Search Results (3,161)

Obesity is a chronic and complex disease defined by the excessive deposition of fat and is highly associated with oxidative stress. Adzuki bean saponins (ABS) showed anti-obesity activity in our previous in vivo study; however, the active saponins of adzuki beans and potential mechanisms are still unclear. This research aims to elucidate the anti-obesity effects of ABS in improving lipid metabolism and oxidative stress, exploring the effective ingredients and potential molecular mechanisms through UHPLC-QE-MS analysis, network pharmacology, bioinformatics, and in vitro experiments both in the 3T3-L1 cell line and HepG2 cell line. The results indicate that ABS can improve intracellular lipid accumulation, adipogenesis, oxidative stress, and mitochondrial damage caused by lipid accumulation including ROS generation, abnormal mitochondrial membrane potential, and ATP disorder. Fifteen saponin components were identified with the UHPLC-QE-MS analysis. The network pharmacology and bioinformatics analyses indicated that the PI3K/Akt signaling pathway is associated with the bioactive effect of ABS. Through Western blotting and immunofluorescence analysis, the anti-obesity effect of ABS is achieved through regulation of the PI3K/Akt/GSK3β/β-catenin signaling pathway and activation of downstream transcription factor c-Myc in the lipid accumulation cell model, and regulation of β-catenin signaling and inhibition of downstream transcription factor C/EBPα in the adipocyte cell model. These results illustrate the biological activity of ABS in improving fat metabolism and oxidative stress by restoring mitochondrial function through β-catenin signaling, the PI3K/Akt/GSK3β/β-catenin signaling pathway, laying the foundation for its further development. Full article

The aim of this study was to analyze the functional properties of newly obtained films based on sodium alginate and lecithin with the addition of antioxidant-rich coffee extracts and to verify their potential as safe edible food packaging materials. In our study, we developed alginate–lecithin films enriched with green or roasted coffee bean extracts. The roasting process of coffee beans had a significant impact on the total phenolic content (TPC) in the studied extracts. The highest value of TPC (2697.2 mg GAE/dm³), as well as antioxidant activity (AA) (17.6 mM T/dm³), was observed for the extract of light-roasted coffee beans. Films with the addition of medium-roasted coffee extracts and baseline films had the highest tensile strength (21.21 ± 0.73 N). The addition of coffee extract improved the barrier properties of the films against UV light with a decrease in the transmittance values (200–400 nm), regardless of the type of extract added. Studies on Caco-2, HepG2 and BJ cells showed that digestated films were non-cytotoxic materials (100–0.1 μg/cm³) and had no negative effect on cell viability; an increase was noted for all cell lines, the highest after 48 h in a dose of 1 μg/cm³ for a film with medium-roasted coffee (194.43 ± 38.30) for Caco-2. The tested films at 20% digestate concentrations demonstrated the ability to reduce nitric oxide (NO) production in the RAW264.7 cell line by 25 to 60% compared to the control. Each of the tested films with coffee extracts had growth inhibitory properties towards selected species of bacteria. Full article

The early diagnosis of tumorigenesis is crucial for clinical treatment, but the resolution and sensitivity of conventional short-wavelength biomarkers are not ideal because of the complicated interference in living tissue. Herein, a nicotinamide adenine dinucleotide (NAD⁺)-responsive probe with deep-red emissive ratiometric fluorescence was synthetized as a promising target for energy metabolism patterns during tumorigenesis. Interestingly, the solvents H₃PO₄ and 2,2′-dithiodibenzoic acid enhanced the red emission (640 and 680 nm) of o-phenylenediamine-based carbon dots (CDs), leading to the formation of a nanoscale graphite-like skeleton covered with -P=O, -CONH-, -COOH and -NH₂ on their surfaces. Meanwhile, this method exhibited high sensitivity to the discriminating target NAD⁺, with a detection limit of 63 μM due to the inner filter effect and fluorescence resonance energy transfer process between NAD⁺ and CDs, which is superior to the reported capillary electrophoresis and liquid chromatographic detection methods (the reported detection limit was about 0.2 mM) in complex biological samples and even cancer cells. Encouragingly, NAD⁺ significantly promoted nucleus-targeting fluorescence and cell migration compared to GSH and pH stimulation, which were gradually eliminated in human hepatocellular carcinoma (HepG2) cells after 2-deoxy-d-Glucose inhibited the glycolytic phenotype. The proposed method holds great potential for the temporal and spatial resolution of NAD⁺-dependent tumor diagnosis in complex living systems. Full article

