Search Results (3,373)

Annona amazonica R.E. Fries (synonyms Annona amazonica var. lancifolia R.E. Fries), popularly known in Brazil as “envireira”, is a tropical tree belonging to the Annonaceae family and is traditionally used as a food source. In this work, the in vitro and in vivo anti-liver cancer effects of essential oil (EO) from A. amazonica leaves were investigated for the first time. The chemical composition of the EO was evaluated via GC–MS and GC–FID. The alamar blue assay was used to evaluate the cytotoxicity of EOs against different cancerous and noncancerous cell lines. Cell cycle analyses, YO-PRO-1/PI staining, and rhodamine 123 staining were performed via flow cytometry in HepG2 cells treated with EO. The in vivo antitumor activity of EO was evaluated in NSG mice that were xenografted with HepG2 cells and treated with EO at a dose of 60 mg/kg. The major constituents (>5%) of the EO were (E)-caryophyllene (32.01%), 1,8-cineole (13.93%), α-copaene (7.77%), α-humulene (7.15%), and α-pinene (5.13%). EO increased apoptosis and proportionally decreased the number of viable HepG2 cells. The induction of DNA fragmentation and cell shrinkage together with a significant reduction in the ΔΨm in EO-treated HepG2 cells confirmed that EO can induce apoptosis. A significant 39.2% inhibition of tumor growth in vivo was detected in EO-treated animals. These data indicate the anti-liver cancer potential of EO from A. amazonica leaves. Full article

Aizoon africanum (L.) Klak (Synonym Galenia africana L.) is traditionally used for a variety of medicinal purposes; however, it has been reported to cause liver damage and severe ascites, particularly in sheep and Angora goats in the arid regions of the Western Cape. This study explores its cytotoxic properties to identify potential cytotoxic compound(s) in the plant. The methanolic extract of A. africanum was re-investigated and subjected to various chromatographic techniques, including preparative HPLC, resulting in the isolation of eight compounds (1–8). Structural elucidation was primarily based on NMR data. Among the isolated compounds, four were flavanones, one was a flavonone, and three were chalcones. Notably, compound 8 was identified as a new chalcone, while compounds 2 and 3 were reported for the first time from this plant. The toxicity of these isolated compounds was evaluated against the HepG2 and SH-SY5Y cancer cell lines using the MTT assay. We further investigated markers of cell death using spectrophotometric and luminometric methods. Among the isolated compounds, 7 and 8 exhibited cytotoxic activities within the range of 3.0–20.0 µg/mL. Notably, the compounds demonstrated greater cytotoxicity towards liver-derived HepG2 cells compared to the neuronal SH-SY5Y cell line. Compound 7 (2′,4′-dihydroxychalcone) was identified as inducing apoptosis through the intrinsic pathway without causing overt necrosis. The findings indicate that the phytochemicals derived from A. africanum exhibit differential cytotoxic effects based on cell type, suggesting potential for developing novel anticancer agents, particularly compound 7. Additionally, the identification of compound 8 provides insight into the liver toxicity of this plant observed in sheep in South Africa. Full article

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article

Several natural products have been shown to display antiviral activity against the hepatitis B virus (HBV), among a number of other viruses. In a previous study, the hydro-alcoholic extracts (n = 66) of 31 species from the Venezuelan Amazonian rain forest were tested on the hepatoma cell line HepG2.2.15, which constitutively produces HBV. One of the species that exerted inhibitory activity on HBV replication was Senna silvestris. The aim of this study was the bioassay-guided purification of the ethanol fraction of leaves of S. silvestris, which displayed the most significant inhibitory activity against HBV. After solvent extraction and two rounds of reverse-phase HPLC purification, NMR analysis identified salsolinol as the compound that may exert the desired antiviral activity. The purified compound exerted inhibition of both HBV DNA and core HBV DNA. Pure salsolinol obtained from a commercial source also displayed anti-HBV DNA inhibition, with an approximate MIC value of 12 µM. Although salsolinol is widely used in Chinese traditional medicine to treat congestive heart failure, it has also been associated with Parkinson’s disease. More studies are warranted to analyze the effect of changes in its chemical conformation, searching for potent antiviral, perhaps dual agents against HBV and HIV, with reduced toxicity. Full article

