Modulatory Effect of Chelidonium majus Extract and Its Alkaloids on LPS-Stimulated Cytokine Secretion in Human Neutrophils

Due to certain differences in terms of molecular structure, isoquinoline alkaloids from Chelidonium majus engage in various biological activities. Apart from their well-documented antimicrobial potential, some phenanthridine and protoberberine derivatives as well as C. majus extract present with anti-inflammatory and cytotoxic effects. In this study, the LC–MS/MS method was used to determine alkaloids, phenolic acids, carboxylic acids, and hydroxybenzoic acids. We investigated five individually tested alkaloids (coptisine, berberine, chelidonine, chelerythrine, and sanguinarine) as well as C. majus root extract for their effect on the secretion of IL-1β, IL-8, and TNF-α in human polymorphonuclear leukocytes (neutrophils). Berberine, chelidonine, and chelerythrine significantly decreased the secretion of TNF-α in a concentration-dependent manner. Sanguinarine was found to be the most potent inhibitor of IL-1β secretion. However, the overproduction of IL-8 and TNF-α and a high cytotoxicity for these compounds were observed. Coptisine was highly cytotoxic and slightly decreased the secretion of the studied cytokines. The extract (1.25–12.5 μg/mL) increased cytokine secretion in a concentration-dependent manner, but an increase in cytotoxicity was also noted. The alkaloids were active at very low concentrations (0.625–2.5 μM), but their potential cytotoxic effects, except for chelidonine and chelerythrine, should not be ignored.

Download Full-text

Bioactivity-Guided Extract Optimization of Osmanthus fragrans var. aurantiacus Leaves and Anti-Inflammatory Activities of Phillyrin

Plants ◽

10.3390/plants10081545 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1545

Author(s):

Hwa-Young Song ◽

Da-Eun Jeong ◽

Mina Lee

Keyword(s):

Biological Activities ◽

Radical Scavenging ◽

No Production ◽

Dependent Manner ◽

Optimal Method ◽

Concentration Dependent Manner ◽

Osmanthus Fragrans ◽

Tnf Α ◽

Anti Inflammatory ◽

Extracellular Regulated Kinase

The aim of this study was to identify the optimal extraction conditions for leaves of Osmanthus fragrans var. aurantiacus. Inhibitory effects of various extracts on NO production were compared. Antioxidant evaluations for total phenol and flavonoid contents were carried out using various extracts of O. fragrans var. aurantiacus leaves obtained under optimal extraction conditions that showed the greatest effect on NO production. The optimal method for extracting O. fragrans var. aurantiacus leaves resulted in an extract named OP OFLE. OP OFLE showed DPPH and ABTS radical scavenging activities in a concentration-dependent manner. Phillyrin (PH) was isolated as a major compound from OP OFLE by HPLC/DAD analysis. OP OFLE and PH reduced inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 protein expression and downregulated proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 and HT-29 cells. To determine the signal pathway involved in the inhibition of NO production, a Western blot analysis was performed. Results showed that OP OFLE decreased phosphorylation of extracellular regulated kinase (pERK) 1/2 and the expression of nuclear factor-kappa B (NF-κB). Our results suggest that extracts of O. fragrans var. aurantiacus leaves and its major components have biological activities such as antioxidative and anti-inflammatory properties.

Download Full-text

Responsiveness of human neutrophils to interleukin-4: induction of cytoskeletal rearrangements, de novo protein synthesis and delay of apoptosis

Biochemical Journal ◽

10.1042/bj3250147 ◽

1997 ◽

Vol 325 (1) ◽

pp. 147-153 ◽

Cited By ~ 87

Author(s):

Denis GIRARD ◽

Robert PAQUIN ◽

André D. BEAULIEUL

Keyword(s):

Protein Synthesis ◽

De Novo ◽

Biological Activities ◽

Interleukin 4 ◽

Human Neutrophils ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Cytoskeletal Rearrangements ◽

