Protective effects of curcumin against lipopolysaccharide-induced toxicity

2021 ◽  
Vol 28 ◽  
Author(s):  
Ali Ganji ◽  
Iman Farahani ◽  
Amir Mohammad Saeedifar ◽  
Ghasem Mosayebi ◽  
Ali Ghazavi ◽  
...  
Keyword(s):  
Septic Shock ◽  
Inflammatory Responses ◽  
Experimental Investigations ◽  
Inflammasome Activation ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Therapeutic Approaches ◽  
Cell Wall Component ◽  
Gram Negative ◽  
Surface Receptors

Background: Lipopolysaccharide (LPS), a Gram-negative bacterial cell wall component, evokes intensive inflammatory responses in the human body. Naturally, inflammation is a part of the host immune response to an infection; nonetheless, an exaggerated response can lead to a series of pathophysiological consequences, collectively known as LPS toxicity or septic shock. Objective: This review will explore the cellular and experimental investigations that mainly focus on Curcumin's therapeutic effects on the LPS-mediated inflammatory responses. Method: A literature review of all relevant studies was performed. Conclusion : Curcumin has been reported to exert anti-inflammatory properties by interfering with LPS-induced inflammatory pathways, including binding to cell surface receptors of LPS, NF-kB activation pathway, and inflammasome activation. Further clinical studies on the effect of Curcumin in reducing the pathophysiological consequences of LPS toxicity would substantiate the use of this molecule for future therapeutic approaches.

scholarly journals Orientin Ameliorates LPS-Induced Inflammatory Responses through the Inhibitory of the NF-κB Pathway and NLRP3 Inflammasome

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Qingfei Xiao ◽  
Zhihui Qu ◽  
Ying Zhao ◽  
Liming Yang ◽  
Pujun Gao
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Receptor Protein ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Inflammasome Activation ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Nlrp3 Inflammasome Activation ◽  
Underlying Mechanisms

Inflammation is a complex response to diverse pathological conditions, resulting in negative rather than protective effects when uncontrolled. Orientin (Ori), a flavonoid component isolated from natural plants, possesses abundant properties. Thus, we aimed to discover the potential therapeutic effects of orientin on lipopolysaccharide- (LPS-) induced inflammation in RAW 264.7 cells and the underlying mechanisms. In our studies, we evaluated the effects of Ori on proinflammatory mediator production stimulated by LPS, including tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-18, and IL-1β, along with prostaglandin E2 (PGE2) and NO. Our data indicated that orientin dramatically inhibited the levels of these mediators. Consistent with these results, the expression levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were also reduced. Further study demonstrated that such inhibitory effects of Ori were due to suppression of the nuclear factor-kappa B (NF-κB) pathway and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) inflammasome activation, which may contribute to its anti-inflammatory effects. Together, these findings show that Ori may be an effective candidate for ameliorating LPS-induced inflammatory responses.

scholarly journals Antiseptic Effect of Ps-K18: Mechanism of Its Antibacterial and Anti-Inflammatory Activities

2019 ◽  
Vol 20 (19) ◽  
pp. 4895 ◽  
Author(s):  
Mihee Jang ◽  
Jieun Kim ◽  
Yujin Choi ◽  
JeongKyu Bang ◽  
Yangmee Kim
Keyword(s):  
Septic Shock ◽  
Antibacterial Activity ◽  
Bioactive Peptides ◽  
Liver Toxicity ◽  
Inflammatory Responses ◽  
Lung Damage ◽  
Peptide Antibiotic ◽  
Gram Negative ◽  
Innate Defense ◽  
Anti Inflammatory

Recently, bioactive peptides have attracted attention for their therapeutic applications in the pharmaceutical industry. Among them, antimicrobial peptides are candidates for new antibiotic drugs. Since pseudin-2 (Ps), isolated from the skin of the paradoxical frog Pseudis paradoxa, shows broad-spectrum antibacterial activity with high cytotoxicity, we previously designed Ps-K18 with a Lys substitution for Leu18 in Ps, which showed high antibacterial activity and low toxicity. Here, we examined the potency of Ps-K18, aiming to develop antibiotics derived from bioactive peptides for the treatment of Gram-negative sepsis. We first investigated the antibacterial mechanism of Ps-K18 based on confocal micrographs and field emission scanning electron microscopy, confirming that Ps-K18 targets the bacterial membrane. Anti-inflammatory mechanism of Ps-K18 was investigated by secreted alkaline phosphatase reporter gene assays and RT-PCR, which revealed that Ps-K18 activates innate defense via Toll-like receptor 4-mediated nuclear factor-kappa B signaling pathways. Moreover, we investigated the antiseptic effect of Ps-K18 using a lipopolysaccharide or Escherichia coli K1-induced septic shock mouse model. Ps-K18 significantly reduced bacterial growth and inflammatory responses in the septic shock model. Ps-K18 showed low renal and liver toxicity and attenuated lung damage effectively. This study suggests that Ps-K18 is a potent peptide antibiotic that could be applied therapeutically to Gram-negative sepsis.

scholarly journals MMP-2: is too low as bad as too high in the cardiovascular system?

