Search Results (79)

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe hepatic steatosis, lobular inflammation, and fibrosis. Although hesperidin, a citrus-derived flavanone, has been reported to exert metabolic and anti-inflammatory effects, its role in severe inflammatory and fibrotic conditions such as MASH remains incompletely understood. This study aimed to evaluate the effects of hesperidin in MASH using integrated in silico and in vivo approaches. Methods: Potential targets of hesperidin were identified using network pharmacology and molecular docking. For in vivo validation, C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for five weeks, with oral administration of hesperidin (150 or 300 mg/kg/day) starting from week two. The MCD model induces severe hepatic inflammation and fibrosis but does not fully reflect metabolic features such as obesity and insulin resistance. Hepatic histology, serum transaminases, immune cell populations, and hypothalamic neuroinflammatory markers were assessed. Results: In silico analyses suggested that hesperidin interacts with key regulators associated with MASH, including PPARG, TGFB1, and TNF. In the in vivo MCD-induced model, hesperidin treatment reduced hepatic lipid accumulation and collagen deposition, accompanied by significant decreases in serum ALT and AST levels (by approximately 30–34% and 42–53%, respectively, depending on dose). These effects were associated with downregulation of pro-inflammatory and pro-fibrogenic gene expression and increased expression of antioxidant markers. In addition, hesperidin decreased circulating Ly6C^high monocytes and hepatic Kupffer cells, along with reduced hypothalamic microglial and astrocyte activation. Conclusions: Hesperidin attenuated key pathological features of MASH, including steatosis, inflammation, and fibrosis, and was associated with modulation of peripheral immune responses and central neuroinflammatory markers. These findings suggest that hesperidin may influence the liver–immune–brain axis and warrant further investigation in models that more closely reflect human metabolic conditions. Full article

Objective: This study examined the pharmacological mechanisms of the therapeutic benefits of SWT to MASLD via regulating the gut–liver axis. Methods: The components of SWT were analyzed by liquid chromatograph mass spectrometer (LC-MS). After establishing an MCD-induced MASLD mice model, we invested the protective mechanism of SWT through 16S rRNA sequencing combined with molecular biological experiments. After eliminating the intestinal microbiota through an antibiotic cocktail experiment, we identified the key microbiota by which SWT improves MASLD. Results: SWT markedly reduced MASLD injury by alleviating intestinal inflammation and restoring the intestinal mucosal barrier, which could be reversed following alcohol exposure. Additionally, SWT altered the intestinal flora of MASLD mice, significantly raising the relative abundance of Parabacteroides goldsteinii-like taxa, while alcohol caused the destruction of P. goldsteinii-like-taxa-centered probiotic habitats and a proliferation of pathogenic bacteria, especially Bacteroides intestinalis-like taxa. After the elimination of intestinal flora, the anti-MASLD effect of SWT was lost. Moreover, the supplement of P. goldsteinii could significantly ameliorate liver damage caused by an MCD diet, functioning similarly to SWT. However, the liver-protective effect of SWT was suppressed following the administration of B. intestinalis. Conclusions: SWT ameliorates MCD diet-induced MASLD via modulating intestinal microbiota homeostasis and restoring intestinal mucosal barriers. Given that P. goldsteinii is effective for treating MASLD, it provides insights into new therapeutic strategies. Full article