This research focuses on designing polymer membranes as biocompatible materials using home-built electrospinning equipment, offering alternative solutions for tissue regeneration applications. This technological development supports cell growth on biomaterial substrates, including hepatocellular carcinoma (Hep-G2) cells. This work researches the compatibility of polymer membranes (fiber mats) made of polyvinylidene difluoride (PVDF) for possible use in cellular engineering. A standard culture medium was employed to support the proliferation of Hep-G2 cells under controlled conditions (37 °C, 4.8% CO₂, and 100% relative humidity). Subsequently, after the incubation period, electrochemical impedance spectroscopy (EIS) assays were conducted in a physiological environment to characterize the electrical cellular response, providing insights into the biocompatibility of the material. Scanning electron microscopy (SEM) was employed to evaluate cell adhesion, morphology, and growth on the PVDF polymer membranes. The results suggest that PVDF polymer membranes can be successfully produced through electrospinning technology, resulting in the formation of a dipole structure, including the possible presence of a polar β-phase, contributing to piezoelectric activity. EIS measurements, based on R_ct and C_dl values, are indicators of ion charge transfer and strong electrical interactions at the membrane interface. These findings suggest a favorable environment for cell proliferation, thereby enhancing cellular interactions at the fiber interface within the electrolyte. SEM observations displayed a consistent distribution of fibers with a distinctive spherical agglomeration on the entire PVDF surface. Finally, integrating piezoelectric properties into cell culture systems provides new opportunities for investigating the influence of electrical interactions on cellular behavior through electrochemical techniques. Based on the experimental results, this electrospun polymer demonstrates great potential as a promising candidate for next-generation biomaterials, with a probable application in tissue regeneration. Full article

(1) Background: Epidemiological studies link ozone (O₃) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O₃ were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related to impaired glucose tolerance and insulin resistance were screened through the Comparative Toxicogenomics Database (CTD), and verified using quantitative real-time PCR. In addition, liver histopathological observations and the determination of basic biochemical indicators were conducted, and targeted metabolomics analysis was performed on the liver to verify glycogen levels and gene expression. In vitro validation was conducted with HepG2 and Min6 cell lines. (3) Results: Fasting blood glucose and insulin resistance were elevated following O₃ exposure. Given that the liver plays a critical role in glucose metabolism, we further investigated hepatocyte apoptosis and alterations in glycogen metabolism, including reduced glycogen levels and genetic dysregulation. Metabolomics analysis revealed abnormalities in fructose metabolism and glycogen synthesis in the livers of the O₃-exposed group. In vitro studies demonstrated that oxidative stress enhances both liver cell apoptosis and insulin resistance in pancreatic islet β cells. (4) Conclusions: O₃ triggers prediabetes symptoms via hepatic metabolic dysfunction and hepatocyte apoptosis. The identified metabolites and genes offer potential as early biomarkers and therapeutic targets. Full article

In this study, using 70% anhydrous ethanol as the extraction solvent, Moringa oleifera Lam. seed powder was extracted with the microwave-assisted extraction method, followed by purification using macroporous adsorbent resin NKA-9. The purified glucosinolate was subsequently hydrolyzed with myrosinase. The glucosinolate and its enzymatic product were identified as 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (4-RBMG) and benzyl isothiocyanate (BITC) by UV–Vis, FT-IR, NMR, and MS. The bioactivities, including anti-oxidation, anti-inflammation, and anti-tumor activities of 4-RBMG and BITC, were systematically evaluated and compared. The results show that at 5–20 mg/mL, the anti-oxidation effects of 4-RBMG on DPPH and ABTS free radicals are superior to those of BITC. However, at the same concentrations, BITC has stronger anti-inflammatory and anti-tumor activities compared to 4-RBMG. Notably, at a concentration of 6.25 μmol/L, BITC significantly inhibited NO production with an inhibitory rate of 96.67% without cytotoxicity. Additionally, at a concentration of 40 μmol/L, BITC exhibited excellent inhibitory effects on five tumor cell lines, with the cell inhibitory rates of leukemia HL-60, lung cancer A549, and hepatocellular carcinoma HepG2 exceeding 90%. This study provides some evidence that the enzymatic product, BITC, shows promise as a therapeutic agent for tumor suppression and inflammation reduction. Full article

