Cell Line HepG2 Research Articles

Anti-Obesity Effects of Adzuki Bean Saponins in Improving Lipid Metabolism Through Reducing Oxidative Stress and Alleviating Mitochondrial Abnormality by Activating the PI3K/Akt/GSK3β/β-Catenin Signaling Pathway

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.

Exploring the cytotoxic and antioxidant properties of lanthanide-doped ZnO nanoparticles: a study with machine learning interpretation

BackgroundLanthanide-based nanomaterials offer a promising alternative for cancer therapy because of their selectivity and effectiveness, which can be modified and predicted by leveraging the improved accuracy and enhanced decision-making of machine learning (ML) modeling.MethodsIn this study, erbium (Er3+) and ytterbium (Yb3+) were used to dope zinc oxide (ZnO) nanoparticles (NPs). Various characterization techniques and biological assays were employed to investigate the physicochemical and optical properties of the (Er, Yb)-doped ZnO NPs, revealing the influence of the lanthanide elements.ResultsThe (Er, Yb)-doped ZnO NPs exhibited laminar-type morphologies, negative surface charges, and optical bandgaps that vary with the presence of Er3+ and Yb3+. The incorporation of lanthanide ions reduced the cytotoxicity activity of ZnO against HEPG-2, CACO-2, and U87 cell lines. Conversely, doping with Er3+ and Yb3+ enhanced the antioxidant activity of the ZnO against DPPH, ABTS, and H2O2 radicals. The extra tree (ET) and random forest (RF) models predicted the relevance of the characterization results vis-à-vis the cytotoxic properties of the synthesized NPs.ConclusionThis study demonstrates, for the first time, the synthesis of ZnO NPs doped with Er and Yb via a solution polymerization route. According to characterization results, it was unveiled that the effect of optical bandgap variations influenced the cytotoxic performance of the developed lanthanide-doped ZnO NPs, being the undoped ZnO NPs the most cytotoxic ones. The presence alone or in combination of Er and Yb enhanced their scavenging capacity. ML models such as ET and RF efficiently demonstrated that the concentration and cell line type are key parameters that influence the cytotoxicity of (Er, Yb)-doped ZnO NPs achieving high accuracy rates of 98.96% and 98.67%, respectively. This study expands the knowledge of lanthanides as dopants of nanomaterials for biological and medical applications and supports their potential in cancer therapy by integrating robust ML approaches.Graphical abstract

The role of neopterin in cross-talk between tumor and tumor microenvironment in hepatocellular carcinoma

Abstract Neopterin is a marker of activated immune response, but its role in hepatocarcinogenesis is unknown. The present study aims to evaluate the effects of neopterin on prooncogenic/proinflammatory, apoptotic pathways, and other molecular mechanisms in HCC. We used SNU449, Huh-7, SK-Hep-1, and HepG2 cell lines. A cell viability assay was performed with different concentrations of neopterin. RT-PCR, Western blotting, transwell migration, scratch assay, and reactive oxygen species (ROS) production assays were performed at inhibition concentration 50 of neopterin, which was 40 µM for SNU449 and 80 µM for other cell lines. There were significant changes in mTOR, STAT3, PI3K, and interleukin-6 gene expressions, which were also supported by the protein expressions. Neopterin did not affect apoptosis in SNU449, while apoptosis increased by all doses of neopterin in SK-Hep-1 and HepG2. ROS production was increased in all cell lines in response to neopterin. Cell migration was reduced in SK-Hep1 and HepG2 but did not change in SNU449 and Huh-7. Our study showed that neopterin is not just a byproduct. The results suggest that neopterin may be a paracrine factor that modulates pro-inflammatory and pro-oncogenic pathways responsible for the biological behavior of HCC in a chronic inflammatory tumor microenvironment.

Natural Products-Based Anticancer Agents: Synthesis and Anticancer Activities of Funtumine Amide/Sulfonamide Derivatives.

