scholarly journals Alpha-1-Antitrypsin Ameliorates Pristane Induced Diffuse Alveolar Hemorrhage in Mice

2019 ◽  
Vol 8 (9) ◽  
pp. 1341
Author(s):  
Ahmed S. Elshikha ◽  
Georges Abboud ◽  
Lonneke van der Meijden-Erkelens ◽  
Yuanqing Lu ◽  
Mong-Jen Chen ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Regulatory Protein ◽  
Myeloid Cell ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Inflammatory Monocytes ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Alpha 1 Antitrypsin ◽  
First Time

Diffuse alveolar hemorrhage (DAH) is a fatal complication in patients with lupus. DAH can be induced in B6 mice by an intraperitoneal injection of pristane. Since human alpha-1-antitrypsin (hAAT) is an anti-inflammatory and immuno-regulatory protein, we investigated the protective effect of hAAT against pristane-induced DAH in B6 mice and hAAT transgenic (hAAT-Tg) mice. We first showed that hAAT Tg expression lowers TNF-α production in B cells, as well as CD4+ T cells in untreated mice. Conversely, the frequency of regulatory CD4+CD25+ and CD4+CD25-IL-10+ cells was significantly higher in hAAT-Tg than in B6 mice. This confirmed the anti-inflammatory effect of hAAT that was observed even at steady state. One week after a pristane injection, the frequency of peritoneal Ly6Chi inflammatory monocytes and neutrophils in hAAT-Tg mice was significantly lower than that in B6 mice. Importantly, pristane-induced DAH was completely prevented in hAAT-Tg mice and this was associated with a modulation of anti- to pro-inflammatory myeloid cell ratio/balance. We also showed that treatment with hAAT decreased the severity of DAH in B6 mice. These results showed for the first time that hAAT has a therapeutic potential for the treatment of DAH.

scholarly journals BAM15, a Mitochondrial Uncoupling Agent, Attenuates Inflammation in the LPS Injection Mouse Model: An Adjunctive Anti-Inflammation on Macrophages and Hepatocytes

2021 ◽  
pp. 1-17
Author(s):  
Cong Phi Dang ◽  
Jiraphorn Issara-Amphorn ◽  
Awirut Charoensappakit ◽  
Kanyarat Udompornpitak ◽  
Thansita Bhunyakarnjanarat ◽  
...  
Keyword(s):  
Atp Depletion ◽  
Organ Injury ◽  
Flux Analysis ◽  
Energy Status ◽  
Mitochondrial Uncoupling ◽  
Inflammatory Monocytes ◽  
Tnf Α ◽  
Cell Energy ◽  
Anti Inflammatory ◽  
Anti Inflammation

Controlof immune responses through the immunometabolism interference is interesting for sepsis treatment. Then, expression of immunometabolism-associated genes and BAM15, a mitochondrial uncoupling agent, was explored in a proinflammatory model using lipopolysaccharide (LPS) injection. Accordingly, the decreased expression of mitochondrial uncoupling proteins was demonstrated by transcriptomic analysis on metabolism-associated genes in macrophages (RAW246.7) and by polymerase chain reaction in LPS-stimulated RAW246.7 and hepatocytes (Hepa 1–6). Pretreatment with BAM15 at 24 h prior to LPS in macrophages attenuated supernatant inflammatory cytokines (IL-6, TNF-α, and IL-10), downregulated genes of proinflammatory M1 polarization (iNOS and IL-1β), upregulated anti-inflammatory M2 polarization (Arg1 and FIZZ), and decreased cell energy status (extracellular flux analysis and ATP production). Likewise, BAM15 decreased expression of proinflammatory genes (IL-6, TNF-α, IL-10, and iNOS) and reduced cell energy in hepatocytes. In LPS-administered mice, BAM15 attenuated serum cytokines, organ injury (liver enzymes and serum creatinine), and tissue cytokines (livers and kidneys), in part, through the enhanced phosphorylated αAMPK, a sensor of ATP depletion with anti-inflammatory property, in the liver, and reduced inflammatory monocytes/macrophages (Ly6C +ve, CD11b +ve) in the liver as detected by Western blot and flow cytometry, respectively. In conclusion, a proof of concept for inflammation attenuation of BAM15 through metabolic interference-induced anti-inflammation on macrophages and hepatocytes was demonstrated as a new strategy of anti-inflammation in sepsis.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

