scholarly journals Myrrh Inhibits LPS-Induced Inflammatory Response and Protects from Cecal Ligation and Puncture-Induced Sepsis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Min-Sun Kim ◽  
Gi-Sang Bae ◽  
Kyoung-Chel Park ◽  
Bon Soon Koo ◽  
Byung-Jin Kim ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Inhibitory Effect ◽  
Peritoneal Macrophages ◽  
Prostaglandin E ◽  
Cecal Ligation And Puncture ◽  
Extracellular Signal ◽  
Alanine Aminotransferase Level ◽  
Anti Inflammatory

Myrrh has been used as an antibacterial and anti-inflammatory agent. However, effect of myrrh on peritoneal macrophages and clinically relevant models of septic shock, such as cecal ligation and puncture (CLP), is not well understood. Here, we investigated the inhibitory effect and mechanism(s) of myrrh on inflammatory responses. Myrrh inhibited LPS-induced productions of inflammatory mediators such as nitric oxide, prostaglandin E2, and tumor necrosis factor-αbut not of interleukin (IL)-1βand IL-6 in peritoneal macrophages. In addition, Myrrh inhibited LPS-induced activation of c-jun NH2-terminal kinase (JNK) but not of extracellular signal-regulated kinase (ERK), p38, and nuclear factor-κB. Administration of Myrrh reduced the CLP-induced mortality and bacterial counts and inhibited inflammatory mediators. Furthermore, administration of Myrrh attenuated CLP-induced liver damages, which were mainly evidenced by decreased infiltration of leukocytes and aspartate aminotransferase/alanine aminotransferase level. Taken together, these results provide the evidence for the anti-inflammatory and antibacterial potential of Myrrh in sepsis.

scholarly journals The Dietary Flavonoid Kaempferol Mediates Anti-Inflammatory Responses via the Src, Syk, IRAK1, and IRAK4 Molecular Targets

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Shi Hyoung Kim ◽  
Jae Gwang Park ◽  
Jongsung Lee ◽  
Woo Seok Yang ◽  
Gye Won Park ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Molecular Targets ◽  
Peritoneal Macrophages ◽  
Cellular Adhesion ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Genes Encoding ◽  
Anti Inflammatory

Even though a lot of reports have suggested the anti-inflammatory activity of kaempferol (KF) in macrophages, little is known about its exact anti-inflammatory mode of action and its immunopharmacological target molecules. In this study, we explored anti-inflammatory activity of KF in LPS-treated macrophages. In particular, molecular targets for KF action were identified by using biochemical and molecular biological analyses. KF suppressed the release of nitric oxide (NO) and prostaglandin E2(PGE2), downregulated the cellular adhesion of U937 cells to fibronectin (FN), neutralized the generation of radicals, and diminished mRNA expression levels of inflammatory genes encoding inducible NO synthase (iNOS), TNF-α, and cyclooxygenase- (COX-) 2 in lipopolysaccharide- (LPS-) and sodium nitroprusside- (SNP-) treated RAW264.7 cells and peritoneal macrophages. KF reduced NF-κB (p65 and p50) and AP-1 (c-Jun and c-Fos) levels in the nucleus and their transcriptional activity. Interestingly, it was found that Src, Syk, IRAK1, and IRAK4 responsible for NF-κB and AP-1 activation were identified as the direct molecular targets of KF by kinase enzyme assays and by measuring their phosphorylation patterns. KF was revealed to havein vitroandin vivoanti-inflammatory activity by the direct suppression of Src, Syk, IRAK1, and IRAK4, involved in the activation of NF-κB and AP-1.

scholarly journals AP-1/IRF-3 Targeted Anti-Inflammatory Activity of Andrographolide Isolated fromAndrographis paniculata

