Regulation and targeting of SREBP-1 in hepatocellular carcinoma

Cancer and Metastasis Reviews, Journal Year: 2023, Volume and Issue: 43(2), P. 673 - 708

Published: Dec. 1, 2023

Abstract Hepatocellular carcinoma (HCC) is an increasing burden on global public health and associated with enhanced lipogenesis, fatty acid uptake, lipid metabolic reprogramming. De novo lipogenesis under the control of transcription factor sterol regulatory element-binding protein 1 (SREBP-1) essentially contributes to HCC progression. Here, we summarize current knowledge regulation SREBP-1 isoforms in based cellular, animal, clinical data. Specifically, (i) address overarching mechanisms for regulating transcription, proteolytic processing, nuclear stability, transactivation (ii) critically discuss their impact HCC, taking into account (iii) insights from pharmacological approaches. Emphasis placed cross-talk phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt)-mechanistic target rapamycin (mTOR) axis, AMP-activated (AMPK), A (PKA), other kinases that directly phosphorylate SREBP-1; factors, such as liver X receptor (LXR), peroxisome proliferator-activated receptors (PPARs), γ co-activator (PGC-1), signal transducers activators (STATs), Myc; epigenetic mechanisms; post-translational modifications SREBP-1-regulatory metabolites oxysterols polyunsaturated acids. By carefully scrutinizing role development, progression, metastasis, therapy resistance, shed light potential SREBP-1-targeting strategies prevention treatment.

Language: Английский

---

Catechin and quercitrin mitigate the cytotoxic effects of aflatoxin-B1 on liver and colon cells by inhibiting cytochrome P450 1A2 and 3A4, in silico

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 105989 - 105989

Published: Jan. 1, 2025

Language: Английский

---

The Chemical Profile, Antioxidant, and Anti-Lipid Droplet Activity of Fluid Extracts from Romanian Cultivars of Haskap Berries, Bitter Cherries, and Red Grape Pomace for the Management of Liver Steatosis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16849 - 16849

Published: Nov. 28, 2023

This study aimed to investigate, for the first time, chemical composition and antioxidant activity of fluid extracts obtained from three Romanian cultivars haskap berries (Lonicera caerulea L.) var. Loni, bitter cherries (Prunus avium sylvestris Ser.) Silva, pomace red grapes (Vitis vinifera Mamaia, their capacity modulate in vitro steatosis, view developing novel anti-obesity products. Total phenolic, flavonoid, anthocyanin, ascorbic acid content was spectrophotometrically assessed free radical scavenging evaluated using Trolox Equivalent Antioxidant Capacity (TEAC) 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition assays. The Pearson coefficients showed a moderate correlation between phenolic content, but strong anthocyanin content. HPLC analysis identified quantified main compounds chlorogenic syringic acid, catechin, glycosylated kaempferol, apigenin, quercetin, variable proportions. An experimental model steatosis developed HepG2 hepatocytes treated with mixture fatty acids. Cell culture analyses that cytocompatible concentrations could significantly reduce lipid accumulation inhibit reactive oxygen species, malondialdehyde, nitric oxide secretion stressed hepatocytes. In conclusion, these results put an emphasis on compounds’ high liver protection unstudied Silva similar extract particular, positive modulation fat deposition next oxidative stress peroxidation process triggered by acids Consequently, this indicated be further exploited as hepatoprotective agents which provides basis development mixtures synergistic

Language: Английский

---

Plant miR8126-3p and miR8126-5p Decrease Lipid Accumulation through Modulation of Metabolic Genes in a Human Hepatocyte Model That Mimics Steatosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1721 - 1721

Published: Jan. 31, 2024

Plant-based food interventions are promising therapeutic approaches for non-alcoholic fatty liver disease (NAFLD) treatment, and microRNAs (miRNAs) have emerged as functional bioactive components of dietary plants involved in cross-kingdom communication. Deeper investigations needed to determine the potential impact plant miRNAs NAFLD. This study aimed identify that could eventually modulate expression human metabolic genes protect against progression hepatic steatosis. Plant from miRBase were used predict target genes, miR8126-3p miR8126-5p selected candidates their role inhibiting glucose lipid metabolism-related genes. Human HepG2 cells transfected with miRNA mimics then exposed a mixture oleic palmitic acids mimic transfections inhibited putative QKI MAPKAPK2, respectively, had an on profile key including PPARA SREBF1. Quantification intrahepatic triglycerides revealed attenuated accumulation. These findings suggest would induce changes hepatocytes protecting accumulation, thus, they be tools preventing alleviating

Language: Английский

---

Phytochemical Composition of Ziziphus lotus (L.) Lam and Its Impact on the Metabolic Syndrome: A Review

Advances in Pharmacological and Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

The long‐term pathological state known as metabolic syndrome is characterized by hypertension, insulin resistance diabetes, abdominal obesity, and hyperlipidemia. Seeking healthcare strategies with fewer side effects, such herbal remedies, preferable in terms of mitigating the negative consequences synthetic medications. Ziziphus lotus (L.) (Rhamnaceae) or wild jujube, commonly “Sedra,” one best choices it contains a variety phytochemicals biologically active compounds. Several flavonoids stilbenes have been recognized primary bioactive components including rutin, hyperin, isoquercitrin, resveratrol. These polyphenols are pharmacologically broad‐spectrum beneficial effects for reducing risk factors associated syndrome. They exhibit antioxidant anti‐inflammatory properties, regulate lipid metabolism, possess antiobesity, antihypertensive, antidiabetic characteristics. However, there certain limitations to their therapeutic application, low bioavailability. Various proposed enhance pharmacokinetic profile potential future use. main goal this review explore underlying mechanisms related jujube its compounds treatment prevention

