Melatonin Prevents Alcohol- and Metabolic Dysfunction- Associated Steatotic Liver Disease by Mitigating Gut Dysbiosis, Intestinal Barrier Dysfunction, and Endotoxemia

Antioxidants, Journal Year: 2023, Volume and Issue: 13(1), P. 43 - 43

Published: Dec. 25, 2023

Melatonin (MT) has often been used to support good sleep quality, especially during the COVID-19 pandemic, as many have suffered from stress-related disrupted patterns. It is less known that MT an antioxidant, anti-inflammatory compound, and modulator of gut barrier dysfunction, which plays a significant role in disease states. Furthermore, produced at 400–500 times greater concentrations intestinal enterochromaffin cells, supporting maintaining functions intestines gut–organ axes. Given this information, focus article review molecular mechanisms by it prevents alcohol-associated liver (ALD) metabolic dysfunction-associated steatotic (MASLD), including its metabolism interactions with mitochondria exert antioxidant activities gut–liver axis. We detail various acts function prevent progression ALD MASLD via axis, on how these conditions are modeled animal studies. Using prevention studies described, we suggest behavioral modifications several exogenous sources MT, food supplements. Further clinical research should be performed develop field preventing diseases so mention few considerations regarding supplementation context trials order advance research.

Language: Английский

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Microbiota and Resveratrol: How Are They Linked to Osteoporosis?

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1145 - 1145

Published: July 3, 2024

Osteoporosis (OP), which is characterized by a decrease in bone density and increased susceptibility to fractures, closely linked the gut microbiota (GM). It increasingly realized that GM plays key role maintenance of functioning multiple organs, including bone, producing bioactive metabolites such as short-chain fatty acids (SCFA). Consequently, imbalances GM, referred dysbiosis, have been identified with significant reduction beneficial metabolites, decreased SCFA associated chronic inflammatory processes, activation NF-κB at epigenetic level, recognized main cause many diseases, OP. Furthermore, regular or long-term medications antibiotics non-antibiotics proton pump inhibitors, chemotherapy, NSAIDs, found contribute development highlighting an urgent need for new treatment approaches. A promising preventive adjuvant approach combat dysbiosis natural polyphenols resveratrol, prebiotic functions ensure optimal microenvironment GM. Resveratrol offers range benefits, anti-inflammatory, anti-oxidant, analgesic, effects. In particular, has shown convert into highly metabolically active molecules even more potent properties, supporting synergistic polyphenol–GM axis. This review addresses question how can enhance effects resveratrol modulator, promote growth diversity thus providing important insights prevention co-treatment

Language: Английский

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Protection of Inonotus hispidus (Bull.) P. Karst. against Chronic Alcohol-Induced Liver Injury in Mice via Its Relieving Inflammation Response

Nutrients, Journal Year: 2023, Volume and Issue: 15(16), P. 3530 - 3530

Published: Aug. 10, 2023

Alcoholic liver disease (ALD) can be induced by excessive alcohol consumption, and has a worldwide age-standardized incidence rate (ASIR) of approximately 5.243%. Inonotus hispidus (Bull.) P. Karst. (IH) is mushroom with pharmacological effects. In ALD mice, the hepatoprotective effects IH were investigated. strongly ameliorated alcohol-induced pathological changes in liver, including structures its function-related indices. Intestinal microbiota serum metabolomics analysis showed that altered associated anti-inflammatory metabolites. According to results obtained from Western blot, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), downregulated levels pro-inflammation factors interleukin (IL)-1β, IL-6 tumor necrosis factor-α (TNF-α), enhanced expressions peroxisome proliferator-activated receptor alpha (PPARα) 15-hydroxprostaglandin dehydrogenase (15-PGDH), inhibited phosphorylated activation Janus kinase (JAK) 1 signal transducer activator transcription (STAT) 3, confirming hepatoprotection against damage via anti-inflammation. This study provides experimental evidence for chronic ALD.

Language: Английский

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Pharmacological inhibition of the Src homology phosphatase 2 confers partial protection in a mouse model of alcohol-associated liver disease

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116590 - 116590

Published: April 22, 2024

Alcohol-associated liver disease (ALD) is a leading factor of liver-related death worldwide. ALD has various manifestations that include steatosis, hepatitis, and cirrhosis currently without approved pharmacotherapies. The Src homology phosphatase 2 (Shp2) drug target in some cancers due to its positive regulation Ras-mitogen-activated protein kinase signaling cell proliferation. Shp2 pharmacological inhibition yields beneficial outcomes animal models, but impact on remains unexplored. This study aims investigate the effects validity using preclinical mouse model ALD. We report administration SHP099, potent selective allosteric inhibitor Shp2, partially ameliorated ethanol-induced hepatic injury, inflammation, steatosis mice. Additionally, was associated with reduced ethanol-evoked activation extracellular signal-regulated (ERK), oxidative, endoplasmic reticulum (ER) stress liver. Besides liver, excessive alcohol consumption induces multi-organ injury dysfunction, including intestine. Notably, diminished intestinal inflammation permeability, abrogated reduction tight junction expression, ERK ileum. Collectively, mitigates deleterious ethanol intestine Given multifactorial aspects underlying pathogenesis, additional studies are needed decipher utility alone or as component multitherapeutic regimen combat this deadly malady.