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Ting Shen ◽  
Woo Seok Yang ◽  
Young-Su Yi ◽  
Gi-Ho Sung ◽  
Man Hee Rhee ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Peritoneal Macrophages ◽  
Luciferase Reporter ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Molecular Signaling ◽  
Luciferase Reporter Gene ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

Andrographolide (AG) is an abundant component of plants of the genusAndrographisand has a number of beneficial properties including neuroprotective, anticancer, anti-inflammatory, and antidiabetic effects. Despite numerous pharmacological studies, the precise mechanism of AG is still ambiguous. Thus, in the present study, we investigated the molecular mechanisms of AG and its target proteins as they pertain to anti-inflammatory responses. AG suppressed the production of nitric oxide (NO) and prostaglandin E2(PGE2), as well as the mRNA abundance of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX)-2, and interferon-beta (IFN-β) in a dose-dependent manner in both lipopolysaccharide- (LPS-) activated RAW264.7 cells and peritoneal macrophages. AG also substantially ameliorated the symptoms of LPS-induced hepatitis and EtOH/HCl-induced gastritis in mice. Based on the results of luciferase reporter gene assays, kinase assays, and measurement of nuclear levels of transcription factors, the anti-inflammatory effects of AG were found to be clearly mediated by inhibition of both (1) extracellular signal-regulated kinase (ERK)/activator protein (AP)-1 and (2) IκB kinaseε(IKKε)/interferon regulatory factor (IRF)-3 pathways. In conclusion, we detected a novel molecular signaling pathway by which AG can suppress inflammatory responses. Thus, AG is a promising anti-inflammatory drug with two pharmacological targets.

scholarly journals BAY 11-7082 Is a Broad-Spectrum Inhibitor with Anti-Inflammatory Activity against Multiple Targets

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jaehwi Lee ◽  
Man Hee Rhee ◽  
Eunji Kim ◽  
Jae Youl Cho
Keyword(s):  
Inflammatory Responses ◽  
Janus Kinase ◽  
Prostaglandin E ◽  
Activator Protein 1 ◽  
Toll Like Receptor 4 ◽  
Multiple Targets ◽  
Extracellular Signal ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Necrosis Factor

BAY 11-7082 (BAY) is an inhibitor ofκB kinase (IKK) that has pharmacological activities that include anticancer, neuroprotective, and anti-inflammatory effects. In this study, BAY-pharmacological target pathways were further characterized to determine how this compound simultaneously suppresses various responses. Primary and cancerous (RAW264.7 cells) macrophages were activated by lipopolysaccharide, a ligand of toll-like receptor 4. As reported previously, BAY strongly suppressed the production of nitric oxide, prostaglandin E2, and tumor necrosis factor-αand reduced the translocation of p65, major subunit of nuclear factor-κB, and its upstream signaling events such as phosphorylation of IκBα, IKK, and Akt. In addition, BAY also suppressed the translocation and activation of activator protein-1, interferon regulatory factor-3, and signal transducer and activator of transcription-1 by inhibiting the phosphorylation or activation of extracellular signal-related kinase, p38, TANK-binding protein, and Janus kinase-2. These data strongly suggest that BAY is an inhibitor with multiple targets and could serve as a lead compound in developing strong anti-inflammatory drugs with multiple targets in inflammatory responses.

scholarly journals Protective Effects of Huang-Lian-Jie-Du-Tang against Polymicrobial Sepsis Induced by Cecal Ligation and Puncture in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Yufen Wei ◽  
Lei Shan ◽  
Liming Qiao ◽  
Runhui Liu ◽  
Zhenlin Hu ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cecal Ligation ◽  
Peritoneal Macrophages ◽  
Protective Effects ◽  
Bacterial Clearance ◽  
Cecal Ligation And Puncture ◽  
Th2 Response ◽  
Th1 Predominance ◽  
Septic Condition

Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional formula that has long been used for treatment of inflammatory diseases in Traditional Chinese Medicine. In this study, we examined its protective effect against sepsis in an experimental septic model induced by cecal ligation and puncture (CLP) in rats. The results demonstrated that prophylactic administration of HLJDT protected rats from CLP-induced lethality and ameliorated CLP-induced liver and lung injury. HLJDT treatment suppressed the production of proinflammatory cytokines, including TNF-α, IL-1, IL-6, and IL-17A, indicating HLJDT could limit excessive inflammatory responses in septic condition. In addition, HLJDT facilitated bacterial clearance by increasing phagocytic activities of peritoneal macrophages. Furthermore, HLJDT treatment reversed CLP-induced suppression of IFN-γexpression and blocked CLP-induced increase in IL-4 expression in spleens of rats at 24 h after CLP, indicating that HLJDT could reverse the shift from Th1 to Th2 response and promote Th1/Th2 balance toward Th1 predominance in septic rats. Moreover, HLJDT also inhibited the expression of IL-17A and ROR-γt in spleens of septic rats, indicating HLJDT is able to inhibit Th17 activation in septic condition. In conclusion, the present study demonstrated the protective effects of HLJDT against sepsis and highlighted the potential of HLJDT as a medication for septic patients.

Effect of the Semen Extract of Thuja orientalis on Inflammatory Responses in Transient Focal Cerebral Ischemia Rat Model and LPS-Stimulated BV-2 Microglia

2013 ◽  
Vol 41 (01) ◽  
pp. 99-117 ◽  
Author(s):  
Hyo Won Jung ◽  
Seok Yong Kang ◽  
Ki Ho Park ◽  
Tae Woo Oh ◽  
Jin Ki Jung ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Focal Cerebral Ischemia ◽  
Microglia Activation ◽  
Prostaglandin E ◽  
Activated Microglia ◽  
Anti Inflammatory ◽  
Thuja Orientalis

In the central nervous system inflammation is dependent upon the synthesis of various inflammatory mediators by local neurons, astrocytes and especially microglia. In this study, we investigated the anti-inflammatory activities of the semen extract of Thuja orientalis (Thujae Orientalis Semen; TOS) on transient middle cerebral artery occlusion (tMCAO)-induced ischemia in rats and the production of inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2) and proinflammatory cytokine, interleukin (IL)-1β in lipopolysaccharide (LPS)-stimulated BV-2 mouse microglia. TOS extract significantly decreased the infarction volumes of ischemic brains and also inhibited microglia activation and neuronal death. In addition, TOS extract significantly decreased the production of NO, PGE2 and IL-1β in LPS-stimulated BV-2 microglia. TOS extract also attenuated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and IL-1β mRNAs and proteins in activated microglia. Furthermore, TOS extract significantly suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK, and the nuclear translocation of NF-κB p65 in activated microglia. Our results indicate that TOS extract is capable of inhibiting microglia activation in an ischemic brain through the down-regulation of inflammatory responses, suggesting that the TOS extract may have therapeutic potential as an anti-inflammatory drug for ischemic stroke.

scholarly journals Preventive Effects of a Kampo Medicine, Kakkonto, on Inflammatory Responses via the Suppression of Extracellular Signal-Regulated Kinase Phosphorylation in Lipopolysaccharide-Treated Human Gingival Fibroblasts

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hiroyuki Kitamura ◽  
Hiroko Urano ◽  
Toshiaki Ara
Keyword(s):  
Periodontal Disease ◽  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Kampo Medicine ◽  
Prostaglandin E ◽  
Gingival Fibroblasts ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Cox 2

Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. The chemical mediator prostaglandin E2 (PGE2) and cytokines such as interleukin- (IL-)6 and IL-8 have been known to play important roles in inflammatory responses and tissue degradation. In the present study, we investigated the effects of a kampo medicine, kakkonto (TJ-1), on the production of prostaglandin E2 (PGE2), IL-6, and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Kakkonto concentration dependently suppressed LPS-induced PGE2 production but did not alter basal PGE2 levels. In contrast, kakkonto significantly increased LPS-induced IL-6 and IL-8 production. Kakkonto decreased cyclooxygenase- (COX-)1 activity to approximately 70% at 1 mg/mL but did not affect COX-2 activity. Kakkonto did not affect cytoplasmic phospholipase A2 (cPLA2), annexin1, or LPS-induced COX-2 expression. Kakkonto suppressed LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA2 phosphorylation. These results suggest that kakkonto decreased PGE2 production by inhibition of ERK phosphorylation which leads to inhibition of cPLA2 phosphorylation and its activation. Therefore, kakkonto may be useful to improve gingival inflammation in periodontal disease.

scholarly journals p38/AP-1 Pathway in Lipopolysaccharide-Induced Inflammatory Responses Is Negatively Modulated by Electrical Stimulation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Deok Jeong ◽  
Jaehwi Lee ◽  
Young-Su Yi ◽  
Yanyan Yang ◽  
Kyoung Won Kim ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Physiological Role ◽  
Peritoneal Macrophages ◽  
Cellular Level ◽  
Transcriptional Level ◽  
Weak Current ◽  
Anti Inflammatory

Electrical stimulation with a weak current has been demonstrated to modulate various cellular and physiological responses, including the differentiation of mesenchymal stem cells and acute or chronic physical pain. Thus, a variety of investigations regarding the physiological role of nano- or microlevel currents at the cellular level are actively proceeding in the field of alternative medicine. In this study, we focused on the anti-inflammatory activity of aluminum-copper patches (ACPs) under macrophage-mediated inflammatory conditions. ACPs generated nanolevel currents ranging from 30 to 55 nA in solution conditions. Interestingly, the nanocurrent-generating aluminum-copper patches (NGACPs) were able to suppress both lipopolysaccharide-(LPS-) and pam3CSK-induced inflammatory responses such as NO and PGE2production in both RAW264.7 cells and peritoneal macrophages at the transcriptional level. Through immunoblotting and immunoprecipitation analyses, we found that p38/AP-1 could be the major inhibitory pathway in the NGACP-mediated anti-inflammatory response. Indeed, inhibition of p38 by SB203580 showed similar inhibitory activity of the production of TNF-αand PGE2and the expression of TNF-αand COX-2 mRNA. These results suggest that ACP-induced nanocurrents alter signal transduction pathways that are involved in the inflammatory response and could therefore be utilized in the treatment of various inflammatory diseases such as arthritis and colitis.

scholarly journals Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2and Cytokines

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Bona Linke ◽  
Yannick Schreiber ◽  
Bettina Picard-Willems ◽  
Patrick Slattery ◽  
Rolf M. Nüsing ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Innate Immune ◽  
Prostaglandin E ◽  
Murine Bone Marrow ◽  
Activated Platelets ◽  
Monocytes And Macrophages ◽  
Inflammatory Processes ◽  
Necrosis Factor

Platelets are well known for their role in hemostasis and are also increasingly recognized for their roles in the innate immune system during inflammation and their regulation of macrophage activation. Here, we aimed to study the influence of platelets on the production of inflammatory mediators by monocytes and macrophages. Analyzing cocultures of platelets and murine bone marrow-derived macrophages or human monocytes, we found that collagen-activated platelets release high amounts of prostaglandin E2(PGE2) that leads to an increased interleukin- (IL-) 10 release and a decreased tumor necrosis factor (TNF)αsecretion out of the monocytes or macrophages. Platelet PGE2mediated the upregulation of IL-10 in both cell types via the PGE2receptor EP2. Notably, PGE2-mediated IL-10 synthesis was also mediated by EP4 in murine macrophages. Inhibition of TNFαsynthesis via EP2 and EP4, but not EP1, was mediated by IL-10, since blockade of the IL-10 receptor abolished the inhibitory effect of both receptors on TNFαrelease. This platelet-mediated cross-regulation between PGE2and cytokines reveals one mechanism how monocytes and macrophages can attenuate excessive inflammatory responses induced by activated platelets in order to limit inflammatory processes.

