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Article ; Online: Incomplete Hydrolysis of Curcumin Conjugates by β-Glucuronidase: Detection of Complex Conjugates in Plasma.

Luis, Paula B / Kunihiro, Andrew G / Funk, Janet L / Schneider, Claus

2020 Volume 64, Issue 6, Page(s) e1901037

Abstract: Scope: The diphenol curcumin from turmeric is rapidly metabolized into phase II conjugates following oral administration, resulting in negligible plasma concentration of the free compound, which is considered the bioactive form. Total plasma ... ...

Abstract	Scope: The diphenol curcumin from turmeric is rapidly metabolized into phase II conjugates following oral administration, resulting in negligible plasma concentration of the free compound, which is considered the bioactive form. Total plasma concentration of curcumin is often quantified after treatment with β-glucuronidase to hydrolyze curcumin-glucuronide, the most abundant conjugate in vivo. The efficiency of enzymatic hydrolysis has not been tested. Methods and results: Using liquid chromatography-mass spectrometry (LC-MS) analyses the efficiency of β-glucuronidase and sulfatase from Helix pomatia is compared to hydrolyze curcumin conjugates in human and mouse plasma after oral administration of turmeric. Both β-glucuronidase and sulfatase completely hydrolyze curcumin-glucuronide. Unexpectedly, β-glucuronidase hydrolysis is incomplete, affording a large amount of curcumin-sulfate, whereas sulfatase hydrolyzed both glucuronide and sulfate conjugates. With sulfatase, the concentration of free curcumin is doubled in human and increased in mouse plasma compared to β-glucuronidase treatment. Incomplete hydrolysis by β-glucuronidase suggests the presence of mixed glucuronide-sulfate conjugates. LC-MS based searches detect diglucuronide, disulfate, and mixed sulfate-glucuronide and sulfate-diglucuronide conjugates in plasma that likely contribute to the increase of free curcumin upon sulfatase treatment. Conclusion: β-Glucuronidase incompletely hydrolyzes complex sulfate-containing conjugates that appear to be major metabolites, resulting in an underestimation of the total plasma concentration of curcumin.
MeSH term(s)	Adult ; Animals ; Curcumin/analogs & derivatives ; Curcumin/analysis ; Curcumin/pharmacokinetics ; Female ; Glucuronidase/chemistry ; Glucuronidase/metabolism ; Glucuronides/blood ; Glucuronides/pharmacokinetics ; Humans ; Hydrolysis ; Male ; Mice, Inbred C57BL ; Middle Aged
Chemical Substances	Glucuronides ; curcumin glucuronide (BE1PK7RL4M) ; Glucuronidase (EC 3.2.1.31) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2020-01-29
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201901037
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Article ; Online: Thiol Reactivity of Curcumin and Its Oxidation Products.

Luis, Paula B / Boeglin, William E / Schneider, Claus

Chemical research in toxicology

2018 Volume 31, Issue 4, Page(s) 269–276

Abstract: The polypharmacological effects of the turmeric compound curcumin may be partly mediated by covalent adduction to cellular protein. Covalent binding to small molecule and protein thiols is thought to occur through a Michael-type addition at the enone ... ...

