Protective effect of anisodamine on bleomycin-induced acute lung injury in immature rats via modulating oxidative stress, inflammation, and cell apoptosis by inhibiting the JAK2/STAT3 pathway

Hydrostatin-SN1 (peptide sequence, DEQHLETELHTLTSVLTANGFQ), a kind of peptides extracted from snake venom, has been reported to have anti-inflammatory effect, but its truncated mutant hydrostatin-SN10 (peptide sequence, DEQHLETELH) on pancreatitis-induced acute lung injury has not been well documented. Interleukin- (IL-) 6-induced Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway is involved with inflammatory and oxidative stress activities and may be associated with the pathogenesis of lung injury, and related molecules were measured. Taurocholate-induced pancreatitis associated with acute lung injury was established and treated with hydrostatin-SN10. Pancreatitis was confirmed by measuring the serum levels of amylase, lipase, and trypsinogen and urinary amylase. Lung injury was determined by histologically assessing acinar cell changes. The related molecules of IL-6-induced JAK2/STAT3-associated inflammation and oxidative stress were quantitated by real time-PCR, Western blot, and/or immunochemical assay. Hydrostatin-SN10 reduced the levels of serum amylase, lipase, and trypsinogen and urinary amylase when compared with the model group (p<0.05). Hydrostatin-SN10 significantly inhibited the IL-6-stimulated JAK2/STAT3 pathway and reduced the number of apoptotic cells via the downregulation of caspase 3 and BAX (proapoptotic) and upregulation of Bcl2 (antiapoptotic) (p<0.05). IL-6 induced the increase in the levels of JAK2 and STAT3, which was reversed by hydrostatin-SN10 treatment (p<0.05). In addition, hydrostatin-SN10 reduced the expression of IL-6 and TNF- (tumor necrosis factor-) α and increased the level of IL-10 (p<0.05). On the other hand, hydrostatin-SN10 treatment increased the levels of superoxide dismutase (SOD) and reduced glutathione (GSH) and the levels of malondialdehyde (MDA) and alanine aminotransferase (ALT) (p<0.05). These results suggest that hydrostatin-SN10 may inhibit pancreatitis-induced acute lung injury by affecting IL-6-mediated JAK2/STAT3 pathway-associated inflammation and oxidative stress.

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Protective Effect of Corynoline in Sepsis-Induced Acute Lung Injury in Rats via Inhibition of NF-ĸB

Natural Product Communications ◽

10.1177/1934578x20961188 ◽

2020 ◽

Vol 15 (11) ◽

pp. 1934578X2096118

Author(s):

Min Shu ◽

Yulu Tang ◽

Jianzhen Liu

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Protective Effect ◽

Lung Tissue ◽

Significant Inhibition ◽

Tissue Homogenate ◽

Necrosis Factor Alpha ◽

Lung Tissue Homogenate ◽

And Migration

The present study was conducted to determine the effect of corynoline (COR) against sepsis-induced acute lung injury (ALI) in Wistar rats. Results of the study suggested that COR causes significant inhibition of lipid peroxidation (malondialdehyde) together with inhibition of oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and myeloperoxidase). The level of various proinflammatory (tumor necrosis factor-alpha, interleukin-8, and migration inhibitory factor) was also found to be reduced in COR-treated rats after sepsis. The protective effect of COR was further substantiated by the histopathology of lung tissue, where it improves the architecture of alveolar spaces. In western blot analysis, COR causes significant inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells activation in the lung tissue homogenate. Our results demonstrated that COR was able to prevent the progression of ALI in rats via inhibition of inflammation and oxidative stress.

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Protective effect of pterostilbene on sepsis-induced acute lung injury in a rat model via the JAK2/STAT3 pathway

Annals of Translational Medicine ◽

10.21037/atm-20-5814 ◽

2020 ◽

Vol 8 (21) ◽

pp. 1452-1452

Author(s):

Hua Xue ◽

Manxiang Li

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Protective Effect ◽

Rat Model ◽

Stat3 Pathway

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Antia, a Natural Antioxidant Product, Attenuates Cognitive Dysfunction in Streptozotocin-Induced Mouse Model of Sporadic Alzheimer’s Disease by Targeting the Amyloidogenic, Inflammatory, Autophagy, and Oxidative Stress Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4386562 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Nesrine S. El Sayed ◽

