Liquiritigenin, a flavonoid aglycone from licorice, has a choleretic effect and the ability to induce hepatic transporters and phase-II enzymes

2009 ◽  
Vol 296 (2) ◽  
pp. G372-G381 ◽  
Author(s):  
Young Woo Kim ◽  
Hee Eun Kang ◽  
Myung Gull Lee ◽  
Se Jin Hwang ◽  
Sang Chan Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Time Curve ◽  
Phase Ii Enzymes ◽  
Tnf Α ◽  
Hepatic Transporters ◽  
Bile Flow Rate ◽  
Oxide Synthase ◽  
Choleretic Effect

Liquiritigenin (LQ), an active component of licorice, has an inhibitory effect on LPS-induced inhibitory nitric oxide synthase expression. This study investigated the effects of LQ on choleresis, the expression of hepatic transporters and phase-II enzymes, and fulminant hepatitis. The choleretic effect and the pharmacokinetics of LQ and its glucuronides were monitored in rats. After intravenous administration of LQ, the total area under the plasma concentration-time curve of glucuronyl metabolites was greater than that of LQ in plasma, which accompanied elevations in bile flow rate and biliary excretion of bile acid, glutathione, and bilirubin. The expressions of hepatocellular transporters and phase-II enzymes were assessed by immunoblots, real-time PCR, and immunohistochemistry. In the livers of rats treated with LQ, the protein and mRNA levels of multidrug resistance protein 2 and bile salt export pump were increased in the liver, which was verified by their increased localizations in canalicular membrane. In addition, LQ treatment enhanced the expression levels of major hepatic phase-II enzymes. Consistent with these results, LQ treatments attenuated galactosamine/LPS-induced hepatitis in rats, as supported by decreases in the plasma alanine aminotransferase, liver necrosis, and plasma TNF-α. These results demonstrate that LQ has a choleretic effect and the ability to induce transporters and phase-II enzymes in the liver, which may be associated with a hepatoprotective effect against galactosamine/LPS. Our findings may provide insight into understanding the action of LQ and its therapeutic use for liver disease.

scholarly journals Naphthoquinone Derivatives with Anti-Inflammatory Activity from Mangrove-Derived Endophytic Fungus Talaromyces sp. SK-S009

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 576 ◽  
Author(s):  
Hongju Liu ◽  
Chong Yan ◽  
Changqun Li ◽  
Tingting You ◽  
Zhigang She
Keyword(s):  
Nitric Oxide ◽  
Endophytic Fungus ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
No Production ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Tnf Α ◽  
Ic50 Values ◽  
Oxide Synthase

Twelve 1, 4-naphthoquinone derivatives, including two new (1 and 2) and 10 known (3–12), were obtained from endophytic fungus Talaromyces sp. SK-S009 isolated from the fruit of Kandelia obovata. All structures were identified through extensive analysis of the nuclear magnetic resonance (NMR), mass spectrometry (MS) and circular dichroism (CD), as well as by comparison with literature data. These compounds significantly inhibited the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in the murine macrophage cell line (RAW 264.7 cells). The half maximal inhibitory concentration (IC50) values, except for compound 2, were lower than that of indomethacin (26.3 μM). Compound 9 inhibited the LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expressions in RAW 264.7 macrophages. Additionally, compound 9 reduced the mRNA levels of pro-inflammatory factors interleukin (IL)1β, IL-6, and tumor necrosis factor (TNF)-α. The results of this study demonstrated that these 1, 4-naphthoquinone derivatives can inhibit LPS-induced inflammation.

“Subclinical” gentamicin nephrotoxicity: a potential risk factor for exaggerated endotoxin-driven TNF-α production

2007 ◽  
Vol 293 (1) ◽  
pp. F43-F49 ◽  
Author(s):  
Richard A. Zager
Keyword(s):  
Antimicrobial Effect ◽  
Specific Response ◽  
Mrna Levels ◽  
Gram Negative ◽  
Protein Levels ◽  
Target Organs ◽  
Gentamicin Treatment ◽  
Tnf Α ◽  
Oxide Synthase ◽  
And Control

