Humiria balsamifera extract inhibits nitric oxide and tumor necrosis factor production in LPS-stimulated macrophages

Abstract Humiria balsamifera is used in traditional medicine as anthelmintic, expectorant, to treat hepatitis, diarrhea, hemorrhoids; to cure chronic wounds; and to alleviate toothaches. This species occurs in Jurubatiba shoal, Rio de Janeiro state-Brazil, a rich region which offers a variety of promising bioactive product sources. The present study focuses on the chemical and pharmacological evaluation of H. balsamifera. The n-hexane, dichloromethane and ethyl acetate leaf fractions exhibited higher inhibitory potential on NO production. Friedelin (1), quercetin (2) and quercetin-3-α-O-arabinopyranoside (3) were isolated and characterized; the latter is described for the first time for H. balsamifera. Quercetin (2) showed the best inhibitory activity on NO production and moderate inhibition of TNF-α production. These results contribute to the knowledge of Humiria balsamifera as a source of anti-inflammatory compounds. Furthermore, the identification of the terpenes ß-amyrone, betulin, citronellol, eremophillene, dihydroactinolide and borneol, and the isolation of quercetin-3-α-O-arabinopyranoside are being reported for the first time for this species.

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Activity-guided Fractionation of Ipomea fistulosa Leaves for Pro-inflammatory Cytokines and Nitric Oxide Inhibitory Constituents

Natural Product Communications ◽

10.1177/1934578x1400901223 ◽

2014 ◽

Vol 9 (12) ◽

pp. 1934578X1400901

Author(s):

Neeraj K. Patel ◽

Ramandeep ◽

Kamlesh K. Bhutani

Keyword(s):

Nitric Oxide ◽

Ethyl Acetate ◽

No Production ◽

Necrosis Factor Alpha ◽

Etoac Extract ◽

Potent Inhibition ◽

Tnf Α ◽

Factor Alpha ◽

First Time ◽

Necrosis Factor

In the continuous search for new anti-inflammatory agents from natural products, dichloromethane (DCM), ethyl acetate (EtOAc) and methanol (MeOH) extracts of Ipomea fistulosa leaves were evaluated for inhibition of production of nitric oxide (NO), interleukin 1beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in lipopolysaccharide (LPS) stimulated J774A.1 cells. Among the tested extracts, the ethyl acetate (EtOAc) extract was found to be most active and activity based fractionation of this extract by column chromatography led to the identification of seven compounds for the first time from this plant. Furthermore, 3,4-dimethoxy cinnamic acid (1) exhibited two folds more potent inhibition of LPS-induced NO production (IC50 = 10.7 μg/mL) as compared with the standard, L-NAME (IC50=19.8 μg/mL). The present study supports the use of Ipomea fistulosa leaves for the treatment of inflammation.

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EPEC-activated ERK1/2 participate in inflammatory response but not tight junction barrier disruption

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.281.4.g890 ◽

2001 ◽

Vol 281 (4) ◽

pp. G890-G898 ◽

Cited By ~ 56

Author(s):

Suzana D. Savkovic ◽

Akila Ramaswamy ◽

Athanasia Koutsouris ◽

Gail Hecht

Keyword(s):

Tight Junction ◽

Signaling Cascades ◽

Extracellular Signal Regulated Kinase ◽

Intestinal Epithelia ◽

Extracellular Signal ◽

Tnf Α ◽

Functional Consequences ◽

First Time ◽

Necrosis Factor ◽

Iκbα Degradation

Enteropathogenic Escherichia coli (EPEC) alters many functions of the host intestinal epithelia. Inflammation is initiated by activation of nuclear factor (NF)-κB, and paracellular permeability is enhanced via a Ca2+- and myosin light-chain kinase (MLCK)-dependent pathway. The aims of this study were to identify signaling pathways by which EPEC triggers inflammation and to determine whether these pathways parallel or diverge from those that alter permeability. EPEC-induced phosphorylation and degradation of the primary inhibitor of NF-κB (IκBα) were tumor necrosis factor (TNF)-α and interleukin (IL)-1β independent. In contrast to Salmonella typhimurium, EPEC-stimulated IκBα degradation and IL-8 expression did not require Ca2+. Instead, extracellular signal-regulated kinase (ERK)-1/2 was significantly and rapidly activated. ERK1/2 inhibitors attenuated IκBα degradation and IL-8 expression. Although ERK1/2 can activate MLCK, its inhibition had no impact on EPEC disruption of the tight junction barrier. In conclusion, EPEC-induced inflammation 1) is TNF-α and IL-1β receptor independent, 2) utilizes pathways differently from S. typhimurium, 3) requires ERK1/2, and 4) employs signals that are distinct from those that alter permeability. This is the first time that EPEC-activated signaling cascades have been linked to independent functional consequences.

