scholarly journals A Novel Peptide Ameliorates LPS-Induced Intestinal Inflammation and Mucosal Barrier Damage via Its Antioxidant and Antiendotoxin Effects

2019 ◽  
Vol 20 (16) ◽  
pp. 3974 ◽  
Author(s):  
Lulu Zhang ◽  
Xubiao Wei ◽  
Rijun Zhang ◽  
Dayong Si ◽  
James N. Petitte ◽  
...  

Intestinal inflammation is an inflammatory disease resulting from immune dysregulation in the gut. It can increase the risk of enteric cancer, which is a common malignancy globally. As a new class of anti-inflammatory agents, native peptides have potential for use in the treatment of several intestinal inflammation conditions; however, their potential cytotoxicity and poor anti-inflammatory activity and stability have prevented their development. Hybridization has been proposed to overcome this problem. Thus, in this study, we designed a hybrid peptide (LL-37-TP5, LTP) by combing the active centre of LL-37 (13–36) with TP5. The half-life and cytotoxicity were tested in vitro, and the hybrid peptide showed a longer half-life and lower cytotoxicity than its parental peptides. We also detected the anti-inflammatory effects and mechanisms of LTP on Lipopolysaccharide (LPS)-induced intestinal inflammation in murine model. The results showed that LTP effectively prevented LPS-induced weight loss, impairment of intestinal tissues, leukocyte infiltration, and histological evidence of inflammation. Additionally, LTP decreased the levels of tumour necrosis factor-alpha, interferon-gamma, and interleukin-6; increased the expression of zonula occludens-1 and occludin; and reduced permeability in the jejunum of LPS-treated mice. Notably, LTP appeared to be more potent than the parental peptides LL-37 and TP5. The anti-inflammatory effects of LTP may be associated with the neutralization of LPS, inhibition of oxidative stress, and inhibition of the NF-κB signalling pathway. The findings of this study suggest that LTP might be an effective therapeutic agent for treating intestinal inflammation.

2003 ◽  
Vol 12 (6) ◽  
pp. 323-328 ◽  
Author(s):  
Shigeru Abe ◽  
Naho Maruyama ◽  
Kazumi Hayama ◽  
Hiroko Ishibashi ◽  
Shigeharu Inoue ◽  
...  

Background:In aromatherapy, essential oils are used as anti-inflammatory remedies, but experimental studies on their action mechanisms are very limited.Aims:To assess their anti-inflammatory activities, effects of essential oils on neutrophil activation were examinedin vitro.Methods:Neutrophil activation was measured by tumor necrosis factor-alpha (TNF-α)-induced adherence reaction of human peripheral neutrophils.Results:All essential oils tested at 0.1% concentration suppressed TNF-α-induced neutrophil adherence, and, in particular, lemongrass, geranium and spearmint oils clearly lowered the reaction even at 0.0125%. Similar inhibitory activities for the neutrophil adherence were obtained by their major constituent terpenoids: citral, geraniol, citronellol and carvone. In contrast, very popular essential oils, tea tree oil and lavender oil, did not display the inhibitory activity at the concentration.Conclusion:Thus, some essential oils used as anti-inflammatory remedies suppress neutrophil activation by TNF-α at a low concentration (0.0125-0.025%)in vitro.


2019 ◽  
Vol 156 (6) ◽  
pp. S-623
Author(s):  
Julia B. Krajewska ◽  
Jakub Wlodarczyk ◽  
Przemyslaw Taciak ◽  
Remigiusz Szczepaniak ◽  
Jakub Fichna

2007 ◽  
Vol 35 (02) ◽  
pp. 317-328 ◽  
Author(s):  
Jun Liu ◽  
Zheng-Tao Wang ◽  
Li-Li Ji

