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Article ; Online: Methyl 2-[3-(4-hydroxyphenyl)prop-2-enoylamino]-3-phenylpropanoate Is a Potent Cell-Permeable Anti-Cytokine Compound To Inhibit Inflammatory Cytokines in Monocyte/Macrophage-Like Cells.

Park, Jae B

The Journal of pharmacology and experimental therapeutics

2024 Volume 388, Issue 1, Page(s) 181–189

Abstract: Cytokines are signaling molecules involved in inflammation process. Interleukin (IL)-6 is one of pivotal inflammatory cytokines associated with many human diseases. Therefore, there are on-going efforts to find a therapeutic to inhibit IL-6 and other ... ...

Abstract	Cytokines are signaling molecules involved in inflammation process. Interleukin (IL)-6 is one of pivotal inflammatory cytokines associated with many human diseases. Therefore, there are on-going efforts to find a therapeutic to inhibit IL-6 and other cytokines. Methyl 2-[3-(4-hydroxyphenyl)prop-2-enoylamino]-3-phenylpropanoate (MHPAP) is a phenolic amide ester, transported better than its non-ester form (NEF) in monocyte/macrophage-like cells. However, there is no information about the effects of their cell permeability on cytokines. Therefore, the effects of MHPAP and NEF on cytokines were investigated in lipopolysaccharide (LPS)-stimulated THP-1 and human peripheral blood mononuclear cells (PBMCs). In the THP-1 cells, MHPAP significantly inhibited IL-6, IL-1beta, IL-8, and tumor necrosis factor (TNF)-alpha (
MeSH term(s)	Humans ; Cytokines/metabolism ; NF-kappa B/metabolism ; Tumor Necrosis Factor-alpha ; Monocytes ; Interleukin-6 ; Leukocytes, Mononuclear/metabolism ; Lipopolysaccharides/pharmacology ; Interleukin-8 ; Macrophages/metabolism
Chemical Substances	Cytokines ; NF-kappa B ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Lipopolysaccharides ; Interleukin-8
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.123.001830
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Article ; Online: Finding a cell-permeable compound to inhibit inflammatory cytokines: Uptake, biotransformation, and anti-cytokine activity of javamide-I/-II esters.

Park, Jae B

Life sciences

2022 Volume 291, Page(s) 120280

Abstract: Aim: Currently, there is limited information available about cell-permeability and anti-cytokine activity of javamide-I/-II esters in monocyte/macrophage-like cells. Therefore, the aim of this study was to investigate their cell-permeability and anti- ... ...

Abstract	Aim: Currently, there is limited information available about cell-permeability and anti-cytokine activity of javamide-I/-II esters in monocyte/macrophage-like cells. Therefore, the aim of this study was to investigate their cell-permeability and anti-cytokine activity in the cells. Materials and methods: The uptake of javamide-I/-II and esters was studied in THP-1 cells and PBMCs. Also, kinetic and inhibition studies were conducted using THP-1 cells. Western Blot was performed to determine the level of ATF-2 phosphorylation in THP-1 cells, and ELISA assays were carried out to measure TNF-alpha, MCP-1, IL-1beta and IL-8 levels in PBMCs. Key findings: In THP-1 cells, the uptake of javamide-I/-II esters was significantly higher than javamide-I/-II (P < 0.001), and the K Significance: Javamide-I/-II esters can be transported, biotransformed and inhibit inflammatory cytokines significantly in monocyte/macrophage-like cells, suggesting that they may be utilized as a potent cell-permeable carrier to inhibit inflammatory cytokines in the cells. Chemical compounds: Javamide-I, javamide-I-O-methyl ester, javamide-II, javamide-II-O-methyl ester, tryptophan, coumaric acid, caffeic acid, GlySar, enalapril.
MeSH term(s)	Biotransformation/drug effects ; Biotransformation/physiology ; Caffeic Acids/pharmacology ; Cytokines/drug effects ; Cytokines/metabolism ; Esters ; Humans ; Indoles/metabolism ; Indoles/pharmacokinetics ; Indoles/pharmacology ; Inflammation/metabolism ; Leukocytes, Mononuclear/metabolism ; Permeability ; Phenols/metabolism ; Phenols/pharmacokinetics ; Phenols/pharmacology ; Protein Binding ; Signal Transduction/drug effects ; THP-1 Cells
Chemical Substances	Caffeic Acids ; Cytokines ; Esters ; Indoles ; Phenols ; javamide-I-O-methyl ester ; caffeic acid (U2S3A33KVM)
Language	English
Publishing date	2022-01-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2021.120280
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Article ; Online: In Vivo Effects of Coffee Containing Javamide-I/-II on Body Weight, LDL, HDL, Total Cholesterol, Triglycerides, Leptin, Adiponectin, C-Reactive Protein, sE-Selectin, TNF-α, and MCP-1.

