Jackson, Giulia Corona, Julie Anne LovegroveAbstract:Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived Acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric Acid, protocatechuic Acid and Isoferulic Acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity. Champagne wine intake: Endothelial-independent vascular function: Matrix metalloproteinase-9 activity: Cardiovascular disease
Imin Liu - One of the best experts on this subject based on the ideXlab platform.
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mediation of beta endorphin by Isoferulic Acid to lower plasma glucose in streptozotocin induced diabetic rats
Journal of Pharmacology and Experimental Therapeutics, 2003Co-Authors: Imin Liu, Wangchuan Chen, Jueitang ChengAbstract:We investigated the mechanism(s) by which Isoferulic Acid lowers plasma glucose levels in streptozotocin-induced diabetic rats (STZ-diabetic rats). In STZ-diabetic rats, Isoferulic Acid dose dependently lowered plasma glucose concentrations and increased plasma beta-endorphin-like immunoreactivity (BER). Both of these effects of Isoferulic Acid were abolished by pretreatment of rats with tamsulosin or 2-[2,6-dimethoxyphenoxyethyl]aminomethyl-1,4-benzodioxane hydrochloride (WB 4101) at doses sufficient to block alpha1-adrenoceptors. Also, Isoferulic Acid enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that could be abolished by treatment with alpha1-adrenoceptor antagonists. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of Isoferulic Acid, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Naloxone and naloxonazine inhibited the plasma glucose-lowering activity of Isoferulic Acid at doses sufficient to block opioid mu-receptors. In contrast with the effect in wild-type diabetic mice, Isoferulic Acid failed to lower plasma glucose levels in opioid mu-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with Isoferulic Acid three times in 1 day resulted in an increase in the expression of the glucose transporter subtype 4 form in soleus muscle. This effect was blocked by alpha1-adrenoceptor or opioid mu-receptor antagonists. The reduction of elevated mRNA or protein level of hepatic phosphoenolpyruvate carboxykinase was also impeded in the same groups of STZ-diabetic rats. In conclusion, our results suggest that Isoferulic Acid may activate alpha1-adrenoceptors to enhance the secretion of beta-endorphin, which can stimulate the opioid mu-receptors to increase glucose use or/and reduce hepatic gluconeogenesis, resulting in a decrease of plasma glucose in STZ-diabetic rats.
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Mediation of -Endorphin by Isoferulic Acid to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats
2003Co-Authors: Imin Liu, Wangchuan Chen, Jueitang ChengAbstract:We investigated the mechanism(s) by which Isoferulic Acid lowers plasma glucose levels in streptozotocin-induced dia-betic rats (STZ-diabetic rats). In STZ-diabetic rats, Isoferulic Acid dose dependently lowered plasma glucose concentrations and increased plasma -endorphin-like immunoreactivity (BER). Both of these effects of Isoferulic Acid were abolished by pretreatment of rats with tamsulosin or 2-[2,6-dimethoxyphe-noxyethyl]aminomethyl-1,4-benzodioxane hydrochloride (WB 4101) at doses sufficient to block 1-adrenoceptors. Also, isof-erulic Acid enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that could be abolished by treatment with 1-adrenoceptor antagonists. Moreover, bilateral adrenalectomy in STZ-diabetic rats elimi-nated the activities of Isoferulic Acid, including the plasm
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stimulatory effect of Isoferulic Acid on α1a adrenoceptor to increase glucose uptake into cultured myoblast c2c12 cell of mice
Autonomic Neuroscience: Basic and Clinical, 2001Co-Authors: Imin Liu, Chinchuan Tsai, Tungyuan Lai, Jueitang ChengAbstract:In an attempt to elucidate the effect of Isoferulic Acid on alpha1-adrenoceptor (AR), the myoblast C2C12 cells of mice were employed to investigate the change of glucose uptake in the present study. Isoferulic Acid enhanced the uptake of radioactive glucose into C2C12 cells in a concentration-dependent manner, which were abolished by pretreatment with prazosin. Effect of Isoferulic Acid on alpha1-AR was further characterized using the displacement of [3H]YM617 binding in C2C12 cells. The radioactive glucose uptake increasing action of Isoferulic Acid was abolished by tamsulosin or WB 4101 at concentration sufficient to block alpha1A-adrenoceptor (alpha1A-AR) but it was not modified by chlorethylclonidine (CEC) at the concentration sufficient to abolish alpha1B-AR. An activation of alpha1A-AR by Isoferulic Acid in C2C12 cells can thus be considered. Pharmacological inhibition of phospholipase C (PLC) by U73312 resulted in a concentration-dependent reduction of Isoferulic Acid-stimulated glucose uptake in C2C12 cells. This inhibition by U73112 was specific because the inactive congener, U73343, failed to modify the action of Isoferulic Acid. Also, chelerythrine and GF 109203X diminished the action of Isoferulic Acid at concentration sufficient to inhibit the activity of protein kinase C (PKC). The obtained data suggest that an activation of alpha1A-AR by Isoferulic Acid may increase the glucose uptake via PLC-PKC pathway in C2C12 cells.