Neoandrographolide, one of the principal diterpene lactones, isolated from a medicinal herb Andrographis paniculata Nees, was tested in vivo and in vitro for its anti-inflammatory activities and mechanism. Oral administration of neoandrographolide (150 mg/kg) significantly suppressed ear edema induced by dimethyl benzene in mice. Oral administration of neoandrographolide (100–150 mg/kg) also reduced the increase in vascular permeability induced by acetic acid in mice. In vitro studies were performed using the macrophage cell line RAW264.7 to study the effect of neoandrographolide on suppressing phorbol-12-myristate-13-acetate (PMA)-stimulated respiratory bursts and lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). Respiratory bursts were quantified by chemiluminescence (CL) measurements.Results showed that neoandrographolide suppressed PMA-stimulated respiratory bursts dose-dependently from 30 μM to 150 μM. Neoandrographolide also inhibited NO and TNF-α production in LPS-induced macrophages, contributing to the anti-inflammatory activity of A. paniculata. These results indicate that neoandrographolide possesses significant anti-inflammatory effects, which implies that it would be one of the major contributing components to participate in the anti-inflammatory effect of A. paniculata. and a potential candidate for further clinical trial.


Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 986
Author(s):  
Soo-Yeon Cho ◽  
Heon-Woong Kim ◽  
Min-Ki Lee ◽  
Hyeon-Jung Kim ◽  
Jung-Bong Kim ◽  
...  

The chili pepper (Capsicum annuum L.) is a food source that is rich in flavonoids such as luteolin and apigenin. Flavonoids are known to have anti-inflammatory and antioxidant activities; however, studies on the flavonoids composition identified and the anti-inflammatory and antioxidant effects in pepper leaves (PL) and fruits (PF) are insufficient. In the present study, we investigated the antioxidant and anti-inflammatory effects in vitro, and the flavonoids contents of the PL and PF. Pepper extracts showed radical scavenging activities and ameliorated the lipopolysaccharide (LPS)-stimulated inflammatory response by decreasing nitric oxide production and interluekin-6 and tumor necrosis factor alpha levels in RAW 264.7 cells, with more effective activities noted for PL than for PF. Furthermore, PL extracts markedly inhibited the LPS-induced production of reactive oxygen species accumulation. The flavonoid profile and content of pepper were dependent on the part, with PL showing higher total flavonoids than PF. In particular, the content of luteolin glycosides in PL was twice that in PF. Thus, PL may be useful to prevent oxidative stress and inflammation-related diseases.


Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 56
Author(s):  
Emanuela Berrino ◽  
Simone Carradori ◽  
Andrea Angeli ◽  
Fabrizio Carta ◽  
Claudiu T. Supuran ◽  
...  

Low concentrations of carbon monoxide (CO) were reported to exhibit anti-inflammatory effects when administered in cells by suitable chemotypes such as CO releasing molecules (CO-RMs). In addition, the pH-modulating abilities of specific carbonic anhydrase isoforms played a crucial role in different models of inflammation and neuropathic pain. Herein, we report a series of chemical hybrids consisting of a Carbonic Anhydrase (CA) inhibitor linked to a CO-RM tail (CAI/CO-RMs). All compounds and their precursors were first tested in vitro for their inhibition activity against the human CA I, II, IX, and XII isoforms as well their CO releasing properties, aiming at corroborating the data by means of molecular modelling techniques. Then, their impact on metabolic activity modulation of RAW 264.7 mouse macrophages for 24 and 48 h was assessed with or without lipopolysaccharide (LPS) stimulation. The compounds were shown to counteract the inflammatory stimulus as also indicated by the reduced tumor necrosis factor alpha (TNF-α) release after treatment. All the biological results were compared to those of N-acetylcysteine (NAC) as a reference antioxidant compound. Within the series, two CAI/CO-RM hybrids (1 and 2), bearing both the well-known scaffold able to inhibit CAs (acesulfame) and the cobalt-based CO releasing portion, induced a higher anti-inflammatory effect up to 48 h at concentrations lower than NAC.


2009 ◽  
Vol 20 (20) ◽  
pp. 4412-4423 ◽  
Author(s):  
Arianne L. Theiss ◽  
Aaron K. Jenkins ◽  
Ngozi I. Okoro ◽  
Jan-Michael A. Klapproth ◽  
Didier Merlin ◽  
...  