First Time ◽

De Novo Protein Synthesis

Interleukin-4 (IL-4) and IL-13 are cytokines that share many biological activities. We have previously demonstrated that IL-13 affects a number of neutrophil responses, and here we extend our observations to IL-4. We present, for the first time, direct evidence for the presence of functional IL-4 receptors on human neutrophils. We report that IL-4 induces RNA synthesis in a concentration-dependent manner and, based on observations of the induction of morphological cell shape changes and spreading onto glass, we demonstrate that IL-4 activates neutrophil cytoskeletal rearrangements. We further show that IL-4 is a potent activator of de novo protein synthesis in neutrophils, and we identify by microsequencing one of these proteins as the cytoskeletal protein actin. We were also able to demonstrate for the first time that actin is cleaved into at least two fragments of ∼ 30 kDa (pI 5.4) and ∼ 25 kDa (pI 5.0) in neutrophils. Finally, we report that IL-4 delays neutrophil apoptosis, as assessed by morphological observations from cytocentrifuge preparations, as well as by measurement of differences in staining by flow cytometry with both propidium iodide and Hoechst reagent. Taken together, we conclude that IL-4 is a more potent neutrophil agonist than previously believed. We discuss the possibility that the induction of the de novo synthesis of actin by IL-4 is related to the mechanism by which this cytokine delays apoptosis; in addition, the cleavage of this protein is likely to contribute to the apoptotic process.

Download Full-text

Effects of irbesartan on phenotypic alterations in monocytes and the inflammatory status of hypertensive patients with left ventricular hypertrophy

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02004-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jingsi Zhang ◽

Lina Yang ◽

Yanchun Ding

Keyword(s):

Ventricular Hypertrophy ◽

Target Organ Damage ◽

Organ Damage ◽

Left Ventricular ◽

Target Organ ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Hypertensive Patients ◽

Inflammatory Status ◽

Tnf Α

Abstract Background Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension and the resulting target organ damage. In this study, we observed alterations in the monocyte phenotype and inflammatory state of hypertensive patients with left ventricular hypertrophy (LVH) and studied the effects of irbesartan in these patients. This study might reveal a novel mechanism by which irbesartan alleviates LVH, and it could provide new targets for the prevention and treatment of hypertensive target organ damage. Methods CD163 and CD206 expression on monocytes and IL-10 and TNF-α levels in the serum of hypertensive patients with or without LVH and of healthy volunteers were detected. Furthermore, we treated monocytes from the LVH group with different concentrations of irbesartan, and then, CD163, CD206, IL-10 and TNF-α expression was detected. Results We found, for the first time, that the expression of CD163, CD206 and IL-10 in the LVH group was lower than that in the non-LVH group and healthy control group, but the TNF-α level in the LVH group was significantly higher. Irbesartan upregulated the expression of CD163 and CD206 in hypertensive patients with LVH in a concentration-dependent manner. Irbesartan also increased the expression of IL-10 and inhibited the expression of TNF-α in monocyte culture supernatants in a concentration-dependent manner. Conclusions Our data suggest that inflammation was activated in hypertensive patients with LVH and that the monocyte phenotype was mainly proinflammatory. The expression of proinflammatory factors increased while the expression of anti-inflammatory factors decreased. Irbesartan could alter the monocyte phenotype and inflammatory status in hypertensive patients with LVH. This previously unknown mechanism may explain how irbesartan alleviates LVH. Trail registration The study protocols were approved by the Ethical Committee of the Second Affiliated Hospital of Dalian Medical University. Each patient signed the informed consent form.

Download Full-text

Modulatory Effects of Osthole on Lipopolysaccharides-Induced Inflammation in Caco-2 Cell Monolayer and Co-Cultures with THP-1 and THP-1-Derived Macrophages

Nutrients ◽

10.3390/nu13010123 ◽

2020 ◽

Vol 13 (1) ◽

pp. 123

Author(s):

Natalia K. Kordulewska ◽

Justyna Topa ◽

Małgorzata Tańska ◽

Anna Cieślińska ◽

Ewa Fiedorowicz ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Reaction ◽

Wide Spectrum ◽

Cell Monolayer ◽

In Vivo Studies ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Tnf Α

Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150–450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1β, -6, -8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/μL for IL1R1 and COX-2 (p < 0.01) and 300 ng/μL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.

