Ellagic Acid Prevents Binge Alcohol-Induced Leaky Gut and Liver Injury through Inhibiting Gut Dysbiosis and Oxidative Stress.
TL;DR: In this paper, the authors investigated whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation.
Abstract: Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.
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TL;DR: In this paper , the authors reviewed the current evidence on the role of the microbiome in autoimmune liver diseases from both clinical and basic research and gave an outlook on future developments and potential for clinical applications.
Abstract: Autoimmune liver diseases are a group of immune-mediated liver diseases with three distinct entities, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. The interplay of genetic and environmental factors leads to the breakdown of self-tolerance, resulting in hyper-responsiveness, and auto-aggressive immune activation. Emerging evidence links autoimmune liver diseases with alterations of the commensal microbiome configuration and aberrant immune system activation by microbial signals, mainly via the gut-liver axis. Thus, the microbiome is a new frontier to deepen the pathogenetic understanding, uncover biomarkers, and inspire innovative treatments. Herein, we review the current evidence on the role of the microbiome in autoimmune liver diseases from both clinical and basic research. We highlight recent achievements and also bottlenecks and limitations. Moreover, we give an outlook on future developments and potential for clinical applications.
15 citations
TL;DR: This review focuses on alcohol-metabolite-associated hepatotoxicity due to oxidative and non-oxidative alcohol metabolites and the role of interorgan crosstalk in alcoholic liver disease pathogenesis.
7 citations
TL;DR: In this paper , a vesicle-based controlled release system for ellagic acid (EA) was proposed, involving the exploitation of chestnut wood mud (CWM), an industrial byproduct from chestnut tannin production, as a largely available and low-cost source of this compound.
Abstract: Ellagic acid (EA) has long been recognized as a very active antioxidant, anti-inflammatory, and antimicrobial agent. However, its low bioavailability has often hampered its applications in health-related fields. Here, we report a phospholipid vesicle-based controlled release system for EA, involving the exploitation of chestnut wood mud (CWM), an industrial by-product from chestnut tannin production, as a largely available and low-cost source of this compound. Two kinds of CWM with different particle size distributions, indicated as CWM-A and CWM-B (<100 and 32 µm, respectively), containing 5 ± 1% w/w EA, were incorporated into transfersomes. The latter were small in size (~100 nm), homogeneously dispersed, and negatively charged. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays indicated up to three-fold improvement in the antioxidant properties of CWM upon incorporation into transfersomes. The kinetics of EA released under simulated physiological conditions were evaluated by UV-Vis spectroscopy and HPLC analysis. The best results were obtained with CWM-B (100% of EA gradually released after 37 days at pH 7.4). A stepwise increase in the antioxidant properties of the released material was also observed. Cell-based experiments confirmed the efficacy of CWM-B transfersomes as antioxidant agents in contrasting photodamage.
3 citations
TL;DR: In this article , the effect of ellagic acid (EA) pretreatment against hepatic IRI-induced injury and the underlying mechanisms were investigated, and it was shown that EA pre-treatment improved hepatic ischemia-reperfusion injury.
Abstract: Ellagic acid (EA) has improving function against oxidative damage and inflammatory reaction in many disorders. Hepatic ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon in the veterinary clinic. In the present study, the protective effects of EA pretreatment against hepatic IRI-induced injury and the underlying mechanisms were investigated.We found that pyroptosis is involved in hepatic IRI, which is manifested in increasing the expression of pyroptosis-related genes and promoting the expression of active caspase-1, thereby cleaving GSDMD-N to cause pyroptosis, and caspase-1-/- mice were used to verify this conclusion. In addition, we found that EA protects against hepatic IRI by inhibiting pyroptosis, including reducing the activity of caspase-1 and its expression in the liver, inhibiting the lysis of GSDMD-N, and reducing the levels of IL-18 and IL-1β.The present results have demonstrated that prophylactic administration of EA ameliorated hepatic IRI by inhibiting pyroptosis induced in hepatic ischemia-reperfusion in vivo through the caspase-1-GSDMD axis, providing a potential therapeutic option prevent hepatic IRI in pets.
3 citations
TL;DR: Results showed for the first time that hemp-derived nanovesicles (HNVs) exhibited a protective effect on DSS-induced gut leaky and liver injury through the gut–liver axis by inhibiting oxidative stress marker proteins.
Abstract: Hemp (Cannabis sativa L.) is used for medicinal purposes owing to its anti-inflammatory and antioxidant activities. We evaluated the protective effect of nanovesicles isolated from hemp plant parts (root, seed, hemp sprout, and leaf) in dextran sulfate sodium (DSS)-induced colitis in mice. The particle sizes of root-derived nanovesicles (RNVs), seed-derived nanovesicles (SNVs), hemp sprout-derived nanovesicles (HSNVs), and leaf-derived nanovesicles (LNVs) were within the range of 100–200 nm as measured by nanoparticle tracking analysis. Acute colitis was induced in C57BL/N mice by 5% DSS in water provided for 7 days. RNVs were administered orally once a day, leading to the recovery of both the small intestine and colon lengths. RNVs, SNVs, and HSNVs restored the tight (ZO-1, claudin-4, occludin) and adherent junctions (E-cadherin and α-tubulin) in DSS-induced small intestine and colon injury. Additionally, RNVs markedly reduced NF-κB activation and oxidative stress proteins in DSS-induced small intestine and colon injury. Tight junction protein expression and epithelial cell permeability were elevated in RNV-, SNV-, and HSNV-treated T84 colon cells exposed to 2% DSS. Interestedly, RNVs, SNVs, HSNVs, and LNVs reduced ALT activity and liver regeneration marker proteins in DSS-induced liver injury. These results showed for the first time that hemp-derived nanovesicles (HNVs) exhibited a protective effect on DSS-induced gut leaky and liver injury through the gut–liver axis by inhibiting oxidative stress marker proteins.
3 citations
References
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TL;DR: BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function, and is advocated as a factor when converting a dose for translation from animals to humans.
Abstract: As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.
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TL;DR: This protocol describes the dextran sulfate sodium (DSS)‐induced colitis model, focusing on details and factors that could affect DSS‐induced pathology.
Abstract: Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis and Crohn's Disease, are complex and multifactorial diseases with unknown etiology. For the past 20 years, to study human IBD mechanistically, a number of murine models of colitis have been developed. These models are indispensable tools to decipher underlying mechanisms of IBD pathogenesis as well as to evaluate a number of potential therapeutics. Among various chemically induced colitis models, the dextran sulfate sodium (DSS)-induced colitis model is widely used because of its simplicity and many similarities with human ulcerative colitis. This model has both advantages and disadvantages that must be considered when employed. This protocol describes the DSS-induced colitis model, focusing on details and factors that could affect DSS-induced pathology.
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