Park, Jae B

Current developments in nutrition

2021 Volume 6, Issue 1, Page(s) nzab145

Abstract: Background: Diet plays an unequivocal role in the development of obesity. Interestingly, recent studies have demonstrated that coffee products containing javamide-I/-II may be commonly found in the market. However, there is no information about in vivo ... ...

Abstract	Background: Diet plays an unequivocal role in the development of obesity. Interestingly, recent studies have demonstrated that coffee products containing javamide-I/-II may be commonly found in the market. However, there is no information about in vivo effects of coffee containing javamide-I/-II (CCJ12) on obesity-related metabolic factors (body weight, LDL, HDL, total cholesterols, triglycerides, adiponectin, and leptin) in nonobese people. Objectives: The objective of this study was to investigate in vivo effects of CCJ12 on these metabolic factors as well as inflammatory/cardiovascular disease risk factors [C-reactive protein (CRP), soluble E-selectin (sE-selectin), TNF-α, monocyte chemoattractant protein-1 (MCP-1)] in a nonobese model. Methods: Sprague-Dawley male rats were fed a complete diet for 20 wk with either drinking water containing CCJ12 [coffee containing javamide-I/-II group (CG), Results: There was no significant difference in water/food consumption between the NCG and CG during the study. Also, no significant difference was found in average body weights between the groups either. In addition, after 20 wk, both groups did not show any significant difference in plasma LDL, HDL, and total cholesterol concentrations. Likewise, adiponectin and leptin concentrations were not significantly different between the groups. As expected, the 2 groups did not show any significant difference in plasma concentrations of CRP and sE-selectin. Furthermore, there was no significant difference in plasma concentrations of TNF-α and MCP-1 between the groups. Conclusions: The data suggest that CCJ12 may not have significant effects on the metabolic/inflammatory/cardiovascular disease risk factors in the CG, compared with the NCG.
Language	English
Publishing date	2021-11-30
Publishing country	United States
Document type	Journal Article
ISSN	2475-2991
ISSN (online)	2475-2991
DOI	10.1093/cdn/nzab145
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Article: Finding a cell-permeable compound to inhibit inflammatory cytokines: Uptake, biotransformation, and anti-cytokine activity of javamide-I/-II esters

Park, Jae B.

Life sciences. 2022 Feb. 15, v. 291

2022

Abstract: Currently, there is limited information available about cell-permeability and anti-cytokine activity of javamide-I/-II esters in monocyte/macrophage-like cells. Therefore, the aim of this study was to investigate their cell-permeability and anti-cytokine ...

Abstract	Currently, there is limited information available about cell-permeability and anti-cytokine activity of javamide-I/-II esters in monocyte/macrophage-like cells. Therefore, the aim of this study was to investigate their cell-permeability and anti-cytokine activity in the cells. The uptake of javamide-I/-II and esters was studied in THP-1 cells and PBMCs. Also, kinetic and inhibition studies were conducted using THP-1 cells. Western Blot was performed to determine the level of ATF-2 phosphorylation in THP-1 cells, and ELISA assays were carried out to measure TNF-alpha, MCP-1, IL-1beta and IL-8 levels in PBMCs. In THP-1 cells, the uptake of javamide-I/-II esters was significantly higher than javamide-I/-II (P < 0.001), and the Kₘ for javamide-I ester was 27 μM. Also, the uptake of the esters was inhibited by PepT2 substrate/blocker. In THP-1 cells, javamide-I/-II esters were also biotransformed into javamide-I/-II. Furthermore, javamide-I ester could inhibit ATF-2 phosphorylation better than javamide-I in the cells, suggesting that the ester could be transported inside the cells better than javamide-I. Similarly, javamide-I/-II esters were found to be transported and biotransformed in PBMCs involved in inflammation processes. As anticipated, the esters were found to inhibit TNF-alpha and MCP-1 significantly in PBMCs (P < 0.005). Especially, javamide-I ester inhibited TNF-alpha, MCP-1, IL-1beta and IL-8 with IC₅₀ values of 1.79, 0.88, 0.91 and 2.57 μM in PBMCs. Javamide-I/-II esters can be transported, biotransformed and inhibit inflammatory cytokines significantly in monocyte/macrophage-like cells, suggesting that they may be utilized as a potent cell-permeable carrier to inhibit inflammatory cytokines in the cells. Javamide-I, javamide-I-O-methyl ester, javamide-II, javamide-II-O-methyl ester, tryptophan, coumaric acid, caffeic acid, GlySar, enalapril.
Keywords	Western blotting ; biotransformation ; caffeic acid ; inflammation ; interleukin-1beta ; interleukin-8 ; phosphorylation ; tryptophan ; tumor necrosis factor-alpha
Language	English
Dates of publication	2022-0215
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2021.120280
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Article ; Online: Kahweol Found in Coffee Inhibits IL-2 Production Via Suppressing the Phosphorylations of ERK and c-Fos in Lymphocytic Jurkat Cells.