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disorder with limited effective therapeutic options. Emerging lipidomic studies suggest that alterations in membrane-associated lipids contribute to MASH pathophysiology; however, nutritional interventions capable of modifying these lipid alterations remain poorly defined. This study aimed to investigate the effects of coenzyme Q10 (CoQ) supplementation on hepatic lipidomic remodeling in a methionine- and choline-deficient (MCD) diet-induced mouse model of MASH. Methods: Male C57BL/6J mice were fed a methionine- and choline-sufficient diet or an MCD diet for 4 weeks, with MCD-fed mice receiving vehicle or CoQ (100 mg/kg body weight/day). Hepatic lipid profiles were assessed using untargeted LC–MS-based lipidomics, and expression of genes involved in phospholipid and sphingolipid metabolism was quantified by quantitative real-time PCR. Results: CoQ supplementation significantly attenuated liver injury induced by the MCD diet, as evidenced by reduced histological severity and decreased serum ALT and AST levels. Lipidomic analyses revealed marked alterations in hepatic phospholipid and sphingolipid profiles during MASH development. CoQ was associated with remodeling of phospholipid composition, increasing phosphatidylcholine (PC) species and reducing phosphatidylethanolamine (PE) species, resulting in an increased hepatic PC to PE ratio. This change was accompanied by upregulation of Pemt (phosphatidylethanolamine N-methyltransferase). In contrast, sphingolipid accumulation induced by the MCD diet remained largely unchanged by CoQ, and Smpd1 (sphingomyelin phosphodiesterase 1) expression was not altered. Conclusions: CoQ supplementation was associated with attenuation of MCD diet-induced MASH and modulation of hepatic phospholipid homeostasis, supporting its potential as a nutritional intervention targeting membrane lipid dysregulation in MASH. Full article

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a multifactorial liver disease in which mitochondrial dysfunction, oxidative stress, and inflammation play key roles in driving the progression toward metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Dysfunctional mitochondria generate excess reactive oxygen species (ROS), impair antioxidant defenses, activate pro-inflammatory pathways and hepatic stellate cells, and perpetuate liver injury. Mitochondrial Complex I is a major ROS source, particularly under conditions of dysregulated energy metabolism. Since Complex I inhibition by metformin was shown to reduce ROS and activate the adenosine monophosphate-activated protein kinase (AMPK), this study aimed to evaluate whether a novel Complex I Modulator (CIM, BI4500) could attenuate oxidative stress, inflammation, and consequently reduce lipid accumulation and fibrosis in a methionine- and choline-deficient diet (MCD)-fed rat model of MASH. Methods: Rats were fed an MCD or an isocaloric control diet for six weeks. From week four, animals received daily oral treatment with CIM (10 mg/kg) or vehicle (Natrosol). At the endpoint, liver tissue was collected for histological, biochemical, and molecular analyses. Lipid droplet area, inflammatory infiltration, and collagen deposition were evaluated on tissue sections; total lipid content and oxidative stress markers were assessed in homogenates and isolated mitochondria. Molecular pathways related to oxidative stress, lipid metabolism, and fibrosis were assessed at protein and mRNA levels. Results: CIM treatment significantly reduced oxidative stress (ROS, lipid peroxidation, nitrogen species), promoting AMPK activation and metabolic reprogramming. This included increased expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its target genes, and decreased sterol regulatory element binding protein-1c (SREBP-1c)-driven lipogenesis. These changes halted fibrosis progression, as confirmed by Picro-Sirius Red staining and fibrosis markers. Conclusions: these findings indicate that Complex I modulation may represent a promising strategy to counteract MASLD progression toward MASH. Full article

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a systemic condition with neuropsychiatric comorbidities, including depression. Growing evidence for the neuroprotective, antidepressant, and anxiolytic potential of Portulaca oleracea (PO) extract, provides a compelling rationale for investigating its effects in the interaction between dietary models of NAFLD and vulnerability to stress-related disorders. Fifty-four 14- to 18-week-old male and female C57BL/6N mice were distributed in two equal groups and fed either a methionine- and choline-deficient diet (MCD) or a methionine- and choline-controlled diet (MC). Subsequently, half of each group was subjected to chronic unpredictable mild stress (CUMS) and PO treatment. MCD caused significant weight loss, whereas MC promoted weight gain. Behaviorally, MCD induced anhedonia- and anxiety-like behaviors, worsened by CUMS. MC diet reduced CUMS-induced anhedonia, though anxiety-like behavior emerged only under stress. Recognition memory was impaired in stressed MCD-fed mice, while MC-fed mice showed enhanced novel object preference. At the cellular level, MCD suppressed hippocampal microglia and caused cortical astrocyte dysfunction, whereas the MC diet promoted cortical neurogenesis potentiated through PO, abolished by chronic stress. These findings underscore the impact of dietary composition on PO’s systemic effects under chronic stress and support a mechanistic link between NAFLD-related dysfunction and depression-like phenotypes. Full article

