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

This study explored the potential of saponins from Korean Red Ginseng to target the PINK1/Parkin mitophagy pathway, aiming to enhance insulin sensitivity in hepatocytes—a key factor in metabolic disorders like metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes. Results from both in vitro and in vivo experiments showed increased expression of PINK1 and Parkin, activating mitophagy and reducing oxidative stress through reduction in mitochondrial and total reactive oxygen species. Additionally, improvements in insulin signaling were observed, including the upregulation of phosphorylated IRS and AKT, and downregulation of gluconeogenic enzymes, underscoring the saponins’ efficacy in boosting insulin sensitivity. The findings highlighted Korean Red Ginseng-derived saponins as potential treatments for insulin resistance and related metabolic conditions.

Background/Objectives: Chronic stress disrupts neurochemical balance, triggers inflammation, and compromises neuronal integrity, contributing to the development of stress-related disorders. This study aimed to evaluate the preventative effects of Tremella fuciformis Berk (TF) enzymatic extracts on chronic restraint stress (CRS)-induced behavioral, neurochemical, and inflammatory dysfunctions in mice. Methods: Male C57BL/6N mice were administered TF at doses of 50 mg/kg and 100 mg/kg daily via oral gavage for 21 days during CRS exposure. Behavioral assessments, including anxiety and depression-like behavior tests, were conducted. Neurochemical and inflammatory markers were analyzed using PCR and ELISA, while histological examinations of hippocampal regions were performed to assess neuronal integrity. In vitro assays evaluated neuronal cell viability, protection against corticosterone (CORT)-induced cytotoxicity, and inhibition of monoamine oxidase (MAO) activity. Results: TF supplementation alleviated CRS-induced weight loss, normalized serum CORT levels, increased locomotor activity, reduced immobility time, and decreased anxiety-like behaviors. TF upregulated brain-derived neurotrophic factor (BDNF) mRNA, downregulated pro-inflammatory markers (CXCL2, iNOS, IFNG), and mitigated neuronal apoptosis in the hippocampus. In vitro, TF improved neuronal cell viability, protected against CORT-induced cytotoxicity, and significantly inhibited MAO activity, particularly MAO-A. Conclusions: These findings demonstrate the neuroprotective and anti-stress effects of Tremella fuciformis Berk enzymatic extracts, supporting its potential as a natural therapeutic intervention for stress-related disorders.