Pinus species are notable in Mediterranean regions due to their ecological and economic importance. Various parts of these species are widely used in traditional medicine, especially pinecones, which are a significant source of bioactive compounds. The current study aimed to evaluate the phytochemical composition and biological properties of the aqueous extracts obtained by maceration from three Pinus petal fractions, from P. halepensis Mill., P. brutia Ten., and P. pinea L. (APW, BPW, and PPW respectively), and the core fractions of the same species (ACW, BCW, and PCW respectively). The results showed that APW demonstrated superior performance compared to other species and fractions (p ≤ 0.05), with the highest total polyphenol content (203.51 mg GAE/g DW) and the highest antioxidant potential (IC₅₀ = 13.51 µg/mL) against DPPH free radical. All extracts showed high anticancer activity against HeLa and HepG2 cancer cell lines, and low inhibition against HEK-293, a normal cell line (<15%), indicating that none of extracts have any toxicity effect. Furthermore, only APW exhibits a significant inhibition against α-glucosidase with 77.20% at 50 µg/mL. HPLC-DAD analysis was conducted to identify 14 compounds. GC-MS analysis was conducted to identify 28 compounds, of which 11 were detected for the first time in this species. This study offers valuable insights into phytochemistry and potential therapeutic applications of pinecones. Full article

Background/Objectives: Sorafenib and lenvatinib are tyrosine kinase inhibitors used in hepatocellular carcinoma (HCC) treatment. This study investigates how hepatitis B virus (HBV) infection affects their efficacy in HepG2 hepatoma cells. Methods: HepG2 and HBV-infected HepG2/2215 cells were treated with varying concentrations of both drugs. The cell viability, cell cycle gene expression, cycle progression, and phosphorylation levels of ERK and AKT were analyzed. Results: The HBV-infected cells showed significant alterations in their cell cycle gene expressions, with an 80-fold increase in CCND2 expression and a higher proportion of cells in the G2/M phase, indicating enhanced proliferation. While both drugs decreased HepG2 cell viability in a concentration-dependent manner, HBV infection conferred resistance, as evidenced by the increased viable cells in the HepG2/2215 cultures. Sorafenib and lenvatinib decreased key cyclin and cyclin-dependent kinase expressions in uninfected cells, with less effect on the HBV-infected cells. Both drugs lowered the pERK and pAKT levels in the HepG2 cells. In the HBV-infected cells, sorafenib reduced the pERK and pAKT levels to a lesser extent. However, treatment with lenvatinib elevated the levels of pERK and pAKT. Conclusions: In conclusion, HBV infection increases resistance to both sorafenib and lenvatinib in hepatoma cells by influencing the cell cycle regulatory genes and critical signaling pathways. However, the resistance mechanisms likely differ between the two medications. Full article

(1) Background: A preliminary investigation of Protected Designation of Origin (PDO) wines (red and rosé) produced from Negroamaro grapes—a native Salento (Apulia, Southern Italy) vine that is part of the Salice s.no PDO area—was performed in this work. (2) Methods: ¹H-NMR spectroscopy, in combination with multivariate statistical analysis (MVA), was employed to characterize the metabolic profiles of 39 wine samples. Spectrophotometric methods were used to obtain preliminary information on the phenolic composition of wines and the associated antioxidant activity. The HepG2 liver cell line was used to assess the biological activity (effect on cell viability and genotoxicity activity) of wine samples. (3) Results: The NMR spectra analysis revealed the presence of signals ascribable to phenolic compounds such as gallic, hydroxycinnamic, and syringic acids. Relative content of these metabolites has been shown to be higher in red than in rosés wines and related to the wine producers. Interestingly, a similar pattern was observed in biological analyses. Red wines compared to the rosé wines display great variations in antioxidant capacity when evaluated as fresh samples using the DPPH and ORAC methods. Furthermore, all red wines exhibited a concentration-dependent decrease in cellular viability and live cells; this phenomenon is much less pronounced in rosé wines. (4) Conclusions: The resulting findings from this study reveal that winemaking operations could lead to final products with different chemical compositions and related properties. Even when starting from the same crop variety and cultivation region, significant differences were observed in the wine samples NMR-metabolic profiles and in vitro biotoxicological activity. Full article

