The Experts below are selected from a list of 1791 Experts worldwide ranked by ideXlab platform
Sueharu Horinouchi - One of the best experts on this subject based on the ideXlab platform.
-
identification and characterization of multiple curcumin synthases from the herb curcuma longa
FEBS Letters, 2009Co-Authors: Yohei Katsuyama, Tomoko Kita, Sueharu HorinouchiAbstract:Curcuminoids are pharmaceutically important compounds isolated from the herb Curcuma longa. Two additional type III polyketide synthases, named CURS2 and CURS3, that are capable of Curcuminoid synthesis were identified and characterized. In vitro analysis revealed that CURS2 preferred feruloyl-CoA as a starter substrate and CURS3 preferred both feruloyl-CoA and p-coumaroyl-CoA. These results suggested that CURS2 synthesizes curcumin or demethoxycurcumin and CURS3 synthesizes curcumin, bisdemethoxycurcumin and demethoxycurcumin. The availability of the substrates and the expression levels of the three different enzymes capable of Curcuminoid synthesis with different substrate specificities might influence the composition of Curcuminoids in the turmeric and in different cultivars.
-
Curcuminoid biosynthesis by two type iii polyketide synthases in the herb curcuma longa
Journal of Biological Chemistry, 2009Co-Authors: Yohei Katsuyama, Tomoko Kita, Nobutaka Funa, Sueharu HorinouchiAbstract:Curcuminoids found in the rhizome of turmeric, Curcuma longa, possess various biological activities. Despite much attention regarding the biosynthesis of Curcuminoids because of their pharmaceutically important properties and biosynthetically intriguing structures, no enzyme systems have been elucidated. Here we propose a pathway for Curcuminoid biosynthesis in the herb C. longa, which includes two novel type III polyketide synthases. One of the type III polyketide synthases, named diketide-CoA synthase (DCS), catalyzed the formation of feruloyldiketide-CoA by condensing feruloyl-CoA and malonyl-CoA. The other, named curcumin synthase (CURS), catalyzed the in vitro formation of Curcuminoids from cinnamoyldiketide-N-acetylcysteamine (a mimic of the CoA ester) and feruloyl-CoA. Co-incubation of DCS and CURS in the presence of feruloyl-CoA and malonyl-CoA yielded curcumin at high efficiency, although CURS itself possessed low activity for the synthesis of curcumin from feruloyl-CoA and malonyl-CoA. These findings thus revealed the curcumin biosynthetic route in turmeric, in which DCS synthesizes feruloyldiketide-CoA, and CURS then converts the diketide-CoA esters into a Curcuminoid scaffold.
-
In Vitro Synthesis of Curcuminoids by Type III Polyketide Synthase from Oryza sativa
The Journal of biological chemistry, 2007Co-Authors: Yohei Katsuyama, Miku Matsuzawa, Nobutaka Funa, Sueharu HorinouchiAbstract:Curcuminoids, major components of the spice turmeric, are used as a traditional Asian medicine and a food additive. Curcumin, a representative Curcuminoid, has received a great deal of attention because of its anti-inflammatory, anticarcinogenic, and antitumor activities. Here we report a novel type III polyketide synthase named Curcuminoid synthase from Oryza sativa, which synthesizes bisdemethoxycurcumin via a unique mechanism from two 4-coumaroyl-CoAs and one malonyl-CoA. The reaction begins with the thioesterification of the thiol moiety of Cys-174 by a starter molecule, 4-coumaroyl-CoA. Decarboxylative condensation of the first extender substrate, malonyl-CoA, onto the thioester of 4-coumarate results in the formation of a diketide-CoA intermediate. Subsequent hydrolysis of the intermediate yields a β-keto acid, which in turn acts as the second extender substrate. The β-keto acid is then joined to the Cys-174-bound 4-coumarate by decarboxylative condensation to form bisdemethoxycurcumin. This reaction violates the traditional head-to-tail model of polyketide assembly; the growing diketide intermediate is hydrolyzed to a β-keto acid that subsequently serves as the second extender to form Curcuminoids. Curcuminoid synthase appears to be capable of the synthesis of not only diarylheptanoids but also gingerol analogues, because it synthesized cinnamoyl(hexanoyl)methane, a putative intermediate of gingerol, from cinnamoyl-CoA and 3-oxo-octanoic acid.
Yohei Katsuyama - One of the best experts on this subject based on the ideXlab platform.
