scholarly journals Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages

2015 ◽  
Vol 36 (4) ◽  
pp. 1316-1330 ◽  
Author(s):  
Xin-Hua Liu ◽  
Xi-Ling Wang ◽  
Hong Xin ◽  
Dan Wu ◽  
Xiao-Ming Xin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Heme Oxygenase ◽  
Inos Expression ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Nuclear Factor ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Inflammatory Effect

Background/Aim: Sodium 9-acetoxyltanshinone IIA sulfonate (ZY-1A4), a novel compound derived from sodium 9-hydroxyltanshinone IIA sulfonate, was synthesized with potential biological activities. This study aimed to explore the effects of ZY-1A4 on lipopolysaccharide (LPS)-triggered inflammatory response and the underlying mechanisms. Methods: Activation of RAW264.7 macrophages was induced by LPS. The effects of ZY-1A4 on inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) generation, nuclear factor-κB (NF-κB) activation, heme oxygenase-1 (HO-1) expression, and nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway were evaluated to elucidate its underlying mechanisms on inflammatory responses. Results: ZY-1A4 concentration-dependently reduced iNOS expression and NO production, and inhibited c-Jun-N-terminal kinase 1/2 (JNK1/2) phosphorylation and NF-κB activation in LPS-stimulated macrophages. In addition, ZY-1A4 concentration- and time-dependently induced HO-1 expression associated with degradation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear translocation of Nrf2, while the effect of ZY-1A4 was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Intriguingly, pharmacological inactivation of HO-1 with zinc protoporphyrin IX reversed anti-inflammatory effect of ZY-1A4, but the anti-inflammatory effect of ZY-1A4 was largely mimicked by HO-1 by-products carbon monoxide and bilirubin. Furthermore, the inhibitory effect of ZY-1A4 on LPS-induced iNOS expression and NO release was abolished by HO-1 siRNA or LY294002. Conclusion: Our results demonstrated that ZY-1A4 suppressed LPS-induced iNOS expression and NO generation via modulation of NF-κB activation and HO-1 expression. This new finding might shed light to the prevention and therapy of cardiovascular diseases.

scholarly journals The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jens Haugbølle Thomsen ◽  
Anders Etzerodt ◽  
Pia Svendsen ◽  
Søren K. Moestrup
Keyword(s):  
Carbon Monoxide ◽  
Plasma Concentration ◽  
Inflammatory Response ◽  
Heme Oxygenase ◽  
Enzyme System ◽  
Limiting Factor ◽  
Heme Oxygenase 1 ◽  
Future Studies ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex in macrophages followed by lysosomal Hp-Hb breakdown and HO-1-catalyzed conversion of heme into the metabolites carbon monoxide (CO), biliverdin, and iron. The plasma concentration of Hp is a limiting factor as evident during accelerated hemolysis, where the Hp depletion may cause serious Hb-induced toxicity and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6), but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway in the anti-inflammatory response.

Anti-inflammatory effect of grape seed may involve the induction of heme oxygenase-1 and suppression of nuclear factor-κB activation

2011 ◽  
Vol 20 (6) ◽  
pp. 1713-1719 ◽  
Author(s):  
Jeehye Sung ◽  
Younghwa Kim ◽  
Youngmin Choi ◽  
Hyeonmi Ham ◽  
Heon-Sang Jeong ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Nuclear Factor Κb ◽  
Grape Seed ◽  
Heme Oxygenase 1 ◽  
Nuclear Factor ◽  
Anti Inflammatory ◽  
Inflammatory Effect

scholarly journals Anti-Inflammatory Effect of Phytoncide in an Animal Model of Gastrointestinal Inflammation

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1895
Author(s):  
Azra Memon ◽  
Bae Yong Kim ◽  
Se-eun Kim ◽  
Yuliya Pyao ◽  
Yeong-Geun Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Animal Model ◽  
Gastric Ulcer ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Inos Expression ◽  
Gastrointestinal Inflammation ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Inflammatory Effect

Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent.

scholarly journals In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosangela Montanaro ◽  
Alessio D’Addona ◽  
Andrea Izzo ◽  
Carlo Ruosi ◽  
Vincenzo Brancaleone
Keyword(s):  
Inflammatory Markers ◽  
In Vitro Study ◽  
Inos Expression ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

Heme oxygenase-1 mediates the anti-inflammatory effect of mushroom Phellinus linteus in LPS-stimulated RAW264.7 macrophages

2006 ◽  
Vol 106 (3) ◽  
pp. 364-371 ◽  
Author(s):  
Byung-Chul Kim ◽  
Joung-Woo Choi ◽  
Hye-Young Hong ◽  
Sin-Ae Lee ◽  
Suntaek Hong ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Phellinus Linteus ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Carbon Monoxide-Neuroglobin Axis Targeting Metabolism Against Neuroinflammation

2021 ◽  
Author(s):  
Daniela Dias-Pedroso ◽  
José S. Ramalho ◽  
Vilma A. Sardão ◽  
John G. Jones ◽  
Carlos C. Romão ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Oxygen Consumption ◽  
Inflammatory Response ◽  
Microglial Cell ◽  
Cell Metabolism ◽  
Competent Cell ◽  
Metabolic Shift ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Microglia are the immune competent cell of the central nervous system (CNS), promoting brain homeostasis and regulating inflammatory response against infection and injury. Chronic or exacerbated neuroinflammation is a cause of damage in several brain pathologies. Endogenous carbon monoxide (CO), produced from the degradation of heme, is described as anti-apoptotic and anti-inflammatory in several contexts, including in the CNS. Neuroglobin (Ngb) is a haemoglobin-homologous protein, which upregulation triggers antioxidant defence and prevents neuronal apoptosis. Thus, we hypothesized a crosstalk between CO and Ngb, in particular, that the anti-neuroinflammatory role of CO in microglia depends on Ngb. A novel CO-releasing molecule (ALF826) based on molybdenum was used for delivering CO in microglial culture.BV-2 mouse microglial cell line was challenged with lipopolysaccharide (LPS) for triggering inflammation, and after 6h ALF826 was added. CO exposure limited inflammation by decreasing inducible nitric oxide synthase (iNOS) expression and the production of nitric oxide (NO) and tumour necrosis factor-a (TNF-a), and by increasing interleukine-10 (IL-10) release. CO-induced Ngb upregulation correlated in time with CO’s anti-inflammatory effect. Moreover, knocking down Ngb reversed the anti-inflammatory effect of CO, suggesting that dependents on Ngb expression. CO-induced Ngb upregulation was independent on ROS signalling, but partially dependent on the transcriptional factor SP1. Finally, microglial cell metabolism is also involved in the inflammatory response. In fact, LPS treatment decreased oxygen consumption in microglia, indicating a switch to glycolysis, which is associated with a proinflammatory. While CO treatment increased oxygen consumption, reverting LPS effect and indicating a metabolic shift into a more oxidative metabolism. Moreover, in the absence of Ngb this phenotype was no longer observed, indicating Ngb is needed for CO’s modulation of microglial metabolism. Finally, the metabolic shift induced by CO did not depend on alteration of mitochondrial population. In conclusion, neuroglobin emerges for the first time as a key player for CO signalling against exacerbated neuroinflammation in microglia.

scholarly journals Role of nuclear factor-κ B and heme oxygenase-1 in the mechanism of action of an anti-inflammatory chalcone derivative in RAW 264.7 cells

2004 ◽  
Vol 142 (7) ◽  
pp. 1191-1199 ◽  
Author(s):  
María José Alcaraz ◽  
Ana María Vicente ◽  
Amparo Araico ◽  
José N Dominguez ◽  
María Carmen Terencio ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Mechanism Of Action ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Nuclear Factor ◽  
Chalcone Derivative ◽  
Anti Inflammatory ◽  
Nuclear Factor Κ B
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