This study sought to determine whether gentamicin, a mainstay in treating Gram-negative sepsis, alters endotoxin (lipopolysaccharide; LPS)-driven TNF-α increases. CD-1 mice received 1 day of gentamicin treatment. Either 0, 24, or 72 h later, gentamicin-treated and control mice were injected with LPS. Renal cortical and plasma TNF-α, as well as MCP-1, protein levels were measured 2 or 24 h post-LPS injection. Renal cortical mRNAs for TNF-α, MCP-1, IL-10, and inducible nitric oxide synthase (iNOS) were also determined. Finally, gentamicin's potential impact(s) on TNF-α/MCP-1 mRNA levels in nontraditional “target” organs (liver, spleen) was assessed. Gentamicin, when administered alone, slightly increased renal cortical TNF-α and MCP-1 mRNAs, but without changing plasma or renal TNF-α/MCP-1 protein levels. The gentamicin protocol induced no overt renal damage (assessed by blood urea nitrogen, creatinine, and histology). Nevertheless, gentamicin augmented LPS responsiveness, as manifested, in part, by a doubling of LPS-induced plasma TNF-α increases (vs. LPS injection alone). Plasma and renal cortical MCP-1 protein levels were also selectively enhanced. Gentamicin augmented LPS-driven renal mRNA increases (TNF-α, MCP-1, IL-10, iNOS). However, this was not an entirely renal-specific response, since gentamicin also enhanced basal and LPS-stimulated hepatic TNF-α mRNA levels. Subclinical gentamicin toxicity can potentiate LPS-driven TNF-α increases. Alterations in multiple proinflammatory (TNF-α; MCP-1; iNOS) and anti-inflammatory (IL-10) genes in the kidney, and possibly in extrarenal organs, may be involved. Thus gentamicin's activity in Gram-negative sepsis may extend beyond its traditional antimicrobial effect.

scholarly journals Dihydromyricetin attenuates inflammation through TLR4/NF-kappaB pathway

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 719-725 ◽  
Author(s):  
Nianshui Jing ◽  
Xinnan Li
Keyword(s):  
Primary Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α ◽  
Cox 2 ◽  
Nf Kappab ◽  
Factor Α ◽  
Oxide Synthase

AbstractMicroglia plays a complex role in neuroinflammation, which has been implicated in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. This study aims to explore the effect and mechanism of Dihydromyricetin (DHM) on lipopolysaccharide (LPS)-induced inflammation in microglial BV-2 cells. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) assay. The pro-inflammatory mediators and cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α); inducible nitric oxide synthase (iNOS); and cyclooxygenase 2 (COX-2) were measured by enzyme-linked immunosorbent assay (ELISA) and/or quantitative real-time PCR (qRT-PCR). The expression of p-p65, p-IκBα, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) were analyzed by western blot. The present study showed that DHM treatment alleviated LPS-induced viability reduction, suppressed the mRNA levels of IL-6, IL‐1β and TNF-α, inhibited the mRNA and protein expression of iNOS and COX-2, and attenuated the activation of NF-кB and TLR4 signaling in a concentration-dependent manner. In conclusion, DHM exerts an anti-inflammatory effect on LPS-induced BV-2 microglial cells, possibly through TRL4/NF-κB signaling pathway.

Increased expression of TNF-α, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels

2003 ◽  
Vol 285 (5) ◽  
pp. E1072-E1080 ◽  
Author(s):  
Aina S. Lihn ◽  
Bjørn Richelsen ◽  
Steen B. Pedersen ◽  
Steen B. Haugaard ◽  
Gulla Søby Rathje ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Sensitivity ◽  
Highly Active Antiretroviral Therapy ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Plasma Adiponectin ◽  
Tnf Α ◽  
Adiponectin Mrna ◽  
Circulating Levels

Human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is a side effect of highly active antiretroviral therapy of HIV-infected patients; however, the mechanism of the lipodystrophy and insulin resistance seen in this syndrome remains elusive. Adiponectin, an adipocyte-specific protein, is thought to play an important role in regulating insulin sensitivity. We investigated circulating levels and gene expression of adiponectin in subcutaneous abdominal adipose tissue (AT) from 18 HIV-infected patients with HALS compared with 18 HIV-infected patients without HALS. Implications of cytokines for adiponectin levels were investigated by determining circulating levels of TNF-α, IL-6, and IL-8 as well as gene expression of these cytokines in AT. HALS patients exhibited 40% reduced plasma adiponectin levels ( P < 0.05) compared with non-HALS subjects. Correspondingly, adiponectin mRNA levels in AT were reduced by >50% ( P = 0.06). HALS patients were insulin resistant, and a positive correlation was found between plasma adiponectin and insulin sensitivity ( r = 0.55, P < 0.01) and percent limb fat ( r = 0.61, P < 0.01). AT mRNA of TNF-α, IL-6, and IL-8 was increased in AT of HALS subjects ( P < 0.05), and both AT TNF-α mRNA and plasma TNF-α were negatively correlated to plasma adiponectin ( P < 0.05). Finally, TNF-α was found in vitro to inhibit human AT adiponectin mRNA by 80% ( P < 0.05). In conclusion, HALS patients have reduced levels of plasma adiponectin and adiponectin mRNA in AT. Increased cytokine mRNA in AT is hypothesized to exert an inhibitory effect on adiponectin gene expression and, consequently, to play a role in the reduced plasma adiponectin levels found in HALS patients.