Abstract	The polypharmacological effects of the turmeric compound curcumin may be partly mediated by covalent adduction to cellular protein. Covalent binding to small molecule and protein thiols is thought to occur through a Michael-type addition at the enone moiety of the heptadienedione chain connecting the two methoxyphenol rings of curcumin. Here we show that curcumin forms the predicted thiol-Michael adducts with three model thiols, glutathione, N-acetylcysteine, and β-mercaptoethanol. More abundant, however, are respective thiol adducts of the dioxygenated spiroepoxide intermediate of curcumin autoxidation. Two electrophilic sites at the quinone-like ring of the spiroepoxide are identified. Addition of β-mercaptoethanol at the 5'-position of the ring gives a 1,7-dihydroxycyclopentadione-5' thioether, and addition at the 1'-position results in cleavage of the aromatic ring from the molecule, forming methoxyphenol-thioether and a tentatively identified cyclopentadione aldehyde. The curcuminoids demethoxy- and bisdemethoxycurcumin do not form all of the possible thioether adducts, corresponding with their increased stability toward autoxidation. RAW264.7 macrophage-like cells activated with phorbol ester form curcumin-glutathionyl and the 1,7-dihydroxycyclopentadione-5'-glutathionyl adducts. These studies indicate that the enone of the parent compound is not the only functional electrophile in curcumin, and that its oxidation products provide additional electrophilic sites. This suggests that protein binding by curcumin may involve oxidative activation into reactive quinone methide and spiroepoxide electrophiles.
MeSH term(s)	Animals ; Curcumin/chemical synthesis ; Curcumin/chemistry ; Curcumin/metabolism ; Macrophages/chemistry ; Macrophages/metabolism ; Mice ; Molecular Structure ; Oxidation-Reduction ; RAW 264.7 Cells ; Sulfhydryl Compounds/chemistry ; Sulfhydryl Compounds/metabolism
Chemical Substances	Sulfhydryl Compounds ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2018-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/acs.chemrestox.7b00326
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Article ; Online: A Curcumin Degradation Product, 7-Norcyclopentadione, Formed by Aryl Migration and Loss of a Carbon from the Heptadienedione Chain.

Joseph, Akil I / Luis, Paula B / Schneider, Claus

Journal of natural products

2018 Volume 81, Issue 12, Page(s) 2756–2762

Abstract: Evidence that anti-inflammatory and other biological effects of curcumin may at least in part be mediated by its metabolites underscores the importance of identifying novel transformation products. Spontaneous degradation of curcumin in buffer pH 7.5 ... ...

Abstract	Evidence that anti-inflammatory and other biological effects of curcumin may at least in part be mediated by its metabolites underscores the importance of identifying novel transformation products. Spontaneous degradation of curcumin in buffer pH 7.5 results mainly in dioxygenated products with a characteristic cyclopentadione ring composed of carbons 2 through 6 of the former heptadienedione chain. When analyzing degradation reactions of 4'- O-methylcurcumin, a product was identified missing one of the terminal carbons of the heptadienedione moiety while containing a cyclopentadione ring and adjacent hydroxy group typical of curcumin degradation products. Analysis of curcumin autoxidation reactions showed formation of an analogous compound, 7-norcyclopentadione, a degradation product exhibiting net loss of a carbon and gain of an oxygen atom. Removal of the carbon is proposed to occur via a peroxide-linked curcumin dimer in conjunction with radical-mediated 1,2-aryl migration of a guaiacol moiety. Oxidation reactions of demethoxycurcumin gave demethoxy-7-norcyclopentadione, whereas an analogous product was not observed from bis-demethoxycurcumin. Incubation of RAW264.7 macrophage-like cells with curcumin showed the presence of 7-norcyclopentadione, the formation of which was not increased upon activation of the cells with 12- O-tetradecanoylphorbol-13-acetate . 7-Norcyclopentadione is a novel type of degradation product that is most likely formed via autoxidative processes when cells are incubated with curcumin.
MeSH term(s)	Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Carbon/chemistry ; Curcumin/chemistry ; Cyclopentanes/chemistry ; Magnetic Resonance Spectroscopy ; Mice ; Molecular Structure ; RAW 264.7 Cells
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Cyclopentanes ; Carbon (7440-44-0) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2018-12-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	304325-3
ISSN	1520-6025 ; 0163-3864
ISSN (online)	1520-6025
ISSN	0163-3864
DOI	10.1021/acs.jnatprod.8b00822
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Article: A Curcumin Degradation Product, 7-Norcyclopentadione, Formed by Aryl Migration and Loss of a Carbon from the Heptadienedione Chain