The signal transducer and activator of transcription 3 (STAT3) in myeloid cells suppresses proinflammatory cytokine production and reduces collagen deposition. However, its role in methionine- and choline-deficient (MCD) diet-fed mice remains unclear. This study investigates the effects of myeloid-specific STAT3 deficiency on hepatic inflammation and fibrosis in MCD diet-fed mice. Myeloid-specific STAT3 knockout (mSTAT3KO) mice were fed the MCD diet for four weeks to induce metabolic dysfunction-associated steatohepatitis (MASH). MCD diet-fed mice displayed MASH-like pathological phenotypes, including hepatic steatosis, inflammation, and fibrosis. Compared with MCD diet-fed WT mice, mSTAT3KO mice fed the MCD diet exhibited reduced hepatic lipid accumulation but increased fibrosis. Notably, mSTAT3KO mice showed elevated hepatic STAT3 and lipocalin-2 (LCN2) protein levels in hepatocytes. Some proinflammatory cytokines were increased by the MCD diet in mSTAT3KO mice, which also exhibited increased hepatocyte apoptosis. Conversely, MCD diet-induced CD36, perilipin-2, acyl-CoA thioesterase 2, and 4-hydroxynonenal proteins were reduced by mSTAT3KO. Myeloid-specific STAT3 deficiency may induce a compensatory STAT3/LCN2 axis in hepatocytes, thereby exacerbating MASH progression. Full article

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) encompasses a spectrum of liver conditions and involves gut–liver axis crosstalk. We aimed to evaluate whether oral vancomycin modifies liver injury and the cecal microbiota in a methionine–choline-deficient (MCD) diet model of NASH. Male C57BL/6J mice (n = 28) were block-randomized to four groups (n = 7 each) for 10 weeks: standard diet (STD); MCD diet; STD + vancomycin (VANC); and MCD + VANC (2 mg/mouse ≈ 50 mg/kg, every 72 h). After 10 weeks, liver tissues were analyzed for histological changes, cytokine levels [interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor beta 1 (TGF-β1)], and immunohistochemical markers [ubiquitin and cytokeratin 18 (CK18)]. Cecal microbiota composition was evaluated with 16S ribosomal RNA (rRNA) sequencing. The MCD reproduced key NASH features (macrovesicular steatosis, lobular inflammation). Vancomycin shifted steatosis toward a microvesicular pattern and reduced hepatocyte injury: CK18 and ubiquitin immunoreactivity were decreased in MCD + VANC vs. MCD, and hepatic IL-8 and TGF-β1 levels were lower in MCD + VANC vs. STD. Taxonomically, STD mice had Lactobacillus-rich microbiota. The MCD diet alone reduced alpha diversity (α-diversity), modestly lowered Firmicutes and increased Desulfobacterota/Fusobacteriota. Vancomycin alone caused a much larger collapse in richness, depleting Gram-positive commensals and promoting blooms of Escherichia–Shigella, Klebsiella, Parabacteroides, and Akkermansia. In the MCD + VANC group, vancomycin profoundly remodeled the microbiota, eliminating key commensals (e.g., Lactobacillus) and enriching Desulfobacterota, Fusobacteriota, and Campylobacterota. Oral vancomycin in the MCD model of NASH improved liver injury markers and altered steatosis morphology, but concurrently reprogrammed the gut into a low-diversity, pathobiont-enriched ecosystem with near-loss of Lactobacillus. These findings highlight a therapeutic trade-off—hepatic benefit accompanied by microbiome cost—that should guide microbiota-targeted strategies for NAFLD/NASH. Full article

