Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spilanthes acmella (Paracress), a common spice, has been administered as a traditional folk medicine for years to cure toothaches, stammering, and stomatitis. Previous studies have demonstrated its diuretic, antibacterial, and anti-inflammatory activities. However, the active compounds contributing to the anti-inflammatory effect have seldom been addressed. This study isolates the active compound, spilanthol, by a bioactivity-guided approach and indicates significant anti-inflammatory activity on lipopolysaccharide-activated murine macrophage model, RAW 264.7. The anti-inflammatory mechanism of paracress is also investigated. Extracts of S. acmella are obtained by extraction with 85% ethanol, followed by liquid partition against hexane, chloroform, ethyl acetate, and butanol. The ethyl acetate extract exhibits a stronger free radical scavenging capacity than other fractions do, as determined by DPPH and ABTS radical scavenging assays. The chloroform extract significantly inhibits nitric oxide production ( p < 0.01) and is selected for further fractionation to yield the active compound, spilanthol. The diminished levels of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) mRNA and protein expression support the postulation that spilanthol inhibits proinflammatory mediator production at the transcriptional and translational levels. Additionally, the LPS-stimulated IL-1beta, IL-6, and TNF-alpha productions are dose-dependently reduced by spilanthol. The LPS-induced phosphorylation of cytoplasmic inhibitor-kappaB and the nuclear NF-kappaB DNA binding activity are both restrained by spilanthol. Results of this study suggest that spilanthol, isolated from S. acmella, attenuates the LPS-induced inflammatory responses in murine RAW 264.7 macrophages partly due to the inactivation of NF-kappaB, which negatively regulates the production of proinflammatory mediators.
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PMID:Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-induced inflammatory mediators. 1832 Oct 49

Kaempferia parviflora Wall. ex Baker, is one of the plants in the Zingiberaceae family, locally known in Thai as kra-chai-dam. The rhizome of this plant has been used for treatment of gout, apthous ulcer and abscesses. Since K. parviflora rhizomes have long been used for treatment of inflammation and possessed marked nitric oxide (NO) inhibitory activity (IC(50)=7.8microg/ml), we thus investigated the inhibitory activity of compounds isolated from this plant against lipopolysaccharide (LPS)-induced NO release in RAW264.7 cells. From bioassay-guided fractionation of K. parviflora, seven methoxyflavones were isolated from the hexane fraction and were tested for their anti-inflammatory effects. Among the isolated compounds, compound 5 (5-hydroxy-3,7,3',4'-tetramethoxyflavone) exhibited the highest activity against NO release with an IC(50) value of 16.1microM, followed by 4 (IC(50)=24.5microM) and 3 (IC(50)=30.6microM). Compound 5 was also tested on LPS-induced prostaglandin E(2) (PGE(2)) and tumor necrosis factor-alpha (TNF-alpha) releases from RAW264.7 cells. It was revealed that 5 showed appreciable inhibitory effect on PGE(2) release (IC(50)=16.3microM), but inactive on TNF-alpha (IC(50)>100microM). These findings may support the use in Thai traditional medicine of K. parviflora for treatment of inflammatory-related diseases through the inhibition of NO and PGE(2) releases but partly due to that of TNF-alpha.
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PMID:Effects of compounds from Kaempferia parviflora on nitric oxide, prostaglandin E2 and tumor necrosis factor-alpha productions in RAW264.7 macrophage cells. 1872 83

Nuruk, which is a natural inoculator and source of amylolytic enzymes, is used in Korean traditional rice wine. A methanol extract of nuruk (NE) attenuated lipopolysaccharide (LPS)- induced nitrite and interleukin (IL)-6 in RAW 264.7 cells. Both the n-hexane and water fractions from NE (MEH and MW, respectively) inhibited the production of nitrite and IL-6 in RAW 264.7 cells. MEH and MW also inhibited the LPS-induced inducible nitric oxide synthase expression. Further, and MEH protected against the LPS-induced activation of p38 mitogen-activated protein kinase. Together, these results indicate that nuruk may contribute to the anti-inflammatory and cancer-preventive effects of Korean traditional rice wine.
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PMID:Nuruk extract inhibits lipopolysaccharide-induced production of nitrite and interleukin-6 in RAW 264.7 cells through blocking activation of p38 mitogen-activated protein kinase. 1875 3

Excessive production of inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE2), and proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) from activated microglia contributes to uncontrolled inflammation in neurodegenerative diseases. It seems possible that treatment with anti-inflammatory agents, including plants used in Oriental medicine, might delay the progression of neurodegeneration through the inhibition of microglial activation. The present study is focused on the inhibitory effect of the rhizome hexane fraction extract of Zingiber officinale Roscoe (ginger hexan extract; GHE) on the production of inflammatory mediators such as NO, PGE(2), and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV-2 cells, a mouse microglial cell line. GHE significantly inhibited the excessive production of NO, PGE(2), TNF-alpha, and IL-1beta in LPS-stimulated BV2 cells. In addition, GHE attenuated the mRNA expressions and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines. The molecular mechanisms that underlie GHE-mediated attenuation are related to the inhibition of the phosphorylation of three mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase (JNK), and the activation of nuclear factor-kappaB (NF-kappaB). Our results indicate that GHE exhibits anti-inflammatory properties by suppressing the transcription of inflammatory mediator genes through the MAPK and NF-kappaB signaling pathways. The anti-inflammatory properties of GHE may make it useful as a therapeutic candidate for the treatment of human neurodegenerative diseases.
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PMID:Hexane fraction of Zingiberis Rhizoma Crudus extract inhibits the production of nitric oxide and proinflammatory cytokines in LPS-stimulated BV2 microglial cells via the NF-kappaB pathway. 1923 41