Funtumine is a pregnene-type steroidal alkaloid exhibiting moderate anticancer activity. To discover novel natural product-based anticancer drugs, a series of novel funtumine amide/sulfonamide derivatives were papered and identified using spectroscopic techniques. Additionally, the structures of compounds 2j, 3a, and 4k were further confirmed through X-ray diffraction analysis. Biological activity experiments conducted against three cancer cell lines revealed that several of the synthesized compounds demonstrated inhibition activities comparable to or exceeding those of the commercial anticancer agent, 5-Fluorouracil. Especially compound 4i demonstrated a notably strong growth inhibitory effect on HePG2 (IC50=14.89 μM) and HCT116 (IC50=15.67 μM) cell lines, while exhibiting minimal cytotoxicity towards human normal BEAS-2B cells. Preliminary structure-activity relationships (SARs) analysis indicated that the conversion of the carbonyl group at the C-20 position of funtumine to a hydroxyl group could yield more potent compounds.

Rare Sesterterpenoids from the Soil Derived Fungus, Aspergillus variecolor Strain SDG, Therapeutic Potential of Stellatic Acid and Docking Studies

Ethyl acetate extract of the cultures of the soil‐derived filamentous fungus, Aspergillus variecolor SDG strain from Nallamala forest resulted in the isolation of extremely rare sesterterpenoids, stellatic acid (1) and andilesin C (2). We report a thorough chemical characterization of these compounds using various spectroscopic techniques and evaluation of their in vitro preclinical therapeutic potential. Stellatic acid exhibits potent antioxidant activity with an IC50 of 38 µg/mL and significant anticancer activity against HeLa, HepG2, MCF7, and A549 cancer cell lines with an IC50 of 7‐12 µM. On the other hand, andilesin C displayed moderate cytotoxicity against DU145 and B16F10 cancer cell lines but lacked antioxidant activity. Furthermore, the potential hypoglycemic property of stellatic acid was evaluated by measuring its inhibitory effect against α‐glucosidase. It exhibited tenfold potency against yeast α‐glucosidase (IC50 101.73 µg/mL) than mammalian α‐glucosidase (IC50 1000.00 µg/mL). Docking studies were also performed to suggest the interaction mode of stellatic acid in the α‐glucosidase enzyme active site. Notably, yeast α‐glucosidase shows a higher affinity towards stellatic acid than mammalian α‐glucosidase (3TOP). Thus, the in vitro preclinical study of stellatic acid suggests its potential efficacy in therapeutic drug development.

Stability of immobilized L-arginine deiminase from Penicillium chrysogenum and evaluation of its anticancer activity

The aim of the present work was to immobilize L-arginine deiminase on suitable supports such as chitosan, alginate, and silica gel to study its stability. Additionally, the study aims to investigate the anticancer effects of the free purified enzyme on hepatocellular carcinoma (Hep-G2) and breast cancer (MCF-7) cell lines. L-arginine deiminase (ADI: EC 3.5.3.6) was immobilized on chitosan, Ca-alginate, and silica gel, with immobilization efficiencies of 89.0%, 72.8%, and 66.5%, respectively. The optimal immobilization time for the highest efficiency was 4 h. Increasing the concentration of glutaraldehyde improved the immobilization efficiency of ADI on chitosan. The chitosan-immobilized ADI retained about 45% of its activity after 8 cycles. The optimal pH values were 6 for the free purified ADI and 7 for the chitosan-immobilized ADI. The optimal temperature increased from 40 °C for the free enzyme to 45 °C after immobilization. The activation energies for the free and chitosan-immobilized enzymes were 71.335 kJ/mol and 64.011 kJ/mol, respectively. The Km values for the free and chitosan-immobilized ADI were 0.76 mM and 0.77 mM, respectively, while the Vmax values were 80.0 U/mg protein for the free ADI and 71.4 U/mg protein for the chitosan-immobilized ADI. After 30 days of storage at 4 °C, the residual activities were 40% for the free purified ADI and 84% for the chitosan-immobilized ADI. At 25 °C, the residual activities were 10% for the free ADI and 75% for the chitosan-immobilized ADI. The chitosan-immobilized ADI exhibited significantly higher stability against proteases such as pepsin and trypsin compared to the free enzyme. The purified ADI also demonstrated enhanced potential anticancer effects and significant cytotoxicity against the Hep-G2 and MCF-7 tumor cell lines compared to doxorubicin. These findings suggest that purified ADI has potential as an anticancer agent, though further in-depth studies are required.