Mamdooh H. Ghoneum

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Diseases ◽

Protective Effect ◽

Cognitive Dysfunction ◽

Protective Role ◽

Sporadic Alzheimer’S Disease ◽

Stat3 Pathway ◽

And Oxidative Stress

Background. Many neurodegenerative diseases such as Alzheimer’s disease are associated with oxidative stress. Therefore, antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Objective. We investigated the ability of the antioxidant Antia to exert a protective effect against sporadic Alzheimer’s disease (SAD) induced in mice. Antia is a natural product that is extracted from the edible yamabushitake mushroom, the gotsukora and kothala himbutu plants, diosgenin (an extract from wild yam tubers), and amla (Indian gooseberry) after treatment with MRN-100. Methods. Single intracerebroventricular (ICV) injection of streptozotocin (STZ) (3 mg/kg) was used for induction of SAD in mice. Antia was injected intraperitoneally (i.p.) in 3 doses (25, 50, and 100 mg/kg/day) for 21 days. Neurobehavioral tests were conducted within 24 h after the last day of injection. Afterwards, mice were sacrificed and their hippocampi were rapidly excised, weighed, and homogenized to be used for measuring biochemical parameters. Results. Treatment with Antia significantly improved mice performance in the Morris water maze. In addition, biochemical analysis showed that Antia exerted a protective effect for several compounds, including GSH, MDA, NF-κB, IL-6, TNF-α, and amyloid β. Further studies with western blot showed the protective effect of Antia for the JAK2/STAT3 pathway. Conclusions. Antia exerts a significant protection against cognitive dysfunction induced by ICV-STZ injection. This effect is achieved through targeting of the amyloidogenic, inflammatory, and oxidative stress pathways. The JAK2/STAT3 pathway plays a protective role for neuroinflammatory and neurodegenerative diseases such as SAD.

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Protective effect of Astragaloside IV against sepsis-induced acute lung injury in rats

Saudi Pharmaceutical Journal ◽

10.1016/j.jsps.2016.04.014 ◽

2016 ◽

Vol 24 (3) ◽

pp. 341-347 ◽

Cited By ~ 10

Author(s):

Ruiqin Huang ◽

Min Li

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Protective Effect ◽

Astragaloside Iv

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In vitro and in vivo assessment of the protective effect of sufentanil in acute lung injury

Journal of International Medical Research ◽

10.1177/0300060520986351 ◽

2021 ◽

Vol 49 (2) ◽

pp. 030006052098635

Author(s):

Qi Gao ◽

Ningqing Chang ◽

Donglian Liu

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Protective Effect ◽

High Mobility ◽

Terminal Deoxynucleotidyl Transferase ◽

Inflammatory Factors ◽

Luciferase Reporter ◽

Hmgb1 Protein

Objectives To investigate the mechanisms underlying the protective effect of sufentanil against acute lung injury (ALI). Material and Methods Rats were administered lipopolysaccharide (LPS) by endotracheal instillation to establish a model of ALI. LPS was used to stimulate BEAS-2B cells. The targets and promoter activities of IκB were assessed using a luciferase reporter assay. Apoptosis of BEAS-2B cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Results Sufentanil treatment markedly reduced pathological changes in lung tissue, pulmonary edema and secretion of inflammatory factors associated with ALI in vivo and in vitro. In addition, sufentanil suppressed apoptosis induced by LPS and activated NF-κB both in vivo and in vitro. Furthermore, upregulation of high mobility group box protein 1 (HMGB1) protein levels and downregulation of miR-129-5p levels were observed in vivo and in vitro following sufentanil treatment. miR-129-5p targeted the 3ʹ untranslated region and its inhibition decreased promoter activities of IκB-α. miR-129-5p inhibition significantly weakened the protective effect of sufentanil on LPS-treated BEAS-2B cells. Conclusion Sufentanil regulated the miR-129-5p/HMGB1 axis to enhance IκB-α expression, suggesting that sufentanil represents a candidate drug for ALI protection and providing avenues for clinical treatment.

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Protective effect of combination of anakinra and MCC950 against acute lung injury is achieved through suppression of the NF-κB-mediated-MAPK and NLRP3-caspase pathways

International Immunopharmacology ◽

10.1016/j.intimp.2021.107506 ◽

2021 ◽

Vol 97 ◽

pp. 107506

Author(s):

Xiuhong Wang ◽

Shibiao Chen ◽

Lili Zhao ◽

Xiaoyun Shi

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Protective Effect

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Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01589-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qingsong Sun ◽

Man Luo ◽

Zhiwei Gao ◽

Xiang Han ◽

Weiqin Wu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Response ◽

Cell Apoptosis ◽

Quantitative Polymerase Chain Reaction ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Interacting Protein ◽

Wide Range

Abstract Background Acute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI. Methods We used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI. Result TLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis. Conclusion OIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.

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