(1) Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver damage similar to alcoholic fatty liver disease, including triglyceride infiltration of hepatocytes, regardless of alcohol consumption. It leads to progressive liver damage, such as loss of liver function, cirrhosis, and liver cancer, and the response rate of drugs under clinical research is less than 50%. There is an urgent need for biomarkers to evaluate the efficacy of these drugs. (2) Methods: MASLD was induced in mice using a High-Fat diet (HF), Western diet (WD), and Methionine/Choline-Deficient diet (MCD) for 20 weeks (4 weeks for MCD). Liver tissue biopsies were performed, and the treatment effects of saponin and non-saponin feeds were evaluated. Fat accumulation and hepatic inflammation were measured, and mRNA sequencing analysis was conducted. The therapeutic effects were validated using patient-derived liver organoids. (3) Results: The NAFLD Activity Score (NAS) significantly increased in all MASLD models compared with controls. Saponin treatment decreased NAS in the HF and WD groups but not in the MCD group. RNA sequencing and PCA analysis showed that the HF saponin response samples were similar to normal controls. DAVID analysis revealed significant changes in lipid, triglyceride, and fatty acid metabolic processes. qRT-PCR confirmed decreased fibrosis markers in the HF saponin response group, and GSEA analysis showed reduced HAMP1 gene expression. (4) Conclusions: Among the diets, red ginseng was most effective in the HF diet, with significant effects in the saponin-treated group. The therapeutic efficacy was better when HAMP1 expression was increased. Therefore, we propose HAMP1 as a potential exploratory biomarker to assess the saponin response in a preclinical setting. In addition, the reduction of inflammation and hepatic iron accumulation suggests that saponins may exert antioxidant effects through modulation of oxidative stress. Full article

Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), involves inflammation, fibrosis, steatosis, and oxidative stress. Previous research from our lab shows that cannabigerol (CBG) reduces inflammation and fibrosis in male MASH mice, but its effects in females remain unknown. Given immune cell population changes in MASLD patients, this study examines CBG’s impact on methionine-choline deficient (MCD) diet-induced MASH in female mice. Methods: MCD-fed female mice are supplemented with two different doses for three weeks. Liver fibrosis, steatosis, oxidative stress, ductular reaction, and inflammation are assessed via Sirius Red, Oil Red O, immunohistochemistry, and immunofluorescence staining. Immune cell changes in non-parenchymal cells (NPCs) are analyzed via flow cytometry. Results: CBG treatment improves liver health by reducing leukocyte infiltration. Both CBG doses significantly decrease fibrosis, oxidative stress, ductular proliferation, and inflammation in MCD-fed mice, including monocyte and T lymphocyte reductions. Additionally, CBG downregulates mast cell activation, inhibiting transforming growth factor (TGF)-β1 release, thereby suppressing hepatic stellate cell activation. This reduces collagen deposition, fibrosis, and ductular proliferation. Conclusions: Our findings provide insights for pre-clinical and clinical research, highlighting CBG’s potential therapeutic role and dosage considerations in mitigating liver fibrosis and inflammation in female patients. Full article

Non-alcoholic fatty liver disease (NAFLD) has been associated with depression and inadequate response to antidepressants. While ketamine has demonstrated efficacy in treating depression, its impact on pre-existing liver injury and depression remains unclear. This study aimed to evaluate the effects of ketamine treatment in a murine model of depression and liver damage, considering age-related differences. Young and aged male C57BL/6N mice were submitted to chronic unpredictable mild stress (CUMS) and methionine–choline-deficient (MCD) diet to induce depressive-like behavior and NAFLD. Behavioral testing (sucrose preference test, open field test, novel object recognition test, Crawley’s sociability test) were used to assess ketamine’s (50 mg/kg) effect on behavior. Hepatic ultrasonography was utilized to evaluate liver status. The cortical and hippocampal NeuN+, GFAP+, and Iba1+ signals were quantified for each animal. Ketamine administration proved effective in relieving anhedonia and anxiety-like behavior, regardless of liver damage. Although ketamine treatment did not improve memory in animals with liver damage, it enhanced sociability, particularly in aged subjects. The acute administration of ketamine did not affect the severity of liver injury, but seems to affect astrogliosis and neuronal loss. Although animal models of depression only replicate certain clinical features of the condition, they remain valuable for evaluating the complex and varied effects of ketamine. By applying such models, we could demonstrate ketamine’s therapeutic versatility, and also indicate that responses to the treatment may differ across different age groups. Full article