-
identification and characterization of multiple curcumin synthases from the herb curcuma longa
FEBS Letters, 2009Co-Authors: Yohei Katsuyama, Tomoko Kita, Sueharu HorinouchiAbstract:Curcuminoids are pharmaceutically important compounds isolated from the herb Curcuma longa. Two additional type III polyketide synthases, named CURS2 and CURS3, that are capable of Curcuminoid synthesis were identified and characterized. In vitro analysis revealed that CURS2 preferred feruloyl-CoA as a starter substrate and CURS3 preferred both feruloyl-CoA and p-coumaroyl-CoA. These results suggested that CURS2 synthesizes curcumin or demethoxycurcumin and CURS3 synthesizes curcumin, bisdemethoxycurcumin and demethoxycurcumin. The availability of the substrates and the expression levels of the three different enzymes capable of Curcuminoid synthesis with different substrate specificities might influence the composition of Curcuminoids in the turmeric and in different cultivars.
-
Curcuminoid biosynthesis by two type iii polyketide synthases in the herb curcuma longa
Journal of Biological Chemistry, 2009Co-Authors: Yohei Katsuyama, Tomoko Kita, Nobutaka Funa, Sueharu HorinouchiAbstract:Curcuminoids found in the rhizome of turmeric, Curcuma longa, possess various biological activities. Despite much attention regarding the biosynthesis of Curcuminoids because of their pharmaceutically important properties and biosynthetically intriguing structures, no enzyme systems have been elucidated. Here we propose a pathway for Curcuminoid biosynthesis in the herb C. longa, which includes two novel type III polyketide synthases. One of the type III polyketide synthases, named diketide-CoA synthase (DCS), catalyzed the formation of feruloyldiketide-CoA by condensing feruloyl-CoA and malonyl-CoA. The other, named curcumin synthase (CURS), catalyzed the in vitro formation of Curcuminoids from cinnamoyldiketide-N-acetylcysteamine (a mimic of the CoA ester) and feruloyl-CoA. Co-incubation of DCS and CURS in the presence of feruloyl-CoA and malonyl-CoA yielded curcumin at high efficiency, although CURS itself possessed low activity for the synthesis of curcumin from feruloyl-CoA and malonyl-CoA. These findings thus revealed the curcumin biosynthetic route in turmeric, in which DCS synthesizes feruloyldiketide-CoA, and CURS then converts the diketide-CoA esters into a Curcuminoid scaffold.
-
In Vitro Synthesis of Curcuminoids by Type III Polyketide Synthase from Oryza sativa
The Journal of biological chemistry, 2007Co-Authors: Yohei Katsuyama, Miku Matsuzawa, Nobutaka Funa, Sueharu HorinouchiAbstract:Curcuminoids, major components of the spice turmeric, are used as a traditional Asian medicine and a food additive. Curcumin, a representative Curcuminoid, has received a great deal of attention because of its anti-inflammatory, anticarcinogenic, and antitumor activities. Here we report a novel type III polyketide synthase named Curcuminoid synthase from Oryza sativa, which synthesizes bisdemethoxycurcumin via a unique mechanism from two 4-coumaroyl-CoAs and one malonyl-CoA. The reaction begins with the thioesterification of the thiol moiety of Cys-174 by a starter molecule, 4-coumaroyl-CoA. Decarboxylative condensation of the first extender substrate, malonyl-CoA, onto the thioester of 4-coumarate results in the formation of a diketide-CoA intermediate. Subsequent hydrolysis of the intermediate yields a β-keto acid, which in turn acts as the second extender substrate. The β-keto acid is then joined to the Cys-174-bound 4-coumarate by decarboxylative condensation to form bisdemethoxycurcumin. This reaction violates the traditional head-to-tail model of polyketide assembly; the growing diketide intermediate is hydrolyzed to a β-keto acid that subsequently serves as the second extender to form Curcuminoids. Curcuminoid synthase appears to be capable of the synthesis of not only diarylheptanoids but also gingerol analogues, because it synthesized cinnamoyl(hexanoyl)methane, a putative intermediate of gingerol, from cinnamoyl-CoA and 3-oxo-octanoic acid.
Amirhossein Sahebkar - One of the best experts on this subject based on the ideXlab platform.
