Curcumin therapy: Immune booster in present and post-pandemic (COVID-19) Era

COVID-19 pandemic, which has traumatized the world population, in principle, is an inflammatory lung disease secondary to SARS-COV2 virus infection. Inflammatory lung injury progressing to Acute Respiratory Distress Syndrome (ARDS) is a recognized clinical feature of the disease. Inflammatory cytokines released in response to COVID-19 activate the transcription factor - the nuclear factor-қB (NF-қB) and series of pro-inflammatory cytokines, which are responsible for lung injury. Accurate yet precise treatment of coronavirus disease still remains inconclusive, and intervention is mainly symptomatic treatment, respiratory support, antiviral therapies and vaccination. Currently, the major focus of therapy is on reducing lung inflammation by elevating the host immunity. In this scenario, NF-қB inhibition can be conceptualized as a promising approach to down-regulate the overproduction of cytokines, such that inflammatory lung tissue injury could be prevented in COVID-19 infected patients. Towards this, curcumin from Curcuma longa (Turmeric) would play a vital role in the intervention and suppress NF-қB activation via translocation of p65 into the nucleus. Moreover, Curcumin is a proven therapeutic agent against various inflammatory pathologies as it also has the potential to inhibit the expression of certain genes that are critical for the regulation of inflammation. Keeping this phenomenon and the current medical significance in view, we have explored and computed the anti-inflammatory properties of curcumin to develop it as a potent therapeutic agent to prevent NF-қB induced lung tissue injury in COVID-19 with the main goal of elevating immunity in the post-covid-19 situations as well as in healthy human beings.

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IL-6 knockout alleviates inflammatory response and improve acute lung injury via regulating macrophage polarization in sepsis

10.21203/rs.3.rs-618570/v2 ◽

2021 ◽

Author(s):

Jinxin Zhang ◽

Kuo Shen ◽

Jiangang Xie ◽

Shanshou Liu ◽

Xiaozhi Bai ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Western Blot ◽

Bronchoalveolar Lavage ◽

Inflammatory Cytokines ◽

Lung Tissue ◽

General Condition ◽

Death Rate ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid

Abstract BackgroundSepsis is a fatal disease with a high rate of morbidity and mortality, during which acute lung injury is the earliest and most serious complication. Macrophage plays a crucial role in the initiation and progress of sepsis. This study meant to explore the effect of IL-6 knockout in CLP induced sepsis.MethodsIn this study, cecal ligation and puncture (CLP) was performed on wildtype and interleukin 6 (IL-6) knockout C57 mice. General condition and death rate of sepsis mice were observed. organ samples (lungs, livers, kidneys and hearts) and serum were collected for histology observation and inflammatory cytokine detection. Lung tissue injury detection were conducted via lung injury score, wet/dry ration and protein concentrations measurement of Bronchoalveolar lavage fluid (BALF). In in vivo studies, RAW264.7 macrophages were transfected with IL-6 specific siRNA and treated with LPS. After exposed to IL-6 specific siRNA and LPS, expression of inflammatory cytokines interleukin 1 (IL-1), tumor necrosis factor- (TNF-), IL-6 and interleukin 10 (IL-10) were detected by RT-qPCR, concentration of IL-1 and TNF- in culture supernatant were detected by ELISA and M1 and M2 markers were detected by western blot and flow cytometry.ResultsWe constructed CLP induced sepsis models and found that inhibition of IL-6 could improve general condition and death rate of sepsis mice. Mice in IL-6 knockout group display improved tissue damage, especially in the lung tissue. IL-6 knockout relieved inflammatory cytokines storm in both serum and bronchoalveolar lavage fluid while polarized macrophage to an anti-inflammatory M2 phenotype. In cell model, inhibition of IL-6 could alleviate LPS induced expression of inflammatory cytokines IL-1, TNF-, and IL-6 in macrophages. Western blot and Flow cytometry results indicated that expression of M1 markers (iNOS and CD86) in LPS stimulated macrophages were significantly declined while M2 (Arg-1 and CD206) were enhanced when expression of IL-6 was blocked.Conclusion Inhibition of IL-6 alleviated LPS induced inflammation and exerted protective effect in sepsis via regulating macrophage function and polarization.