Identification of New Compounds from the Roots of Rubia tibetica Hook. f.

Rubia tibetica Hook. f is a traditional Tibetan medicinal plant, with its roots serving as the primary medicinal part. Two new compounds, Rubiaxylm C and E (1 and 3), and one new natural compound, Rubiaxylm D (2) were isolated from R. tibetica, along with five known compounds (4-8). The structures of the previously undescribed compounds were elucidated by HR-ESIMS, 1D/2D NMR spectroscopic data and electronic circular dichroism calculations. Compound 1 is a rare anthrone substituted with a carbonyl group at position 1. Furthermore, all isolated compounds were tested for their cytotoxicity against HepG2 cell lines.

Versatile properties of Opuntia ficus-indica (L.) Mill. flowers: In vitro exploration of antioxidant, antimicrobial, and anticancer activities, network pharmacology analysis, and In-silico molecular docking simulation.

Opuntia ficus-indica (L.) Mill. has been used in folk medicine against several diseases. The objectives of the present study were to investigate the chemical composition of the methanolic extract of O. ficus-indica (L.) Mill. flowers and their antioxidant, antimicrobial, and anticancer properties. Besides, network pharmacology and molecular docking were used to explore the potential antitumor effect of active metabolites of O. ficus-indica (L.) Mill. against breast and liver cancer. The results revealed many bioactive components known for their antimicrobial and anticancer properties. Furthermore, scavenging activity was obtained, which indicated strong antioxidant properties. The plant extract exhibited antimicrobial activities against Aspergillus brasiliensis (MIC of 0.625 mg/mL), Candida albicans, Saccharomyces cerevisiae, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa at MICs of 1.25 mg/mL. The results revealed proapoptotic activities of the O. ficus-indica (L.) Mill. extract against MCF7, MDA-MB-231, and HepG2 cell lines, where it induced significant early apoptosis and cell cycle arrest at sub-G1 phases, besides increasing the expression levels of p53, cyclin D1, and caspase 3 (p <0.005). The network pharmacology and molecular docking analysis revealed that the anticancer components of O. ficus-indica (L.) Mill. flower extract targets the PI3K-Akt pathway. More investigations might be required to test the mechanistic pathways by which O. ficus-indica (L.) Mill. might exhibit its biological activities in vivo.

Effective Synthesis of C20-Epi-Isothiocyanato-Salinomycin and its Thiourea Derivatives as Potential Anticancer Agents.

Salinomycin, a naturally occurring polyether ionophore antibiotic isolated from Streptomyces albus, has been demonstrated potent cytotoxic activity against a variety of cancer cell lines. In particular, it exhibits selective targeting of cancer stem cells. However, systemic toxicity, drug resistance and low bioavailability of the drug significantly limit its potential applications. In this study, the C20-epi-isothiocyanate of salinomycin was designed and synthesized, and then reacted with amines as a versatile synthon to assemble a series of salinomycin thiourea derivatives, which improved the druggability of salinomycin. The antiproliferative activities of the compounds were evaluated in vitro against A549, HepG2, HeLa, 4T1, and MCF-7 cancer cell lines using the CCK-8 assay. The pharmacological results showed that some salinomycin thiourea derivatives exhibited excellent inhibitory activity against at least one of the tested tumor cells and high selectivity. Further mechanistic studies showed that compound 9 f, containing a 3,5-difluorobenzyl moiety, could directly induce apoptosis, probably by increasing caspase-9 protein expression and cell cycle arrest in G1 phase in a concentration dependent manner.

