miR-302 protects the liver from glucolipotoxicity-induced lipid accumulation through activating AMPK and suppressing Elovl6 in HepG2 cells and also in mice.

Identification and molecular mechanism of novel antioxidant peptides from okara fermentation broth with Bacillus amyloliquefaciens YP2: In silico and in vitro analysis.

Macrocyclic histone deacetylase inhibitor-based near-infrared-responsive ionic nanomedicines for enhanced cancer therapy.

Isoastragaloside II modulates PPAR-α/FXR signaling and bile acid metabolism to ameliorate cholestatic liver diseases (CLD).

Mitochondria-targeted redox-logic carbon dots for in vivo realtime visualization of peroxynitrite during wound-healing.

Novel benzimidazole-based thioamide derivatives as potential anticancer agents: synthesis, biological evaluation, and in silico studies.

Total glucosides of picrorhizae rhizome (TGPR) are a promising candidate drug for treating non-alcoholic steatohepatitis (NASH). To clarify the material basis underlying its efficacy, it is crucial to characterize the cellular pharmacokinetics of TGPR. A highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established in this study for the simultaneous quantification of picroside I, II, III, and IV from TGPR in HepG2 cells and their subcellular fractions (nucleus, mitochondria, cytoplasm). Additionally, molecular docking and cellular thermal shift assay (CETSA) were employed to investigate the binding of TGPR to ATP-citrate lyase (ACLY). The results showed that the analytical method was fully validated and within acceptable limits. All four TGPR components could enter HepG2 cells, reaching peak time at approximately 1.5 h, with picroside II exhibiting the highest exposure levels. In the nucleus and cytoplasm, picroside I and II exhibited relatively high affinity and did not reach saturation within 24 h. CETSA and molecular docking confirmed that TGPR directly bound to ACLY to enhance its thermal stability. In conclusion, this study first reveals the cellular pharmacokinetic characteristics of TGPR in HepG2 cells and identifies ACLY as its direct target, providing scientific evidence for further exploring the potential targets and mechanisms of TGPR.

Hypercholesterolemia is a major risk factor for cardiovascular disease, necessitating the development of effective and safe lipid-lowering interventions. This study evaluated the antihypercholesterolemic effects of KGC11o, a red ginseng oil obtained via supercritical fluid extraction, using both HepG2 cells and a high-fat/high-cholesterol diet-induced hypercholesterolemic rat model. KGC11o treatment significantly improved serum and hepatic lipid profiles, reduced markers of liver injury, and enhanced fecal cholesterol excretion. At the molecular level, KGC11o modulated the expression of key genes involved in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl-CoA reductase), esterification (acyl-CoA:cholesterol acyltransferase), transport (CETP, LPL), and catabolism (LCAT, cholesterol 7α-hydroxylase). Collectively, these findings suggest that KGC11o may serve as a safe, food-derived functional ingredient with potential benefits for the management of hypercholesterolemia and related metabolic disorders. Further studies are warranted to elucidate its molecular mechanisms and to confirm its clinical efficacy.

Polychlorinated biphenyls (PCBs), particularly Aroclor 1254 (A1254), are persistent environmental contaminants with hepatotoxic, genotoxic, and pro-oxidant properties. The liver, as the main organ for xenobiotic metabolism, is highly vulnerable to PCB-induced oxidative stress and DNA damage. Curcumin, a polyphenolic compound from Curcuma longa, exhibits potent antioxidant, anti-inflammatory, and cytoprotective effects. This study investigated the oxidative, genotoxic, apoptotic, and mutagenic effects of A1254 in HepG2 cells and evaluated curcumin's protective potential. Cells were exposed to sub-cytotoxic concentrations of A1254 (2.5-25 µM), curcumin (0.5-2 µM), and their combinations. ROS levels, antioxidant enzyme activities, oxidative biomarkers, and total antioxidant capacity were measured. DNA damage was assessed via 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-oxoguanine glycosylase (OGG1), and Comet assays. Apoptosis was evaluated by caspase-3 and -8 activities, and mutagenicity via Ames (TA98/TA100) and HPRT assays. A1254 disrupted redox homeostasis, elevating ROS and oxidative damage while depleting glutathione, thiols, and enzymatic antioxidants. Curcumin co-treatment restored antioxidant defenses and mitigated oxidative damage. Genotoxicity induced by A1254, indicated by increased 8-OHdG and DNA strand breaks, was markedly reduced by curcumin, which also attenuated apoptotic responses. These results demonstrate that A1254 exerts multifaceted cytotoxicity via oxidative stress, DNA damage, apoptosis, and mutagenicity, and that curcumin effectively ameliorates these effects, supporting its potential as a hepatoprotective and genoprotective agent against PCB-induced toxicity.

