Flavonoids from Scutellaria amoena C. H. Wright alleviate mitochondrial dysfunction and regulate oxidative stress via Keap1/Nrf2/HO-1 axis in rats with high-fat diet-induced nonalcoholic steatohepatitis DOI Open Access

Qionglian Fang,

Xue Qiao,

Xunqing Yin

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 158, P. 114160 - 114160

Published: Dec. 24, 2022

Nonalcoholic steatohepatitis (NASH) is among the most common liver diseases in world. Flavonoids from Scutellaria amoena (SAF) are used treatment of hepatopathy China. However, effect and mechanism against NASH remain unclear. We investigated alleviating SAF on via regulating mitochondrial dysfunction oxidative stress. The effects were evaluated using vitro vivo methods. L02 cells induced by fat emulsion to establish an adipocytes model, followed with for 24 h. rat models established administration a high-fat diet 12 weeks administered six weeks. Changes body weight, organ indexes, lipid levels, inflammatory cytokines, indicators, fatty acid metabolism investigated. significantly improved injury, infiltration rats. notably regulated interleukin-6, tumor necrotic factor-alpha, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), kelch-like ECH-associated protein 1 (Keap1), nuclear factor-erythroid factor 2-related 2 (Nrf2), heme oxygenase-1 (HO-1). Additionally, dysfunction, increased levels GSH, SOD, ATP synthase, complex I II, decreased level MDA mitochondria. expression β-oxidation genes, including peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) A, CPT1B, medium-chain acyl-CoA dehydrogenase, long-chain very PPARα. can alleviate function stress Keap1/Nrf2/HO-1 axis.

Language: Английский

Structure and hepatoprotective activity of Usp10/NF-κB/Nrf2 pathway-related Morchella esculenta polysaccharide DOI

Shanshan Teng,

Yongfeng Zhang,

Xinghui Jin

et al.

Carbohydrate Polymers, Journal Year: 2022, Volume and Issue: 303, P. 120453 - 120453

Published: Dec. 13, 2022

Language: Английский

Citations

45
Investigating the Link between Ketogenic Diet, NAFLD, Mitochondria, and Oxidative Stress: A Narrative Review DOI Creative Commons
Antonio Paoli, Giuseppe Cerullo

Antioxidants, Journal Year: 2023, Volume and Issue: 12(5), P. 1065 - 1065

Published: May 8, 2023

Together with the global rise in obesity and metabolic syndrome, prevalence of individuals who suffer from nonalcoholic fatty liver disease (NAFLD) has risen dramatically. NAFLD is currently most common chronic includes a continuum disorders initial fat accumulation to steatohepatitis (NASH), considered more severe forms, which can evolve in, cirrhosis, hepatocellular carcinoma. Common features altered lipid metabolism mainly linked mitochondrial dysfunction, which, as vicious cycle, aggravates oxidative stress promotes inflammation and, consequence, progressive death hepatocytes form NAFLD. A ketogenic diet (KD), i.e., very low carbohydrates (<30 g/die) that induces “physiological ketosis”, been demonstrated alleviate restore function. Based on this, aim present review analyze body evidence regarding potential therapeutic role KD NAFLD, focusing interplay between mitochondria liver, effects ketosis pathways, impact

Language: Английский

Citations

42
The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases DOI Creative Commons
Jeong-Su Park, Nodir Rustamov,

Yoon-Seok Roh

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(11), P. 1928 - 1928

Published: Oct. 29, 2023

Chronic liver disease (CLD) affects a significant portion of the global population, leading to substantial number deaths each year. Distinct forms like non-alcoholic fatty (NAFLD) and alcoholic (ALD), though they have different etiologies, highlight shared pathologies rooted in oxidative stress. Central metabolism, mitochondria are essential for ATP production, gluconeogenesis, acid oxidation, heme synthesis. However, diseases NAFLD, ALD, fibrosis, mitochondrial function is compromised by inflammatory cytokines, hepatotoxins, metabolic irregularities. This dysfunction, especially electron leakage, exacerbates production reactive oxygen species (ROS), augmenting damage. Amidst this, nuclear factor erythroid 2-related 2 (NRF2) emerges as cellular protector. It not only counters stress regulating antioxidant genes but also maintains health overseeing autophagy biogenesis. The synergy between NRF2 modulation introduces new therapeutic potentials CLD, focusing on preserving integrity against threats. review delves into intricate role shedding light innovative strategies its prevention treatment, through pathways.