Long-Lasting Exendin-4-Coated Gold Nanoparticles: Synthesis and In Vivo Evaluation of Hypoglycemic Activity

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.

Downregulation of GLYAT correlates with tumour progression and poor prognosis in hepatocellular carcinoma.

Glycine N-acyltransferase (GLYAT), known to influence glycine metabolism, has been implicated in the progression of various malignant tumours. However, its clinical relevance in hepatocellular carcinoma (HCC) remains unexplored. Here, GLYAT expression levels in HCC tissues were significantly reduced compared to normal liver tissues. Similarly, GLYAT expression levels in Huh 7, HepG2, PLC and SK-HEP1 were lower than those in LO2. Receiver operating characteristic curve analysis demonstrated that GLYAT exhibited good diagnostic performance for HCC. Kaplan-Meier analyses suggested that decreased GLYAT expression was correlated with poorer progress in HCC. Low GLYAT expression was significantly associated with gender and histologic grade. Multivariate Cox regression analysis identified low GLYAT expression and T stage as independent prognostic factors. Nomograms based on GLYAT mRNA expression and T stage showed good concordance with actual survival rates at 1, 2, 3 and 5 years. Moreover, GLYAT downregulation in the Huh 7 cell line enhanced cell proliferation, invasion and migration abilities, while GLYAT overexpression in the HepG2 cell line inhibited these abilities. HCC patients with low GLYAT expression exhibited a predisposition to immune escape and poor response to immunotherapy. This research revealed that GLYAT holds promise as both a prognostic biomarker and a potential therapeutic target in HCC.

In silico identification and verification of Tanshinone IIA-related prognostic genes in hepatocellular carcinoma

BackgroundCurrently, adequate treatment and prognostic prediction means for Hepatocellular Carcinoma (HCC) haven’t entered into medical vision. Tanshinone IIA (TanIIA) is a natural product, which can be utilized as a potential treatment of HCC due to its high anti-tumor activity. However, the effect on HCC prognosis, as well as the potential targets and molecular mechanism of TanIIA still remain ambiguous. Herein, we investigated them via network pharmacology, explored TanIIA-related prognostic genes by machine learning methods, and verified using molecular docking and cell experiments.MethodsPotential TanIIA-targeted genes and HCC-related genes were obtained from the corresponding database. The Protein-Protein Interaction (PPI) network and enrichment analyses of the intersection targets were conducted. Furthermore, a TanIIA-related prognostic model was built and verified. We attempted to explore the expression of the TanIIA-related prognostic genes and evaluate its chemotherapeutic sensitivities and the immune infiltrations. Followed by exploration of anti-tumor activity on the human HCC cells Hep3B and HepG2 cell lines in vitro (CCK-8, flow cytometry and transwell assay), the docking molecular was performed. Ultimately, the corresponding protein expressions were determined by western blotting.ResultsA total of 64 intersecting targets were collected. Similarly, GO/KEGG enrichment analysis showed that TanIIA can inhibit HCC by affecting multiple pathways, especially the MAPK signaling pathway. A five-gene signature related to TanIIA was constructed on account of Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. Among five genes, ALB, ESR1 and SRC tend to be core genes because of probable status as potential targets for sorafenib. Molecular docking results demonstrated the potential for active interaction between the core genes relevant proteins and TanIIA. Studies in vitro had shown that TanIIA regulated the expressions of Bcl-2, Bax and MMP9 in HCC cells, inhibiting their growth, inducing apoptosis and preventing cell invasion. Additionally, we are able to detect an up-regulated trend in the expression of ALB and ESR1, while a down-regulated in the expression of SRC by TanIIA.ConclusionRegulating the expression of TanIIA-related gene signatures (ALB, SRC and ESR1), and inhibiting the SRC/MAPK/ERK signaling axis might potentially contribute to the TanIIA treatment of HCC. And the three gene signatures could be identified for predicting the prognosis of HCC, which may provide novel biomarkers for HCC treatment.