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Nitric Oxide and Tumor Necrosis Factor-Alpha Inhibitory Substances from the Rhizomes of Kaempferia Marginata

Natural Product Communications ◽

10.1177/1934578x1300800904 ◽

2013 ◽

Vol 8 (9) ◽

pp. 1934578X1300800 ◽

Cited By ~ 2

Author(s):

Kanidta Kaewkroek ◽

Chatchai Wattanapiromsakul ◽

Palangpon Kongsaeree ◽

Supinya Tewtrakul

Keyword(s):

Nitric Oxide ◽

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

No Production ◽

Significant Activity ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

The ethanol extract of the rhizomes of Kaempferia marginata showed a potent inhibitory effect against lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) release in RAW264.7 cells. Moreover, the partition with various organic solvents also inhibited NO production. One new pimarane-type diterpene, 1α-acetoxysandaracopimaradien-2α-ol (5), along with four known diterpenes (1–4), were isolated from the n-hexane and chloroform layers, respectively. Among these metabolites, compounds 1 and 4 were isolated for the first time from K. marginata. Compounds 1–5 showed significant inhibitory effects on NO production, with IC50 values ranging from 38.6 to 51.9 μM. Furthermore, compound 2 also exhibited significant activity against TNF-α release (IC50 = 48.3 μM). These findings may support the use of K. marginata by traditional doctors for treatment of inflammatory-related diseases.

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Effects of MRP8, LPS, and Lenalidomide on the Expressions of TNF-α, Brain-Enriched, and Inflammation-Related MicroRNAs in the Primary Astrocyte Culture

The Scientific World JOURNAL ◽

10.1155/2013/208309 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Ahmed Omran ◽

Muhammad Usman Ashhab ◽

Na Gan ◽

Huimin Kong ◽

Jing Peng ◽

...

Keyword(s):

Therapeutic Interventions ◽

Necrosis Factor Alpha ◽

Small Noncoding Rnas ◽

Primary Astrocyte ◽

Tnf Α ◽

Factor Alpha ◽

Novel Target ◽

First Time ◽

Primary Astrocyte Culture ◽

Necrosis Factor

Astrocytes are now recognized as a heterogeneous class of cells with many important and diverse functions in healthy and diseased central nervous system (CNS). MicroRNAs (miRNAs) are small, noncoding RNAs which may have key roles in astrocytes activation in response to various stimuli. We performed quantitative real-time PCR (qPCR) to detect changes in the expressions of brain-enriched miRNAs (124, 134, 9, 132, and 138), inflammation-related miRNAs (146a, 21, 181a, 221, and 222), and tumor necrosis factor alpha (TNF-α) in the rat primary astrocyte cultures after stimulation with myeloid-related protein 8 (MRP8) and lipopolysaccharides (LPS). Further, we inhibited the expression of TNF-αin the astrocytes by using TNF-αinhibitor (lenalidomide) and tested for the first time the effect of this inhibition on the expressions of the same tested miRNAs. Stimulation of the astrocytes with MRP8 or LPS leads to significant upregulation of miRNAs (124, 134, 9, 132, 146a, 21, 181a, 221, and 222), while miRNA-138 was downregulated. TNF-αinhibition with lenalidomide leads to opposite expressions of the tested miRNAs. These miRNAs may play an important role in activation of the astrocytes and may be a novel target for cell-specific therapeutic interventions in multiple CNS diseases.

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Expression of LOXs and MMP-1, 2, 3 by ACL Fibroblasts and Synoviocytes Impact of Coculture and TNF-α

The Journal of Knee Surgery ◽

10.1055/s-0038-1641592 ◽

2018 ◽

Vol 32 (04) ◽

pp. 352-360 ◽

Cited By ~ 2

Author(s):

Chunli Wang ◽

Qingjia Chi ◽

Chunming Xu ◽

Kang Xu ◽

Yanjun Zhang ◽

...

