scholarly journals Curcumin alone and in combination with augmentin protects against pulmonaryinflammation and acute lung injury generated during Klebsiella pneumoniae B5055-induced lung infection in BALB/c mice

2010 ◽  
Vol 59 (4) ◽  
pp. 429-437 ◽  
Author(s):  
Shruti Bansal ◽  
Sanjay Chhibber

Acute lung injuries due to acute lung infections remain a major cause ofmortality. Thus a combination of an antibiotic and a compound with immunomodulatoryand anti-inflammatory activities can help to overcome acute lung infection-inducedinjuries. Curcumin derived from the rhizome of turmeric has been used fordecades and it exhibits anti-inflammatory, anti-carcinogenic, immunomodulatoryproperties by downregulation of various inflammatory mediators. Keeping theseproperties in mind, we investigated the anti-inflammatory properties of curcuminin a mouse model of acute inflammation by introducing Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal instillationof bacteria in this mouse model of acute pneumonia-induced inflammation resultedin a significant increase in neutrophil infiltration in the lungs along withincreased production of various inflammatory mediators [i.e. malondialdehyde (MDA),myeloperoxidase (MPO), nitric oxide (NO), tumour necrosisfactor (TNF)-α] in the lung tissue. The animalsthat received curcumin alone orally or in combination with augmentin, 15 daysprior to bacterial instillation into the lungs via the intranasal route, showeda significant (P <0.05) decrease in neutrophil influxinto the lungs and a significant (P <0.05) decreasein the production of MDA, NO, MPO activity and TNF-α levels.Augmentin treatment alone did not decrease the MDA, MPO, NO and TNF-α levels significantly (P >0.05) as compared tothe control group. We therefore conclude that curcumin ameliorates lung inflammationinduced by K. pneumoniae B5055 without significantly (P <0.05) decreasing the bacterial load in the lung tissue whereasaugmentin takes care of bacterial proliferation. Hence, curcumin can be usedas an adjunct therapy along with antibiotics as an anti-inflammatory or animmunomodulatory agent in the case of acute lung infection.

2014 ◽  
Vol 8 (07) ◽  
pp. 838-844 ◽  
Author(s):  
Shruti Bansal ◽  
Sanjay Chhibber

Introduction: Curcumin, a polyphenol derived from the herb Curcuma longa, has number of antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Its anti-inflammatory property was here studied alone and in combination with clarithromycin in a mouse model of acute inflammation. Methodology: A total of 80 mice divided into four groups were used. Mice receiving curcumin and/or clarithromycin were fed orally with curcumin (150 mg/kg/day) for 15 days prior to infection, whereas clarithromycin was administered orally (30 mg/kg/day) 12 hours post infection. Simultaneously, the control group receiving only infection but no treatment was also set up. Bacterial load estimation, histopathological examination and analysis of inflammatory parameters was performed on various days for all groups. Results: Intranasal inoculation of bacteria resulted in significant increase in neutrophil infiltration along with increased production of various inflammatory mediators (malondialdehyde, myeloperoxidase, nitric oxide, TNFα) in lung tissue. Clarithromycin treatment significantly decreased the bacterial load and other inflammatory components in infected mice, but animals receiving curcumin alone or in combination with clarithromycin showed a much more significant (p < 0.05) reduction in neutrophil influx along with reduced levels of various inflammatory parameters. Though treatment with curcumin did not reduce the bacterial load, in combination with clarithromycin, both bacterial proliferation and lung tissue damage were checked. Conclusions: Though clarithromycin, because of its associated side effects, may not be the preferred treatment, it can be used in conjunction with curcumin. The latter as an adjunct therapy will help to down regulate the exaggerated state of immune response during acute lung infection.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Qian Yu ◽  
YaJie Shi ◽  
Chang Shu ◽  
XuChun Ding ◽  
ShiPing Zhu ◽  
...  

Asthma has long been considered a disease of airway inflammation. The excessive or prolonged production of inflammatory mediators can result in airway remodeling and severe clinical syndromes such as dyspnea or even apnea. Therefore, pharmaceutical intervention is required to restrain the excessive release of such inflammatory mediators in control of asthma. Novel therapeutics and mechanistic insight are sought for the management of this chronic inflammatory disease. Andrographolide (AG) is a type of diterpenoid ester compound and is reported to demonstrate multiple properties such as antioxidation and anti-inflammation. However, the anti-inflammatory capacity of AG by regulating immunologic function in airway of asthma has not been fully studied to date. Therefore, this study investigates whether AG is capable of suppressing the inflammatory response of asthma in OVA-stimulated mice and the mechanism by which this is achieved. Animals were randomly divided into 4 groups: control group, OVA model group, OVA + AG (0.1 mg/ml) group, and OVA + dimethylsulfoxide (DMSO) group. The serum, BALF, and lung tissue of the mice were collected separately for the administration of ELISA, rt-PCR, western blot and pathological section and staining. We found that AG attenuated the OVA-induced production of IL-6, IL-17A, IL-17F, and RORγt; inhibited the OVA-mediated phosphorylation of JAK 1 and STAT3; and alleviated airway remodeling and the neutrophil infiltration of lung tissue. We conclude that AG inhibits the inflammatory response of asthma in OVA-stimulated mice by blocking the activation of Th17-regulated cytokines and the JAK1/STAT3 signaling pathway.


Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Soyon Yoon ◽  
Seokcheon Song ◽  
Jae Woo Shin ◽  
Sini Kang ◽  
Hye Young Kim ◽  
...  

The increasing prevalence of allergic asthma has become the world’s major health issue. Current treatments for allergic asthma focus on treating symptoms, while permanent cures still remain undiscovered. In this study, we investigated the effect of Korean traditional herbal remedy, Pyunkang-tang (PGT)—composed of six plants—on asthma alleviation in a mouse model. The PGT mixture was orally gavaged to mice (PM group, 20 mg/mouse/day) from 7 days before sensitization with ovalbumin (OVA) (day −7). On day 0 and day 14, mice from OVA-control (n = 9) and PM group (n = 8) were sensitized with OVA and alum through intraperitoneal injection. On days 18~20, OVA was challenged to mice through nasal injection and sacrificed next day. Cell profile in lung tissue was analyzed by flow cytometry and RT-qPCR analysis, and the number of eosinophils and expression of siglec-F were significantly reduced in the PM group. Lung tissue was examined with hematoxylin and eosin (H&E) and Alcian blue/periodic acid–Schiff (AB-PAS) staining. Noticeably reduced eosinophil infiltration around bronchioles was displayed in the PM group compared to the OVA-control group. Furthermore, PGT-treated mice showed a significant reduction in IL-13 and a mild reduction in IL-5 in lungs. A decreasing tendency of IL-5/13 (+) CD4+ T cells and IL-13(+) innate lymphoid cells (ILCs) and a significant reduction in IL5(+) ILCs were also observed. When treating PGT on murine lung epithelial cells stimulated by papain, there was a significant reduction in IL-33 mRNA expression levels. Taken together, oral delivery of PGT successfully alleviated asthmatic responses provoked by OVA in a mouse model and could lead to novel therapies for allergic asthma.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marina Petrella ◽  
Ivan Aprahamian ◽  
Ronei Luciano Mamoni ◽  
Carla Fernanda de Vasconcellos Romanini ◽  
Natália Almeida Lima ◽  
...  

Abstract Background To investigate whether an exercise intervention using the VIVIFRAIL© protocol has benefits for inflammatory and functional parameters in different frailty status. Methods/design This is a randomized clinical trial in an outpatient geriatrics clinic including older adults ≥60 years. For each frailty state (frail, pre-frail and robust), forty-four volunteers will be randomly allocated to the control group (n = 22) and the intervention group (n = 22) for 12 weeks. In the control group, participants will have meetings of health education while those in the intervention group will be part of a multicomponent exercise program (VIVIFRAIL©) performed five times a week (two times supervised and 3 times of home-based exercises). The primary outcome is a change in the inflammatory profile (a reduction in inflammatory interleukins [IL-6, TNF- α, IL1beta, IL-17, IL-22, CXCL-8, and IL-27] or an increase in anti-inflammatory mediators [IL-10, IL1RA, IL-4]). Secondary outcomes are change in physical performance using the Short Physical Performance Battery, handgrip strength, fatigue, gait speed, dual-task gait speed, depressive symptoms, FRAIL-BR and SARC-F scores, and quality of life at the 12-week period of intervention and after 3 months of follow-up. Discussion We expect a reduction in inflammatory interleukins or an increase in anti-inflammatory mediators in those who performed the VIVIFRAIL© protocol. The results of the study will imply in a better knowledge about the effect of a low-cost intervention that could be easily replicated in outpatient care for the prevention and treatment of frailty, especially regarding the inflammatory and anti-inflammatory pathways involved in its pathophysiology. Trial registration Brazilian Registry of Clinical Trials (RBR-9n5jbw; 01/24/2020). Registred January 2020. http://www.ensaiosclinicos.gov.br/rg/RBR-9n5jbw/.


2017 ◽  
Vol 67 (1) ◽  
pp. 125-135 ◽  
Author(s):  
Nouf M. Al-Rasheed ◽  
Laila Fadda ◽  
Hala A. Attia ◽  
Iman A. Sharaf ◽  
Azza M. Mohamed ◽  
...  

AbstractThe study aims to compare, through histological and biochemical studies, the effects of quercetin, melatonin and their combination in regulation of immuno-inflammatory mediators and heat shock protein expressions in sodium nitrite induced hypoxia in rat lungs. The results revealed that NaNO2injection caused a significant decrease in Hb in rats, while serum levels of TNF-α, IL-6 and CRP, VEGF and HSP70 were elevated compared to the control group. Administration of melatonin, quercetin or their combination before NaNO2injection markedly reduced these parameters. Histopathological examination of the lung tissue supported these biochemical findings. The study suggests that melatonin and/or quercetin are responsible for lung tissue protection in hypoxia by downregulation of immuno-inflammatory mediators and heat shock protein expressions. Pre-treatment of hypoxic animals with a combination of melatonin and quercetin was effective in modulating most of the studied parameters to near-normal levels.