The impact of cathepsins on liver hepatocellular carcinoma: Insights from genetic and functional analyses

Liver Hepatocellular Carcinoma (LIHC), ranked as the second deadliest cancer globally, poses a major health challenge because of its widespread occurrence and poor prognosis. The mechanisms underlying LIHC development and progression remain unclear. Cathepsins are linked to tumorigenesis in other cancers, but their role in LIHC is underexplored. This study employed integrative analyses, including Mendelian Randomization (MR), bulk RNA-sequencing (bulk-seq), single-cell RNA sequencing (scRNA-seq), immunohistochemical (IHC) analysis, and cellular experiments with siRNA technology, to investigate the role of cathepsin E (CTSE) in LIHC. MR analysis identified CTSE as a factor associated with increased LIHC risk. Prognostic analysis using TCGA data showed that higher CTSE levels are linked to poorer survival, establishing CTSE as an independent prognostic risk factor. Integrative transcriptome analysis revealed close relation of CTSE to the extracellular matrix. scRNA-seq from TISCH2 demonstrated that CTSE is predominantly expressed in malignant LIHC cells. IHC confirmed higher CTSE expression in LIHC tissues compared to peritumoral tissues. Functional assays, such as qRT-PCR, Western blot, cell proliferation, and colony formation experiments, demonstrated that siRNA-mediated CTSE knockdown in HepG2 and Huh7 cell lines notably suppressed cell proliferation and altered the FAK/Paxillin/Akt signaling cascade. This research enhances our comprehension of LIHC development, emphasizing CTSE as a promising prognostic marker and potential therapeutic target. Inhibiting CTSE could slow the progression of LIHC, presenting novel opportunities for therapeutic approaches.

Computational metal-flavonoids complexes presentation of greenly synthesized silver nanoparticles combined flavonoids from Lens culinaris L. as anticancer agents using BcL-2 and IspC proteins

Lens culinaris L., has been widely recognized for its medical applications. LC-ESI-TOF-MS identified 22 secondary metabolites including phenolics, flavonoids, and anthocyanidin glycosides among its total extract (LCTE). The study aimed to apply LCTE as a biogenic material for reducing and capping the silver nanoparticles (LC-AgNPs). The ynthesized LC-AgNPs were characterized using different techniques. The UV absorption was observed at λ max 379 nm. LC-AgNPs were spherical, with 19.22 nm average size. The face cubic centre nature was demonstrated by HR-TEM and XRD. The LC-AgNPs were then evaluated for their anticancer and antimicrobial potentials. LC-AgNPs showed an extremely potent cytotoxic activity against MCF-7, HCT-116 and HepG2 cell lines (IC50= 0.37, 0.35 and 0.1 µg/mL, respectively). LC-AgNPs induced significant apoptotic effects in the three examined cancer cell lines. LC-AgNPs resulted in sequestration of cells in G1 phase of the cell cycle in both MCF-7 and HCT-116 cells, meanwhile it trapped cells at the G2 phase in HepG2 cells. Moreover, the antimicrobial activity of LC-AgNPs was highly confirmed against Klebsiella pneumoniae and Acinetobacter baumannii. Molecular docking study designated Kaempferol-3-O-robinoside-7-O-rhamnoside and Quercetin-3-D-xyloside as the topmost LCTE active constituents that caused inhibition of both Bcl-2 and IspC cancer targets in combination with the produced silver nanoparticles.