Language: Английский

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Gut Bacteria in Alcohol-Associated Liver Disease

Clinics in Liver Disease, Journal Year: 2024, Volume and Issue: 28(4), P. 663 - 679

Published: July 24, 2024

Language: Английский

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Enteromorpha prolifera Polysaccharide Alleviates Acute Alcoholic Liver Injury in C57 BL/6 Mice through the Gut–Liver Axis and NF-κB Pathway

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(42), P. 23258 - 23270

Published: Oct. 15, 2024

polysaccharide (EP2) protection against acute alcoholic liver injury (AALI) in mice was investigated. By integration of physiological indicators, gut microbiota, and short-chain fatty acids (SCFAs), the mechanism EP2 alleviating AALI disclosed. The results showed that significantly ameliorated alcohol-induced abnormal transaminase activities, intestinal systemic inflammation, environmental disorders. reduces serum LPS contents by 1.69-fold 1.54-fold. Furthermore, inhibition NF-κB signaling pathway reduced production proinflammatory cytokines such as TNF-α (1.83-fold), IL-6 (11.09-fold), IL-1β (1.99-fold). restored SCFAs to normal levels upregulating abundance beneficial bacteria (

Language: Английский

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Reducing the harms of alcohol: nutritional interventions and functional alcohol alternatives

International review of neurobiology, Journal Year: 2024, Volume and Issue: unknown, P. 241 - 276

Published: Jan. 1, 2024

Language: Английский

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Current Approaches to Prevent or Reverse Microbiome Dysbiosis in Chronic Inflammatory Rheumatic Diseases

Mediterranean Journal of Rheumatology, Journal Year: 2024, Volume and Issue: 35(2), P. 220 - 220

Published: June 1, 2024

Advances in knowledge of the microbiome and its relationship with immune system have led to a better understanding pathogenesis chronic inflammatory rheumatic diseases (CIRD). Indeed, dysbiosis now occupies particular place implications for determinism clinical expression CIRD, as well therapeutic response affected patients. Several approaches exist limit impact during CIRD. This review aimed present current strategies prevent or reverse based on existing knowledge, order provide practical information healthcare professionals treating patients suffering from

Language: Английский

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Clinical outcomes and associated bacterial and fungal microbiota changes after high dose probiotic therapy for severe alcohol-associated hepatitis: An observational study

Medicine, Journal Year: 2024, Volume and Issue: 103(45), P. e40429 - e40429

Published: Nov. 8, 2024

Alcohol-associated hepatitis (AH) is a critical condition with high mortality rates and worsened by infections. Organ failure strongly associated intestinal dysbiosis. Emerging research suggests that gut microbiota modulation probiotics can improve AH outcomes. This study investigated the clinical microbiome effects of high-dose probiotic infusion (HDPI) compared corticosteroid therapy (CST) fecal transplantation (FMT) in severe AH. Patients biopsy-proven severe-AH were enrolled from March 2019 to June 2020 matched for age disease severity. The patients received HDPI (n = 20), FMT 16), or CST 14). consists potent mix delivered via nasoduodenal tube 6 days. primary outcome was survival at 90-days. Stool samples subjected 16S 18S rRNA sequencing assess significant bacterial fungal taxa their interactions baseline post treatment. At 90-days, 55%, 64.3%, 87.5% (HDPI, CST, respectively). did not beneficially impact alpha-diversity but significantly altered beta-diversity. Notably, number pathogenic bacteria, such as Bilophila Roseburia increased. Fungal analysis revealed no changes alpha diversity, dissimilarities beta diversity post-HDPI. New genera Basidiomycota Phragmoplastophyta have emerged, deleterious expansion communities damaging modifications between fungal-bacterial interactions. failed outperform improving outcomes While influenced both microbiomes, it also led persistence communities. showed superior outcomes, highlighting urgent need further controlled trials.

Language: Английский

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Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: June 20, 2024

Introduction Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction contributing development alcoholic liver disease (ALD), which is most prevalent cause advanced diseases. In this study, we investigated protective effects action mechanism an aqueous extraction Pericarpium citri reticulatae Amomi fructus (PFE) on injury. Methods C57BL/6 mice were used establish mouse model injury orally administered 500 1,000 mg/kg/d PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, 16S rDNA amplicon sequencing analyze in treatment alcohol-induced Results Treatment with significantly improved injury, as illustrated by normalization serum alanine aminotransferase, aspartate total triglyceride, cholesterol levels ALD a dose-dependent manner. Administration not only maintained integrity prominently upregulating mucous production tight junction protein expressions but also sensibly reversed dysregulation microecology alcohol-treated mice. Furthermore, reduced hepatic lipopolysaccharide (LPS) attenuated oxidative stress well inflammation related TLR4/NF-κB signaling pathway. The supplementation promoted short-chain fatty acids (SCFAs) Conclusion effectively prevents may regulate LPS-involved gut–liver axis; could provide valuable insights drugs prevent treat ALD.

Language: Английский

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