scholarly journals Oral, but not rectal delivery of epigallocatechin-3-gallate alleviates colitis by regulating the gut microbiota, oxidative stress, inflammation, and barrier integrity

2020 ◽  
Author(s):  
Zhenhua Wu ◽  
Shimeng Huang ◽  
Tiantian Li ◽  
Na Li ◽  
Dandan Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Gut Microbiota ◽  
Barrier Function ◽  
Cell Number ◽  
Therapeutic Effects ◽  
Strong Positive Correlation ◽  
Rectal Delivery ◽  
Anti Inflammatory ◽  
Butyrate Production

Abstract Background: Alteration of the gut microbiota may contribute to the development of inflammatory bowel diseases (IBDs). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBDs alleviation. However, it is unclear whether EGCG attenuates IBDs through direct improvement of gastrointestinal function or indirect alteration of the structure and function of the gut microbiota.Results: We first investigated the therapeutic effects of EGCG on disease severity, oxidative stress, inflammation, barrier function, and gut microbiota in murine colitis model, and further demonstrate it via EGCG pre-supplementation. We revealed that, oral, but not rectal, delivery of EGCG alleviated the severity of colitis through attenuation of anti-oxidative and anti-inflammatory response. Mucin-secreting goblet cell number, barrier function gene expression levels, and the integrity of tight junctions in the colon were also enhanced by oral EGCG. Additionally, we observed distinct EGCG-mediated alternation in the gut microbiome, as highlighted by increased Akkermansia abundance and butyrate production. Furthermore, we revealed that prophylactic oral application of EGCG for 21 days prior to the onset of dextran sodium sulfate (DSS)-induced colitis also ameliorated colonic damage, oxidative stress, and inflammatory response. Prophylactic EGCG significantly enriched Akkermansia, Faecalibaculum, and Bifidobacterium and enhanced acetate, propionate and butyrate production in DSS-treated mice. Moreover, scores of differential microbes, in particular Akkermansia, showed a strong positive correlation with short-chain fatty acids (SCFAs) and antioxidant enzyme levels in both the plasma and colon, but a negative association with inflammatory cytokines and malondialdehyde.Conclusions: EGCG is capable of treating DSS-induced colitis both therapeutically and prophylactically by inducing a pronounced anti-oxidative and anti-inflammatory response. Attenuation of colitis by oral, but not rectal administration of, EGCG suggests an intimate involvement of the gut microbiota. Increased Akkermansia and subsequent protective SCFAs production may be largely responsible for the anti-inflammatory and anti-oxidative function of EGCG, leading to restoration of intestinal epithelial homeostasis of the host. These findings provide novel insights into EGCG-mediated remission of IBDs and the rationale for devising more effective therapeutic strategies for IBDs.

Abstract 16009: Y RNA Fragments Enriched in Exosomes From Cardiosphere-derived Cells Mediate Cardioprotection and Macrophage Polarization

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Linda Cambier ◽  
Geoffrey de Couto ◽  
Ahmed Ibrahim ◽  
Eduardo Marbán
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Noncoding Rna ◽  
Neonatal Rat ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Data Set ◽  
Rna Content ◽  
Rna Fragments ◽  
Anti Inflammatory

Background: Exosomes secreted by cardiosphere-derived cells (CDCs) are critical agents of regeneration and cardioprotection following ischemic injury, mediating the beneficial therapeutic effects of CDCs. Transfer of exosomal RNA to target cells is important for bioactivity. Objective: We sought to determine the RNA content of CDCs-secreted exosomes (CDC-exo), and to assess the contributions of selected small non-coding RNAs to the therapeutic efficacy of CDC-exo. Methods: Using next-generation sequencing (Illumina), we characterized the RNA content of CDC-exo. By direct transfection of fluorescently-labelled oligoribonucleotides, we delivered and tracked selected RNA fragments that are highly enriched in CDC-exo. In order to examine potential cytoprotective effects, neonatal rat ventricular myocytes (NRVMs) were pretreated with each of these fragments or a scrambled control fragment prior to H2O2-induced oxidative stress. Effects on gene expression were assessed by transfection of the fragments into bone marrow-derived macrophages. Results: Several noncoding RNA species were present in CDC-exo. Among these, Y RNAs (either whole or in fragments of the 5’ end) constituted 18% of all hits. From this data set, we selected two highly-enriched Y RNA fragments. Both fragments localized to the cytoplasm of CDC, NRVM and macrophages, and conferred augmented resistance to oxidative stress of NRVM (64.25±31.13% viability vs. 44±26.85%; p=0.06). Additionally, macrophages transfected with Y fragments exhibit rapid, robust polarization to a distinctive gene expression profile notable for upregulation of IL-10 (83.07 vs. 0.59 fold; p<0.0001), an anti-inflammatory cytokine. Conclusions: Here, we demonstrated that abundant noncoding RNA components of CDC-exo, Y RNA fragments, are bioactive components of CDC-exo. Two distinct fragments confer cardioprotection and also induce a strong anti-inflammatory response in macrophages. Although several components of the CDC-exo payload (including miRNA) contribute to functional efficacy, the present findings demonstrate the capacity of Y RNA fragments, an RNA species of previously-unknown function, to elicit therapeutic effects in vitro.