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Therapeutic Efficacy of Excretory-Secretory Products of Trichinella spiralis Adult Worms on Sepsis-Induced Acute Lung Injury in a Mouse Model

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.653843 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huihui Li ◽

Dapeng Qiu ◽

Huijuan Yang ◽

Yuan Yuan ◽

Lingqin Wu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Therapeutic Effect ◽

Inflammatory Cytokines ◽

Lung Tissue ◽

Therapeutic Efficacy ◽

Trichinella Spiralis ◽

Inflammatory Diseases ◽

Secretory Products ◽

Pro Inflammatory Cytokines

Acute lung injury (ALI) is a common complication of systemic inflammation or sepsis with high morbidity and mortality. Although many studies have confirmed that helminth-derived proteins had strong immunomodulatory functions and could be used to treat inflammatory diseases, there is no report on the therapeutic effect of excretory-secretory products of Trichinella spiralis adult worms (Ts-AES) on sepsis-induced ALI. In this study, the therapeutic efficacy of Ts-AES on sepsis-induced ALI and the underlying immunological mechanism and the signaling pathway were investigated. The results indicated that after being treated with Ts-AES, the survival rate of mice with CLP-induced sepsis was significantly increased to 50% for 72 hours after CLP surgery compared to PBS control group with all mice died. The sepsis-induced ALI was largely mitigated characterized by reduced inflammation cell infiltration and pathological changes in lung tissue, with decreased lung injury scores and lung wet/dry weight ratio. The therapeutic efficacy of Ts-AES is associated with stimulated Tregs response with increased regulatory cytokines IL-10 and TGF-β and downregulated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). The expression of HMGB1, TLR2 and MyD88 in lung tissue was inhibited after treatment of Ts-AES. Our results demonstrated that Ts-AES play an important role in immunomodulation and confer a therapeutic effect on sepsis-induced ALI through inhibiting pro-inflammatory cytokines. The activation of Tregs and increased level of regulatory cytokines IL-10 and TGF-β are possibly involved in the immunomodulatory functions of Ts-AES through HMGB1/TLR2/MyD88 signal pathway. The findings suggest Ts-AES is a potential therapeutic agent for prevention and treatment of sepsis-induced ALI and other inflammatory diseases.

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Saquinavir Ameliorates Liver Warm Ischemia-Reperfusion-Induced Lung Injury via HMGB-1- and P38/JNK-Mediated TLR-4-Dependent Signaling Pathways

Mediators of Inflammation ◽

10.1155/2017/7083528 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Zhuang Yu ◽

Yao Tong ◽

Renlingzi Zhang ◽

Xibing Ding ◽

Quan Li

Keyword(s):

Lung Injury ◽

Signaling Pathways ◽

Lung Tissue ◽

Tissue Injury ◽

Ischemia Reperfusion ◽

High Mobility ◽

Tissue Expression ◽

Hiv Protease ◽

Lung Edema ◽

Beneficial Effects

Liver ischemia and reperfusion (I/R) induce local and distant tissue injuries, contributing to morbidity and mortality in a wider range of pathologies. This is especially seen under uncontrolled aseptic inflammatory conditions, leading to injury of remote organs, such as lung injury, and even failure. Saquinavir (SQV) is a kind of HIV protease inhibitor that possesses an anti-inflammatory property. In this study, we investigated whether SQV suppresses Toll-like receptor 4- (TLR4-) dependent signaling pathways of high-mobility group box 1 (HMGB1) and P38/JNK, conferring protection against murine liver I/R-induced lung injury. To investigate our hypothesis, C57BL/6 mice and TLR4 knockout mice (TLR4−/−) were used to perform the study. SQV administration markedly attenuated remote lung tissue injury after 1-hour ischemia and 6-hour reperfusion of the liver. To our expectation, SQV attenuated I/R-induced lung edema, hyperpermeability, and pathological injury. The beneficial effects of SQV were associated with decreased levels of circulating and lung tissue inflammatory cytokines, such as IL-6, IL-1β, TNF-α, and iNOS. The protective effect of SQV was also associated with decreased lung tissue expression of HMGB1, TLR-4, and p-P38/JNK, but not p-ERK in wild-type liver I/R mice. Overall, this study demonstrated a new role of SQV, facilitating negative regulation of HMGB1- and P38/JNK-mediated TLR-4-dependent signaling pathways, conferring protection against liver I/R-induced lung injury.