Joseph, Akil I / Luis, Paula B / Schneider, Claus

Journal of natural products. 2018 Dec. 18, v. 81, no. 12

2018

Abstract	Evidence that anti-inflammatory and other biological effects of curcumin may at least in part be mediated by its metabolites underscores the importance of identifying novel transformation products. Spontaneous degradation of curcumin in buffer pH 7.5 results mainly in dioxygenated products with a characteristic cyclopentadione ring composed of carbons 2 through 6 of the former heptadienedione chain. When analyzing degradation reactions of 4′-O-methylcurcumin, a product was identified missing one of the terminal carbons of the heptadienedione moiety while containing a cyclopentadione ring and adjacent hydroxy group typical of curcumin degradation products. Analysis of curcumin autoxidation reactions showed formation of an analogous compound, 7-norcyclopentadione, a degradation product exhibiting net loss of a carbon and gain of an oxygen atom. Removal of the carbon is proposed to occur via a peroxide-linked curcumin dimer in conjunction with radical-mediated 1,2-aryl migration of a guaiacol moiety. Oxidation reactions of demethoxycurcumin gave demethoxy-7-norcyclopentadione, whereas an analogous product was not observed from bis-demethoxycurcumin. Incubation of RAW264.7 macrophage-like cells with curcumin showed the presence of 7-norcyclopentadione, the formation of which was not increased upon activation of the cells with 12-O-tetradecanoylphorbol-13-acetate . 7-Norcyclopentadione is a novel type of degradation product that is most likely formed via autoxidative processes when cells are incubated with curcumin.
Keywords	autoxidation ; bioactive properties ; buffer index ; buffers ; carbon ; curcumin ; guaiacol ; metabolites ; moieties ; oxygen ; pH
Language	English
Dates of publication	2018-1218
Size	p. 2756-2762.
Publishing place	American Chemical Society and American Society of Pharmacognosy
Document type	Article
ZDB-ID	304325-3
ISSN	1520-6025 ; 0163-3864
ISSN (online)	1520-6025
ISSN	0163-3864
DOI	10.1021/acs.jnatprod.8b00822
Database	NAL-Catalogue (AGRICOLA)

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Article: Curcumin Inhibition of TGFβ signaling in bone metastatic breast cancer cells and the possible role of oxidative metabolites

Kunihiro, Andrew G. / Brickey, Julia A. / Frye, Jennifer B. / Cheng, Julia N. / Luis, Paula B. / Schneider, Claus / Funk, Janet L.

Journal of nutritional biochemistry. 2022 Jan., v. 99

2022

Abstract: TGFβ signaling promotes progression of bone-metastatic (BMET) breast cancer (BCa) cells by driving tumor-associated osteolysis, a hallmark of BCa BMETs, thus allowing for tumor expansion within bone. Turmeric-derived bioactive curcumin, enriched in bone ... ...

Abstract	TGFβ signaling promotes progression of bone-metastatic (BMET) breast cancer (BCa) cells by driving tumor-associated osteolysis, a hallmark of BCa BMETs, thus allowing for tumor expansion within bone. Turmeric-derived bioactive curcumin, enriched in bone via local enzymatic deconjugation of inactive circulating curcumin-glucuronides, inhibits osteolysis and BMET progression in human xenograft BCa BMET models by blocking tumoral TGFβ signaling pathways mediating osteolysis. This is a unique antiosteolytic mechanism in contrast to current osteoclast-targeting therapeutics. Therefore, experiments were undertaken to elucidate the mechanism for curcumin inhibition of BCa TGFβ signaling and the application of this finding across multiple BCa cell lines forming TGFβ-dependent BMETs, including a possible role for bioactive curcumin metabolites in mediating these effects. Immunoblot analysis of TGFβ signaling proteins in bone tropic human (MDA-SA, MDA-1833, MDA-2287) and murine (4T1) BCa cells revealed uniform curcumin blockade of TGFβ-induced Smad activation due to down-regulation of plasma membrane associated TGFβR2 and cellular receptor Smad proteins that propagate Smad-mediated gene expression, resulting in downregulation of PTHrP expression, the osteolytic factor driving in vivo BMET progression. With the exception of early decreases in TGFβR2, inhibitory effects appeared to be mediated by oxidative metabolites of curcumin and involved inhibition of gene expression. Interestingly, while not contributing to changes in Smad-mediated TGFβ signaling, curcumin caused early activation of MAPK signaling in all cell lines, including JNK, an effect possibly involving interactions with TGFβR2 within lipid rafts. Treatment with curcumin or oxidizable analogs of curcumin may have clinical relevancy in the management of TGFβ-dependent BCa BMETs.
Keywords	bone resorption ; breast neoplasms ; curcumin ; gene expression ; gene expression regulation ; humans ; lipids ; metabolites ; metastasis ; mice ; plasma membrane ; xenotransplantation
Language	English
Dates of publication	2022-01
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2021.108842
Database	NAL-Catalogue (AGRICOLA)