Expression of prohibitin 1 (PHB), a multifunctional protein in the cell, is decreased during inflammatory bowel disease (IBD). Little is known regarding the regulation and role of PHB during intestinal inflammation. We examined the effect of tumor necrosis factor alpha (TNF-α), a cytokine that plays a central role in the pathogenesis of IBD, on PHB expression and the effect of sustained PHB expression on TNF-α activation of nuclear factor-kappa B (NF-κB) and epithelial barrier dysfunction, two hallmarks of intestinal inflammation. We show that TNF-α decreased PHB protein and mRNA abundance in intestinal epithelial cells in vitro and in colon mucosa in vivo. Sustained expression of prohibitin in intestinal epithelial cells in vitro and in vivo (prohibitin transgenic mice, PHB TG) resulted in a marked decrease in TNF-α–induced nuclear translocation of the NF-κB protein p65, NF-κB/DNA binding, and NF-κB–mediated transcriptional activation despite robust IκB-α phosphorylation and degradation and increased cytosolic p65. Cells overexpressing PHB were protected from TNF-α–induced increased epithelial permeability. Expression of importin α3, a protein involved in p50/p65 nuclear import, was decreased in cells overexpressing PHB and in colon mucosa of PHB TG mice. Restoration of importin α3 levels sustained NF-κB activation by TNF-α during PHB transfection. These results suggest that PHB inhibits NF-κB nuclear translocation via a novel mechanism involving alteration of importin α3 levels. TNF-α decreases PHB expression in intestinal epithelial cells and restoration of PHB expression in these cells can protect against the deleterious effects of TNF-α and NF-κB on barrier function.


Planta Medica ◽  
2017 ◽  
Vol 83 (09) ◽  
pp. 770-777 ◽  
Author(s):  
Franciane Marques ◽  
Maycow da Costa ◽  
Cátia Vittorazzi ◽  
Luciane Gramma ◽  
Thiago Barth ◽  
...  

Abstract Struthanthus vulgaris is probably the most common medicinal mistletoe plant in Brazil, and has been used in folk medicine as an anti-inflammatory agent and for cleaning skin wounds. Our proposal was to evaluate the anti-inflammatory activity of S. vulgaris ethanol leaf extract and provide further insights of how this biological action could be explained using in vitro and in vivo assays. In vitro anti-inflammatory activity was preliminarily investigated in lipopolysaccharide/interferon gamma-stimulated macrophages based on their ability to inhibit nitric oxide production and tumor necrosis factor-alpha. In vivo anti-inflammatory activity of S. vulgaris ethanol leaf extract was investigated in the mice carrageenan-induced inflammation air pouch model. The air pouches were inoculated with carrageenan and then treated with 50 and 100 mg/kg of S. vulgaris ethanol leaf extract or 1 mg/kg of dexamethasone. Effects on the immune cell infiltrates, pro- and anti-inflammatory mediators such as tumor necrosis factor-alpha, interleukin 1, interleukin 10, and nitric oxide, were evaluated. The chemical composition of S. vulgaris ethanol leaf extract was characterized by LC-MS/MS. In vitro S. vulgaris ethanol leaf extract significantly decreased the production of nitric oxide and tumor necrosis factor-alpha in macrophages and did not reveal any cytotoxicity. In vivo, S. vulgaris ethanol leaf extract significantly suppressed the influx of leukocytes, mainly neutrophils, protein exudation, nitric oxide, tumor necrosis factor-alpha, and interleukin 1 concentrations in the carrageenan-induced inflammation air pouch. In conclusion, S. vulgaris ethanol leaf extract exhibited prominent anti-inflammatory effects, thereby endorsing its usefulness as a medicinal therapy against inflammatory diseases, and suggesting that S. vulgaris ethanol leaf extract may be a source for the discovery of novel anti-inflammatory agents.


Author(s):  
Yuyuan Li ◽  
Man Liu ◽  
He Liu ◽  
Xue Sui ◽  
Yinhui Liu ◽  
...  