2018 ◽  
Vol 315 (5) ◽  
pp. H1332-H1340 ◽  
Author(s):  
Eugenio Hardy ◽  
Anette Hardy-Sosa ◽  
Carlos Fernandez-Patron
Keyword(s):  
Inflammatory Responses ◽  
Gene Mutations ◽  
Hypertensive Heart Disease ◽  
Tissue Remodeling ◽  
Therapeutic Effects ◽  
Therapeutic Approaches ◽  
Target Organs ◽  
Extracellular Matrix Components ◽  
Cardiovascular Pathologies ◽  
Matrix Components

Matrix metalloproteinase (MMP)-2 cleaves a broad spectrum of substrates, including extracellular matrix components (responsible for normal tissue remodeling) and cytokines (modulators of the inflammatory response to physiological insults such as tissue damage). MMP-2 expression is elevated in many cardiovascular pathologies (e.g., myocardial infarction, hypertensive heart disease) where tissue remodeling and inflammatory responses are perturbed. Thus, it has generally been assumed that blockade of MMP-2 activity will yield therapeutic effects. Here, we provide a counterargument to this dogma based on 1) preclinical studies on Mmp2-null ( Mmp2−/−) mice and 2) clinical studies on patients with inactivating MMP2 gene mutations. Furthermore, we put forward the hypothesis that, when MMP-2 activity falls below baseline, the bioavailability of proinflammatory cytokines normally cleaved and inactivated by MMP-2 increases, leading to the production of cytokines and cardiac secretion of phospholipase A2activity into the circulation, which stimulate systemic inflammation that perturbs lipid metabolism in target organs. Finally, we suggest that insufficient understanding of the consequences of MMP-2 deficiency remains a major factor in the failure of MMP-2 inhibitor-based therapeutic approaches. This paucity of knowledge precludes our ability to effectively intervene in cardiovascular and noncardiovascular pathologies at the level of MMP-2.

scholarly journals Highly Purified Vitamin B2 Presents a Promising Therapeutic Strategy for Sepsis and Septic Shock

2004 ◽  
Vol 72 (3) ◽  
pp. 1820-1823 ◽  
Author(s):  
Toshio Toyosawa ◽  
Mamoru Suzuki ◽  
Kohtarou Kodama ◽  
Seiichi Araki
Keyword(s):  
Septic Shock ◽  
Bacterial Infection ◽  
Intravenous Infusion ◽  
Sodium Phosphate ◽  
Therapeutic Strategy ◽  
Therapeutic Effects ◽  
Vitamin B2 ◽  
Gram Positive ◽  
Gram Negative ◽  
Sepsis And Septic Shock

ABSTRACT Highly purified vitamin B2 (riboflavin 5′-sodium phosphate; purity > 97%) treatment by intravenous infusion at doses above those used clinically to treat vitamin B2 deficiency showed therapeutic effects in mice not only in cases of endotoxin- and exotoxin-induced shock but also in cases of gram-negative and gram-positive bacterial infection even after the toxemia had already begun.

scholarly journals A Real-World Study for Polymyxin B in the Treatment of Carbapenems Resistant Gram-Negative Bacilli

2020 ◽  
Author(s):  
Xiaojuan Zhang ◽  
Shaoyan Qi ◽  
Xiaoguang Duan ◽  
Bing Han ◽  
Shuguang Zhang ◽  
...  
Keyword(s):  
Septic Shock ◽  
Mechanical Ventilation ◽  
Hospital Mortality ◽  
Real World ◽  
Positive Impact ◽  
Polymyxin B ◽  
High Morbidity ◽  
Therapeutic Effects ◽  
Gram Negative ◽  
Carbapenem Resistant