scholarly journals Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Dextran Sodium Sulfate-Induced Ulcerative Colitis

2021 ◽  
Author(s):  
Desheng Hu ◽  
Mingyue Li ◽  
Weina Guo ◽  
Yalan Dong ◽  
Wenzhu Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Protective Effect ◽  
Intestinal Permeability ◽  
Chronic Inflammatory Bowel Disease ◽  
Protective Mechanism ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Colonic Inflammation ◽  
Anti Inflammatory

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by multi-factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that Celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and the mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR preforms the protective effect. We characterized the therapeutic effects and the potential mechanism of CSR in treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation approaches. CSR administration significantly ameliorated DSS-induced colitis, as evidenced by the recovery of body weight and colon length, decreased disease activity index (DAI) score, as well as decreased intestinal permeability. CSR down-regulated the secretion of proinflammatory cytokines, upregulated the anti-inflammatory mediators, and improved the balances of Treg/Th1 and Treg/Th17 to maintain colonic immune homeostasis. However, the protective effects of CSR disappeared when the antibiotic cocktail was applied to deplete the gut microbiota, and the gut microbiota-mediated effect was confirmed by FMT. Furthermore, CSR treatment increased the gut microbiota diversity and composition, and raised the metabolic productions of pyruvate and adenosine, which probably involve in gut microbiota mediated protective effect. In conclusion, CSR ameliorates colonic inflammation in a gut microbiota-dependent manner. The underlying protective mechanism is associated with the rectified Treg/Th1 and Treg/Th17 balance, and increased pyruvate and adenosine production. The study provided the solid evidence that CSR might be a promising therapeutic drug for UC.

scholarly journals Integrative Analysis of Gut Microbiota and Fecal Metabolites in Rats after Prednisone Treatment

2021 ◽  
Author(s):  
Jing Zhang ◽  
Dan Feng ◽  
Helen Ka-Wai Law ◽  
Ying Wu ◽  
Guang-hua Zhu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Rheumatic Diseases ◽  
Integrative Analysis ◽  
Therapeutic Effects ◽  
Glomerular Diseases ◽  
Immunological Disorders ◽  
Prednisone Treatment ◽  
Anti Inflammatory ◽  
Synthetic Glucocorticoid

Prednisone is widely used in chronic glomerular diseases, immunological disorders, and rheumatic diseases for its anti-inflammatory and immunosuppressive properties. It is a synthetic glucocorticoid (GC) that shows therapeutic effects after conversion to prednisolone by the liver.

scholarly journals IPSE, a urogenital parasite-derived immunomodulatory protein, ameliorates ifosfamide-induced hemorrhagic cystitis through downregulation of pro-inflammatory pathways

2018 ◽  
Author(s):  
Evaristus C. Mbanefo ◽  
Loc Le ◽  
Rebecca Zee ◽  
Nirad Banskota ◽  
Kenji Ishida ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Cellular Proliferation ◽  
Transcriptional Profiling ◽  
Hemorrhagic Cystitis ◽  
Underlying Mechanism ◽  
Protective Mechanism ◽  
Therapeutic Effects ◽  
Anti Inflammatory ◽  
Oxidative Stress Responses