The aims of this study were to investigate the effects of adlay testa (AT) on Cu(2+)-treated low-density lipoprotein (LDL) oxidation, 2,2'-diphenyl-1-picrylhydrazyl (DPPH)-scavenging capacity, and lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages and determine its active components. The AT ethanolic extract (ATE) was partitioned into four fractions by various solvents as follows: n-hexane (ATE-Hex), ethyl acetate (ATE-Ea), n-butanol (ATE-Bu), and water (ATE-H(2)O). ATE-Ea and ATE-Bu were further fractionated into ATE-Ea-a-ATE-Ea-h and ATE-Bu-A-ATE-Bu-F, respectively, by column chromatography. Results showed that ATE-Ea, ATE-Bu, ATE-Ea-e, and ATE-Bu-C expressed antiradical, antioxidative, and anti-inflammatory activities with respect to the DPPH-scavenging capacity, LDL protection effect, and nitric oxide (NO) inhibitory activity. Inflammation was further modulated by ATE-Ea, ATE-Bu, ATE-Ea-e, and ATE-Bu-C through downregulating the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) proteins. The following components were found in ATE-Ea-e and ATE-Bu-C after purification and high-performance liquid chromatographic analysis: chlorogenic acid (CGA), vanillic acid (VA), caffeic acid (CA), p-coumaric acid (PCA), ferulic acid (FA), and 2-O-beta-glucopyranosyl-7-methoxy-4((2)H)-benzoxazin-3-one (GMBO). Results showed that CGA, CA, and FA were the major components responsible for the antioxidative and anti-inflammatory activities of ATE-Ea-e and ATE-Bu-C. Subsequently, each gram of ATE-Bu-C had 30.3 mg of CGA, 9.02 mg of CA, and 189 mg of GMBO, while each gram of ATE-Ea-e had 1.31 mg of VA, 3.89 mg of PCA, and 47.6 microg of FA. In conclusion, ATE has antioxidative and anti-inflammatory activities, and its effects are partially related to its phenolic components. Thus, ATE has the potential to be developed as a functional food targeting chronic diseases.
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PMID:Effect of Adlay ( Coix lachryma-jobi L. var. ma-yuen Stapf) Testa and its phenolic components on Cu2+-treated low-density lipoprotein (LDL) oxidation and lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. 1924 96

Overproduction of pro-inflammatory mediators resulting from chronic activation of microglia has been implicated in many neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease. In this study, we investigated the effects of (3R) 1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, or compound 049 on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-treated microglia. Compound 049 is a pure compound fractionated from the hexane extract of Curcuma comosa, an indigenous plant of Thailand traditionally used as an anti-inflammatory agent for the treatment of uterine inflammation. It was found that pretreatment of the highly aggressively proliferating immortalized (HAPI), rat microglial cell line, with compound 049, at the concentrations of 0.1, 0.5 and 1microM significantly decreased LPS-induced NO and PGE(2) production in a concentration-dependent manner. Parallel to the decreases in NO and PGE(2) production was a reduction in the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) as measured by mRNA and protein levels. These results indicate that compound 049 possesses an anti-inflammatory activity and may have a therapeutic potential for the treatment of neurodegenerative diseases related to microglial activation.
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PMID:Transcriptional regulation of iNOS and COX-2 by a novel compound from Curcuma comosa in lipopolysaccharide-induced microglial activation. 1958 97

In this study, the antioxidant and anti-inflammatory activities of Salicornia herbacea were evaluated. The crude CH(2)Cl(2)/methanol extract of S. herbacea showed 52% and 86% scavenging activities of the authentic ONOO(-) and ONOO(-) from 3-morpholinosydnomimine (SIN-1) at a concentration of 50 microg/mL, respectively, and was subjected to a further fractionation with n-hexane, 85% aqueous methanol, n-butanol, and water. Additional purification of the n-butanol fraction revealed that the most potent scavenging activity led to the isolation of isorhamnetin 3-O-beta-d-glucopyranoside as the active principle. The structure of isorhamnetin 3-O-beta-d-glucopyranoside was elucidated by extensive two-dimensional nuclear magnetic resonance experiments such as (1)H correlation spectroscopy nuclear Overhauser effect spectroscopy, heteronuclear single quantum correlation, and heteronuclear multiple-bond correlation as well as by comparison with the published spectral data. Isorhamnetin 3-O-beta-d-glucopyranoside exhibited dose-dependent scavenging activities of the authentic ONOO(-) and ONOO(-) from SIN-1. The electron spin resonance spin-trap techniques confirmed that reactive oxygen species, including the hydroxyl, superoxide, carbon-centered, and 1,1-diphenyl-2-picrylhydrazyl radicals, were actively quenched by addition of isorhamnetin 3-O-beta-d-glucopyranoside. In addition, isorhamnetin 3-O-beta-d-glucopyranoside suppressed the lipopolysaccharide-induced nitric oxide production and the expression of cytokines such as inducible nitric oxide synthase, tumor necrosis factor-alpha, and interleukin-1beta in Raw 264.7 cells. Findings from this study should underscore the nutraceutical value of S. herbacea-derived isorhamnetin 3-O-beta-d-glucopyranoside as a potent antioxidative and anti-inflammatory agent via alleviation of radical-induced toxicities and pro-inflammatory responses.
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PMID:Evaluation of Salicornia herbacea as a potential antioxidant and anti-inflammatory agent. 1962 18