scholarly journals N-Acetylcysteine (NAC): Impacts on Human Health

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 967
Author(s):  
Micaely Cristina dos Santos Tenório ◽  
Nayara Gomes Graciliano ◽  
Fabiana Andréa Moura ◽  
Alane Cabral Menezes de Oliveira ◽  
Marília Oliveira Fonseca Goulart
Keyword(s):  
Human Health ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Primary Role ◽  
Necrosis Factor Alpha ◽  
Biochemical Basis ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

scholarly journals Protective effects of Panax notoginseng saponins in a rat model of severe acute pancreatitis occur through regulation of inflammatory pathway signaling by upregulation of miR-181b

2018 ◽  
Vol 32 ◽  
pp. 205873841881863
Author(s):  
Ming-wei Liu ◽  
Yun-qiao Huang ◽  
Ya-ping Qu ◽  
Dong-mei Wang ◽  
Deng-yun Tang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Rat Model ◽  
Therapeutic Potential ◽  
Sodium Taurocholate ◽  
Panax Notoginseng ◽  
Serum Levels ◽  
Panax Notoginseng Saponins ◽  
Tnf Α ◽  
Anti Inflammatory

Panax notoginseng saponins are extracted from Chinese ginseng— Panax notoginseng Ledeb—and are known to have therapeutic anti-inflammatory effects. However, the precise mechanism behind their anti-inflammatory effects remains relatively unknown. To better understand how Panax notoginseng saponins exert their therapeutic benefit, we tested them in a rat model of severe acute pancreatitis (SAP). Rats received a tail vein injection of Panax notoginseng saponins and were administered 5% sodium taurocholate 2 h later. Pancreatic tissue was then harvested and levels of miR-181b, FSTL1, TREM1, TLR4, TRAF6, IRAK1, p-Akt, p-p38MAPK, NF-κBp65, and p-IκB-α were determined using Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assays were used to determine serum levels of tumor necrosis factor-α (TNF-α), TREM1, interleukin (IL)-6, ACAM-1, IL-8, and IL-12 and DNA-bound levels of NF-KB65 and TLR4 in pancreatic and ileum tissue. Serum levels of lipase and amylase, pancreatic myeloperoxidase (MPO) activity, and pancreatic water content were also measured. Hematoxylin and eosin staining was used for all histological analyses. Results indicated upregulation of miR-181b, but negligible levels of FSTL1, p-p38MAPK, TLR4, TRAF6, p-Akt, IRAK1, TREM1, p-NF-κBp65, and p-IκB-α, as well as negligible DNA-bound levels of NF-KB65 and TLR4. We also observed lower levels of IL-8, IL-6, ACAM-1, TNF-α, MPO, and IL-12 in the Panax notoginseng saponin–treated group when compared with controls. In addition, Panax notoginseng saponin–treated rats had significantly reduced serum levels of lipase and amylase. Histological analyses confirmed that Panax notoginseng saponin treatment significantly reduced taurocholate-induced pancreatic inflammation. Collectively, our results suggest that Panax notoginseng saponin treatment attenuated acute pancreatitis and pancreatic inflammation by increasing miR-181b signaling. These findings suggest that Panax notoginseng saponins have therapeutic potential in the treatment of taurocholate-induced SAP.

scholarly journals Anti-Inflammatory Activity of N-docosahexaenoylethanolamine and N-eicosapentaenoylethanolamine in a Mouse Model of Lipopolysaccharide-Induced Neuroinflammation

2021 ◽  
Vol 22 (19) ◽  
pp. 10728
Author(s):  
Anna Tyrtyshnaia ◽  
Sophia Konovalova ◽  
Anatoly Bondar ◽  
Ekaterina Ermolenko ◽  
Ruslan Sultanov ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Long Term Potentiation ◽  
Inflammatory Activity ◽  
Treatment And Prevention ◽  
Term Potentiation ◽  
Urgent Task ◽  
Tnf Α ◽  
Microglia Polarization ◽  
Anti Inflammatory