LC-ESI-MS and GC-MS Profiling, Chemical Composition, and Cytotoxic Activity of Endophytic Fungus Pleosporales sp. Derived from Artemisia annua

The chemical profiling of ethyl acetate extract of the endophytic fungus Pleosporales sp. using liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS) revealed the presence of 12 metabolites of different chemical classes such as steroids, α-pyrones, asterric acid derivatives, and quinones. Additionally, the gas chromatography–mass spectrometry (GC-MS) profiling of the ethyl acetate (EtOAc) and methanol extracts exhibited the presence of fatty acids and their esters, in which methyl palmitate (18.72%, and 25.48%, respectively) and methyl linoleate (11.92% and 23.39%, respectively) were found in both extracts. On the other hand, palmitic acid (12.60%), methyl oleate (26.90%), oleic acid (4.01%) and linoleic acid (3.25%) were present only in methanol extract. Furthermore, ethyl palmitate (12.60%), 13-octadecenoic acid (19.36%), and ethyl linoleate (3.25%) occurred in EtOAc extract. A phytochemical investigation of both extracts led to the isolation of fatty acids such as palmitic acid (18), oleic acid (20), and linoleic acid (21) and their esters including methyl palmitate (13), methyl stearate (22), methyl linoleate (16), methyl 3-hydroxy-5-methylhexanoate (23), and monomethyl azelate (27), in addition to monoacyl derivatives of glycerol such as 3,3-dihydroxypropyl hexadecanoate (24), 2,3-dihydroxypropyl elaidate (25), and 1-linoleoyl-sn-glycerol (26). The structures of the isolated compounds were identified by different spectroscopic analyses including 1H- and 13C-NMR and GC-MS. The EtOAc extract exhibited a cytotoxic effect against MCF-7 and HepG-2 cell lines, with IC50 values of 4.12 ± 0.10 and 10.05 ± 0.05 μg/mL, respectively.

In vitro toxicity of microalgae species of the phyla chlorophyta and ochrophyta in CHO-k1 and HEP G2 cells for potential use in human nutrition

Microalgae are a promising component to enhance human nutrition, but to date only a few species have been authorized to be used in human nutrition. In this study, the in vitro toxicity of eight novel microalgae strains (Botryococcus braunii, Chlorococcum novae-angliae, Microchloropsis salina, Myrmecia bisecta, Stichococcus sp. Tetraselmis suecica, Tetradesmus obliquus and Spongiochloris minor) selected for their potential for human nutrition was investigated. N-hexane, acetone, ethanol and aqueous extracts of the lyophilized biomass were tested in the CHO-k1 and HEP G2 cell lines at concentrations of up to 1.81 mg ml-1 extracted biomass per well. None of the tested microalgae extracts reached values defined as a significant cytotoxic effect (IC50 &lt; 0.02 mg ml-1). The highest cytotoxic effects were measured for Stichococcus sp. in both cell lines with IC50 values of 0.17 mg ml-1 for the acetone extract in CHO-k1 cell culture and 0.18 mg ml-1 for the acetone extract in HEP G2 cell culture. Most cytotoxic effects occurred with the acetone and ethanol extracts, while the water and n-hexane extracts showed almost no measurable cytotoxic effects. Only Tetraselmis suecica showed no cytotoxic effect under the chosen conditions in both tested cell lines, marking this microalgae as particularly interesting for further investigations into its use in human nutrition.

Anabasis setifera leaf extract from arid habitat: A treasure trove of bioactive phytochemicals with potent antimicrobial, anticancer, and antioxidant properties.