Background/Objective: Long-term intake of a high-fat diet (HFD) leads to obesity and gut dysbiosis. AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Herein, we investigated the impacts of Lactobacillus (Lactiplantibacillus) plantarum P111 and Bifidobacterium longum P121, which suppressed dexamethasone-induced adipogenesis in 3T3 L1 cells and increased lipopolysaccharide-suppressed AMPK activation in HepG2 cells, on HFD-induced obesity, liver steatosis, gut inflammation and dysbiosis, and depression/cognitive impairment (DCi)-like behavior in mice. Methods: Obesity is induced in mice by feeding with HFD. Biomarker levels were measured using immunoblotting, enzyme-linked immunosorbent assay, and immunofluorescence staining. Results: Orally administered P111, P121, or their mix LpBl decreased HFD-induced body weight gain, epididymal fat pad weight, and triglyceride (TG), total cholesterol (TC), and lipopolysaccharide levels in the blood. Additionally, they downregulated HFD-increased NF-κB activation and TNF-α expression in the liver and colon, while HFD-decreased AMPK activation was upregulated. They also suppressed HFD-induced DCi-like behavior and hippocampal NF-κB activation, NF-κB-positive cell population, and IL-1β and TNF-α levels, while increasing the hippocampal BDNF-positive cell population and BDNF level. The combination of P111 and P122 (LpBl) also improved body weight gain, liver steatosis, and DCi-like behavior. LpBl also mitigated HFD-induced gut dysbiosis: it decreased Desulfovibrionaceae, Helicobacteriaceae, Coriobacteriaceae, and Streptococcaceae populations and lipopolysaccharide production, which were positively correlated with TNF-α expression; and increased Akkermansiaceae, Bifidobacteriaceae, and Prevotellaceae populations, which were positively correlated with the BDNF expression. Conclusions: P111 and/or P121 downregulated adipogenesis, gut dysbiosis, and NF-κB activation and upregulatde AMPK activation, leading to the alleviation of obesity, liver steatosis, and DCi. Full article

Background: Sulfonamide acridine derivatives have garnered significant attention from medicinal chemists due to their diverse range of biological activities. Methods: In this study, eleven compounds were synthesized according to the literature, and their impact on cell growth inhibition, induction of apoptosis, and cell cycle distribution were assessed in three different cell lines. Their inhibitory effects on the topoisomerase (Topo) I and II were investigated in vitro. Molecular docking studies were conducted to predict the binding affinities of these compounds for crystallized downloaded topoisomerases. Results: The compounds were examined in vitro for their anticancer activity against human hepatic (HepG2) colon (HCT-8) and breast (MCF-7) carcinoma cell lines. Compound 8b was the most active against HepG2, HCT-116, and MCF-7 with IC₅₀ 14.51, 9.39, and 8.83 µM, respectively, compared to Doxorubicin as reference. In addition, it demonstrated the highest potency among the tested compounds against Topo-I, with an IC₅₀ value of 3.41 µg/mL compared to the control camptothecin (IC₅₀ of 1.46 μM). Compound 7c displayed a significant inhibitory effect on Topo-II, with an IC₅₀ of 7.33 μM, compared to an IC₅₀ value of 6.49 μM via Doxorubicin, the control. Compounds 7c and 8b were assessed against topoisomerases showing induction of apoptosis and a reduction in the S phase of the cell cycle. Molecular docking demonstrated interaction with the active site as with those exhibited by the co-crystallized ligands of the crystallized proteins in both topoisomerases. Conclusion: Compounds 7c and 8b hold promise as potential anticancer drugs due to their anti-proliferative and proapoptotic effects, which are mediated by their action on the topoisomerase enzyme, particularly Topo II. Full article