-
Novel nanomicelle formulation to enhance bioavailability and stability of Curcuminoids
Mashhad University of Medical Sciences, 2019Co-Authors: Mahdi Hatamipour, Amirhossein Sahebkar, Seyedeh Hoda Alavizadeh, Mahyar Dorri, Mahmoud Reza JaafariAbstract:Objective(s): Curcuminoids, comprising curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), are bioactive phytochemicals with numerous pharmacological effects. Oral biological availability of Curcuminoids is low due to the low aqueous solubility and rapid metabolism. This study aimed at fabricating a nanomicellar Curcuminoid formula with enhanced pharmacokinetic properties. Materials and Methods: Curcuminoids nanomicelles were prepared and characterized regarding particle properties, stability, release profile and pharmacokinetic parameters.Results: Encapsulation efficiency of Curcuminoids in nanomicelles were 100%. Particle size analysis demonstrated a mean size of around 10 nm that remained stable for 24 months. Dissolution test showed the complete dissolution of encapsulated Curcuminoids from nanomicelles within 20 min while the free Curcuminoids were poorly dissolved (approximately 7% after 60 min). The results of long-term (24 months) and accelerated (6 months) stability studies showed no changes in the size and content of nanomicelles. The release studies in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) showed no release of Curcuminoids for at least 4 hours. In vivo study in BALB/c mice showed improved pharmacokinetic parameters including maximum plasma concentration (Cmax) and time to reach the maximum concentration (Tmax) with nanomicelles as compared to free Curcuminoids and two other commercial products. Tmax for all the three Curcuminoid components was observed 30 min following oral administration. AUC of nanomicellar Curcuminoids was 59.2 times more than free Curcuminoids. Conclusion: These data indicated that nanomicelles could improve solubility, oral bioavailability and also the stability of Curcuminoids. Thus, they merit further investigation for enhancing pharmacological effects of Curcuminoids
-
antioxidant and anti inflammatory effects of Curcuminoid piperine combination in subjects with metabolic syndrome a randomized controlled trial and an updated meta analysis
Clinical Nutrition, 2015Co-Authors: Yunes Panahi, Muhammed Majeed, Mahboobeh Sadat Hosseini, Nahid Khalili, Effat Naimi, Amirhossein SahebkarAbstract:Summary Background Oxidative stress and inflammation have been proposed as emerging components of metabolic syndrome (MetS). Curcuminoids are natural polyphenols with strong antioxidant and anti-inflammatory properties. Objective To study the effectiveness of supplementation with a bioavailable Curcuminoid preparation on measures of oxidative stress and inflammation in patients with MetS. Our secondary aim was to perform a meta-analysis of data from all randomized controlled trials in order to estimate the effect size of Curcuminoids on plasma C-reactive protein (CRP) concentrations. Methods In this randomized double-blind placebo-controlled trial, 117 subjects with MetS (according to the NCEP-ATPIII diagnostic criteria) were randomly assigned to Curcuminoids (n = 59; drop-outs = 9) or placebo (n = 58; drop-outs = 8) for eight weeks. Curcuminoids were administered at a daily dose of 1 g, and were co-supplemented with piperine (10 mg/day) in order to boost oral bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of malondialdehyde (MDA) and CRP were measured at baseline and at study end. Regarding the importance of CRP as a risk marker and risk factor of cardiovascular disease, a random-effects meta-analysis of clinical trials was performed to estimate the overall impact of Curcuminoid therapy on circulating concentrations of CRP. The robustness of estimated effect size was evaluated using leave-one-out sensitivity analysis. Results Supplementation with Curcuminoid-piperine combination significantly improved serum SOD activities ( p p p p = 0.01). This effect was robust in sensitivity analysis. Conclusions Short-term supplementation with Curcuminoid-piperine combination significantly improves oxidative and inflammatory status in patients with MetS. Curcuminoids could be regarded as natural, safe and effective CRP-lowering agents.
-
Curcuminoids modulate pro oxidant antioxidant balance but not the immune response to heat shock protein 27 and oxidized ldl in obese individuals
Phytotherapy Research, 2013Co-Authors: Amirhossein Sahebkar, Akram Mohammadi, Ali Atabati, Shamim Rahiman, Shima Tavallaie, Mehrdad Iranshahi, Saeed Akhlaghi, Gordon A Ferns, Majid GhayourmobarhanAbstract:Curcuminoids have potentially important functional qualities including anti-inflammatory and antioxidant properties. In this randomized double-blind placebo-controlled cross-over trial, the effects of a Curcuminoid supplement on serum pro-oxidant–antioxidant balance (PAB) and antibody titres to Hsp27 (anti-Hsp27) and oxLDL (anti-oxLDL) were investigated. Thirty obese individuals were randomized to receive either Curcuminoids (1 g/day) or placebo for a period of 30 days. After a wash-out period of 2 weeks, subjects were crossed over to the alternate regimen for another 30 days. Serum PAB along with anti-Hsp27 and anti-oxLDL titres was measured at the beginning and at the end of each study period. There was no significant carry-over effect for any of the assessed parameters. Curcuminoid supplementation was associated with a significant decrease in PAB (p=0.044). However, no significant change was observed in serum concentrations of anti-Hsp27 or anti-oxLDL (p>0.05). These findings suggest that oral Curcuminoids supplementation (1g/day) is effective in reducing oxidative stress burden, though this needs to be validated in larger study populations. Copyright © 2013 John Wiley & Sons, Ltd.