Keyword(s):

Cruciate Ligament ◽

Cartilage Degradation ◽

Ligament Injury ◽

Tnf Α ◽

Gene And Protein Expression ◽

Polymerase Chain ◽

Anterior Cruciate ◽

Factor Α ◽

First Time ◽

Necrosis Factor

AbstractThis study aims to confirm the effects of synoviocytes (SCs) on regulating lysyl oxidases (LOXs) and matrix metalloproteinase (MMP)-1, 2, 3 in the normal and injured anterior cruciate ligament (ACL) fibroblasts response to tumor necrosis factor-α(TNF-α). The gene and protein expression levels of LOXs and MMP-1, 2, 3 in SCs cocultured ACL fibroblasts (ACLfs) induced by TNF-α and mechanical injury were analyzed by real-time polymerase chain reaction (PCR) and western bolting; the MMP-2 activity were analyzed by zymography. The results exhibited that TNF-α alone slightly downregulated the expressions of LOXs and upregulated the expression of MMP-1, 2, 3 in both normal and injured ACL fibroblasts. The decrease of LOXs and increase of MMP-1, 2, 3 in ACLfs response to TNF-α were further promoted by coculture. Taken together, these results show for the first time that the crosstalk between ACLfs and SCs could modulate the LOXs and MMP-1, 2, 3 synthesis in ACLfs in the presence of TNF-α. Accumulation of MMPs in the isolated fluid-containing space not only disrupts the balance of ACL healing, but also increases cartilage degradation and accelerates osteoarthritis (OA) in injured joint. Based on this mechanism, targeting inhibition of MMPs could provide a promising therapeutic strategy for acute ligament injury.

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Hyperdynamic Circulation of Cirrhotic Rats with Ascites: Role of Endotoxin, Tumour Necrosis Factor-α and Nitric Oxide

Clinical Science ◽

10.1042/cs0930219 ◽

1997 ◽

Vol 93 (3) ◽

pp. 219-225 ◽

Cited By ~ 46

Author(s):

Chi-Jen Chu ◽

Fa-Yauh Lee ◽

Sun-Sang Wang ◽

LU Rei-Hwa ◽

Yang-Te Tsai ◽

...

Keyword(s):

Nitric Oxide ◽

Tumour Necrosis Factor ◽

Plasma Levels ◽

Tumour Necrosis ◽

Colorimetric Assay ◽

Plasma Concentrations ◽

No Production ◽

Hyperdynamic Circulation ◽

Tnf Α ◽

Necrosis Factor

1. Hyperdynamic circulation observed in portal hypertensive states is characterized by generalized vasodilatation, increased cardiac index and increased systemic and regional blood flows. Endotoxin, tumour necrosis factor-alpha (TNF-α) and nitric oxide (NO) have been reported to be involved in the pathogenesis of hyperdynamic circulation, but the interactions between endotoxin, TNF-α and NO in cirrhotic rats with ascites have never been specifically addressed. 2. This study was designed to determine systemic and portal haemodynamics and plasma levels of endotoxin, TNF-α and nitrate/nitrite in cirrhotic rats with ascites and investigate the relationships between these substances. 3. Plasma concentrations of endotoxin, TNF-α and nitrate/nitrite (an index of NO production) were determined in 25 cirrhotic rats with ascites and 17 control rats using the Limulus assay, ELISA and a colorimetric assay respectively. In addition, haemodynamic studies were performed in another ten cirrhotic rats with ascites and ten control rats. 4. Cirrhotic rats with ascites had hyperdynamic circulation accompanied by increased plasma levels of endotoxin, TNF-α and nitrate/nitrite, as compared with control rats. Significant correlation existed between plasma levels of endotoxin and nitrate/nitrite (r = 0.59, P < 0.0001) and between plasma levels of endotoxin and TNF-α (r = 0.63, P < 0.0001). No correlation was detected between plasma levels of TNF-α and nitrate/nitrite (r = 0.24, P > 0.05). 5. This study suggests that endotoxaemia developed in cirrhotic rats with ascites may stimulate NO formation directly or indirectly via cytokine cascade, and consequently participate in the development and/or maintenance of hyperdynamic circulation.