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver condition with limited therapeutic options. To identify novel drug targets, we integrated bioinformatics, Mendelian randomization (MR), and colocalization analyses. Using the Gene Expression Omnibus (GEO) database, we identified differentially expressed genes and constructed protein–protein interaction (PPI) networks, pinpointing 10 hub genes. MR and colocalization analyses revealed that Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is causally associated with MAFLD and driven by the same causal variant locus, suggesting its potential as a therapeutic target. Molecular docking identified disogenin as a candidate small-molecule drug targeting UHRF1. Drug affinity responsive target stability (DARTS) assays confirmed direct binding between UHRF1 and disogenin. In vitro, disogenin significantly reduced UHRF1 mRNA and protein levels induced by free fatty acids (FFA) in AML12 and HepG2 cells, accompanied by decreased cellular total cholesterol (TC) and triglyceride (TG) levels. In vivo, disogenin administration alleviated hepatic lipid accumulation, inflammation, and fibrosis in methionine/choline-deficient (MCD)-diet-fed mice. This study identifies UHRF1 as a promising therapeutic target for MAFLD and validates disogenin as a potential therapeutic agent, providing a foundation for further investigation. Full article

Liver fibrosis, caused by chronic hepatic injury, is a major threat to human health worldwide, as there are no specific drugs available for its treatment. Natural compounds, such as berberine (BBR) and quercetin (QR), have shown the ability to regulate energy metabolism and protect the liver without significant adverse effects. Additionally, combination therapy (the cocktail therapy approach), using multiple drugs, has shown promise in treating complicated conditions, including liver injury. In this study, we prepared a salt formulation of BBR and QR (BQS) to enhance their combined effect on liver fibrosis. The formation of BQS was confirmed using various analytical techniques, including nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD), and scanning electron microscopy (SEM). The results demonstrated that the dissolution efficiency and bioavailability of QR significantly increased in the BQS form, aligning with that of BBR, compared to the physically mixed (BQP) form. Moreover, BQS exhibited a superior inhibitory effect on fibrosis compared to BQP in the human hepatic stellate cell line LX-2 by modulating lipid accumulation, inflammation, apoptosis, and the cell cycle. Furthermore, in a mouse model of hepatic fibrosis induced by methionine and choline-deficient (MCD) diets, BQS demonstrated enhanced anti-fibrotic activities compared to BQP. These findings suggest that BQS holds promise as a potential alternative treatment for liver fibrosis. Importantly, this study provides novel insights into achieving a cocktail effect through the salt formation of two or more drugs. The results highlight the potential of salt formulations in enhancing the therapeutic efficacy and consistent biological processes of drug combinations. Full article

Two different diets able to induce dietary hyperammonaemia (a methionine–choline-deficient (MCD) diet and a methionine-deficient diet enriched with ammonium acetate (MAD + 20% ammonium acetate)) were tested in a rat model. The diets were shown to have different modes of action, inducing significant hyperammonaemia (HA) and growth retardation in the rats, with different metabolic consequences. The MCD diet resulted in the development of endogenous HA, with a decrease in bilirubin levels and an increase in hepatic fat content. In contrast, the MAD + 20% ammonium acetate diet increased circulating ALP and haptoglobin levels and decreased liver mass. The above results suggest that the MCD diet deteriorated the liver function of the rats, resulting in the development of endogenous HA, while the MAD diet caused moderate changes in liver metabolism, resulting in the development of exogenous HA. Interestingly, the commonly used oral treatments Lactulose and Rifaximin did not ameliorate hyperammonaemia during or after the treatment period. In conclusion, even though the diets used in the current study caused somewhat similar hyperammonaemia, they seemed to provoke different metabolic consequences. The latter can have an impact on the severity of the resulting hyperammonaemia and thus on the hyperammonaemia-induced encephalopathy, resulting in the development of distinguishing cognitive and metabolic (liver) effects compared to other forms of encephalopathy. We hypothesized that these rat models, with significantly increased serum ammonia levels, along with different liver injuries, could serve as a suitable double animal model for the testing of new, oral enzyme therapies for hepatic encephalopathy in future studies. Full article