Rosa Roxburghii (RR), a traditional Chinese medicinal fruit, is rich in bioactive substances that make it a potential natural antioxidant resource. This research aimed to study the antioxidant properties of RR by in vitro experiments and through intracellular assessment in H₂O₂-induced HepG2 cells. A non-targeted metabolic analysis was conducted to indicate changes in intracellular and extracellular metabolites. Differential metabolites and metabolic pathways were explored using PCA, PLS-DA, and KEGG pathway analysis. The results showed that RR rich in bioactive substances exhibited a significant antioxidative property in vitro and intracellularly. This property may be achieved by scavenging free radicals, increasing the activity of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and the levels of bicinchoninic acid (BCA) while reducing the reactive oxygen species (ROS) generation. This study identified 13 differential metabolites intracellularly and 7 extracellularly, among which the key differential metabolites included D-glucopyranose, D-mannose, fructose, citric acid, malic acid, cholesterol, and cholestenone. These key metabolites primarily regulated glucose-related metabolism, the citrate cycle, and the primary bile acid biosynthesis pathway in H₂O₂-induced HepG2 cells. These findings provide potential application evidence of RR in the development of natural resources for functional foods. Full article

Berberine hydrochloride (BH) extracted from Coptis chinensis (CC) and Matrine (MT) separated from Sophora flavescens (SF) are alkaloids with potent anti-bacterial, anti-inflammatory, and anti-tumor effects. Motivated by the clinical practice of using CC and SF together, we aimed to demonstrate that the synergistic application of the natural compounds BH and MT could enhance therapeutic effects and minimize side effects. Two types of liposomes, liposomes containing only BH (BH-LP) and liposomes containing both BH and MT (BH-MT-LP), were successfully prepared via the reverse evaporation method. The liposome preparation process was optimized by single-factor screening and the Box–Behnken experimental design method. The results showed that the liposomes had particle sizes in the range of 222.7 to 235.4 nm, polydispersity indicated in the range of 11.8% to 23.3%, and zeta potentials in the range of −35.9 to −31.1 mv. BH-MT-LP showed superior anti-tumor activity against MDA-MB-231, HepG-2, and HGC-27 cells in vitro. The incorporation of MT effectively promoted the anti-tumor effect of BH, while the controlled release from liposomes further enhanced the therapeutic efficacy of BH. Furthermore, based on the flow cytometry results, we speculated that BH-MT-LP might promote apoptosis by blocking the G1 phase of cells and inducing cell death. In conclusion, BH-MT-LP provides evidence for the combined use of natural compounds as a stable, safe, and practical drug delivery system for the treatment of potential cancers. Meanwhile, the successful preparation for BH-MT-LP also provides a new approach to the combined use of traditional Chinese medicine ingredients. Full article

Background: Gold nanoparticles (NPs) have drawn great attention in the area of biomedical research with their relatively safe and versatile properties. This study aimed to synthesize long-lasting exendin-4-coated gold NPs (EX-ABD-AFF-GoldNPs) and evaluate their anti-diabetic effects in vivo. Methods: In the present study, EX-ABD-AFF-GoldNPs were synthesized using a simple one-step aqueous reduction method. The physical characterization of the prepared particles verified the successful formation of the EX-ABD-AFF-GoldNPs through dynamic light scattering (DLS), transmission electron microscopy (TEM), ultraviolet–visible (UV-VIS) light spectroscopy, and Fourier transform infrared spectroscopy (FTIR). The anti-hyperglycemic and anti-obesity effects were assessed in high-fat diet (HFD)-fed obese diabetic mice. Additionally, pharmacokinetics (PK) and biodistribution studies were performed to verify the long-lasting properties. Results: The EX-ABD-AFF-GoldNPs were conglomerates of smaller globular-shaped particles, and the average size was 110(±14) nm, based on the TEM images. Safety assessments using Min6, HepG2, and B16F10 cell lines demonstrated low cytotoxicity, with over 80% cell viability up to the highest tested concentration of 150 μg/mL (as EX-ABD-AFF). Notably, the animal studies showed that the EX-ABD-AFF-GoldNPs exhibited significant hypoglycemic activity, comparable to the EX-ABD-AFF, in the HFD-fed mice. A 4-week treatment with EX-ABD-AFF-GoldNPs produced similar reductions in blood glucose and body weight to the EX-ABD-AFF, without any apparent toxicity. Furthermore, the PK and biodistribution study results confirmed the long-lasting properties (plasma half-life: 43.6 h) of the particles. Conclusions: Overall, this study demonstrated that the preparation of therapeutic protein-loaded gold NPs is feasible and, despite their much larger size compared with the protein, EX-ABD-AFF-GoldNPs can be successfully absorbed through the subcutaneous route and show nearly equivalent hypoglycemic activity to the EX-ABD-AFF protein. Finally, this study showed that long-lasting properties could be acquired by only coating EX-ABD-AFF onto gold NPs. Full article