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Curcumin protects liver inflammation by suppressing expression of inducible nitric oxide synthase in primary cultured rat hepatocytes

Functional Foods in Health and Disease ◽

10.31989/ffhd.v7i9.362 ◽

2017 ◽

Vol 7 (9) ◽

pp. 716 ◽

Cited By ~ 1

Author(s):

Richi Nakatake ◽

Hidehiko Hishikawa ◽

Hideyuki Matushima ◽

Yusuke Nakamura ◽

Morihiko Ishizaki ◽

...

Keyword(s):

Nitric Oxide ◽

Liver Injury ◽

Rat Hepatocytes ◽

No Production ◽

Type I ◽

Tnf Α ◽

Cultured Rat Hepatocytes ◽

Oxide Synthase ◽

Necrosis Factor ◽

Inducible Nitric Oxide

Background: Curcumin has beneficial effects on organ metabolism. However, there is little evidence that curcumin affects inflammatory mediators, such as tumor necrosis factor (TNF)-α and nitric oxide (NO). In an inflamed liver, proinflammatory cytokines stimulate liver cells, followed by the induction of inducible NO synthase (iNOS). Excessive NO produced by iNOS is one of the factors in liver injury. Therefore, inhibiting iNOS induction for preventing liver injury is important.Objective: This study aimed to investigate liver protective effects of curcumin by examining interleukin (IL)-1β-stimulated hepatocytes.Methods: Primary cultured rat hepatocytes were treated with IL-1β in the presence or absence of curcumin. Induction of NO production and iNOS, and the signaling pathway of iNOS were analyzed.Results: Simultaneous addition of IL-1β and curcumin decreased expression levels of iNOS protein and mRNA, resulting in inhibition of NO production. Curcumin also reduced mRNA expression of TNF-α and IL-6. Curcumin inhibited two essential signaling pathways for iNOS induction, NF-κB activation and type I IL-1 receptor upregulation. Transfection experiments revealed that curcumin reduced iNOS mRNA levels at the promoter activation and mRNA stabilization steps. Delayed administration of curcumin after IL-1β addition also inhibited iNOS induction.Conclusions: Curcumin affects induction of inflammatory mediators, such as iNOS and TNF-α, in part through the inhibition of NF-κB activation in hepatocytes. Curcumin may have therapeutic potential for organ injuries, including the liver.Key words: curcumin, inducible nitric oxide synthase, liver injury, primary cultured hepatocytes, nuclear factor-κB, type I interleukin-1 receptor, tumor necrosis factor-α.

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Anti-inflammatory activity of pectic enzyme-treated pectin on lipopolysaccharide-induced RAW 264.7 cells

Journal of Functional Food and Nutraceutical ◽

10.33555/jffn.v1i1.14 ◽

2019 ◽

Vol 1 (1) ◽

pp. 23-30 ◽

Cited By ~ 1

Author(s):

Cian-Song Huang ◽

Qiao-Lin Li ◽

Diana Lo ◽

Yuh-Tai Wang ◽

Ming-Chang Wu

Keyword(s):

Western Blot ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Pectic Enzyme ◽

Western Blot Method ◽

Tnf Α ◽

Cox 2 ◽

Necrosis Factor ◽

Normal Macrophage

The purpose of this study was to investigate the ability and pathway of the pectic enzyme-treated (PET) pectin to inhibit the inflammation of macrophage RAW 264.7 induced by lipopolysaccharide. Results showed that PET-pectin produced from 1% substrate and 48 h reaction time had the highest antioxidative activity, thus these parameters were used to produce PET-pectin used in this study. PET-pectin showed no cell cytotoxicity to normal macrophage RAW 264.7 and reduce the nitrite secretion from LPS-induced RAW 264.7 by 20%. Finally, the expression of cytokines, including NO synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and tumor necrosis factor (TNF-α) were analyzed by western blot. In the western blot method, it was found that iNOS, COX-2, NF-κB, TNF-α and other proteins that activated NO production had a downtrend. It was found that PET-pectin possess promising activity to mitigate the inflammatory response.

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Abstract 646: The Existence of a Strong Correlation Between Leptin, TNF α Levels and BMI in Morbidly Obese Appalachian Females

Hypertension ◽

10.1161/hyp.64.suppl_1.646 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Ellen Thompson ◽

Kathleen O'Hanlon ◽

Morghan Getty ◽

Komal Sodhi ◽

Eamonn Maher ◽

...