The search for methods of cognitive impairment treatment and prevention in neurological and neurodegenerative diseases is an urgent task of modern neurobiology. It is now known that various diseases, accompanied by dementia, exhibit a pronounced neuroinflammation. Considering the significant docosahexaenoic and eicosapentaenoic polyunsaturated fatty acids’ therapeutic potential, we decided to investigate and compare anti-inflammatory activity of their N-acylethanolamine derivatives. As a result, we found that both N-docosahexaenoylethanolamine (synaptamide) and N-eicosapentaenoylethanolamine (EPEA) prevents an LPS-mediated increase in the proinflammatory cytokines TNF-α and IL-6 production in the SIM-A9 microglia culture. In an in vivo experiment, synaptamide reversed an increase in LPS-mediated hippocampal TNF-α and IL-1β, but EPEA did not. However, both compounds contributed to the microglia polarization towards the M2-phenotype. Synaptamide, rather than EPEA, inhibited the Iba-1-positive microglia staining area increase. However, both synaptamide and EPEA prevented the LPS-mediated astrogliosis. A study of BDNF immunoreactivity showed that synaptamide, but not EPEA, reversed an LPS-mediated decrease in BDNF production. Despite the more pronounced anti-inflammatory activity of synaptamide, both compounds were effective in maintaining a normal level of hippocampal long-term potentiation in neuroinflammation. The results indicate a high therapeutic potential for both compounds. However, some tests have shown higher activity of synaptamide compared to EPEA.

Terpenoids from Dicliptera chinensis (L.) Nees Grown in Vietnam and their Anti-inflammatory Activities

2018 ◽  
Vol 11 (2) ◽  
pp. 4052-4062
Author(s):  
Loi Vu Duc ◽  
Tung Bui Thanh ◽  
Tung Nguyen Huu
Keyword(s):  
Therapeutic Potential ◽  
Inhibitory Effects ◽  
Chromatographic Methods ◽  
Ic50 Values ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
First Time

The main goal of this study was to isolate and screen the therapeutic potential of some terpenoids from Dicliptera chinensis (L.) Nees grown in Vietnam. From the leaves of Dicliptera chinensis (L.) Nees (Acanthaceae) collected in Nam Dinh province, one new terpenoid (1) together with five known (2-6) were isolated by chromatographic methods. These compounds were identified as 6-hydroxy-1,12-oleanadien-3-on (1), 1β,4β-dihydroxyeudesm-11-ene (2), 3β-hydroxylup-20(29)-en (3), stigmast-5,22-dien-3-β-ol (4), rutaevine (5), mangiferin (6). All of them were isolated from this plant for the first time. Compound 4 showed signficant potential for COX-2 inhibitory effects with IC50 values of 7.32± 1.82 µg/mL. These pilot results suggest the potential of Dicliptera terpenoids for treating inflamatory conditions. 

scholarly journals Phenolic Compounds and Ginsenosides in Ginseng Shoots and Their Antioxidant and Anti-Inflammatory Capacities in LPS-Induced RAW264.7 Mouse Macrophages

2019 ◽  
Vol 20 (12) ◽  
pp. 2951 ◽  
Author(s):  
Fan Yao ◽  
Qiang Xue ◽  
Ke Li ◽  
Xinxin Cao ◽  
Liwei Sun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Phenolic Compounds ◽  
High Performance ◽  
Raw264.7 Cells ◽  
Inflammatory Factors ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
First Time