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A Novel Anti-Histone H1 Monoclonal Antibody, SSV Monoclonal Antibody, Improves Lung Injury and Survival in a Mouse Model of Lipopolysaccharide-Induced Sepsis-Like Syndrome

BioMed Research International ◽

10.1155/2015/491649 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Toru Kusano ◽

Kuei-Chen Chiang ◽

Masafumi Inomata ◽

Yayoi Shimada ◽

Naoya Ohmori ◽

...

Keyword(s):

Monoclonal Antibody ◽

Lung Injury ◽

Inflammatory Cytokines ◽

Lung Tissue ◽

Acute Inflammation ◽

Histone H1 ◽

Protective Effects ◽

Microbial Infection ◽

Igg Antibody ◽

Histological Score

Background. Histones play important roles in both host defenses and inflammation related to microbial infection. A peptide mimotope (SSV) was identified from a novel histone H1 monoclonal antibody (16G9 mAb) that was shown to inhibit the mixed lymphocyte reaction. In the present study, an anti-SSV producing hybridoma was established. We investigated the effects of SSV mAb in a mouse acute inflammation model induced by intraperitoneal injection of lipopolysaccharide (LPS).Methods. SSV mAb was generated and characterized. Mice were treated with SSV mAb or a control IgG antibody prior to LPS injection. Evaluation of survival rate and lung tissue on histological score was performed. The levels of inflammatory cytokines and histones H1, H3, and H4 in plasma and lung tissue were measured by ELISA.Results. Competitive ELISA revealed that SSV mAb binds to histone H1. SSV mAb improved lung injury and prolonged the survival of LPS-injected mice. Increased levels of histones H1, H3, and H4 and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in plasma and lung tissue after LPS injection were ameliorated by SSV mAb.Conclusion. SSV mAb is shown to have anti-inflammatory activity and organ-protective effects, highlighting the importance of controlling histone H1 as well as H3 and H4 levels during inflammation.

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HMGB1 and inflammatory cytokines in experimental acute lung injury induced in rabbits

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/1678-4162-11499 ◽

2020 ◽

Vol 72 (4) ◽

pp. 1329-1338

Author(s):

C.S. Kurokawa ◽

J.P. Araújo Júnior ◽

R.B. Pires ◽

M.F. Carpi ◽

M.A. Moraes ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Bronchoalveolar Lavage ◽

Inflammatory Cytokines ◽

Lung Tissue ◽

Tnf Alpha ◽

Control Group ◽

Early Expression

ABSTRACT The aim of this work was to measure HMGB1, TNF-alpha, and IL-8 in bronchoalveolar lavage (BAL), serum and TLR2 and TLR4mRNA expression in lung tissue of rabbits with two grades of acute lung injury (ALI). The animals were randomly assigned to groups with severe (S) and mild/moderate (MM) ALI, induced with warm saline, and a control group. HMGB1, TNF-alpha, IL-8, TLR2mRNA and TLR4mRNA were measured after ALI induction. The results showed increased levels of IL-8, TNF-alpha, HMGB1 and TLR4mRNA in the ALI groups. HMGB1, IL-8 and TNF-alpha concentrations in BAL were higher in S compared MM. Increased TLR4mRNA was observed in S and MM versus control. The results suggest an early participation of HMGB1 in ALI together with IL-8 and TNF-alpha and association with severity. TLR4 has early expression and role in ALI pathophysiology but is not associated with severity.

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Echinacoside attenuates lipopolysaccharide-induced acute lung injury in newborn mice via inactivation of NF- κB/NLRP3 signaling pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i9.3 ◽

2020 ◽

Vol 19 (9) ◽

pp. 1815-1819

Author(s):