-
effects of supplementation with Curcuminoids on dyslipidemia in obese patients a randomized crossover trial
Phytotherapy Research, 2013Co-Authors: Akram Mohammadi, Amirhossein Sahebkar, Mehrdad Iranshahi, Majid Ghayourmobarhan, Maral Amini, Roshanak Khojasteh, Gordon A FernsAbstract:Dyslipidemia is a leading risk factor for cardiovascular disease and is also a common feature of obesity. Curcumin is a bioactive phytochemical with well-known antioxidant, anti-inflammatory, and cardioprotective properties. The present study investigated the hypolipidemic activity of curcumin in obese individuals. Participants (n = 30) were treated with Curcuminoids (1 g/day), or placebo in a randomized, double-blind, placebo-controlled, crossover trial. Serum concentrations of total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, together with anthropometric parameters and high-sensitivity C-reactive protein were measured before and after each treatment period. Anthropometric parameters including weight, BMI, waist circumference, hip circumference, arm circumference, and body fat remained statistically unchanged by the end of trial (p > 0.05). As for the lipid profile parameters, serum triglycerides were significantly reduced following curcumin supplementation (p = 0.009). However, Curcuminoids were not found to affect serum levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (p > 0.05). In summary, the findings of the present study indicated that Curcuminoid supplementation (1 g/day for 30 days) leads to a significant reduction in serum triglycerides concentrations but do not have a significant influence on other lipid profile parameters as well as body mass index and body fat. Copyright © 2012 John Wiley & Sons, Ltd.
Hisamuddin Nadia - One of the best experts on this subject based on the ideXlab platform.
-
Anti-inflammatory activity of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (synthetic Curcuminoid analogue) in mice
2019Co-Authors: Hisamuddin NadiaAbstract:The rhizome of Curcuma longa (C. longa) plant consists of 3-5% Curcuminoids. Curcuminoids comprises of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Among these, curcumin has been reported to be responsible for most of the C. longa pharmacological activities. However, the biological activities of curcumin are limited due to its solubility and low bioavailability in vivo. Numerous Curcuminoid analogues with better bioavailability and solubility were synthesized to overcome these limitations. Novel synthetic Curcuminoid analogues such as the 5-(3,4- dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (abbrev. DHHPD), showed good anti-inflammatory activities in vitro. Hence, the current study was conducted to evaluate the anti-inflammatory activity of DHHPD in mice using the carrageenan-induced paw oedema and cotton pellet-induced granuloma tests. Mice that received DHHPD (0.1, 0.3, 1 and 3 mg/kg, intraperitoneal) showed a significant decrease (p
Tomoko Kita - One of the best experts on this subject based on the ideXlab platform.
-
identification and characterization of multiple curcumin synthases from the herb curcuma longa
FEBS Letters, 2009Co-Authors: Yohei Katsuyama, Tomoko Kita, Sueharu HorinouchiAbstract:Curcuminoids are pharmaceutically important compounds isolated from the herb Curcuma longa. Two additional type III polyketide synthases, named CURS2 and CURS3, that are capable of Curcuminoid synthesis were identified and characterized. In vitro analysis revealed that CURS2 preferred feruloyl-CoA as a starter substrate and CURS3 preferred both feruloyl-CoA and p-coumaroyl-CoA. These results suggested that CURS2 synthesizes curcumin or demethoxycurcumin and CURS3 synthesizes curcumin, bisdemethoxycurcumin and demethoxycurcumin. The availability of the substrates and the expression levels of the three different enzymes capable of Curcuminoid synthesis with different substrate specificities might influence the composition of Curcuminoids in the turmeric and in different cultivars.
-
Curcuminoid biosynthesis by two type iii polyketide synthases in the herb curcuma longa
Journal of Biological Chemistry, 2009Co-Authors: Yohei Katsuyama, Tomoko Kita, Nobutaka Funa, Sueharu HorinouchiAbstract:Curcuminoids found in the rhizome of turmeric, Curcuma longa, possess various biological activities. Despite much attention regarding the biosynthesis of Curcuminoids because of their pharmaceutically important properties and biosynthetically intriguing structures, no enzyme systems have been elucidated. Here we propose a pathway for Curcuminoid biosynthesis in the herb C. longa, which includes two novel type III polyketide synthases. One of the type III polyketide synthases, named diketide-CoA synthase (DCS), catalyzed the formation of feruloyldiketide-CoA by condensing feruloyl-CoA and malonyl-CoA. The other, named curcumin synthase (CURS), catalyzed the in vitro formation of Curcuminoids from cinnamoyldiketide-N-acetylcysteamine (a mimic of the CoA ester) and feruloyl-CoA. Co-incubation of DCS and CURS in the presence of feruloyl-CoA and malonyl-CoA yielded curcumin at high efficiency, although CURS itself possessed low activity for the synthesis of curcumin from feruloyl-CoA and malonyl-CoA. These findings thus revealed the curcumin biosynthetic route in turmeric, in which DCS synthesizes feruloyldiketide-CoA, and CURS then converts the diketide-CoA esters into a Curcuminoid scaffold.