We conducted this study for the first time to evaluate changes in the composition and contents of phenolic compounds and ginsenosides in ginseng shoot extracts (GSEs) prepared with different steaming times (2, 4, and 6 h) at 120 °C, as well as their antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages (RAW264.7 cells). The results show that total phenol and flavonoid contents were both significantly higher in steamed versus raw GSEs, and the same trend was found for 2,2′-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) scavenging capacities. Among the 18 ginsenosides quantified using high-performance liquid chromatography (HPLC) with the aid of pure standards, polar ginsenosides were abundant in raw GSEs, whereas less-polar or rare ginsenosides appeared after steaming at 120 °C and increased with steaming time. Furthermore, steamed GSEs exhibited a greater ability to inhibit the production of inflammatory mediators and pro-inflammatory cytokines, such as nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in LPS-induced RAW264.7 cells at the same concentration. Relative expression levels of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, and cyclooxygenase-2 (COX-2) mRNAs were attenuated by the GSEs, probably due to the enrichment of less-polar ginsenosides and enhanced antioxidant activity in steamed GSEs. These findings, combined with correlation analysis, showed that less-polar ginsenosides were major contributors to the inhibition of the overproduction of various inflammatory factors, while the inhibitory effects of total phenols and total flavonoids, and their antioxidant abilities, are also important.

scholarly journals F. prausnitzii and its supernatant increase SCFAs-producing bacteria to restore gut dysbiosis in TNBS-induced colitis

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Youlian Zhou ◽  
Haoming Xu ◽  
Jing Xu ◽  
Xue Guo ◽  
Hailan Zhao ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Throughput Sequencing ◽  
Therapeutic Potential ◽  
Protective Effects ◽  
Trinitrobenzenesulfonic Acid ◽  
Gut Dysbiosis ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Gut Microbiota Dysbiosis

AbstractAn increasing number of studies have shown that Faecalibacterium prausnitzii (F. prausnitzii) is a promising anti-inflammatory bacterium that colonizes in the gut and that gut microbiota dysbiosis plays an important role in the pathogenesis of inflammatory bowel disease (IBD). In this study, we report the gut microbiota profile of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis mice treated with F. prausnitzii and its supernatant on the basis of high-throughput sequencing. We interestingly found that both F. prausnitzii and its metabolites exerted protective effects against colitis in mice, which ameliorated gut dysbiosis, with an increase in bacterial diversity and the abundance of short-chain fatty acid (SCFA)-producing bacteria and a decrease in serum TNF-α and the abundance of Proteinbacteria, Acidobacteria, and Bacteroidetes. These findings will provide further evidence of the anti-inflammatory effect of F. prausnitzii, which presents therapeutic potential for IBD treatment.

scholarly journals Chronic Sulfasalazine Treatment in Mice Induces System xc− - Independent Adverse Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Lise Verbruggen ◽  
Lindsay Sprimont ◽  
Eduard Bentea ◽  
Pauline Janssen ◽  
Azzedine Gharib ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Therapeutic Potential ◽  
Negative Impact ◽  
Chronic Administration ◽  
Systemic Circulation ◽  
The Body ◽  
Ample Evidence ◽  
Anti Inflammatory ◽  
First Time

Despite ample evidence for the therapeutic potential of inhibition of the cystine/glutamate antiporter system xc− in neurological disorders and in cancer, none of the proposed inhibitors is selective. In this context, a lot of research has been performed using the EMA- and FDA-approved drug sulfasalazine (SAS). Even though this molecule is already on the market for decades as an anti-inflammatory drug, serious side effects due to its use have been reported. Whereas for the treatment of the main indications, SAS needs to be cleaved in the intestine into the anti-inflammatory compound mesalazine, it needs to reach the systemic circulation in its intact form to allow inhibition of system xc−. The higher plasma levels of intact SAS (or its metabolites) might induce adverse effects, independent of its action on system xc−. Some of these effects have however been attributed to system xc− inhibition, calling into question the safety of targeting system xc−. In this study we chronically treated system xc− - deficient mice and their wildtype littermates with two different doses of SAS (160 mg/kg twice daily or 320 mg/kg once daily, i.p.) and studied some of the adverse effects that were previously reported. SAS had a negative impact on the survival rate, the body weight, the thermoregulation and/or stress reaction of mice of both genotypes, and thus independent of its inhibitory action on system xc−. While SAS decreased the total distance travelled in the open-field test the first time the mice encountered the test, it did not influence this parameter on the long-term and it did not induce other behavioral changes such as anxiety- or depressive-like behavior. Finally, no major histological abnormalities were observed in the spinal cord. To conclude, we were unable to identify any undesirable system xc−-dependent effect of chronic administration of SAS.

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