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stimulatory effect of Isoferulic Acid on a adrenoceptor to increase
2001Co-Authors: Imin Liu, Chinchuan Tsai, Tungyuan Lai, Jueitang ChengAbstract:Ž. In an attempt to elucidate the effect of Isoferulic Acid on a -adrenoceptor AR , the myoblast C C cells of mice were employed to 12 12 investigate the change of glucose uptake in the present study. Isoferulic Acid enhanced the uptake of radioactive glucose into C C cells 21 2 in a concentration-dependent manner, which were abolished by pretreatment with prazosin. Effect of Isoferulic Acid on a -AR was further 1 w 3 x characterized using the displacement of H YM617 binding in C C cells. The radioactive glucose uptake increasing action of Isoferulic 21 2
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antihyperglycemic action of Isoferulic Acid in streptozotocin induced diabetic rats
British Journal of Pharmacology, 2000Co-Authors: Imin Liu, Fenglin Hsu, Chiehfu Chen, Jueitang ChengAbstract:Wistar rats with streptozotocin-induced diabetes (STZ-diabetic rats), which is similar to human insulin-dependent diabetic mellitus (IDDM), were employed to investigate the antihyperglycemic action of Isoferulic Acid. A single intravenous injection of Isoferulic Acid decreased the plasma glucose in a dose-dependent manner in the STZ-diabetic rats. Repeated intravenous administration of STZ-diabetic rats with Isoferulic Acid (5.0 mg kg(-1)) also resulted in the lowering of plasma glucose after one day. Stimulatory effects of Isoferulic Acid on the glucose uptake and glycogen synthesis in soleus muscles isolated from STZ-diabetic rats were also obtained indicating an increase of glucose utilization following Isoferulic Acid treatment which was not dependent on insulin. The mRNA level of glucose transporter subtype 4 form (GLUT4) in soleus muscle was raised by Isoferulic Acid after repeated treatment for 1 day in STZ-diabetic rats. Similar repeated treatment with Isoferulic Acid reversed the elevated mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) in liver of STZ-diabetic rats to the normal level. However, expression of GLUT4 and PEPCK genes in nondiabetic rats were not influenced by similar treatment with Isoferulic Acid. These results suggest that Isoferulic Acid can inhibit hepatic gluconeogenesis and/or increase the glucose utilization in peripheral tissue to lower plasma glucose in diabetic rats lacking insulin.
Gary Williamson - One of the best experts on this subject based on the ideXlab platform.
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in vitro and in vivo conjugation of dietary hydroxycinnamic Acids by udp glucuronosyltransferases and sulfotransferases in humans
Journal of Nutritional Biochemistry, 2010Co-Authors: Chi Chun Wong, Angelique Stalmach, Walter Meinl, Hans Rudolf Prof Glatt, Denis Barron, Heike Steiling, Alan Crozier, Gary WilliamsonAbstract:Hydroxycinnamic Acids are a class of phenolic antioxidants found widely in dietary plants. Their biotransformation in the human organism primarily involves Phase II conjugation reactions. In this study, activities of UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) towards major dietary hydroxycinnamic Acids (caffeic, dihydrocaffeic, dihydroferulic, ferulic and Isoferulic Acids) were investigated. Conjugate formation was evaluated using human liver and intestinal S9 homogenates, and in vitro characterization was carried out using recombinant human UGTs and SULTs. Analysis of the kinetics of hydroxycinnamic Acid conjugation in human S9 homogenates revealed that intrinsic clearance (Vmax/Km) is much greater for sulfation than for glucuronidation. Assessment of activity using a panel of recombinant human SULTs showed that SULT1A1 is most active in the sulfation of caffeic, dihydrocaffeic and Isoferulic Acids, while SULT1E1 is most active in the sulfation of ferulic and dihydroferulic Acids. Only Isoferulic Acid was significantly glucuronidated by human liver S9 homogenates, explained by the high activity of liver-specific UGT1A9. Studies on the kinetics of active SULTs and UGTs demonstrated a markedly lower Km for SULTs. To further corroborate our findings, we carried out an intervention study in healthy humans to determine the hydroxycinnamic Acid conjugates in urine after consumption of hydroxycinnamate-rich coffee (200 ml). Analysis showed that sulfates are the main conjugates in urine, with the exception of Isoferulic Acid, which is mainly glucuronidated. These data suggest that sulfates are the predominant hydroxycinnamic Acid conjugates in humans, and that SULT mediated sulfation is a major factor determining the bioavailability of hydroxycinnamic Acids in vivo.
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bioavailability of chlorogenic Acids following acute ingestion of coffee by humans with an ileostomy
Archives of Biochemistry and Biophysics, 2010Co-Authors: Angelique Stalmach, Heike Steiling, Gary Williamson, Alan CrozierAbstract:Abstract The intestinal absorption and metabolism of 385 μmol chlorogenic Acids following a single intake of 200 mL of instant coffee by human volunteers with an ileostomy was investigated. HPLC–MS 3 analysis of 0–24 h post-ingestion ileal effluent revealed the presence of 274 ± 28 μmol of chlorogenic Acids and their metabolites accounting for 71 ± 7% of intake. Of the compounds recovered, 78% comprised parent compounds initially present in the coffee, and 22% were metabolites including free and sulfated caffeic and ferulic Acids. Over a 24 h period after ingestion of the coffee, excretion of chlorogenic Acid metabolites in urine accounted for 8 ± 1% of intake, the main compounds being ferulic Acid-4- O -sulfate, caffeic Acid-3- O -sulfate, Isoferulic Acid-3- O -glucuronide and dihydrocaffeic Acid-3- O -sulfate. In contrast, after drinking a similar coffee, urinary excretion by humans with an intact colon corresponded to 29 ± 4% of chlorogenic Acid intake [23] . This difference was due to the excretion of higher levels of dihydroferulic Acid and feruloylglycine together with sulfate and glucuronide conjugates of dihydrocaffeic and dihydroferulic Acids. This highlights the importance of colonic metabolism. Comparison of the data obtained in the current study with that of Stalmach et al. [23] facilitated elucidation of the pathways involved in post-ingestion metabolism of chlorogenic Acids and also helped distinguish between compounds absorbed in the small and the large intestine.