Download Full-text

Biosynthesis of silver nanoparticles using Haloferax sp. NRS1: image analysis, characterization, in vitro thrombolysis and cytotoxicity

AMB Express ◽

10.1186/s13568-021-01235-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hend M. Tag ◽

Amna A. Saddiq ◽

Monagi Alkinani ◽

Nashwa Hagagy

Keyword(s):

Silver Nanoparticles ◽

Image Analysis ◽

Biological Activities ◽

Positive Control ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Vis Spectroscopy ◽

Negative Surface ◽

Biosynthesized Agnps

AbstractHaloferax sp strain NRS1 (MT967913) was isolated from a solar saltern on the southern coast of the Red Sea, Jeddah, Saudi Arabia. The present study was designed for estimate the potential capacity of the Haloferax sp strain NRS1 to synthesize (silver nanoparticles) AgNPs. Biological activities such as thrombolysis and cytotoxicity of biosynthesized AgNPs were evaluated. The characterization of silver nanoparticles biosynthesized by Haloferax sp (Hfx-AgNPs) was analyzed using UV–vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). The dark brown color of the Hfx-AgNPs colloidal showed maximum absorbance at 458 nm. TEM image analysis revealed that the shape of the Hfx-AgNPs was spherical and a size range was 5.77- 73.14 nm. The XRD spectra showed a crystallographic plane of silver nanoparticles, with a crystalline size of 29.28 nm. The prominent FTIR peaks obtained at 3281, 1644 and 1250 cm− 1 identified the Functional groups involved in the reduction of silver ion reduction to AgNPs. Zeta potential results revealed a negative surface charge and stability of Hfx-AgNPs. Colloidal solution of Hfx-AgNPs with concentrations ranging from 3.125 to 100 μg/mL was used to determine its hemolytic activity. Less than 12.5 μg/mL of tested agent showed no hemolysis with high significant decrease compared with positive control, which confirms that Hfx-AgNPs are considered non-hemolytic (non-toxic) agents according to the ISO/TR 7405-1984(f) protocol. Thrombolysis activity of Hfx-AgNPs was observed in a concentration-dependent manner. Further, Hfx-AgNPs may be considered a promising lead compound for the pharmacological industry.

Download Full-text

Evaluation of Antioxidant, Anti-Inflammatory and Cytoprotective Properties of Ethanolic Mint Extracts from Algeria on 7-Ketocholesterol-Treated Murine RAW 264.7 Macrophages

Antioxidants ◽

10.3390/antiox7120184 ◽

2018 ◽

Vol 7 (12) ◽

pp. 184 ◽

Cited By ~ 7

Author(s):

Fatiha Brahmi ◽

Thomas Nury ◽

Meryam Debbabi ◽

Samia Hadj-Ahmed ◽

Amira Zarrouk ◽

...

Keyword(s):