Meijiao Fu ◽

Tong Shen ◽

Ying Yang ◽

Yaling Zheng ◽

Lilin Zhong

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Lung Tissue ◽

Tissue Injury ◽

Weight Ratio ◽

Dry Weight ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Newborn Mice ◽

Pyrin Domain

Purpose: To investigate the effect of echinacoside (ECH) on acute lung injury (ALI) and the underlying mechanism of action.Methods: The ALI model was established through intranasal instillation of lipopolysaccharide (LPS). Lung tissue damage was determined using hematoxylin and eosin (H&E) staining and lung wet-to-dry–weight ratio. Bronchoalveolar lavage fluid (BALF) protein concentration, cell count, and cytokine level were evaluated. Western blotting was used to determine protein expression level.Results: ECH attenuated lung tissue injury and lung wet-to-dry–weight ratio in the ALI model (p < 0.01). The total protein content and number of total cells, neutrophils, and macrophages increased in BALF of mice treated with LPS, but these increases were reversed by ECH treatment (p < 0.01). The levels of TNF-α and IL-1β increased in BALF and lung tissue of LPS-treated mice; however, ECH treatment decreased these changes (p < 0.01). In addition, ECH inhibited the activation of the nuclear factor-κB (NF-κB)/NLR family pyrin domain containing 3 (NLRP3) pathway in LPS-treated mice (p < 0.01).Conclusion: Echinacoside attenuates LPS-induced ALI via inactivation of the NF-κB/NLRP3 pathway, making echinacoside a potential drug for the treatment of ALI. Keywords: Echinacoside, Acute lung injury, Lipopolysaccharide, Nuclear factor-κB, NLR family pyrin domain containing 3

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NPC 15669 blocks neutrophil CD18 increase and lung injury during cardiopulmonary bypass in pigs

Mediators of Inflammation ◽

10.1155/s0962935193000201 ◽

1993 ◽

Vol 2 (2) ◽

pp. 135-141 ◽

Cited By ~ 5

Author(s):

J. M. Bator ◽

A. M. Gillinov ◽

K. J. Zehr ◽

J. M. Redmond ◽

I. C. Wilson ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Lung Injury ◽

Lung Tissue ◽

Tissue Damage ◽

Tissue Injury ◽

Neutrophil Infiltration ◽

Significant Inhibition ◽

Cellular Infiltration ◽

Lung Histology ◽

Wet Weight

During cardiopulmonary bypass (CPB), neutrophils become activated due to contact with extracorporeal surfaces and binding of complement fragments C3a and C5a, leading to extravasation and subsequent tissue damage. In this study, the effects of the leumedin NPC 15669 (N [9H - (2,7 dimethylfluorenyl - 9 - methoxy) car bonyl]-L-leucine), a leukocyte recruitment inhibitor, were evaluated in a pig model of CPB. NPC 15669 caused significant inhibition of CPB associated increase in CD18 upregulation, lung tissue myeloperoxidase content, and percentage wet weight compared to controls. Lung histology revealed clear airways and minimal neutrophil infiltration in treated animals vs. significant oedema and cellular infiltration in controls. It is concluded that CPB causes a dramatic increase in neutrophil CD18, and that leumedins are effective in inhibiting neutrophil activation and subsequent tissue injury when administered during CPB.

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Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

Mediators of Inflammation ◽

10.1155/2012/717851 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Talero Elena ◽

Di Paola Rosanna ◽

Mazzon Emanuela ◽

Emanuela Esposito ◽

Motilva Virginia ◽

...

Keyword(s):

Nitric Oxide ◽

Acute Lung Injury ◽

Lung Injury ◽

Lung Tissue ◽

Tissue Injury ◽

Inflammatory Factors ◽

Amino Acid Peptide ◽

Anti Inflammatory ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors.

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Effects of rapamycin and OSI-027 on α-SMA in lung tissue of SD rat pups with hyperoxic lung injury

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2021.02.061 ◽

2021 ◽

Vol 556 ◽

pp. 39-44

Author(s):

Mulin Liang ◽

Hongxing Dang ◽

Qinghe Li ◽

Weiben Huang ◽

Chengjun Liu

Keyword(s):

Lung Injury ◽

Lung Tissue ◽

Rat Pups ◽

Sd Rat ◽

Hyperoxic Lung Injury

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Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis

Respiratory Research ◽

10.1186/s12931-021-01793-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Xin-Yang Wang ◽

Xin-Yu Li ◽

Cheng-Hua Wu ◽

Yu Hao ◽

Pan-Han Fu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Cytokines ◽

Tissue Regeneration ◽

Umbilical Vein ◽

Endothelial Glycocalyx ◽

Lipid Mediator ◽

Protective Effects ◽

Pulmonary Vascular Permeability

Abstract Background Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits. Methods PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration. Results In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1. Conclusion PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.

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