The aim of this study was to investigate the protective effects and potential mechanisms of Tetrahydrocurcumin (THC) on methionine–choline-deficient diet (MCD)-induced MASH in C57BL/6 mice by using multi-omics techniques. The C57BL/6 mice were fed with the MCD for 8 weeks to establish a MASH model, while THC (100 mg·kg⁻¹·d⁻¹) and obeticholic acid (6.5 mg·kg⁻¹·d⁻¹) were administered via gavage to the THC group and the positive control group, respectively. The biochemical indexes of the serum and liver were detected using kits. Liver tissue sections were taken to observe the pathomorphological changes. Serum lipid and bile acid contents were measured via LC-MS, and the changes in ileal intestinal flora were detected by 16S rDNA high-throughput sequencing technology. The results revealed that THC significantly attenuated oxidative stress and lipid accumulation in NCTC-1469 cells and relieved hepatic injury and oxidative stress, reduced hepatic TG content, and improved hepatic steatosis in mice. THC alleviated 34 lipid abnormalities caused by the MCD; increased the abundance and diversity of intestinal flora, the ratio of Firmicutes to Bacteroidota, and the abundance of the probiotic (Verrucomicrobiota, Christensenellaceae, Akkermansiaceae, Lachnospiraceae, Desulfovibrionaceae); and reduced the abundance of obesity-associated pathogenic flora such as Firmicutes. Bile acid analysis showed that THC administration reduced the levels of serum toxic bile acid 7-KDCA and CA. In addition, RT-qPCR studies showed that THC down-regulated the transcript levels of the hepatic lipogenesis-related genes Srebp1c, Acc1, Scd1, and Fas, and up-regulated the transcript levels of the hepatic bile acid secretion-related genes Mrp2 and Bsep. The above results suggest that THC may alleviate MCD-induced MASH by downregulating liver Srebp1c, Acc1, Scd1, and Fas levels to inhibit lipid synthesis, upregulating Mrp2 and Bsep levels to regulate serum toxic BA levels, up-regulating the abundance of intestinal probiotic flora, and down-regulating the abundance of intestinal harmful bacterial flora. The multi-omics findings from the above study identified potential new mechanisms by which THC alleviates MASH, providing new reference targets for the development of anti-MASH drugs. These results also offer a basis for screening clinical diagnostic biomarkers for MASH and provide new directions for personalized diagnosis and treatment. Full article

Background/Objectives: The pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) is closely associated with increased oxidative stress and lipid peroxidation. Coenzyme Q (CoQ) and selenium (Se) are well-established antioxidants with protective effects against oxidative damage. This study aimed to investigate the effects of CoQ and Se in ameliorating MASH induced by a methionine choline-deficient (MCD) diet in mice. Methods: C57BL/6J male mice were fed either a methionine choline-sufficient (MCS) or MCD diet and treated with vehicle, CoQ (100 mg/kg), Se (158 μg/kg), or their combination (CoQ + Se) for 4 weeks. Results: The MCD diet significantly increased hepatic steatosis, inflammation, and fibrosis compared to MCS controls. Treatment with CoQ and Se, particularly in combination, markedly reduced the MAFLD activity score, hepatic inflammation, and fibrosis. Combined supplementation of CoQ and Se significantly decreased serum alanine aminotransferase and aspartate aminotransferase levels and hepatic TG and cholesterol concentrations. CoQ and Se effectively mitigated hepatic oxidative stress by enhancing catalase and superoxide dismutase activities, increasing glutathione peroxidase (GPX) activity, and restoring the GSH/GSSG ratio. Lipid peroxidation markers, such as malondialdehyde and 4-hydroxynonenal, were significantly reduced. Furthermore, the expression of ferroptosis-related markers, including acyl-CoA synthetase long-chain family member 4, arachidonate 12-lipoxygenase, and hepatic non-heme iron content, was significantly downregulated, while GPX4 expression was upregulated by combined CoQ and Se treatment. Conclusions: CoQ and Se synergistically alleviate MASH progression by reducing oxidative stress and lipid peroxidation, which may contribute to the suppression of ferroptosis. Combined CoQ and Se supplementation demonstrates therapeutic potential for managing MASH and related liver injury. Full article