A benzothiazole-based derivative aggregation-induced emission (AIE) fluorescent ‘turn-on’ probe named 2-(2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)benzo[d]thiazole (probe BT-BO) was developed and synthesized successfully for detecting hydrogen peroxide (H₂O₂) in living cells. The synthesis method of probe BT-BO is facile. Probe BT-BO demonstrates a well-resolved emission peak at 604 nm and the ability to prevent the interference of reactive oxygen species (ROS), various metal ions and anion ions, and good sensitivity. Additionally, the probe boasts impressive pH range versatility, a fast response time to H₂O₂ and low cytotoxicity. Finally, probe BT-BO was applied successfully to image A549 and Hep G2 cells to monitor both exogenous and endogenous H₂O₂. Full article

Hydroxycamptothecin (HCPT) is commonly used in the treatment of liver cancer; however, its low water solubility and poor stability significantly limit its clinical application. In recent years, research on exosomes has deepened considerably. Exosomes possess a unique phospholipid bilayer structure, enabling them to traverse tissue barriers, which provides natural advantages as drug carriers. Nevertheless, delivering exosomes safely and efficiently to target cells remains a major challenge. In this study, we utilized the affinity of the SP94 peptide for human liver cancer cell receptors. HCPT was coated with exosomes in our experimental design, and the exosome membrane was modified with SP94 peptide to facilitate drug delivery to liver cancer cells. Exosomes were purified from bone marrow mesenchymal stem cells, and targeted peptides were attached to their surfaces via post-insertion techniques. Subsequently, HCPT was incorporated into the exosomes through electroporation. Using the HepG2 hepatoma cell line, we evaluated a series of in vitro pharmacodynamics and studied pharmacokinetics and tissue distribution in animal models. The results indicated that ligand-targeted, modified drug-carrying exosomes significantly enhance drug bioavailability, prolong retention time in vivo, and facilitate liver targeting. Moreover, this approach reduces drug nephrotoxicity, enhances anti-tumor efficacy, and lays the groundwork for the development of novel liver cancer-targeting agents. Full article

The crystal structure and topology analyses of a new bromo-Mn(II) complex with 2,4-bis(3,5dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine (MBPT) were reported. Its structure was confirmed using single-crystal X-ray diffraction to create the formula [Mn(MBPT)Br(H₂O)₂]ClO₄. Its crystal system was monoclinic and its space group was p2₁. The Mn(II) was coordinated with MBPT as a NNN-pincer ligand, with one bromide ion in the equatorial plane. The two axial terminals were occupied by two trans water molecules. H…H, N…H, Br…H, C…H and O…H were the predominant intermolecular contacts, while Br…H, O…H and C…O were the significant contacts based on Hirshfeld analysis. Moreover, anion–ᴨ interaction was found between C(s-triazine) and O(perchlorate). This complex had better antioxidant activity than the free ligand (MBPT). In addition, the cytotoxicity of the [Mn(MBPT)Br(H₂O)₂]ClO₄ complex showed better results against HepG-2 and MCF-7 cells, recording IC₅₀ values of 31.11 ± 2.04 and 50.05 ± 2.16 µM, respectively, compared to the free ligand (IC₅₀ = 671.44 ± 21.41 and 1113.55 ± 29.77 µM). In comparison to cis-platin as a reference drug, the IC₅₀ values were 63 and 80 μM, respectively, which indicated the promising anticancer activity of the studied compound against both cell lines. In terms of the safety of normal cells, the Mn(II) complex recorded a high IC₅₀ value of 359.10 ± 8.72 µM against the WI-38 non-cancerous cell line. The complex showed better activity towards Staphylococcus aureus, Bacillus subtilis, and Proteus vulgaris relative to the free MBPT, but had low to moderate activity compared to Gentamycin as an antibacterial positive control. Full article