AbstractIfosfamide and other oxazaphosphorines can result in hemorrhagic cystitis, a constellation of complications caused by acrolein metabolites. We previously showed that a single dose of IPSE, a schistosome-derived host modulatory protein, can ameliorate ifosfamide-related cystitis; however, the exact mechanisms underlying this urotoxic effect and its prevention are not fully understood. To provide insights into IPSE’s protective mechanism, we undertook transcriptional profiling of bladders from ifosfamide-treated mice, with or without IPSE pretreatment. Following ifosfamide challenge, there was upregulation of a range of pro-inflammatory genes. The pro-inflammatory pathway involving the IL-1β, TNFαand IL-6 triad via NFκB and STAT3 signaling pathways was identified as the key driver of inflammation. The NRF2-mediated oxidative stress response pathway, which regulates bothHmox1-mediated heme homoeostasis and expression of antioxidant enzymes, was highly activated. Anti-inflammatory and cellular proliferation cascades implicated in tissue repair, namely Wnt, Hedgehog and PPAR pathways, were downregulated. IPSE administration before ifosfamide injection resulted in significant downregulation of major proinflammatory pathways including the triad of IL-1β, TNFαand IL-6 pathways, the interferon signaling pathway, and less apparent reduction in oxidative stress responses. Taken together, we have identified signatures of acute phase inflammation and oxidative stress responses in the ifosfamide-injured bladder, which are reversed by pretreatment with IPSE, a parasite derived anti-inflammatory molecule. In addition to providing new insights into the underlying mechanism of IPSE’s therapeutic effects, this work has revealed several pathways that could be therapeutically targeted to prevent and treat ifosfamide-induced hemorrhagic cystitis.

scholarly journals CYP2J2 and EETs Protect Against Pulmonary Hypertension with Lung Ischemia-Reperfusion Injury In Vivo and In Vitro

2021 ◽  
Author(s):  
Yun Ding ◽  
Pengjie Tu ◽  
Yiyong Chen ◽  
Yangyun Huang ◽  
Xiaojie Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Lung Tissue ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert anti-inflammatory, anti-apoptotic, pro-proliferative, and antioxidant effects on the cardiovascular system. However, the role of CYP2J2 and EETs in pulmonary arterial hypertension (PAH) with lung ischemia-reperfusion injury (LIRI) remains unclear. In the present study, we investigated the effects of CYP2J2 overexpression and exogenous EETs on PAH with LIRI in vitro and in vivo.Methods CYP2J2 gene was transfected into rat lung tissue by recombinant adeno-associated virus (rAAV) to increase the levels of EETs in serum and lung tissue. A rat model of PAH with LIRI was constructed by tail vein injection of monocrotaline (50 mg/kg) for 4 weeks, followed by clamping of the left pulmonary hilum for 1 h and reperfusion for 2 h. In addition, we established a cellular model of human pulmonary artery endothelial cells (HPAECs) with TNF-α combined with hypoxic reoxygenation (anoxia for 8 h and reoxygenation for 16 h) to determine the effect and mechanism of exogenous EETs.Results CYP2J2 overexpression significantly reduced the inflammatory response, oxidative stress and apoptosis associated with lung injury in PAH with LIRI. In addition, exogenous EETs suppressed inflammatory response and reduced intracellular reactive oxygen species (ROS) production and inhibited apoptosis in a tumor necrosis factor alpha (TNF-α) combined hypoxia-reoxygenation model of HPAECs. Our further studies revealed that the anti-inflammatory effects of CYP2J2 overexpression and EETs might be mediated by PPARγ pathway; the anti-apoptotic effects might be mediated by the PI3K/Ak pathway.Conclusions CYP2J2 overexpression and EETs protect against PAH with LIRI via anti-inflammation, anti-oxidative stress and anti-apoptosis, suggesting that increased levels of EETs may be a promising strategy for the prevention and treatment of PAH with LIRI.

Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

2020 ◽  
Author(s):  
Ni Dai ◽  
Chenglin Tang ◽  
Hongdi Zhao ◽  
Pan Dai ◽  
Siqin Huang
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Neuroprotective Effect ◽  
Related Factor ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Abstract Background: Spinal cord injury (SCI) is a catastrophic central nervous system disease. Inflammatory response and oxidative stress are two critical factors in the pathophysiological process of SCI and closely involved with Apolipoprotein E(ApoE) and Nuclear factor erythroid 2-related factor (Nrf2). Electroacupuncture (EA) has perfectly neuroprotective effect on SCI. However, the underlying mechanism by which EA mediates the inflammatory response and oxidative stress is not completely elucidated. In the present study, we investigated the signaling pathways that EA regulates inflammatory response and oxidative stress through elevation of ApoE and Nrf2 after SCI.Methods: C57BL/6 Wide Type (WT) mice and ApoE -/- mice were subjected to SCI model by a serrefine clamping. Neurological function was detected by BMS scores, ultrastructure of demyelinationed axons was observed by transmission electron microscopy. ApoE, pro- and anti- inflammatory cytokines, oxidative stress-relevant proteins were determined by histochemistry technology. Two-way ANOVA was applied to BMS scores. One-way ANOVA and Bonferroni's multiple comparison test were used to analyse differences among groups.Results: BMS scores were increased gradually and demyelinated axons were improved by EA gradually with the expression of ApoE. EA can inhibit inflammatory response by activation of ApoE, which decreased pro-inflammatory cytokines(TNF-α, IL-6, and IL-1β) expression and increased anti-inflammatory cytokines(IL-10 and TGF-β1).Meanwhile, EA can also inhibit oxidative stress by elevation of Nrf2,which induced HO-1 and NQO1 expression in WT and ApoE -/- mice.Conclusions: EA is a reliable treatment for promoting functional recovery of SCI. Thesynergisticrole of ApoE and Nrf2 in EA regulating inflammatory response and oxidative stress is decisiveto recovery after SCI.

Gut microbiota metabolite urolithin B attenuates intestinal immunity function through regulation of oxidative stress and inflammatory signaling in aging mice

2021 ◽  
Author(s):  
Peng Chen ◽  
Fuchao Chen ◽  
lei jiexin ◽  
Benhong Zhou
Keyword(s):  
Oxidative Stress ◽  
Gut Microbiota ◽  
Intestinal Immunity ◽  
Inflammatory Signaling ◽  
Anti Inflammatory ◽  
Immunity Function ◽  
Urolithin B

Urolithin B (Uro B), one of the major subcategories of urolithins (microbiota metabolites) found in various tissues after ellagitannin consumption, has been shown to possess antioxidant and anti-inflammatory effects. The...

Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases

2021 ◽  
pp. 036354652110598
Author(s):  
Halil Sezgin Semis ◽  
Cihan Gur ◽  
Mustafa Ileriturk ◽  
Fatih Mehmet Kandemir ◽  
Ozgur Kaynar
Keyword(s):  
Oxidative Stress ◽  
Achilles Tendinopathy ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Alternative Treatment Option ◽  
Markers Of Oxidative Stress ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The One

Background: Achilles tendinopathy, seen in athletes and manual labor workers, is an inflammatory condition characterized by chronic tendon pain. Owing to the toxicity that develops in various organs attributed to the use of anti–inflammatory drugs, there is a need for new therapeutic agents. Purpose: In the present study, the effects of quercetin (Que), the one that attracted the most attention of researchers studying this group of flavonoids, were investigated against collagenase–induced tendinopathy. Study Design: Controlled laboratory study. Methods: A total of 35 Sprague-Dawley rats were used in the study. Tendinopathy was created by injecting a single dose of collagenase (10 μL; 10 mg/mL) into the tendons of rats. Thirty minutes after the injection, Que was administered at doses of 25 or 50 mg/kg. Que administration was carried out for 7 days. Animals underwent a motility test at the end of the study. In addition, markers of oxidative stress, inflammation, apoptosis, and autophagy, as well as the expression levels of matrix metalloproteinases (MMPs 2, 3, 9, and 13), ICAM-1, and STAT3, were measured in tendon tissues with biochemical, molecular, and Western blot techniques. Results: The results showed that oxidative stress, inflammation, apoptosis, and autophagy were triggered by the injection of collagenase. In addition, MMPs, ICAM-1, and STAT3 were activated to participate in the development of tendinopathy. Que was found to reduce ICAM-1 levels in tendon tissue. Moreover, Que showed antioxidant, anti–inflammatory, antiapoptotic, and antiautophagic effects on tendons against tendinopathy. More important, Que suppressed the expression of MMPs in the tendon tissues. Conclusion: Que has protective properties against collagenase–induced tendon damage in rats. Clinical Relevance: We believe that with further study, Que may be shown to be an alternative treatment option for athletes or others who experience tendon injuries.

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