We attempted to isolate the constituent(s) responsible for the suppressive effect of the juice of shekwasha, a citrus produced in Okinawa Prefecture, on D-galactosamine (GalN)-induced liver injury in rats. Liver injury-suppressive activity, as assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, was found only in the fraction that was extracted with n-hexane when three fractions were added to the diet and fed to rats. Of five compounds isolated from the n-hexane-soluble fraction by silica gel column chromatography, three compounds had liver injury-suppressive effects when five compounds were singly force-fed to rats at a level of 300 mg/kg body wt 4 h before the injection with GalN. The structures of the three active compounds were determined as 3',4',5,6,7,8-hexamethoxyflavanone (citromitin), 4',5,6,7,8-pentamethoxyflavone (tangeretin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin), which are known flavonoids mainly existing in citrus. Nobiletin, the most important compound in the n-hexane-soluble fraction, also had suppressive effects on liver injuries induced by carbon tetrachloride, acetaminophen and GalN/lipopolysaccharide (LPS) in addition to liver injury induced GalN. Nobiletin suppressed GalN/LPS-induced increases in plasma tumor necrosis factor (TNF)-alpha and nitric oxide (NO) concentrations and hepatic mRNA levels for inducible NO synthase and DNA fragmentation. These results suggest that nobiletin suppressed GalN/LPS-induced liver injury at least by suppressing the production of both TNF-alpha and NO. The results obtained here indicate that the hepatoprotective effect of shekwasha juice is mainly ascribed to several polymethoxy flavonoids included in the juice.
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PMID:Hepatoprotective effects of flavonoids from shekwasha (Citrus depressa) against D-galactosamine-induced liver injury in rats. 2035 48

Angelica keiskei has been shown to exhibit antitumor, antioxidant, and antidiabetic activities, and the fresh leaves and dry powder are used for health food. In spite of several beneficial effects, however, the molecular mechanism or mechanisms behind anti-inflammatory activities of A. keiskei remain unclear. Thus, we investigated the effects of A. keiskei on the activities of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. We found that the n-hexane fraction of A. keiskei (HAK) significantly inhibited LPS-induced NO and prostaglandin E(2) production and tumor necrosis factor-alpha secretion. HAK also inhibited the expression of LPS-induced iNOS and COX-2 proteins and their mRNA levels. Furthermore, we hypothesize that anti-inflammatory effects by HAK can be linked to interference with the signaling pathway of mitogen-activated protein kinases (MAPKs) and the activation pathway of nuclear factor kappaB (NF-kappaB). HAK suppressed LPS-induced c-Jun NH(2)-terminal kinase, p38, and p44/p42 MAPK activation. We also found that the cell-based assay system showed that HAK suppressed LPS-induced NF-kappaB activity in transfectant RAW 264.7 cells. In addition, the electrophoretic mobility shift assay showed the same result as in the cell-based assay system. Our data suggest that the anti-inflammatory effect of HAK is mediated through down-modulation of iNOS and COX-2 gene products by blocking the signaling pathways of MAPKs and NF-kappaB.
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PMID:Anti-Inflammatory activity of Angelica keiskei through suppression of mitogen-activated protein kinases and nuclear factor-kappaB activation pathways. 2052 91

Cinnamomum tamala (CT) Linn. (Lauraceae) is a component of Indian spices and is also used as antidiabetic agent. Its antioxidant potential was reported by other authors and recently our group has reported its immune-suppressive property. Here, CT leaves were extracted with methanol (CTT) and also with various organic solvents of increasing polarity such as hexane (CTH), ethyl acetate (CTEA), and methanol (CTE) in successive manner by continuous Soxhlet extractor. The active compounds of CTT and CTH were analyzed by GC-MS and most abundant compound (eugenol) was further analyzed by HPLC. These extracts were tested for their free radical (FR) scavenging potential for different FR species, hypoglycemic potential on alloxan-induced hyperglycemia, and anti-inflammatory property in carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced nitric oxide (NO) production in rat peritoneal macrophage culture. Result showed that CTH was the most active fraction toward these parameters, which was parallel to its eugenol and total phenolic content concentration.
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PMID:Chemical characterization of various fractions of leaves of Cinnamomum tamala Linn toward their antioxidant, hypoglycemic, and anti-inflammatory property. 2117 98


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