Antioxidant Capacity ◽

Total Phenolic Content ◽

Phenolic Content ◽

Cytokine Secretion ◽

Total Phenolic ◽

Raw 264.7 ◽

Dependent Manner ◽

Raw 264.7 Macrophages ◽

Tnf Α ◽

Anti Inflammatory

The present study consisted in evaluating the antioxidant, anti-inflammatory and cytoprotective properties of ethanolic extracts from three mint species (Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L.) Huds (MR)) with biochemical methods on murine RAW 264.7 macrophages (a transformed macrophage cell line isolated from ascites of BALB/c mice infected by the Abelson leukemia virus). The total phenolic, flavonoid and carotenoid contents were determined with spectrophotometric methods. The antioxidant activities were quantified with the Kit Radicaux Libres (KRLTM), the ferric reducing antioxidant power (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The MS extract showed the highest total phenolic content, and the highest antioxidant capacity, while the MR extract showed the lowest total phenolic content and the lowest antioxidant capacity. The cytoprotective and anti-inflammatory activities of the extracts were quantified on murine RAW 264.7 macrophages treated with 7-ketocholesterol (7KC; 20 µg/mL: 50 µM) associated or not for 24 h and 48 h with ethanolic mint extracts used at different concentrations (25, 50, 100, 200 and 400 µg/mL). Under treatment with 7KC, an important inhibition of cell growth was revealed with the crystal violet test. This side effect was strongly attenuated in a dose dependent manner with the different ethanolic mint extracts, mainly at 48 h. The most important cytoprotective effect was observed with the MS extract. In addition, the effects of ethanolic mint extracts on cytokine secretion (Interleukin (IL)-6, IL-10, Monocyte Chemoattractant Protein (MCP)-1, Interferon (IFN)-ϒ, Tumor necrosis factor (TNF)-α) were determined at 24 h on lipopolysaccharide (LPS, 0.2 µg/mL)-, 7KC (20 µg/mL)- and (7KC + LPS)-treated RAW 264.7 cells. Complex effects of mint extracts were observed on cytokine secretion. However, comparatively to LPS-treated cells, all the extracts strongly reduce IL-6 secretion and two of them (MP and MR) also decrease MCP-1 and TNF-α secretion. However, no anti-inflammatory effects were observed on 7KC- and (7KC + LPS)-treated cells. Altogether, these data bring new evidences on the potential benefits (especially antioxidant and cytoprotective properties) of Algerian mint on human health.

Download Full-text

Inter-α inhibitor proteins maintain neutrophils in a resting state by regulating shape and reducing ROS production

Blood Advances ◽

10.1182/bloodadvances.2018018986 ◽

2018 ◽

Vol 2 (15) ◽

pp. 1923-1934 ◽

Cited By ~ 11

Author(s):

Soe Soe Htwe ◽

Hidenori Wake ◽

Keyue Liu ◽

Kiyoshi Teshigawara ◽

Barbara S. Stonestreet ◽

...

Keyword(s):

Resting State ◽

Smooth Surface ◽

Spherical Shape ◽

Human Neutrophils ◽

Dependent Manner ◽

Ros Production ◽

Concentration Dependent Manner ◽

Key Points

Key Points IAIP, but not bikunin, maintains spherical shape, small size, and smooth surface of human neutrophils and supports capillary passage. IAIP reduced ROS production from neutrophils in a concentration-dependent manner probably through the p47phox phosphorylation on Ser328.

Download Full-text

Antioxidant and Anti-Inflammatory Activities of Safflower (Carthamus tinctorius L.) Honey Extract

Foods ◽

10.3390/foods9081039 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1039

Author(s):

Li-Ping Sun ◽

Feng-Feng Shi ◽

Wen-Wen Zhang ◽

Zhi-Hao Zhang ◽

Kai Wang

Keyword(s):

Chemical Composition ◽

Biological Activities ◽

Carthamus Tinctorius ◽

Raw 264.7 Cells ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Unique Type ◽

Antioxidant Genes ◽

Anti Inflammatory

Safflower honey is a unique type of monofloral honey collected from the nectar of Carthamus tinctorius L. in the Apis mellifera colonies of northwestern China. Scant information is available regarding its chemical composition and biological activities. Here, for the first time, we investigated this honey’s chemical composition and evaluated its in vitro antioxidant and anti-inflammatory activities. Basic physicochemical parameters of the safflower honey samples in comparison to established quality standards suggested that safflower honeys presented a good level of quality. The in vitro antioxidant tests showed that extract from Carthamus tinctorius L. honey (ECH) effectively scavenged DPPH and ABTS+ free radicals. In lipopolysaccharides (LPS) activated murine macrophages inflammatory model, ECH treatment to the cells inhibited the release of nitric oxide and down-regulated the expressions of inflammatory-relating genes (iNOS, IL-1β, TNF-α and MCP-1). The expressions of the antioxidant genes TXNRD, HO-1, and NQO-1, were significantly boosted in a concentration-dependent manner. ECH decreased the phosphorylation of IκBα and inhibited the nuclear entry of the NF-κB-p65 protein, in LPS-stimulated Raw 264.7 cells, accompany with the increased expressions of Nrf-2 and HO-1, suggesting that ECH achieved the anti-inflammatory effects by inhibiting NF-κB signal transduction and boosting the antioxidant system via activating Nrf-2/HO-1 signaling. These results, taken together, indicated that safflower honey has great potential into developing as a high-quality agriproduct.