Park, Jae B

Journal of dietary supplements

2020 Volume 18, Issue 4, Page(s) 433–443

Abstract: Interleukin-2 (IL-2) is a cytokine involved in the development and maturation of the subsets of T cells, critically associated with the progression of several immune-related diseases (e.g. liver disease, bowel disease). Interestingly, a recent study ... ...

Abstract	Interleukin-2 (IL-2) is a cytokine involved in the development and maturation of the subsets of T cells, critically associated with the progression of several immune-related diseases (e.g. liver disease, bowel disease). Interestingly, a recent study suggests that coffee may contain several compounds to inhibit IL-2 expression in activated T-lymphocytic cells. However, there is little information about the potential effects of several coffee compounds (e.g. kahweol, cafestol, trigonelline, niacin and chlorogenic acids) on IL-2 expression in activated T-lymphocytic cells. Therefore, in this paper, their effects on IL-2 expression were evaluated in PHA/PMA-activated lymphocytic Jurkat cells. Among the tested compounds, only kahweol and cafestol were able to reduce IL-2 production significantly in the cells (
MeSH term(s)	Coffee/chemistry ; Diterpenes/pharmacology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Interleukin-2 ; Jurkat Cells ; Phosphorylation ; Proto-Oncogene Proteins c-fos/metabolism ; T-Lymphocytes/drug effects
Chemical Substances	Coffee ; Diterpenes ; Interleukin-2 ; Proto-Oncogene Proteins c-fos ; kahweol (6894-43-5) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
Language	English
Publishing date	2020-06-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2020.1784347
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Article ; Online: Impact of roasting on javamide-I/-II in Arabica and Robusta coffee beans.

Park, Jae B / Peters, Renee / Novotny, Janet A

Food chemistry

2023 Volume 412, Page(s) 135586

Abstract: Javamide-I/-II are anti-inflammatory compounds found in coffee beans. However, potential effects of roasting on javamide-I/-II in coffee beans are currently unknown. Therefore, in this paper, the effects of roasting on javamide-I/-II were investigated in ...

Abstract	Javamide-I/-II are anti-inflammatory compounds found in coffee beans. However, potential effects of roasting on javamide-I/-II in coffee beans are currently unknown. Therefore, in this paper, the effects of roasting on javamide-I/-II were investigated in Arabica and Robusta beans. Coffee beans were roasted light, medium and dark, and the amounts of javamide-I/-II in the beans were quantified by a HPLC method. The data showed the different amounts of javamide-I/-II in the beans; not detected and ≤ 3.1 mg in Arabica beans, and 0.5-3.7 mg and 1.0-13.8 mg in Robusta beans, respectively. Furthermore, the data showed that roasting process significantly reduced the amounts of javamide-I/-II in both Arabica and Robusta beans (p < 0.05). These data were also confirmed by multivariate analyses. Additionally, these differences were validated in light, medium and dark roast coffee products in the market. Altogether, roasting can have a significant impact on javamide-I/-II amounts in coffee beans.
MeSH term(s)	Coffea ; Seeds ; Food Handling/methods ; Hot Temperature
Language	English
Publishing date	2023-01-30
Publishing country	England
Document type	Journal Article
ZDB-ID	243123-3
ISSN	1873-7072 ; 0308-8146
ISSN (online)	1873-7072
ISSN	0308-8146
DOI	10.1016/j.foodchem.2023.135586
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Article ; Online: Sympatholytic Effect of the High Thoracic Erector Spinae Plane Block.