Keyword(s):

Odds Ratio ◽

Tumor Necrosis ◽

Linear Regression Analysis ◽

Inflammatory Biomarkers ◽

Morbidly Obese ◽

Tnf Α ◽

First Time ◽

The Relationship ◽

Potential Use ◽

Necrosis Factor

Introduction: Although BMI contributes to increased levels of adipokines, such as leptin, and tumor necrosis factor (TNFα) and to a decrease in adiponectin, few studies have examined the association between leptin, TNFα and body mass index (BMI) in Appalachian females. Methods: A total of 74 subjects from the Appalachian region were examined for the effect of BMI on the levels of leptin, TNF α , and adiponectin. Patients without overt cardiovascular disease were included. Linear regression analysis was used to analyze for changes in the relationship between BMI, leptin, TNFα and adiponectin. Nonlinear regression was used to determine the odds ratio and confidence intervals. Results: Serum TNFα and leptin levels were significantly increased in subjects with an increased BMI of 45-72 (9.9pg/ml ± 0.56 and 7.7pg/ml ± 0.6 respectively; p<0.05), compared to subjects with a BMI of 20-32. This was paralleled by increased levels of leptin, TNFα and IL-6. IL-6 was elevated in subjects with a BMI of 45-72 (4.83pg/ml ± 0.40; p<0.02). IL-6 was increased to a greater extent than leptin. In contrast, adiponectin levels were decreased (p<0.05) in subjects with a BMI of > 45-72 (6.63ng/ml ± 0.5; p<0.05), compared to subjects with a BMI of 20-32 (14.43ng/ml ± 0.32). Conclusion: Our study demonstrates for the first time the unique inflammatory biomarkers profile in morbidly obese females, even before diagnosis of coronary disease, highlighting the possible pathogenic potentials and opens the door for potential use of these biomarkers as a prognostic tool and a therapeutic target that can ameliorate obesity induced cardiovascular dysfunction.

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Anti-inflammatory Activity of Herbal Medicines: Inhibition of Nitric Oxide Production and Tumor Necrosis Factor-α Secretion in an Activated Macrophage-like Cell Line

The American Journal of Chinese Medicine ◽

10.1142/s0192415x05003028 ◽

2005 ◽

Vol 33 (03) ◽

pp. 415-424 ◽

Cited By ~ 87

Author(s):

Eunkyue Park ◽

Susan Kum ◽

Chuanhua Wang ◽

Seung Yong Park ◽

Bo Sook Kim ◽

...

Keyword(s):

Nitric Oxide ◽

Tumor Necrosis ◽

No Production ◽

Dependent Manner ◽

Aqueous Extracts ◽

Tnf Α ◽

Activated Macrophage ◽

Anti Inflammatory ◽

Dose Dependent ◽

Necrosis Factor

Houttuynia cordata Thunb. (HC), Glycyrrhiza uralensis Fischer (GU), Forsythia suspense (Thunb.) Vahl (FS), and Lonicera japonica Thunb. (LJ) are Chinese herbs known to possess anti-inflammatory properties. The effects of aqueous extracts of these herbs on the production of the pro-inflammatory mediators, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were examined in an activated macrophage-like cell line, RAW 264.7 cells. Aqueous extracts from FS at 0.0625–2.0 mg/ml inhibited in vitro production of NO and secretion of TNF-α in a dose-dependent manner. FS at 1.0–2.0 mg/ml and 0.125–2.0 mg/ml significantly inhibited NO production and TNF-α, respectively. An extract of LJ demonstrated potent inhibition of both NO production and TNF-α secretion in a dose-dependent manner. An aqueous extract from HC inhibited NO production in a dose-dependent manner, but minimally (approximately 30%) inhibited TNF-α secretion at 0.0625 and 0.125 mg/ml. In contrast, an aqueous extract of GU had a minimal effect on both the production of NO and the secretion of TNF-α. Viability of cells at all concentrations studied was unaffected as determined by MTT cytotoxicity assay and trypan blue dye exclusion. These results suggest that aqueous extracts from FS, LJ and HC have anti-inflammatory actions as measured by inhibition of NO production and/or TNF-α secretion.

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