Download Full-text

Chemical Composition, and Cytotoxic, Antioxidant and Antibacterial Activities of the Essential Oil from Ginseng Leaves

Natural Product Communications ◽

10.1177/1934578x1400900637 ◽

2014 ◽

Vol 9 (6) ◽

pp. 1934578X1400900 ◽

Cited By ~ 4

Author(s):

Rui Jiang ◽

Liwei Sun ◽

Yanbing Wang ◽

Jianzeng Liu ◽

Xiaodan Liu ◽

...

Keyword(s):

Essential Oil ◽

Biological Activities ◽

Radical Scavenging ◽

Complex Mixture ◽

Annexin V ◽

Antibacterial Activities ◽

Cytotoxic Activities ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Gram Positive Bacteria

Panax ginseng C.A.Meyer is one of the most valuable traditional Chinese medicines. In this study, the essential oil of ginseng leaves (EOGL), collected using hydrodistillation and analyzed by GC/MS, contained a complex mixture of aliphatic (69.0%), terpenoid (21.5%) and aromatic compounds (2.4%). Among 54 components identified, the major ones were palmitic acid (36.1%), β-farnesene (15.4%), linoleic acid (9.8%) and phytol (5.6%). In the cytotoxicity study, EOGL exhibited obvious cytotoxic activities against different cancer cell lines, including Hela, A549, ZR-75-1, HT-29, SGC7901 and B16 cells. Furthermore, Annexin V-FITC/PI staining assay indicated that EOGL can induce late apoptosis of ZR-75-1 cells, and the percentage of apoptotic cells increased in a concentration-dependent manner (0.9% to 5.6% and 67.4%). In addition to this, we also found that EOGL exhibited weak DPPH radical scavenging (12.0 ± 0.4 mg/mL) and ABTS radical scavenging activities (1.6 ± 0.1 mg/mL), and showed antibacterial activity against the Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and the Gram-negative bacterium, Escherichia coli. The data suggest that EOGL, which possesses important biological activities, especially significant anticancer activity, could be a potential medicinal resource.

Download Full-text

Increased Anti-Inflammatory Effects on LPS-Induced Microglia Cells by Spirulina maxima Extract from Ultrasonic Process

Applied Sciences ◽

10.3390/app9102144 ◽

2019 ◽

Vol 9 (10) ◽

pp. 2144 ◽

Cited By ~ 5

Author(s):

Woon Yong Choi ◽

Jae-Hun Sim ◽

Jung-Youl Lee ◽

Do Hyung Kang ◽

Hyeon Yong Lee

Keyword(s):

Mrna Expression ◽

Dependent Manner ◽

Spirulina Maxima ◽

Concentration Dependent Manner ◽

Quantitative Correlation ◽

Tnf Α ◽

Ultrasonic Process ◽

Anti Inflammatory ◽

Low Cytotoxicity ◽

High Concentrations

The Spirulina maxima exact from a non-thermal ultrasonic process (UE) contains 17.5 mg/g of total chlorophyll, compared to 6.24 mg/g of chlorophyll derived from the conventional 70% ethanol extraction at 80 °C for 12 h (EE). The UE also showed relatively low cytotoxicity against murine microglial cells (BV-2) and inhibited the production of the inflammatory mediators, NO and PGE2. The UE also effectively suppresses both mRNA expression and the production of pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, in a concentration-dependent manner. Notably, TNF-α gene and protein production were most strongly down-regulated, while IL-6 was the least affected by all ranges of treatment concentrations. This work first demonstrated a quantitative correlation between mRNA expression and the production of cytokines, showing that suppression of TNF-α gene expression was most significantly correlated with its secretion. These results clearly proved that the anti-inflammatory effects of Spirulina extract from a nonthermal ultrasonic process, which yielded high concentrations of intact forms of chlorophylls, were increased two-fold compared to those of conventional extracts processed at high temperature.

Download Full-text