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Article: Curcumin activates G protein-coupled receptor 97 (GPR97) in a manner different from glucocorticoid

Harada, Naoki / Arahori, Yumi / Okuyama, Mai / Luis, Paula B. / Joseph, Akil I. / Kitakaze, Tomoya / Goshima, Naoki / Schneider, Claus / Inui, Hiroshi / Yamaji, Ryoichi

Biochemical and biophysical research communications. 2022 Mar. 05, v. 595

2022

Abstract: Curcumin is a yellow pigment in turmeric (Curcuma longa) with various physiological effects in the body. To elucidate the molecular mechanisms by which bioactive compounds exert their function, identification of their molecular targets is crucial. In ... ...

Abstract	Curcumin is a yellow pigment in turmeric (Curcuma longa) with various physiological effects in the body. To elucidate the molecular mechanisms by which bioactive compounds exert their function, identification of their molecular targets is crucial. In this study, we show that curcumin activates G protein-coupled receptor 97 (GPR97). Curcumin dose-dependently activated serum-response element-, but not serum-response factor-response element-, nuclear factor of activated T-cell-response element-, or cAMP-response element-, mediated transcription in cells overexpressed with GPR97. The structure–activity relationship indicated that (i) the double-bonds of the central 7-carbon chain were essential for activation; (ii) a methoxy group on the aromatic ring was required for maximal activity; (iii) the addition of glucuronic acid moiety or a methoxy group to the aromatic ring, but not the methylation of the aromatic p-hydroxy group, eliminated the activity; (iv) the stability of curcumin would be related to receptor activation. Both mutant GPR97(T250A) lacking the cleavage at GPCR proteolysis site and mutant GPR97(ΔN) lacking the N-terminal extracellular region were activated by curcumin and its related compounds similar to wild-type GPR97. In contrast, the synthetic glucocorticoid beclomethasone dipropionate and l-Phe activated wild-type GPR97 and GPR97(T250A), but not GPR97(ΔN). Moreover, curcumin exerted an additive effect on the activation of wild-type GPR97 with beclomethasone dipropionate, but not with l-Phe. Taken together, these results indicate that curcumin activates GPR97 coupled to Gi/Go subunit, and suggest that curcumin and glucocorticoid activate GPR97 in a different manner.
Keywords	Curcuma longa ; G-protein coupled receptors ; additive effect ; curcumin ; glucocorticoids ; glucuronic acid ; methylation ; moieties ; mutants ; proteolysis ; research ; structure-activity relationships ; turmeric
Language	English
Dates of publication	2022-0305
Size	p. 41-46.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2022.01.075
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Article ; Online: The 5-lipoxygenase/cyclooxygenase-2 cross-over metabolite, hemiketal E

Nakashima, Fumie / Giménez-Bastida, Juan A / Luis, Paula B / Presley, Sai H / Boer, Robert E / Chiusa, Manuel / Shibata, Takahiro / Sulikowski, Gary A / Pozzi, Ambra / Schneider, Claus

The Journal of biological chemistry

2023 Volume 299, Issue 4, Page(s) 103050

Abstract: Consecutive oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2 yields the hemiketal eicosanoids, ... ...

Abstract	Consecutive oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2 yields the hemiketal eicosanoids, HKE
MeSH term(s)	Mice ; Humans ; Animals ; Cyclooxygenase 2/metabolism ; Arachidonic Acid ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Arachidonate 5-Lipoxygenase ; Vascular Endothelial Growth Factor A/metabolism ; Neovascularization, Physiologic ; Human Umbilical Vein Endothelial Cells/metabolism ; Angiogenesis Inhibitors/pharmacology ; Cell Movement ; Cell Proliferation
Chemical Substances	Cyclooxygenase 2 (EC 1.14.99.1) ; Arachidonic Acid (27YG812J1I) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) ; Arachidonate 5-Lipoxygenase (EC 1.13.11.34) ; Vascular Endothelial Growth Factor A ; Angiogenesis Inhibitors
Language	English
Publishing date	2023-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.103050
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Article ; Online: Curcumin Inhibition of TGFβ signaling in bone metastatic breast cancer cells and the possible role of oxidative metabolites.