Backgroun/Objectives: Recent pharmaceutical research has increasingly focused on eutectic systems to improve the formulation and delivery of active pharmaceutical ingredients (APIs). This study presents the preparation and characterization of three therapeutic eutectic systems (THEESs) based on ibuprofen and menthol at various molar ratios. Methods: The THEESs were prepared and analyzed by assessing their physicochemical properties and rheological properties were evaluated to determine flow behavior. Cytotoxicity assays were conducted on HaCaT and HepG2 cell lines to assess biocompatibility. Results: All systems formed monophasic, homogeneous, clear and viscous liquids. Key physicochemical properties, including density, refractive index, surface tension, speed of sound and isobaric heat capacity, showed a temperature-dependent, inverse proportional trend. Viscosity followed the Vogel–Fulcher–Tammann equation, and rheological analysis revealed non-Newtonian behavior, which is important for pharmaceutical processing. Notably, cytotoxicity assays revealed that Ibu-M3 and Ibu-M4 showed lower toxicity than pure compounds in HaCaT cells, while Ibu-M5 was more toxic; in HepG2 cells, only Ibu-M3 was less toxic, whereas Ibu-M4 and Ibu-M5 were more cytotoxic than the pure compounds. Conclusions: These findings highlight the potential of ibuprofen–menthol eutectic systems for safer and more effective pharmaceutical formulations. Full article

The global burden of hepatitis B virus (HBV) remains high, with ongoing concerted efforts to eliminate viral hepatitis as a public health concern by 2030. The absence of curative treatment against HBV makes it an active area of research to further study HBV pathogenesis. In vitro cell culture systems are essential in exploration of molecular mechanisms for HBV propagation and the development of therapeutic targets for antiviral agents. The lack of an efficient cell culture system is one of the challenges limiting the development and study of novel antiviral strategies for HBV infection. However, the evolution of cell culture systems to study HBV pathogenesis and treatment susceptibility in vitro has made a significant contribution to public health. The currently available cell culture systems to grow HBV have their advantages and limitations, requiring further optimization. The discovery of sodium taurocholate co-transporting polypeptide (NTCP) as a receptor for HBV was a major breakthrough for the development of a robust cell model, allowing the study of de novo HBV infection through NTCP expression in the HepG2 hepatoma cell line. This review is aimed at highlighting the evolution of cell culture systems to study HBV pathogenesis and in vitro treatment susceptibility. Full article

In this study, the ultrasonic-assisted extraction of deep eutectic solvents (UADES) for tea polysaccharides was optimized, and their physicochemical properties and antioxidant activities were analyzed. The optimal DES comprised choline chloride (CC) and ethylene glycol (EG) in a molar ratio of 1:3, with a water content of 40%. The optimized condition was an extraction temperature of 61 °C, an ultrasonic power of 480 W, and an extraction time of 60 min. The UADES extraction rate of polysaccharides (ERP) was 15.89 ± 0.13%, significantly exceeding that of hot water (HW) extraction. The polysaccharide content in the UADES-extracted tea polysaccharides (UADESTPs) was comparable to that of hot-water-extracted tea polysaccharides (HWTPs) (75.47 ± 1.35% vs. 74.08 ± 2.51%); the UADESTPs contained more uronic acid (8.35 ± 0.26%) and less protein (12.91%) than HWTP. Most of the UADESTPs (88.87%) had molecular weights (Mw) below 1.80 × 10³ Da. The UADESTPs contained trehalose, glucuronic acid, galactose, xylose, and glucose, with molar ratios of 8:16:1:10. The free radical scavenging rate and total reducing power of the UADESTPs were markedly superior to those of the HWTPs. Moreover, the UADESTPs had a better alleviating effect on H₂O₂-induced oxidative injury in HepG2 cells. This study develops an eco-friendly and efficient extraction method for tea polysaccharides, offering new insights for the development of tea polysaccharides. Full article

Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients with advanced liver dysfunction. The global rise in these conditions underscores the need for effective interventions. Natural products have attracted attention for their potential to support liver health, particularly through synergistic combinations of plant extracts. Epavin, a dietary supplement from Erbenobili S.r.l., formulated with plant extracts like Taraxacum officinale (L.), Silybum marianum (L.) Gaertn., and Cynara scolymus (L.), known for their liver-supporting properties, has been proposed as adjuvant for liver functions. The aim of this work was to evaluate of Epavin’s antioxidant, anti-inflammatory, and protective effects against heavy metal-induced toxicity. In addition, the antibacterial effect of Epavin against a panel of bacterial strains responsible for infections associated with liver injuries has been evaluated. Methods: The protection against oxidative stress induced by H₂O₂ was evaluated in HepG2 and BALB/3T3 cells using the dichlorofluorescein diacetate (DCFH-DA) assay. Its anti-inflammatory activity was investigated by measuring the reduction in nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages using the Griess assay. Additionally, the cytoprotecting of Epavin against heavy metal-induced toxicity and oxidative stress were evaluated in HepG2 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and DCFH-DA assays. The antibacterial activity of Epavin was assessed by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against Gram-positive (Enterococcus faecalis ATCC 29212, and BS, Staphylococcus aureus 25923, 29213, 43300, and BS) and Gram-negative (Escherichia coli 25922, and BS, Klebsiella pneumoniae 13883, 70063, and BS) bacterial strains using the microdilution method in broth, following the Clinical and Laboratory Standards Institute’s (CLSI) guidelines. Results: Epavin effectively reduced oxidative stress in HepG2 and BALB/3T3 cells and decreased NO production in LPS-stimulated RAW 264.7 macrophages. Moreover, Epavin demonstrated a protective effect against heavy metal-induced toxicity and oxidative damage in HepG2 cells. Finally, it exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 1.5 to 6.0 mg/mL. Conclusions: The interesting results obtained suggest that Epavin may serve as a valuable natural adjuvant for liver health by enhancing detoxification processes, reducing inflammation, and exerting antibacterial effects that could be beneficial in the context of liver-associated infections. Full article

Approximately 90% of liver cancer cases are classified as hepatocellular carcinomas (HCCs), with chemotherapy and immunotherapy being the most recommended treatment options. While conventional chemotherapy specifically targets rapidly dividing cancer cells, it can also impact on healthy cells that are proliferating quickly. This collateral damage to healthy cells, along with the potential for cancer cells to develop resistance, presents significant challenges for conventional chemotherapy in liver cancer patients. Hepatic artery infusion of chemotherapy (HAIC) generally leads to reduced toxicity and fewer side effects. The process of catheter insertion is usually performed under local anesthesia, with lidocaine being the preferred choice to combine with various chemotherapeutics in HCC treatment. In our study, we explored the effects of repurposing lidocaine in combination with cisplatin or 5-fluorouracil (5-FU) on two HCC cell lines, HepG2 and Hep3B. Our cytotoxicity analysis revealed that lidocaine functions as a chemosensitizer for cisplatin and 5-FU in both HepG2 and Hep3B cells. Specifically, we observed an increase in the subG1 population and a reduction in cytosolic reactive oxygen species in cisplatin- or 5-FU-treated HepG2 and Hep3B cells. Interestingly, lidocaine selectively decreased the reduced/oxidized glutathione ratio in cisplatin- or 5-FU-treated HepG2 cells but not in Hep3B cells. Furthermore, lidocaine induced endoplasmic reticulum stress, apoptosis, mitochondrial membrane depolarization, lipid peroxidation, and autophagy while suppressing cellular proliferation HepG2 and Hep3B cells. In conclusion, our study demonstrates the synergistic potential of combining lidocaine with cisplatin or 5-FU for the treatment of HCC, indicating that lidocaine may serve as an effective chemosensitizer. These findings highlight a new clinical advantage of using repurposing lidocaine as a chemosensitizer in the current HAIC procedure, suggesting that this combination warrants further exploration through rigorous clinical trials. In the future, we can better optimize therapeutic regimens, potentially leading to improved patient outcomes in HCCs. Full article