Hong, Ji H / Park, Ji H / Park, Ki B / Lee, Jae Y

Pain physician

2023 Volume 27, Issue 1, Page(s) 43–49

Abstract: Background: The erector spinae plane block (ESPB), which was introduced for the management of thoracic pain, is a technically easy and relatively noninvasive ultrasound (ULSD)-guided technique. Although the ESPB is used widely in variable clinical ... ...

Abstract	Background: The erector spinae plane block (ESPB), which was introduced for the management of thoracic pain, is a technically easy and relatively noninvasive ultrasound (ULSD)-guided technique. Although the ESPB is used widely in variable clinical situations, its sympatholytic effect has never been studied. Objectives: The purpose of this study is to demonstrate the sympatholytic effect of the high thoracic ESPB by comparing the blocked and unblocked sides of patients' upper extremities, using the changes in the perfusion index (PI). Study design: Prospective, single-group, and open-label study. Setting: The study was carried out in the pain clinic of a tertiary university hospital. Methods: This study included 47 patients with upper extremity pain and various diseases who received T2 or T3 ESPBs using 20 mL of 0.2% ropivacaine. For the evaluation of the sympatholytic effect, measurements were taken on the numeric rating scale (NRS), the neck disability index (NDI), and the PI. Results: The PIs of the blocked sides demonstrated significant increases at 10, 20, and 30 minutes compared to the PIs of the baseline and unblocked sides (P < 0.001). The PI ratio at 10 minutes was 2.74 ± 1.65, which was the highest value during the measurement period. Until 30 minutes after the ESPB, the PI ratio was significantly higher in the blocked side than in the unblocked side. During the study period, significant reductions in NRS and NDI scores were found irrespective of disease entity. Limitation: The period of PI measurement was only 30 minutes, so we could not determine the time point when the PI returned to the baseline value. Conclusion: The high thoracic ESPB was effective in relieving upper extremity pain in diverse disease entities, and the PIs of patients' blocked sides demonstrated significant increases over the baseline value and contralateral unblocked sides.
MeSH term(s)	Humans ; Sympatholytics ; Prospective Studies ; Chest Pain ; Pain Clinics ; Nerve Block
Chemical Substances	Sympatholytics
Language	English
Publishing date	2023-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2146393-1
ISSN	2150-1149 ; 1533-3159
ISSN (online)	2150-1149
ISSN	1533-3159
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Article: Kahweol Found in Coffee Inhibits IL-2 Production Via Suppressing the Phosphorylations of ERK and c-Fos in Lymphocytic Jurkat Cells

Park, Jae B.

Journal of dietary supplements. 2021 June 22, v. 18, no. 4

2021

Abstract	Interleukin-2 (IL-2) is a cytokine involved in the development and maturation of the subsets of T cells, critically associated with the progression of several immune-related diseases (e.g. liver disease, bowel disease). Interestingly, a recent study suggests that coffee may contain several compounds to inhibit IL-2 expression in activated T-lymphocytic cells. However, there is little information about the potential effects of several coffee compounds (e.g. kahweol, cafestol, trigonelline, niacin and chlorogenic acids) on IL-2 expression in activated T-lymphocytic cells. Therefore, in this paper, their effects on IL-2 expression were evaluated in PHA/PMA-activated lymphocytic Jurkat cells. Among the tested compounds, only kahweol and cafestol were able to reduce IL-2 production significantly in the cells (p < 0.05). However, the inhibition of kahweol was a bit stronger than cafestol. Therefore, the molecular mechanism underlying the IL-2 inhibition was investigated using kahweol. Kahweol (≤ 20 µM) was able to inhibit the phosphorylations of ERK and c-Fos (p < 0.05) with little effects on p38 and JNK phosphorylations in the Jurkat cells. Subsequently, the inhibition of ERK/c-Fos led to the reduction of IL-2 mRNA expression in the Jurkat cells. In summary, the data suggest that kahweol may be a potential coffee compound to reduce IL-2 production via inhibiting the phosphorylations of ERK/c-Fos in PHA/PMA-activated lymphocytic Jurkat cells.
Keywords	gene expression ; interleukin-2 ; liver diseases ; niacin ; trigonelline
Language	English
Dates of publication	2021-0622
Size	p. 433-443.
Publishing place	Taylor & Francis
Document type	Article
ZDB-ID	2460305-3
ISSN	1939-022X ; 1939-0211
ISSN (online)	1939-022X
ISSN	1939-0211
DOI	10.1080/19390211.2020.1784347
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Article ; Online: Impact of roasting on javamide-I/-II in Arabica and Robusta coffee beans

Park, Jae B. / Peters, Renee / Novotny, Janet A.