2019 ◽  
Vol 47 (6) ◽  
pp. 2655-2665
Author(s):  
Jianfeng Xu ◽  
Wei Li ◽  
Shufen Xu ◽  
Weiyang Gao ◽  
Zhenyu Yu

Objective To test the antifibrotic effect of dermatan sulphate in a bleomycin-induced mouse model of pulmonary fibrosis. Methods C57 mice were randomly divided into four experimental groups: saline-treated control group, bleomycin-induced fibrosis group, prednisolone acetate group and dermatan sulphate group. Lungs were assessed using the lung index, and the extent of interstitial fibrosis was graded using histopathological observation of haematoxylin & eosin-stained lung tissue. Lung tissue hydroxyproline levels and blood fibrinogen levels were measured using a hydroxyproline colorimetric kit and the Clauss fibrinogen assay, respectively. Tissue-type plasminogen activator (tPA) was measured using a chromogenic tPA assay kit. Results Lung index values were significantly lower in the dermatan sulphate group versus the fibrosis group. Histopathological analyses revealed that dermatan sulphate treatment ameliorated the increased inflammatory cell infiltration, and attenuated the reduction in interstitial thickening, associated with bleomycin-induced fibrosis. Hydroxyproline and fibrinogen levels were decreased in the dermatan sulphate group versus the fibrosis model group. Dermatan sulphate treatment was associated with increased tPA levels versus controls and the fibrosis group. Conclusions Damage associated with bleomycin-induced pulmonary fibrosis was alleviated by dermatan sulphate.


2020 ◽  
Vol 48 (10) ◽  
pp. 030006052095647
Author(s):  
Xing Hu ◽  
Yun Cai ◽  
Yuhang Wang ◽  
Rui Wang ◽  
Jin Wang ◽  
...  

Objective To establish a mouse model of bioluminescent Klebsiella pneumoniae-induced lung infection, under different infection states after pretreatment with various dosages of cyclophosphamide (CTX). Methods A K. pneumoniae strain carrying the luxCDABE operon was used to infect immunocompetent mice (intraperitoneal injection of saline at 4 days and 1 day prior to experimental lung infection) and immunodeficient mice (50 mg/kg CTX at 4 days and 50 mg/kg CTX at 1 day prior to lung infection; or 150 mg/kg CTX at 4 days and 100 mg/kg CTX at 1 day prior to lung infection). Disease progression was monitored in living mice using a bioluminescence imaging system. The bioluminescent images, bacterial loads in lungs, blood cytological changes and histopathology of lungs were analysed. Results K. pneumoniae-induced lung infection models were established in mice pretreated with CTX. Different doses of CTX led to different severities of lung infection. Mice pretreated with 150/100 mg/kg CTX were more suitable for real-time monitoring as they had more typical bioluminescent images of lung infection, more obvious changes in the bioluminescent intensity values, more bacterial colonies in the lungs and more distinct pulmonary pathological changes. Conclusions A stable bioluminescent K. pneumonia-induced lung infection model was successfully established in mice pretreated with CTX, which can be semi-quantitatively monitored in real-time.


Author(s):  
Lu-lu Li ◽  
Ying-gang Zhu ◽  
Xin-ming Jia ◽  
Dong Liu ◽  
Jie-ming Qu

BackgroundPseudomonas aeruginosa (PA) is one of the most common Gram-negative bacteria causing hospital-acquired pulmonary infection, with high drug resistance and mortality. Therefore, it is urgent to introduce new non-antibiotic treatment strategies. Mesenchymal stem cells (MSCs), as important members of the stem cell family, were demonstrated to alleviate pathological damage in acute lung injury. However, the potential mechanism how MSC alleviate acute lung infection caused by PA remains unclear.ObjectiveThe purpose of this study was to investigate the effects of Adipose-derived mesenchymal stem cells (ASCs) on acute pulmonary infections and the possible mechanisms how ASCs reduce pulmonary inflammation induced by PA.MethodsThe therapeutic and mechanistic effects of ASCs on PA pulmonary infection were evaluated respectively in a murine model as well as in an in vitro model stimulated by PA and co-cultured with ASCs.Results1. ASCs treatment significantly reduced the bacterial load, inflammation of lung tissue and histopathological damage by PA. 2. PA infection mainly activated Nod-like receptor containing a caspase activating and recruitment domain 4 (NLRC4) inflammasome in the lung of mice. ASCs attenuated acute lung infection in mice by inhibiting NLRC4 inflammasome activation. 3. NLRC4−/− mice showed a significant improvement in survival rate and lung bacterial load after PA infection. 4. ASCs mainly increased expression and secretion of STC‐1 in response to PA‐stimulated NLRC4 inflammasome activation.ConclusionsPA infection attenuated macrophage phagocytosis through activation of NLRC4 inflammasome in macrophages, which eventually led to pulmonary inflammatory damage in mouse; ASCs reduced the activation of NLRC4 inflammasome in macrophages induced by PA infection, thereby increasing the phagocytic ability of macrophages, and ultimately improving lung tissue damage in mouse; ASCs may inhibit NLRC4 inflammasome through the secretion of STC-1.


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