Discovery of Tetrazolone derivatives as potent PPARα/δ dual agonists for metabolic dysfunction-associated steatohepatitis.

Tailoring lipid-polymer hybrid nanoparticles as smart nanocarriers for entacapone delivery for managing Parkinson's disease.

Synthesis of mitochondria-targeted podophyllotoxin derivatives for the imaging and antiproliferation of liver cancer.

A label-free magnetic bead affinity approach for direct target identification of herbal extract: Ganoderma lucidum as a case.

Chilled beef preservation by quaternized areca-husk cellulose nanocrystals and oregano essential oil encapsulated in a zeolitic imidazolate framework-8 in synthesized composite films.

• Three styryl-benzonitrile chromophores 3, 4 , and 5 were synthesized and characterized by IR, NMR, and MS tools. • The styryl-benzonitrile compounds display clear intramolecular charge-transfer behavior, which helps separate charge but also tends to suppress their fluorescence output. • The absorption spectra of styryl-benzonitriles disclosed the piperidinyl 3 had the highest Δ E max , while the emission showed the morpholino 4 . • The cytotoxic activity demonstrated compound 5 as the safest one toward normal cells. • In docking studies against Escherichia coli DNA gyrase B, chromophore 5 displayed the strongest binding energy Styryl-Benzonitrile chromophores 3, 4 , and 5 were synthesized from diethyl 4-cyanobenzyl phosphonate ( 1 ) and benzaldehyde derivatives ( 2 ) via the Horner-Wadsworth-Emmons reaction. The trans configuration of the synthesized chromophores 3 - 5 has been verified by the distinctive nitrile stretching band (at ∼2210 cm⁻¹) and coupling constants (J ≈ 15.5 Hz). The DFT studies indicated that the HOMO was located on the donor fragment and the LUMO was spread on the benzonitrile acceptor fragment, confirming the important intramolecular charge transfer (ICT). Chromophore 5 displayed the smallest HOMO-LUMO gap = 2.82 eV, which correlated well to red-shifted absorption (λ max = 393 nm) and emission (λ em = 561 nm). The absorption spectra of these probes in varied solvents revealed that the piperidinyl 3 had the highest Δ E max (+3.09 kcal.mol -1 ), however, their emission spectral data presented hybrid 4 as the most polarity-induced (Δ E max +3.56 kcal·mol -1 ). Biologically, chromophore 5 unveiled the highest cytotoxic effectiveness towards HepG2 cells (IC₅₀ = 19.04±0.13 μM), with a higher selectivity index (SI = 4.6). Docking studies on DNA gyrase B (PDB: 1HNY, resolution 1.59 Å) showed a good binding (S = -5.97 kcal·mol -1 ) with important H-bonding bindings with Arg195 and Asp300. As well, the pharmacokinetic profiles of the synthesized chromophores indicated that all probes have auspicious drug-likeness properties, rendering them suitable for further evaluation.

Identification of novel quinoxaline linked oxadiazole derivatives as α-glucosidase inhibitors through homology modelling based in silico screening and in vitro evaluation.

Isopsoralen-induced hepatotoxicity: The regulatory role of endoplasmic reticulum stress-triggered mitochondrial dysfunction and apoptosis.

Hesperetin alleviates high-fat diet-induced NAFLD by activating FXR to modulate ferroptosis homeostasis and suppress inflammation.

Rational design of a stable W/O lipid emulsion for enhanced oral delivery of vinblastine.

Chitooligosaccharide-alginate selenium nanoparticles induce ferroptosis in hepatocellular carcinoma by amplifying redox imbalance.