Abstract Background: High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CRGNB) was a challenge for clinicians has led to the resurgence of polymyxin B (PMB) use in the last decade. The goal of our multicenter, real-world study was to evaluate the efficacy and safety of PMB in the treatment of CRGNB.Methods: The real-world study included the patients with intravenous PMB at least 7 days during the period of October 2018 to June 2019. Data was collected from electronic patients register and follow-up. The primary outcome was 28-day mortality, the secondary outcomes included hospital mortality, occurrence of adverse events during PMB therapy. Associations between these variables and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression. At the same time, therapeutic effects were observed. Results: The study included 100 patients. There were 39% presence of septic shock, 49% need mechanical ventilation at the beginning of therapy. The infection and condition improved after 7 days of PMB treatment. The major adverse reactions occurred in 16 cases (16%). The overall 28-day mortality was 40%. In terms of clinical characteristics, mean Sequential Organ Failure Assessment (6.77 versus 9.25，P = 0.004)，mean Acute Physiology and Chronic Health Evaluation II (APACHEII) scores (16.17 versus 19.78, P = 0.016) and the number of patient with mechanical ventilation (21 versus 30, P = 0.000) or septic shock (17 versus 32, P = 0.000) were lower in survivors group than nonsurvivors group. The mortality of 85 patients with identify pathogens was 38.82%, while the mortality of patients with negative pathogen culture results was 46.67% (P = 0.580). Multivariate analysis showed that mechanical ventilation (P = 0.023, OR = 3.5; CI: 1.194–10.739), septic shock (P = 0.002, OR = 5.960; CI: 1.923–18.473) were associated with 28-day mortality.Conclusion: Our research found that PMB may be as effective and safe as standard antibiotics for the treatment of CRGNB. Timely and appropriate use of PMB will have a positive impact on the clinical outcomes of patients with sepsis in CRGNB.

Eucalyptus globulus Inhibits Inflammasome-Activated Pro-Inflammatory Responses and Ameliorate Monosodium Urate-Induced Peritonitis in Murine Experimental Model

2018 ◽  
Vol 46 (02) ◽  
pp. 423-433 ◽  
Author(s):  
Young-Eun Ji ◽  
Xiao Sun ◽  
Myong-Ki Kim ◽  
Wan Yi Li ◽  
Sang Woo Lee ◽  
...  
Keyword(s):  
Eucalyptus Globulus ◽  
Inflammatory Responses ◽  
Experimental Models ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Monosodium Urate ◽  
Traditional Use ◽  
Folk Remedy

Eucalyptus globulus Labill. (E. globulus, Myrtaceae) is used in Europe as a traditional folk remedy for inflammation-related disorders such as arthritis, diabetes, asthma, and gout. We investigated this study to evaluate the protective effects of E. globulus extract (EG) on inflammatory responses, and provide scientific and mechanistic evidence in in vitro and in vivo experimental models. LPS-stimulated murine bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of EG on inflammasome activation in vitro. Monosodium urate (MSU)-induced peritonitis was used to study the effect of EG in an in vivo murine model. EG suppressed IL-[Formula: see text] secretion via the regulation of apoptosis-associated speck-like proteins containing a CARD (ASC) oligomerization and caspase-1 maturation, leading to the inhibition of inflammasome activation. In the in vivo study, EG suppressed the MSU-induced peritonitis by attenuating interleukin (IL)-1[Formula: see text], providing scientific support for its traditional use in the treatment of inflammation-related disorders.

Protective effects of polyethylene oxide on the vascular and organ function of rats with severe hemorrhagic shock

2015 ◽  
Vol 93 (8) ◽  
pp. 597-602
Author(s):  
Qiang Li ◽  
Tao Huang ◽  
Zhen Dong
Keyword(s):  
Hemorrhagic Shock ◽  
Polyethylene Oxide ◽  
Inflammatory Responses ◽  
Tissue Perfusion ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Cytokine Levels ◽  
Ringer’S Lactate ◽  
First Time ◽  
Lactate Solution

This study examined the effects of polyethylene oxide (PEO) on the survival rate, hemodynamics, blood gas indexes, lactic acid levels, microcirculation, and inflammatory cytokine levels in rats subjected to severe hemorrhagic shock. The shocked rats were resuscitated with either Ringer’s lactate solution or 20 ppm of PEO in Ringer’s lactate solution for 1 h. It was found that infusion of PEO effectively improved the survival, metabolic acidosis, oxygen delivery, hyperlactacidemia, tissue perfusion, and inflammatory responses of rats subjected to hemorrhagic shock. In addition, we found, for the first time, that PEO showed protective effects on hepatic and renal injury, as evidenced by the significant decreases in the elevated levels of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine caused by shock induction after infusion of PEO (p < 0.05, 60 min post-resuscitation by comparison with pre-resuscitation). All of these findings indicate that PEO exhibits strong therapeutic effects under conditions of severe hemorrhagic shock,which also provides theoretical and experimental bases for the clinical use of PEO.