Food Chemistry. 2023 June, v. 412 p.135586-

2023

Abstract	Javamide-I/-II are anti-inflammatory compounds found in coffee beans. However, potential effects of roasting on javamide-I/-II in coffee beans are currently unknown. Therefore, in this paper, the effects of roasting on javamide-I/-II were investigated in Arabica and Robusta beans. Coffee beans were roasted light, medium and dark, and the amounts of javamide-I/-II in the beans were quantified by a HPLC method. The data showed the different amounts of javamide-I/-II in the beans; not detected and ≤ 3.1 mg in Arabica beans, and 0.5-3.7 mg and 1.0-13.8 mg in Robusta beans, respectively. Furthermore, the data showed that roasting process significantly reduced the amounts of javamide-I/-II in both Arabica and Robusta beans (p < 0.05). These data were also confirmed by multivariate analyses. Additionally, these differences were validated in light, medium and dark roast coffee products in the market. Altogether, roasting can have a significant impact on javamide-I/-II amounts in coffee beans.
Keywords	Coffea canephora ; food chemistry ; markets ; Javamide-I/-II ; High performance liquid chromatography ; Coffee roasting ; Multivariate analyses ; Arabica and Robusta beans ; HPLC ; CQA ; ANOVA ; PCA
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	243123-3
ISSN	1873-7072 ; 0308-8146
ISSN (online)	1873-7072
ISSN	0308-8146
DOI	10.1016/j.foodchem.2023.135586
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Article ; Online: Javamide-II Found in Coffee Is Better than Caffeine at Suppressing TNF-α Production in PMA/PHA-Treated Lymphocytic Jurkat Cells.

Park, Jae B

Journal of agricultural and food chemistry

2018 Volume 66, Issue 26, Page(s) 6782–6789

Abstract: Recent studies have suggested positive benefits of coffee consumption on inflammation-related diseases, such as liver diseases and diabetes, where activated lymphocytes and TNF-α are critically implicated. Interestingly, some reports suggested that ... ...

Abstract	Recent studies have suggested positive benefits of coffee consumption on inflammation-related diseases, such as liver diseases and diabetes, where activated lymphocytes and TNF-α are critically implicated. Interestingly, some reports suggested that javamide-II found in coffee may have anti-inflammatory activity greater than that of caffeine, but there is limited information about its effect on TNF-α production by activated lymphocytes. Therefore, the inhibitory effect of javamide-II on TNF-α was investigated in PMA/PHA-treated lymphocytic Jurkat cells. At 5 μM, javamide-II, not caffeine, inhibited TNF-α production in the cells (45 ± 4%, P < 0.001). To elucidate the underlying mechanism, the phosphorylation of MAP kinases (ERK, p38, and JNK) was investigated in the Jurkat cells. Javamide-II had little effect on JNK or p38 phosphorylation, but javamide-II (<20 μM) decreased ERK phosphorylation, consequently reducing TNF-α mRNA expression in the cells ( P < 0.001). The involvement of ERK phosphorylation was also confirmed by an ERK1/2 inhibitor (SCH772984). Furthermore, javamide-II was also found to inhibit IL-2 production, which is up-regulated by ERK phosphorylation in cells ( P < 0.001). These data suggested that javamide-II may be a potent compound to suppress TNF-α production more efficiently than caffeine by inhibiting ERK phosphorylation in Jurkat cells.
MeSH term(s)	Anti-Inflammatory Agents/pharmacology ; Caffeine/pharmacology ; Coffee/chemistry ; Extracellular Signal-Regulated MAP Kinases/immunology ; Humans ; Jurkat Cells ; Lymphocytes/drug effects ; Lymphocytes/immunology ; MAP Kinase Signaling System/drug effects ; Phorbol Esters/pharmacology ; Phytohemagglutinins/pharmacology ; Quassins/pharmacology ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/immunology ; p38 Mitogen-Activated Protein Kinases/immunology
Chemical Substances	Anti-Inflammatory Agents ; Coffee ; Phorbol Esters ; Phytohemagglutinins ; Quassins ; Tumor Necrosis Factor-alpha ; Caffeine (3G6A5W338E) ; 12-O-undecadienoylphorbol-13-acetate (85527-86-2) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2018-07-05
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.8b01885
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