The effects of disodium pamidronate on human polymorphonuclear leukocytes and platelets: An in vitro study

AbstractRecent reports have indicated that, as well as having antiresorptive effects, bisphosphonates could have an application as anti-inflammatory drugs. Our aim was to investigate whether this anti-inflammatory action could be mediated by the nitric oxide (NO) released by the leukocytes migrating to the site of inflammation. In particular, we investigated in vitro the intracellular calcium concentration ([Ca2+]i), the level of NO released by PMN and platelets, and the PMN myeloperoxidase activity after incubation with disodium pamidronate, since there was a postulated modulatory effect of this aminosubstituted bisphosphonate on leukocytes both in vitro and in vivo. Our data shows that the pamidronate treatment provoked a significant increase in the [Ca2+]i parallel to the enhancement in NO release, suggesting a possible activation of constitutive nitric oxide synthase, while the myeloperoxidase activity was significantly reduced. In conclusion, we hypothesized that treatment with pamidronate could stimulate NO-production by cells present near the bone compartment, thus constituting a protective mechanism against bone resorption occurring during inflammation. In addition, PMN- and platelet-derived NO could act as a negative feed-back signal to restrict the inflammatory processes.

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In Vitro Study of Nitric Oxide Metabolites Effects on Human Hydatid ofEchinococcus granulosus

Journal of Parasitology Research ◽

10.1155/2009/624919 ◽

2009 ◽

Vol 2009 ◽

pp. 1-7 ◽

Cited By ~ 17

Author(s):

Razika Zeghir-Bouteldja ◽

Manel Amri ◽

Saliha Aitaissa ◽

Samia Bouaziz ◽

Dalila Mezioug ◽

...

Keyword(s):

Nitric Oxide ◽

Hydatid Cyst ◽

Echinococcus Granulosus ◽

In Vitro Study ◽

No Production ◽

In Vitro Effects ◽

Nitric Oxide Metabolites

Hydatidosis is characterized by the long-term coexistence of larvaEchinococcus granulosusand its host without effective rejection. Previous studies demonstrated nitric oxide (NO) production (in vivo and in vitro) during hydatidosis. In this study, we investigated the direct in vitro effects of NO species: nitrite (NO2−), nitrate (NO3−) and peroxynitrite (ONOO−) on protoscolices (PSCs) viability and hydatid cyst layers integrity for 24 hours and 48 hours. Our results showed protoscolicidal activity ofNO2−andONOO−24 hours and 3 hours after treatment with 320 μM and 80 μM respectively. Degenerative effects were observed on germinal and laminated layers. The comparison of the in vitro effects of NO species on the PSCs viability indicated thatONOO−is more cytotoxic thanNO2−. In contrast,NO3−has no effect. These results suggest possible involvement ofNO2−andONOO−in antihydatic action and point the efficacy of these metabolites as scolicidal agents.

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In vitro and in vivo anti-inflammatory activities of a sterol-enriched fraction from freshwater green alga, Spirogyra sp.

Fisheries and Aquatic Sciences ◽

10.1186/s41240-020-00172-9 ◽

2020 ◽

Vol 23 (1) ◽

Author(s):

Lei Wang ◽

You-Jin Jeon ◽

Jae-Il Kim

Keyword(s):

Nitric Oxide ◽

Green Alga ◽

Raw 264.7 Cells ◽

Ros Generation ◽

Prostaglandin E ◽

No Production ◽

Raw 264.7 ◽

Anti Inflammatory

Abstract Background Inflammation plays a crucial role in the pathogenesis of many diseases such as arthritis and atherosclerosis. In the present study, we evaluated anti-inflammatory activity of sterol-rich fraction prepared from Spirogyra sp., a freshwater green alga, in an effort to find bioactive extracts derived from natural sources. Methods The sterol content of ethanol extract of Spirogyra sp. (SPE) was enriched by fractionation with hexane (SPEH), resulting 6.7 times higher than SPE. Using this fraction, the in vitro and in vivo anti-inflammatory activities were evaluated in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells and zebrafish. Results SPEH effectively and dose-dependently decreased the production of nitric oxide (NO) and prostaglandin E2 (PGE2). SPEH suppressed the production of pro-inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β through downregulating nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW 264.7 cells without cytotoxicity. The in vivo test results indicated that SPEH significantly and dose-dependently reduced reactive oxygen species (ROS) generation, cell death, and NO production in LPS-stimulated zebrafish. Conclusions These results demonstrate that SPEH possesses strong in vitro and in vivo anti-inflammatory activities and has the potential to be used as healthcare or pharmaceutical material for the treatment of inflammatory diseases.