scholarly journals NLRP3 Inflammasome Modulation by Melatonin Supplementation in Chronic Pristane-Induced Lupus Nephritis

2019 ◽  
Vol 20 (14) ◽  
pp. 3466 ◽  
Author(s):  
Francesca Bonomini ◽  
Mariane Dos Santos ◽  
Francisco Veríssimo Veronese ◽  
Rita Rezzani
Keyword(s):  
Oxidative Stress ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Morphological Alteration ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Nlrp3 Inflammasome Activation

Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). NLRP3 inflammasome activation is implicated in LN pathogenesis, suggesting its potential targets for LN treatment. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule that has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo. This molecule has also protective effects against the activation of the inflammasomes and, in particular, the NLRP3 inflammasome. Thus, this work evaluated the effect of melatonin on morphological alteration and NLRP3 inflammasome activation in LN pristane mouse models. To evaluate the melatonin effects in these mice, we studied the renal cytoarchitecture by means of morphological analyses and immunohistochemical expression of specific markers related to oxidative stress, inflammation and inflammasome activation. Our results showed that melatonin attenuates pristane-induced LN through restoring of morphology and attenuation of oxidative stress and inflammation through a pathway that inhibited activation of NLRP3 inflammasome signaling. Our data clearly demonstrate that melatonin has protective activity on lupus nephritis in these mice that is highly associated with its effect on enhancing the Nrf2 antioxidant signaling pathway and decreasing renal NLRP3 inflammasome activation.

scholarly journals Taxifolin alleviates FCA-induced arthritis via regulating the Th1/Th2 balance, and down-regulates NLRP3 inflammasome axis activation in Jurkat T cells

2021 ◽  
Author(s):  
Xingyan Zhang ◽  
Huling Li ◽  
Ze Wang ◽  
Wenjing Zhao ◽  
Xin Li ◽  
...  
Keyword(s):  
T Cells ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Pharmacological Action ◽  
Joint Disease ◽  
Inflammasome Activation ◽  
Therapeutic Effects ◽  
Joint Movement ◽  
Active Components ◽  
Jurkat T Cells

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory joint disease mediated by T cells. In traditional Chinese medicine, Smilacis Glabrae Rhizoma is commonly used to treat deoxidation, dampness and ease joint movement. One of its active components, a flavonoid called taxifolin, has been the focus of several studies in recent years. However, the pharmacological action of taxifolin in the development of RA remains unknown. Here, we investigated the therapeutic effects of taxifolin on Freund's complete adjuvant (FCA)-induced arthritis model, and then verified the underlying immunoregulatory mechanisms of taxifolin on activated Jurkat T cells. Taxifolin ameliorated the physical signs including paw volume (PV), arthritis index (AI) and body weight (BW) and reduced the organ coefficients (spleen and thymus) in FCA-induced rats, as well as the inflammatory responses in the left hind paw and plasma. The results also showed that taxifolin greatly improved the imbalance of T helper (Th)1/Th2 status in the plasma and spleen. Further, the Th1/Th2 imbalance status and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in the activated Jurkat T cells was inhibited significantly by taxifolin. In conclusion, these results suggested that taxifolin potentially targeted the Th1/Th2 status and NLRP3 inflammasome axis in T cells, contributing valuable insights to elucidating the mechanism of action of taxifolin for future studies on RA therapeutics.

scholarly journals Protective Effects of Li-Fei-Xiao-Yan Prescription on Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Oxidative Stress and the TLR4/NF-κB Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Lie-Qiang Xu ◽  
Xiu-Ting Yu ◽  
Shu-Hua Gui ◽  
Jian-hui Xie ◽  
Xiu-Fen Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Agent ◽  
Inflammatory Responses ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Lung Histopathology

Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responsesviadecreasing the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment with LFXY significantly prevented LPS-induced TLR4 expression and NF-κB (p65) phosphorylation. Overall, the present study suggests that LFXY protected mice from acute lung injury induced by LPSviainhibition of TLR4/NF-κB p65 activation and upregulation of antioxidative enzymes and it may be a potential preventive and therapeutic agent for ALI in the clinical setting.

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