Background: Fructus Meliae Toosendan (FMT) is a traditional Chinese medicine used to treat ascariasis; however, its reported hepatotoxicity limits its application. Toosendanin (TSN), as a principal active component, is recognized as the primary toxic ingredient responsible for FMT-induced hepatotoxicity, but the underlying mechanisms remain elusive. Methods: HepG2 cells were treated with TSN and analyzed using Western blotting and qPCR assays for related gene transcription and protein expression. Lipid peroxidation and ferroptosis markers were measured. Balb/c and C57BL/6 mice received various doses of TSN administration, and their liver function was assessed with serum biochemistry and histopathology. Network pharmacology and oxidative lipidomics were performed to identify key targets and metabolites. Results: TSN triggered ferroptosis both in vitro and in vivo, accompanied by the elevated expression of 5-lipoxygenase (ALOX5) and its downstream metabolites. The ALOX5 level modulated hepatocyte sensitivity to TSN-induced ferroptotic damage. An ALOX5 knockdown alleviated TSN-induced liver injury and ferroptosis in vivo. Conclusions: Our study demonstrated that TSN induces hepatotoxicity by facilitating ALOX5-mediated lipid peroxidation, thereby sensitizing cells to ferroptosis. Full article

Cardiovascular diseases remain the leading cause of death worldwide, with hypercholesterolemia being a major contributing risk factor. Although cholesterol-lowering drugs are widely available, concerns about several adverse side effects have increased the demand for natural alternatives, with the most common approaches involving the incorporation of foods rich in bioactive compounds into the diet. To explore this growing interest in food-based strategies for cardiovascular health, this study formulated and evaluated an aqueous peel extract of Persea americana to assess its potential role as a complementary approach to managing hypercholesterolemia. The extract was characterized, revealing the presence of various bioactive compounds, including pyridoxine-O-Hex, which was identified for the first time in a P. americana extract component. The safety profile of the extract was confirmed through in vivo assessment. Furthermore, the extract demonstrated protective effects against oxidative stress in HepG2 cells. Additionally, permeability studies using Caco-2 cells, as a model of the gastrointestinal barrier, indicated that the extract effectively reduced cholesterol’s permeation. In summary, these findings suggest that P. americana peel extract may serve as a promising natural product for functional foods for cardiovascular health and hypercholesterolemia management. Full article

Annona neoinsignis H. Rainer (Annonaceae) is a tree native to the Amazon rainforest. Its fruits are also suitable for human consumption in their natural state or are processed to make desserts. In this work, we characterized the chemical composition of the essential oil (EO) from the leaves of A. neoinsignis and evaluated its anti-liver-cancer potential via in vitro and in vivo approaches. Chemical composition analysis revealed β-elemene, (E)-caryophyllene, germacrene D, and germacrene B as the main constituents. The EO had IC₅₀ values ranging from 12.28 to 37.50 μg/mL for B16-F10 cells and MCF-7 cells, whereas an IC₅₀ value of >50 μg/mL was found for noncancerous MRC-5 cells. DNA fragmentation, YO-PRO-1 staining, and loss of mitochondrial transmembrane potential were detected in EO-treated HepG2 cells, indicating the induction of apoptosis. Significant in vivo growth inhibition of 53.7% was observed in mice bearing HepG2 cell xenografts treated with EO at a dosage of 40 mg/kg. These data suggest that EO from A. neoinsignis leaves is a drug source for liver cancer. Full article