This study aimed at determining the beneficial effect of Clostridium butyricum (CB) RH2 on ceftriaxone-induced dysbacteriosis. To this purpose, BALB/c mice were exposed to ceftriaxone (400 mg/ml) or not (control) for 7 days, and administered a daily oral gavage of low-, and high-dose CB RH2 (108 and 1010 CFU/ml, respectively) for 2 weeks. CB RH2 altered the diversity of gut microbiota, changed the composition of gut microbiota in phylum and genus level, decreased the F/B ratio, and decreased the pro-inflammatory bacteria (Deferribacteres, Oscillibacter, Desulfovibrio, Mucispirillum and Parabacteroides) in ceftriaxone-treated mice. Additionally, CB RH2 improved colonic architecture and intestinal integrity by improving the mucous layer and the tight junction barrier. Furthermore, CB RH2 also mitigated intestinal inflammation through decreasing proinflammatory factors (TNF-α and COX-2) and increasing anti-inflammatory factors (IL-10). CB RH2 had direct effects on the expansion of CD4+ T cells in Peyer’s patches (PPs) in vitro, which in turn affected their immune response upon challenge with ceftriaxone. All these data suggested that CB RH2 possessed the ability to modulate the intestinal mucosal and systemic immune system in limiting intestinal alterations to relieve ceftriaxone-induced dysbacteriosis.


2021 ◽  
Vol 22 (14) ◽  
pp. 7482
Author(s):  
Hwan Lee ◽  
Zhiming Liu ◽  
Chi-Su Yoon ◽  
Linsha Dong ◽  
Wonmin Ko ◽  
...  

Aging is associated with immune disregulation and oxidative stress which lead to inflammation and neurodegenerative diseases. We have tried to identify the anti-neuroinflammatory and anti-inflammatory components of Coreopsis lanceolata L. The dried flowers of C. lanceolata were extracted with 70% EtOH, and the obtained extract was divided into CH2Cl2, EtOAc, n-BuOH, and H2O fractions. The CH2Cl2 fraction was separated using silica gel and C-18 column chromatography to yield phenylheptatriyne (1), 2′-hydroxy-3,4,4′-trimethoxychalcone (2), and 4′,7-dimethoxyflavanone (3). Additionally, the EtOAc fraction was subjected to silica gel, C-18, and Sephadex LH-20 column chromatography to yield 8-methoxybutin (4) and leptosidin (5). All the compounds isolated from C. lanceolata inhibited the production of nitric oxide (NO) in LPS-induced BV2 and RAW264.7 cells. In addition, phenylheptatriyne and 4′,7-dimethoxyflavanone reduced the secretion of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6. Among them, phenylheptatriyne was significantly downregulated in the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequently, phenylheptatriyne also effectively inhibited nuclear factor-kappa B (NF-κB) activation in LPS-stimulated BV2 and RAW264.7 cells. Based on these results, the anti-neuroinflammatory effect of phenylheptatriyne isolated from C. lanceolata was confirmed, which may exert a therapeutic effect in treatment of neuroinflammation-related diseases.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 956
Author(s):  
Yonelian Yuyun ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Wiwat Supasena ◽  
Piyapan Suwattananuruk ◽  
Kemika Praengam ◽  
...  

Curcumin (CUR) has been used as adjuvant therapy for therapeutic application in the treatment of psoriasis through several mechanisms of action. Due to the poor oral bioavailability of CUR, several approaches have been developed to overcome the limitations of CUR, including the prodrug strategy. In this study, CUR was esterified with mycophenolic acid (MPA) as a novel conjugate prodrug. The MPA-CUR conjugate was structurally elucidated using FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Bioavailable fractions (BFs) across Caco-2 cells of CUR, MPA, and MPA-CUR were collected for further biological activity evaluation representing an in vitro cellular transport model for oral administration. The antipsoriatic effect of the BFs was determined using antiproliferation and anti-inflammation assays against hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced human keratinocytes (HaCaT). The BF of MPA-CUR provided better antiproliferation than that of CUR (p < 0.001). The enhanced hyperproliferation suppression of the BF of MPA-CUR resulted from the reduction of several inflammatory cytokines, including IL-6, IL-8, and IL-1β. The molecular mechanisms of anti-inflammatory activity were mediated by an attenuated signaling cascade of MAPKs protein, i.e., p38, ERK, and JNK. Our results present evidence for the MPA-CUR conjugate as a promising therapeutic agent for treating psoriasis by antiproliferative and anti-inflammatory actions.


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