Language: Английский

Citations

24
Exploring the impact of the PNPLA3 I148M variant on primary human hepatic stellate cells using 3D extracellular matrix models DOI Creative Commons
Elisabetta Caon, María Manuela Martins, Harry Hodgetts

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 80(6), P. 941 - 956

Published: Feb. 15, 2024

Background and aims The PNPLA3 rs738409 C>G (encoding for I148M) variant is a risk locus the fibrogenic progression of chronic liver diseases, process driven by hepatic stellate cells (HSCs). We investigated how I148M affects HSCs biology using transcriptomic data validated findings in 3D-culture models. Methods RNA sequencing was performed on 2D-cultured primary human biopsies obese individuals, genotyped variant. Data were wild type (WT) or carrying I148M-PNPLA3 cultured 3D extracellular matrix (ECM) scaffolds from healthy cirrhotic with/without TGFB1 Cytosporone-B (Csn-B) treatment. Results Comparison between analysis highlighted shared I148M-driven dysregulated pathways related to mitochondrial function, antioxidant response, ECM remodelling signalling. Analogous WT/I148M-PNPLA3 scaffolds. Mitochondrial dysfunction linked respiratory chain complex IV insufficiency. Antioxidant capacity lower HSCs, while ROS secretion increased higher bioengineered versus signalling pathway followed same trend. In cells, TGFB1-endogenous inhibitor NR4A1 expression activation decreased: treatment with Csn-B agonist total but not regulation TGFB1/Csn-B Akt WT-PNPLA3 Erk HSCs. Conclusion have impaired dampening antifibrotic activity. These features are exacerbated ECM, highlighting dual impact fibrotic microenvironment progressive diseases. Impact implications Hepatic (HSCs) play key role associated disease. genetic mutation has been fibrogenesis, its needs further investigation. Here, comparative novel vitro model, we demonstrate cell behaviour, show that it cell's function as well gene NR4A1. Our publicly available data, platform our could facilitate discovery targets develop more effective treatments

Language: Английский

Citations

17
Dual-Emissive Detection of ATP and Hypochlorite Ions for Monitoring Inflammation-Driven Liver Injury In Vitro and In Vivo DOI

Maxine Mambo Fortibui,

Chaewon Park,

Na Yoon Kim

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(23), P. 9408 - 9415

Published: May 28, 2024

Reactive oxygen species play a pivotal role in liver disease, contributing to severe damage and chronic inflammation. In injury driven by inflammation, adenosine-5′-triphosphate (ATP) hypochlorite ion (ClO–) emerge as novel biomarkers, reflecting mitochondrial dysfunction amplified oxidative stress, respectively. However, the dynamic fluctuations of ATP ClO– hepatocytes mouse livers remain unclear, multidetection techniques for these biomarkers are yet be developed. This study presents RATP-NClO, dual-channel fluorescent bioprobe capable synchronously detecting ions. RATP-NClO exhibits excellent selectivity sensitivity ions, demonstrating fluorescence response murine hepatocyte cell line. Upon intravenous administration, reveals synchronized depletion amplification mice with experimental metabolic dysfunction-associated steatohepatitis (MASH). Through comprehensive analysis principal mechanism developed verification its reliable detection ability both vitro vivo settings, we propose it unique tool monitoring changes intracellular level. These findings underscore potential practical image-based functional phenotyping MASH pathogenesis.

Language: Английский

Citations

15
Deciphering the molecular pathways of saroglitazar: A dual PPAR α/γ agonist for managing metabolic NAFLD DOI
Devaraj Ezhilarasan

Metabolism, Journal Year: 2024, Volume and Issue: 155, P. 155912 - 155912

Published: April 11, 2024

Language: Английский

Citations

14
Si-Wu-Tang attenuates hepatocyte PANoptosis and M1 polarization of macrophages in non-alcoholic fatty liver disease by influencing the intercellular transfer of mtDNA DOI
Zhi Ma,

Kaihong Xie,

Xiaoyong Xue

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 328, P. 118057 - 118057

Published: March 20, 2024

Language: Английский

Citations

11
Improved Detection of Drug-Induced Liver Injury by Integrating Predicted In Vivo and In Vitro Data DOI Creative Commons
Srijit Seal, Dominic P. Williams, Layla Hosseini-Gerami

et al.

Chemical Research in Toxicology, Journal Year: 2024, Volume and Issue: 37(8), P. 1290 - 1305

Published: July 9, 2024

Drug-induced liver injury (DILI) has been a significant challenge in drug discovery, often leading to clinical trial failures and necessitating withdrawals. Over the last decade, existing suite of

Language: Английский

Citations

10
TJ0113 attenuates fibrosis in metabolic dysfunction-associated steatohepatitis by inducing mitophagy DOI
Chun-Lian Huang,

Shen Qi-En,

Xufeng Cen

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 156, P. 114678 - 114678

Published: April 18, 2025

Language: Английский

Citations

1
Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy DOI Creative Commons
Elias Kouroumalis, Ioannis Tsomidis, Argyro Voumvouraki

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1166 - 1166

Published: April 13, 2023

The pathogenesis of hepatocellular carcinoma (HCC) is a multifactorial process that has not yet been fully investigated. Autophagy and apoptosis are two important cellular pathways critical for cell survival or death. balance between autophagy regulates liver turnover maintains intracellular homeostasis. However, the often dysregulated in many cancers, including HCC. may be either independent parallel one influence other. inhibit promote apoptosis, thus regulating fate cancer cells. In this review, concise overview HCC presented, with emphasis on new developments, role endoplasmic reticulum stress, implication microRNAs gut microbiota. characteristics associated specific disease also described brief description provided. initiation, progress metastatic potential reviewed experimental evidence indicating an interplay extensively analyzed. ferroptosis, recently pathway regulated death, presented. Finally, therapeutic implications drug resistance examined.

Language: Английский

Citations

23