scholarly journals Design, Synthesis and Investigation of the Potential Anti-Inflammatory Activity of 7-O-Amide Hesperetin Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3663
Author(s):  
Yilong Zhang ◽  
Yan Zheng ◽  
Wen Shi ◽  
Yahui Guo ◽  
Tao Xu ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Inflammatory Activity ◽  
No Production ◽  
Design Synthesis ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Inducible Nitric Oxide ◽  
Pro Inflammatory Cytokines

To develop new anti-inflammatory agents, a series of 7-O-amide hesperetin derivatives was designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. All compounds showed inhibitory effect on LPS-induced NO production. Among them, 7-O-(2-(Propylamino)-2-oxoethyl)hesperetin (4d) and 7-O-(2-(Cyclopentylamino)-2-oxoethyl)hesperetin (4k) with hydrophobic side chains exhibited the most potent NO inhibitory activity (IC50 = 19.32 and 16.63 μM, respectively), showing stronger inhibitory effect on the production of pro- inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) than indomethacin and celecoxib at 10 μM. The structure-activity relationships (SARs) suggested that the 7-O-amide unit was buried in a medium-sized hydrophobic cavity of the bound receptor. Furthermore, compound 4d could also significantly suppress the expression of inducible nitric oxide synthase enzymes (iNOS) and cyclooxygenase-2 (COX-2), through the nuclear factor-kappa B (NF-κB) signaling pathway.

scholarly journals miR663 Prevents Epo Inhibition Caused by TNF-Alpha in Normoxia and Hypoxia

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Mete Ozkurt ◽  
Thomas Hellwig-Bürgel ◽  
Reinhard Depping ◽  
Selda Kadabere ◽  
Rumeysa Ozyurt ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Inflammatory Diseases ◽  
Experimental Studies ◽  
Inhibitory Effect ◽  
Tnf Alpha ◽  
Control Group ◽  
Mrna Levels ◽  
Normal Medium ◽  
Qrt Pcr ◽  
Tnf Α

Objective. In chronic inflammatory diseases, proinflammatory cytokines such as TNF-α are present in high amounts in the circulation and are associated with anemia in most cases. Experimental studies have shown that TNF-α inhibits the synthesis of erythropoietin (Epo), the main stimulant of hematopoiesis. Our aim was to figure out which microRNAs are involved in the Epo repression by TNF-α. Methods. First, we determined the dose of TNF-α in HepG2 cells that has no cytotoxic effect by using MTT assays and that inhibits Epo synthesis by qRT-PCR and ELISA. Then, we performed the microRNA array study with TNF-α (20 ng/ml)-treated cells, and the array results were confirmed by qRT-PCR. We transfected the miR663 group with the mimic-miR663 (30 pmol) for 24 hrs; other groups were treated with a transfection reagent followed by treatment of TNF-α for 24 hrs; miR663 groups were treated with TNF-α for 24 hrs; and the control group was incubated with normal medium. We analyzed Epo mRNA levels by qRT-PCR. If mimic-miR663 prevents the Epo repression by TNF-α, more Epo-dependent UT-7 cells would survive. Therefore, we cocultured HepG2 cells with UT-7 cells. The percentage of apoptotic UT-7 cells was determined by TUNEL assays. Results. According to our array study, TNF-α significantly decreases miR663 expression. After transfection of miR663 mimics into HepG2 cells, TNF-alpha was unable to decrease Epo mRNA amounts. Furthermore, mimic-miR663 transfection resulted in a lower apoptosis rate of UT-7 cells in coculture experiments. Conclusions. miR663 is involved in Epo mRNA production and that is able to prevent or reverse the inhibitory effect of TNF-α. In our coculture study, transfecting HepG2 cells with miR663 mimics decreased the apoptosis of UT-7 cells.

Inhibitory effect of melatonin on nitric oxide synthase in rat enteric nervous system

2001 ◽  
Vol 120 (5) ◽  
pp. A176-A176
Author(s):  
P KOPPITZ ◽  
M STORR ◽  
D SAUR ◽  
M KURJAK ◽  
H ALLESCHER
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Enteric Nervous System ◽  
Inhibitory Effect ◽  
Oxide Synthase

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

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