Kunihiro, Andrew G / Brickey, Julia A / Frye, Jennifer B / Cheng, Julia N / Luis, Paula B / Schneider, Claus / Funk, Janet L

The Journal of nutritional biochemistry

2021 Volume 99, Page(s) 108842

Abstract	TGFβ signaling promotes progression of bone-metastatic (BMET) breast cancer (BCa) cells by driving tumor-associated osteolysis, a hallmark of BCa BMETs, thus allowing for tumor expansion within bone. Turmeric-derived bioactive curcumin, enriched in bone via local enzymatic deconjugation of inactive circulating curcumin-glucuronides, inhibits osteolysis and BMET progression in human xenograft BCa BMET models by blocking tumoral TGFβ signaling pathways mediating osteolysis. This is a unique antiosteolytic mechanism in contrast to current osteoclast-targeting therapeutics. Therefore, experiments were undertaken to elucidate the mechanism for curcumin inhibition of BCa TGFβ signaling and the application of this finding across multiple BCa cell lines forming TGFβ-dependent BMETs, including a possible role for bioactive curcumin metabolites in mediating these effects. Immunoblot analysis of TGFβ signaling proteins in bone tropic human (MDA-SA, MDA-1833, MDA-2287) and murine (4T1) BCa cells revealed uniform curcumin blockade of TGFβ-induced Smad activation due to down-regulation of plasma membrane associated TGFβR2 and cellular receptor Smad proteins that propagate Smad-mediated gene expression, resulting in downregulation of PTHrP expression, the osteolytic factor driving in vivo BMET progression. With the exception of early decreases in TGFβR2, inhibitory effects appeared to be mediated by oxidative metabolites of curcumin and involved inhibition of gene expression. Interestingly, while not contributing to changes in Smad-mediated TGFβ signaling, curcumin caused early activation of MAPK signaling in all cell lines, including JNK, an effect possibly involving interactions with TGFβR2 within lipid rafts. Treatment with curcumin or oxidizable analogs of curcumin may have clinical relevancy in the management of TGFβ-dependent BCa BMETs.
MeSH term(s)	Animals ; Bone Neoplasms/genetics ; Bone Neoplasms/metabolism ; Bone Neoplasms/prevention & control ; Bone Neoplasms/secondary ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Curcumin/administration & dosage ; Curcumin/chemistry ; Female ; Humans ; Mice ; Oxidation-Reduction ; Receptor, Transforming Growth Factor-beta Type II/genetics ; Receptor, Transforming Growth Factor-beta Type II/metabolism ; Signal Transduction/drug effects ; Smad Proteins/genetics ; Smad Proteins/metabolism ; Transforming Growth Factor beta1/genetics ; Transforming Growth Factor beta1/metabolism
Chemical Substances	Smad Proteins ; Transforming Growth Factor beta1 ; Receptor, Transforming Growth Factor-beta Type II (EC 2.7.11.30) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2021-08-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2021.108842
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Article ; Online: Curcumin activates G protein-coupled receptor 97 (GPR97) in a manner different from glucocorticoid.

Harada, Naoki / Arahori, Yumi / Okuyama, Mai / Luis, Paula B / Joseph, Akil I / Kitakaze, Tomoya / Goshima, Naoki / Schneider, Claus / Inui, Hiroshi / Yamaji, Ryoichi