Language: Английский

---

Steam explosion modified pea peptides alleviates hepatosteatosis by regulating lipid metabolism pathways and promoting autophagy

Food Research International, Journal Year: 2025, Volume and Issue: 208, P. 116182 - 116182

Published: March 14, 2025

Language: Английский

---

Dendrobine alleviates oleic acid-induced lipid accumulation by inhibiting FOS/METTL14 pathway

Journal of Molecular Histology, Journal Year: 2024, Volume and Issue: 55(5), P. 995 - 1007

Published: Aug. 13, 2024

Language: Английский

---

Traditional Chinese medicine and plant-derived natural products in regulating triglyceride metabolism: Mechanisms and therapeutic potential

Pharmacological Research, Journal Year: 2024, Volume and Issue: 208, P. 107387 - 107387

Published: Aug. 30, 2024

The incidence of cardiometabolic disease is increasing globally, with a trend toward younger age onset. Among these, atherosclerotic cardiovascular leading cause mortality worldwide. Despite the efficacy traditional lipid-lowering drugs, such as statins, in reducing low-density lipoprotein cholesterol levels, significant residual risk events remains, which closely related to unmet triglyceride (TG) targets. clinical application current TG-lowering Western medicines has certain limitations, necessitating alternative or complementary therapeutic strategies. Traditional Chinese medicine (TCM) and plant-derived natural products, known for their safety owing origins diverse biological activities, offer promising avenues TG regulation potentially fewer side effects. This review systematically summarises mechanisms metabolism subsequently reviews regulatory effects TCM products on metabolism, including inhibition synthesis (via endogenous exogenous pathways), promotion catabolism, fatty acid absorption transport, enhancement lipophagy, modulation gut microbiota, other mechanisms. In conclusion, through comprehensive analysis recent studies, this consolidates multifaceted roles elucidates potential safer, multi-target agents managing hypertriglyceridemia mitigating risk, thereby providing basis new drug development.

Language: Английский

---

Quercetin’s Potential in MASLD: Investigating the Role of Autophagy and Key Molecular Pathways in Liver Steatosis and Inflammation

Nutrients, Journal Year: 2024, Volume and Issue: 16(22), P. 3789 - 3789

Published: Nov. 5, 2024

Metabolic dysfunction-associated fatty liver disease (MASLD) is a widespread disorder characterized by excessive fat accumulation in the liver, commonly associated with metabolic syndrome components such as obesity, diabetes, and dyslipidemia. With global prevalence of up to 30%, MASLD projected affect over 100 million people U.S. 20 Europe 2030. The ranges from Steatotic Lived Disease (SLD) more severe forms like steatohepatitis (MASH), which can progress cirrhosis hepatocellular carcinoma. Autophagy, cellular process crucial for lipid metabolism homeostasis, often impaired MASLD, leading increased hepatic inflammation. Key autophagy-related proteins, Beclin1, LC3A, SQSTM1 (p62), CD36, Perilipin 3, play significant roles regulating this process. Disruption these proteins contributes pathogenesis MASLD. Quercetin, natural polyphenolic flavonoid antioxidant anti-inflammatory properties, has promising results mitigating It may reduce accumulation, improve mitochondrial function, enhance autophagy. However, further research needed elucidate its mechanisms validate therapeutic potential clinical settings. This underscores need continued investigation into autophagy novel treatments

Language: Английский

---

Pharmacological Activation of AMPK Prevents Drp1-mediated Mitochondrial Fission and Alleviates Hepatic Steatosis In vitro

Current Molecular Medicine, Journal Year: 2024, Volume and Issue: 24(12), P. 1506 - 1517

Published: Feb. 4, 2024

Background: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Adenosine monophosphate-activated protein kinase (AMPK) activation beneficial for NAFLD treatment. Recent studies show the excessive fission mitochondria during progression, so targeting dynamics may be a possible target NAFLD. Still, little known about whether AMPK regulates mitochondrial in hepar. Objective: This study investigated alleviates hepatic steatosis by regulating mediated GTPase dynamin-related 1 (Drp1). Methods: Human hepatocyte line L-02 cells were cultured and subjected to palmitic acid (PA) treatment 24 h establish model vitro, which was pre-treated with different tool drugs. Hepatocyte function, lipid content, reactive oxygen species (ROS) production, membrane potential (MMP) examined. expression levels genes proteins associated assessed using reverse transcription-quantitative PCR western blotting. Results: results indicated that 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an activator, improved as demonstrated decreased alanine aminotransferase (ALT) aspartate (AST) activity (P＜0.05 or P＜0.01). In addition, AICAR total cholesterol (TC) triglyceride (TG) content deposition hepatocytes (P＜0.01); ROS production; MMP reduced fission-1 (Fis1) factor (Mff) mRNA expression; downregulated p-Drp1 (Ser 616) expression. contrast, increased fusion mitofusin-1 (Mfn1) mitofusin-2 (Mfn2) upregulated 637) Mdivi-1, Drp-1 inhibitor, used confirm regulated Drp1-mediated role AICAR. Similar AICAR, Mdivi-1 function significantly, production deposition, Fis1 Mff expression, enhanced Mfn1 Mfn2 However, Compound C, AMPKspecific had less impact on protective effect Mdivi-1. Conclusion: has largely dependent inhibition fission.

Language: Английский

---