scholarly journals Senkyunolide I Protects against Sepsis-Associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jian Xie ◽  
Zhen-zhen Zhao ◽  
Peng Li ◽  
Cheng-long Zhu ◽  
Yu Guo ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Cognitive Dysfunction ◽  
Murine Model ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Signaling Proteins ◽  
Cecal Ligation And Puncture ◽  
Inflammatory Signaling ◽  
Tnf Α ◽  
Senkyunolide I

Sepsis may lead to sleep deprivation, which will promote the development of neuroinflammation and mediate the progression of sepsis-associated encephalopathy (SAE). Senkyunolide I, an active component derived from an herb medicine, has been shown to provide a sedative effect to improve sleep. However, its role in sepsis is unclear. The present study was performed to investigate whether Senkyunolide I protected against SAE in a murine model of cecal ligation and puncture (CLP). Here, we showed that Senkyunolide I treatment improved the 7-day survival rate and reduced the excessive release of cytokines including TNF-α, IL-6, and IL-1β. A fear conditioning test was performed, and the results showed that Senkyunolide I attenuated CLP-induced cognitive dysfunction. Senkyunolide I treatment also decreased the phosphorylation levels of inflammatory signaling proteins, including p-ERK, p-JNK, p-P38, and p-P65, and the level of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, in the hippocampus homogenate. Sleep deprivation was attenuated by Senkyunolide I administration, as demonstrated by the modification of the BDNF and c-FOS expression. When sleep deprivation was induced manually, the protective effect of Senkyunolide I against inflammatory responses and cognitive dysfunction was reversed. Our data demonstrated that Senkyunolide I could protect against sepsis-associated encephalopathy in a murine model of sepsis via relieving sleep deprivation.

scholarly journals α-Lipoic Acid Potentiates the Anti-Inflammatory Activity of Avocado/Soybean Unsaponifiables in Chondrocyte Cultures

Cartilage ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 304-312 ◽  
Author(s):  
Carmelita G. Frondoza ◽  
Lowella V. Fortuno ◽  
Mark W. Grzanna ◽  
Stacy L. Ownby ◽  
Angela Y. Au ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Nuclear Factor Kappa B ◽  
Nuclear Translocation ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Nuclear Factor ◽  
Chondrocyte Cultures ◽  
Potent Inhibitory Effect ◽  
Anti Inflammatory ◽  
Pharmacologic Treatments

Objective Pro-inflammatory mediators such as prostaglandin E-2 (PGE2) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE2 can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA). Design Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) control media, (2) ASU, (3) LA, or (4) ASU + LA combination. Cells were activated with lipopolysaccharide (LPS), interleukin 1β (IL-1β) or hydrogen peroxide (H2O2) for 24 hours and supernatants were immunoassayed for PGE2. Nuclear factor-kappa B (NF-κB) analyses were performed by immunocytochemistry and Western blot following 1 hour of activation with IL-1β. Results LPS, IL-1β, or H2O2 significantly increased PGE2 production. ASU or LA alone suppressed PGE2 production in LPS and IL-1β activated cells. Only LA alone at 2.5 µg/mL was inhibitory in H2O2-activated chondrocytes. ASU + LA inhibited more than either agent alone in all activated cells. ASU + LA also inhibited the IL-1β induced nuclear translocation of NF-κB. Conclusions The present study provides evidence that chondrocyte PGE2 production can be inhibited by the combination of ASU + LA more effectively than either ASU or LA alone. Inhibition of PGE2 production is associated with the suppression of NF-κB translocation. The potent inhibitory effect of ASU + LA on PGE2 production could offer a potential advantage for a combination anti-inflammatory/antioxidant approach in the management of OA.

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