Biochemical and biophysical research communications

2022 Volume 595, Page(s) 41–46

Abstract	Curcumin is a yellow pigment in turmeric (Curcuma longa) with various physiological effects in the body. To elucidate the molecular mechanisms by which bioactive compounds exert their function, identification of their molecular targets is crucial. In this study, we show that curcumin activates G protein-coupled receptor 97 (GPR97). Curcumin dose-dependently activated serum-response element-, but not serum-response factor-response element-, nuclear factor of activated T-cell-response element-, or cAMP-response element-, mediated transcription in cells overexpressed with GPR97. The structure-activity relationship indicated that (i) the double-bonds of the central 7-carbon chain were essential for activation; (ii) a methoxy group on the aromatic ring was required for maximal activity; (iii) the addition of glucuronic acid moiety or a methoxy group to the aromatic ring, but not the methylation of the aromatic p-hydroxy group, eliminated the activity; (iv) the stability of curcumin would be related to receptor activation. Both mutant GPR97(T250A) lacking the cleavage at GPCR proteolysis site and mutant GPR97(ΔN) lacking the N-terminal extracellular region were activated by curcumin and its related compounds similar to wild-type GPR97. In contrast, the synthetic glucocorticoid beclomethasone dipropionate and l-Phe activated wild-type GPR97 and GPR97(T250A), but not GPR97(ΔN). Moreover, curcumin exerted an additive effect on the activation of wild-type GPR97 with beclomethasone dipropionate, but not with l-Phe. Taken together, these results indicate that curcumin activates GPR97 coupled to Gi/Go subunit, and suggest that curcumin and glucocorticoid activate GPR97 in a different manner.
MeSH term(s)	Beclomethasone/chemistry ; Beclomethasone/pharmacology ; Curcuma/chemistry ; Curcumin/chemistry ; Curcumin/metabolism ; Curcumin/pharmacology ; Gene Expression Regulation/drug effects ; Glucocorticoids/chemistry ; Glucocorticoids/pharmacology ; HEK293 Cells ; Humans ; Luciferases/genetics ; Luciferases/metabolism ; Molecular Structure ; Mutation ; Protein Isoforms/chemistry ; Protein Isoforms/metabolism ; Protein Isoforms/pharmacology ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Response Elements/genetics ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Structure-Activity Relationship
Chemical Substances	ADGRG3 protein, human ; Glucocorticoids ; Protein Isoforms ; Receptors, G-Protein-Coupled ; Luciferases (EC 1.13.12.-) ; Curcumin (IT942ZTH98) ; Beclomethasone (KGZ1SLC28Z)
Language	English
Publishing date	2022-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2022.01.075
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Article ; Online: Mechanistic Differences in the Inhibition of NF-κB by Turmeric and Its Curcuminoid Constituents.

Edwards, Rebecca L / Luis, Paula B / Nakashima, Fumie / Kunihiro, Andrew G / Presley, Sai-Han / Funk, Janet L / Schneider, Claus

Journal of agricultural and food chemistry

2020 Volume 68, Issue 22, Page(s) 6154–6160

Abstract: Turmeric extract, a mixture of curcumin and its demethoxy (DMC) and bisdemethoxy (BDMC) isomers, is used as an anti-inflammatory preparation in traditional Asian medicine. Curcumin is considered to be the major bioactive compound in turmeric but less is ... ...

Abstract	Turmeric extract, a mixture of curcumin and its demethoxy (DMC) and bisdemethoxy (BDMC) isomers, is used as an anti-inflammatory preparation in traditional Asian medicine. Curcumin is considered to be the major bioactive compound in turmeric but less is known about the relative anti-inflammatory potency and mechanism of the other components, their mixture, or the reduced in vivo metabolites. We quantified inhibition of the NF-κB pathway in cells, adduction to a peptide mimicking IκB kinase β, and the role of cellular glutathione as a scavenger of electrophilic curcuminoid oxidation products, suggested to be the active metabolites. Turmeric extracts (IC
MeSH term(s)	Animals ; Cell Line ; Curcuma/chemistry ; Curcumin/chemistry ; Curcumin/pharmacology ; Diarylheptanoids/chemistry ; Diarylheptanoids/pharmacology ; Humans ; Kinetics ; NF-kappa B/antagonists & inhibitors ; NF-kappa B/metabolism ; Oxidation-Reduction/drug effects ; Plant Extracts/chemistry ; Plant Extracts/pharmacology
Chemical Substances	Diarylheptanoids ; NF-kappa B ; Plant Extracts ; turmeric extract (856YO1Z64F) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.0c02607
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