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Effect of Peganum Harmala Seeds Extract on Nitric Oxide in U937 Monocytes and Macrophages

International Journal of Medical Laboratory ◽

10.18502/ijml.v7i4.4803 ◽

2020 ◽

Author(s):

Nima Rahmati ◽

Fatemeh Hajighasemi

Keyword(s):

Nitric Oxide ◽

Aqueous Extract ◽

Calf Serum ◽

Peritoneal Macrophages ◽

No Production ◽

Peganum Harmala ◽

Logarithmic Growth Phase ◽

Anti Inflammatory

Background and Aims: Nitric oxide (NO) has an essential role in inflammation and has been related to pathogenesis and the progress of numerous inflammatory-based diseases, including some cancers. Peganum harmala (P. harmala) is a medicinal plant used for the treatment of numerous diseases such as several infections. Also, anti-inflammatory effects of P. harmala extracts and its derivatives (harmaline and harmine) by suppressing myeloperoxidase, NO, and other mediators have been demonstrated in vivo. In this study, the effect of P. harmala seeds aqueous extract on NO production in U937 monocytic cells and peritoneal macrophages has been evaluated in vitro. Materials and Methods: U937 and mice peritoneal macrophages were cultured in Roswell Park Memorial institute-1640 with 10% fetal calf serum. Then, the cells at the logarithmic growth phase were incubated with different concentrations of aqueous extract of P. harmala seeds (0.1-1 mg/ml) for 24 hours. Next, NO production was assessed by the Griess method in the culture medium. Results: P. harmala seeds aqueous extract did not significantly affect lipopolysaccharide-induced NO production in U937 cells and peritoneal macrophages after 24 hours incubation time compared with untreated control cells. Conclusion: These results suggest that the anti-inflammatory effects of P. harmala may be mediated through NO-independent mechanism(s). However, further studies are warranted to define the P. harmala aqueous extract impact on NO expression in other related normal and cancerous cells.

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Antioxidant, Antinociceptive, and Anti-Inflammatory Activities fromActinidia callosavar.callosa In VitroandIn Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/129152 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14

Author(s):

Jung-Chun Liao ◽

Jeng-Shyan Deng ◽

Ying-Chih Lin ◽

Chao-Ying Lee ◽

Min-Min Lee ◽

...

Keyword(s):

Nitric Oxide ◽

Late Phase ◽

Radical Scavenging ◽

Heme Oxygenase 1 ◽

No Production ◽

Traditional Use ◽

Raw264.7 Macrophages ◽

Anti Inflammatory

Actinidia callosavar.callosahas been widely used to treat antipyretic, analgesic, anti-inflammation, abdominal pain, and fever in Taiwan. The aim of this study was to evaluate the antioxidant, antinociceptive, and anti-inflammatory lipopolysaccharide-(LPS-)induced nitric oxide (NO) production in RAW264.7 macrophages and pawedema induced byλ-carrageenan activities of the methanol extract fromA. callosa. In HPLC analysis, the fingerprint chromatogram of ethyl-acetate fraction ofA. callosa(EAAC) was established. EAAC showed the highest TEAC and DPPH radical scavenging activities, respectively. We evaluated that EAAC and the reference compound of catechin and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Treatment of male ICR mice with EAAC significantly inhibited the numbers of acetic acid-induced writhing response and the formalin-induced pain in the late phase. Administration of EAAC showed a concentration-dependent inhibition on paw edema development after Carr treatment in mice. Anti-inflammatory mechanisms of EAAC might be correlated to the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1)in vitroandin vivo. Overall, the results showed that EAAC demonstrated antioxidant, antinociceptive, and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain.

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Antioxidant and Anti-Inflammatory Effects of Korean Black Ginseng Extract through ER Stress Pathway

Antioxidants ◽

10.3390/antiox10010062 ◽

2021 ◽

Vol 10 (1) ◽

pp. 62

Author(s):

Mi-Yeong An ◽

So Rok Lee ◽

Hye-Jeong Hwang ◽

Ju-Gyeong Yoon ◽

Hae-Jeung Lee ◽

...

Keyword(s):

Nitric Oxide ◽

Er Stress ◽

Immune Cell ◽

Antioxidant Effect ◽

No Production ◽

Dependent Manner ◽

Black Ginseng ◽

Anti Inflammatory

The excessive release of reactive oxygen species (ROS) can result in the development of chronic inflammation. The mechanisms involved in inflammation are various, with endoplasmic reticulum (ER) stress known to be among them. We have previously shown that black ginseng (BG) reduced lipid accumulation in and enhanced the antioxidant function of the liver in vitro and in vivo mostly due to ginsenoside Rb1, Rg3 and Rk1 components. Therefore, this study investigated the antioxidant effect of BG on the intestines and its possible mechanistic pathway through ER stress. The results showed that BG extract decreased ROS and nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression levels in vitro, and these results were confirmed by zebrafish embryos in vivo. However, this phenotype was abolished in the absence of inositol-requiring enzyme 1 (IRE1α) but not in the absence of protein kinase RNA (PKR)-like ER-resistant kinase (PERK) or X-box-binding protein 1 (XBP1) in the mouse embryo fibroblast (MEF) knockout (KO) cells, suggesting that BG elicits an antioxidant effect in an IRE1α-dependent manner. Antioxidant and anti-inflammatory effects were assessed in the liver and intestines of the mouse model affected by nonalcoholic fatty liver disease (NAFLD), which was induced by a high-fat/high-fructose diet. In the liver, BG treatment rescued NAFLD-induced glutathione (GSH), catalase (CAT), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 expression. In the intestines, BG also rescued NAFLD-induced shortened villi, inflammatory immune cell infiltration, upregulated IL-6, cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding homologous protein (CHOP) and binding immunoglobulin protein (BiP) expression. In conclusion, our results show that BG reduces ROS and NO production followed by inflammation in an IRE1α-dependent and XBP1-independent manner. The results suggest that BG provides antioxidant and anti-inflammatory effects through an ER stress mechanism.

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In Vitro and In Vivo Anti-Inflammatory Effects of Sulfated Polysaccharides Isolated from the Edible Brown Seaweed, Sargassum fulvellum

Marine Drugs ◽

10.3390/md19050277 ◽

2021 ◽

Vol 19 (5) ◽

pp. 277

Author(s):

Lei Wang ◽

Hye-Won Yang ◽

Ginnae Ahn ◽

Xiaoting Fu ◽

Jiachao Xu ◽

...

Keyword(s):

Nitric Oxide ◽

Brown Seaweed ◽

Sulfated Polysaccharides ◽

Raw 264.7 ◽

Raw 264.7 Macrophages ◽

Sargassum Fulvellum ◽

Pharmaceutical Industries ◽

Anti Inflammatory

In the present study, the in vitro and in vivo anti-inflammatory effects of the sulfated polysaccharides isolated from Sargassum fulvellum (SFPS) were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results indicated that SFPS improved the viability of LPS-stimulated RAW 264.7 macrophages from 80.02 to 86.80, 90.09, and 94.62% at the concentration of 25, 50, and 100 µg/mL, respectively. Also, SFPS remarkably and concentration-dependently decreased the production levels of inflammatory molecules including nitric oxide (NO), tumor necrosis factor-alpha, prostaglandin E2, interleukin-1 beta, and interleukin-6 in LPS-treated RAW 264.7 macrophages. In addition, SFPS significantly inhibited the expression levels of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-treated RAW 264.7 macrophages. Furthermore, the in vivo test results indicated that SFPS improved the survival rate of LPS-treated zebrafish from 53.33 to 56.67, 60.00, and 70.00% at the concentration of 25, 50, and 100 µg/mL, respectively. In addition, SFPS effectively reduced cell death, reactive oxygen species, and NO levels in LPS-stimulated zebrafish. Taken together, these results suggested that SFPS possesses strong in vitro and in vivo anti-inflammatory activities, and could be used as an ingredient to develop anti-inflammatory agents in the functional food and pharmaceutical industries.

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Effects of chitosan on nitric oxide production and inducible nitric oxide synthase activity and mRNA expression in weaned piglets

Czech Journal of Animal Science ◽

10.17221/8405-cjas ◽

2018 ◽

Vol 60 (No. 8) ◽

pp. 359-366

Author(s):

J. Li ◽

B. Shi ◽

S. Yan ◽

L. Jin ◽

Y. Guo ◽

...

Keyword(s):

Nitric Oxide ◽

Mrna Expression ◽

Inducible Nitric Oxide Synthase ◽

No Production ◽

Weaned Piglets ◽

Inos Activity ◽

Oxide Synthase ◽

Inducible Nitric Oxide

The effects of chitosan on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity and gene expression in vivo or vitro were investigated in weaned piglets. In vivo, 180 weaned piglets were assigned to five dietary treatments with six replicates. The piglets were fed on a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. In vitro, the peripheral blood mononuclear cells (PBMCs) from a weaned piglet were cultured respectively with 0 (control), 40, 80, 160, and 320 µg chitosan/ml medium. Results showed that serum NO concentrations on days 14 and 28 and iNOS activity on day 28 were quadratically improved with increasing chitosan dose (P < 0.05). The iNOS mRNA expressions were linearly or quadratically enhanced in the duodenum on day 28, and were improved quadratically in the jejunum on days 14 and 28 and in the ileum on day 28 (P < 0.01). In vitro, the NO concentrations, iNOS activity, and mRNA expression in unstimulated PBMCs were quadratically enhanced by chitosan, but the improvement of NO concentrations and iNOS activity by chitosan were markedly inhibited by N-(3-[aminomethyl] benzyl) acetamidine (1400w) (P < 0.05). Moreover, the increase of NO concentrations, iNOS activity, and mRNA expression in PBMCs induced by lipopolysaccharide (LPS) were suppressed significantly by chitosan (P < 0.05). The results indicated that the NO concentrations, iNOS activity, and mRNA expression in piglets were increased by feeding chitosan in a dose-dependent manner. In addition, chitosan improved the NO production in unstimulated PBMCs but inhibited its production in LPS-induced cells, which exerted bidirectional regulatory effects on the NO production via modulated iNOS activity and mRNA expression.

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In Vitro and In Vivo Anti-Inflammatory Activity of the Rhizomes of Globba pendula Roxb

Natural Product Communications ◽

10.1177/1934578x211055907 ◽

2021 ◽

Vol 16 (10) ◽

pp. 1934578X2110559

Author(s):

Le Minh Ha ◽

Ngo Thi Phuong ◽

Nguyen Thi Thu Hien ◽

Pham Thi Tam ◽

Do Thi Thao ◽

...

Keyword(s):

Ethyl Acetate ◽

Ethyl Acetate Extract ◽

Inhibitory Effect ◽

Potential Effect ◽

Inflammatory Activity ◽

No Production ◽

Anti Inflammatory ◽

Inflammatory Effect

In this study, we aimed at evaluating in vitro and in vivo anti-inflammatory activity of various extracts of the rhizomes of Globba pendula Roxb. Three extracts ( n-hexane, ethyl acetate, and water) were screened for their inhibitory effect on NO production by lipopolysaccharide-stimulated RAW 264.7 macrophages. The ethyl acetate extract of G. pendula rhizomes (EGP) showed a potential effect with an IC50 value of 32.45 µg/mL. For in vivo study, the ethyl acetate extract was further investigated for its anti-inflammatory effect using collagen antibody-induced arthritic mice (CAIA). The level of arthritis in experimental mice significantly reduced ( P < .05) after treatment with EGP at a dose of 500 mg/kg body weight (b.w.). This study also revealed that EGP is orally non-toxic. Ethyl p-methoxy cinamate was identified as the main constituent of EGP, which may result in its anti-inflammatory effect.

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Properties of a New Food Supplement Containing Actinia equina Extract

Antioxidants ◽

10.3390/antiox9100945 ◽

2020 ◽

Vol 9 (10) ◽

pp. 945

Author(s):

Marika Lanza ◽

Giovanna Casili ◽

Giovanna Loredana La Torre ◽

Daniele Giuffrida ◽

Archimede Rotondo ◽

...

Keyword(s):

In Vitro Study ◽

Neutrophil Infiltration ◽

Food Supplement ◽

Biologically Active ◽

In Vivo Model ◽

Related Factor ◽

Nuclear Factor ◽

Anti Inflammatory

Marine species represent a great source of biologically active substances; Actinia equina (AE), an Anthozoa Cnidaria belonging to the Actinidiae family, have been proposed as original food and have already been included in several cooking recipes in local Mediterranean shores, and endowed with excellent nutraceutical potential. The aim of this study was to investigate some unexplored features of AE, through analytical screening and an in-vitro and in-vivo model. An in-vitro study, made on RAW 264.7 stimulated with H2O2, showed that the pre-treatment with AE exerted an antioxidant action, reducing lipid peroxidation and up-regulating antioxidant enzymes. On the other hand, the in-vivo study over murine model demonstrated that the administration of AE extracts is able to reduce the carrageenan (CAR)-induced paw edema. Furthermore, the histological damage due to the neutrophil infiltration is prevented, and this highlights precious anti-inflammatory features of the interesting food-stuff. Moreover, it was assessed that AE extract modulated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and The nuclear factor erythroid 2–related factor 2 (Nrf-2) pathways. In conclusion, our data demonstrated that thanks to the antioxidant and anti-inflammatory properties, AE extract could be used as a new food supplement for inflammatory pathology prevention.

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Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500336 ◽

2016 ◽

Vol 44 (03) ◽

pp. 595-615 ◽

Cited By ~ 34

Author(s):

Tao Yu ◽

Man Hee Rhee ◽

Jongsung Lee ◽

Seung Hyung Kim ◽

Yanyan Yang ◽

...

Keyword(s):

Panax Ginseng ◽

Molecular Mechanisms ◽

Red Ginseng ◽

Korean Red Ginseng ◽

Inhibitory Mechanisms ◽

Inflammatory Processes ◽

Anti Inflammatory ◽

Ginsenoside Rc

Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng’s various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-[Formula: see text] and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-[Formula: see text]B. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that G-Rc may be a major component of KRG with useful anti-inflammatory properties due to its suppression of IRF-3 and AP-1 pathways.

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