The main objective of this study was to evaluate the biological activities of Anabasis setifera extract, including its antimicrobial, anticancer, and antioxidant properties. In the current study, Anabasis setifera leaves extract was evaluated for antimicrobial, anticancer, antioxidant activities and phytochemical analyses. Ethyl acetate extract of Anabasis setifera (EA-AS) exhibited promising antimicrobial activity toward Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, Bacillus subtilis, Candida albicans, Aspergillus brasiliensis, Aspergillus fumigatus with MICs 62.5, 125, 62.5, 31.25, 62.5, 125 and 125 μg/mL respectively. Moreover, EA-AS showed anticancer activity at safe concentrations, where IC50 were 36.4 and 44 μg/mL toward Hep-G2 and MCF-7 cancerous cell lines. EA-AS was found to contain 55 significant compounds identified through gas chromatography mass spectrophotometry (GCMS). The most abundant compounds were 1,4-dimethoxy-6,7,8,9-tetrahydro-5-benzocycloheptenone (26.04%), hexa-2,4-diyn-1-ylbenzene (8.40%), dihydrobenzo[b]fluoranthene (6.10%), ethanone, 1-[2,3-dihydro-2-(1-methylethenyl)-5-benzofuranyl (6.10%), and valerenol (4.08%). GC mass analysis confirmed the antioxidant properties of AS by detecting several compounds with antioxidant activity, including hexa-2,4-diyn-1-ylbenzene, nerolidol, spathulenol, -naphthalenem ethanol, decahydro-4-trimethyl-8-methylene, hexadecenoic acid, tremetone, desmethoxyencecalin, heptadecyn-1-ol, thunbergol, hexadecanol, dotriacontane, taylorione, ligulatin, retinoic acid, and falcarinol. The analysis of EA-AS reveals that it is a rich source of valuable phytochemicals: total Phenolic Content: a promising 4,264 μg/mL /, suggesting substantial biological and pharmacological potential. Total tannin content: 391.17 μg/mL, indicating potential applications in industries like nutraceuticals, pharmaceuticals, and cosmetics. Total flavonoid content exceptionally high at 5,163 μg/mL, while the total alkaloid content measured 1,036.26 μg/mL. Additionally, EA-AS demonstrated antioxidant activity with an EC50 of 30.6 μg/mL. In conclusion, the comprehensive analysis of the EA-AS reveals its immense potential as a rich source of valuable phytochemicals with diverse bioactivities, warranting further in-depth studies to unlock its full pharmaceutical and commercial prospects. Our results suggest substantial biological and pharmacological prospects for EA-AS as a promising antimicrobial, anticancer, and potent antioxidant.

Anticancer Effect of Cycas media: Molecular Basis Through Modulation of PI3K/AKT/mTOR Signaling Pathway

Many researchers are focusing on screening the biological activities of plants owing to their safety and possible pharmacological actions. Consequently, we aimed to explore the antiproliferative and cytotoxic properties of Cycas media methanolic extract on HepG2 cell lines. Moreover, we also explore the antitumor action against the experimentally induced solid Ehrlich carcinoma (SEC) model and investigate the possible involved molecular mechanisms. Also, the antibacterial action of the extract was elucidated. Different concentrations of the extract were incubated with HepG2 to determine cytotoxicity, followed by cell cycle analysis. The in vivo experiment was accomplished by grouping the animals into four different groups (n = 10); normal control, SEC, C. media 100, and C. media 200. The extract was administered at 100 and 200 mg/kg. Tumor volume, tumor inhibition rate, toxicity profile, and antioxidant biomarkers were determined. Moreover, the PI3K/AKT/mTOR signaling pathway was investigated as a possible underlying antitumor mechanism. The tumor control group showed a remarkable upregulation for PI3K, p-AKT, and p-mTOR, along with downregulation for the antioxidant SOD and GPX4, as well as decreased levels of GSH and MDA. C. media extract reversed these parameters to a significant level and the higher dose showed a superior antitumor effect. C. media extract showed antiproliferative effects against HepG2 cells, along with a suppressive action on the PI3K/AKT/mTOR pathway and an antioxidant effect. Additionally, C. media had antibacterial consequences against S. aureus isolates with minimum inhibitory concentrations from 32 to 128 µg/mL. It also caused a noteworthy growth delay as well as a notable reduction in the membrane integrity of S. aureus isolates. These beneficial outcomes suggest C. media to have potential antitumor and antibacterial activities.

Chemical Composition, Anti-microbial, and Cytotoxic Activities of Essential Oil from Magnolia bidoupensis Q. N. Vu leaves, an Endemic Species to the Central Highlands of Vietnam.

An analysis was conducted on the essential oil extracted from the leaves of Magnolia bidoupensis utilizing GC-MS, revealing thirty-three constituents that account for 98.9% of the essential oil. The main components included pogostol (22.4%), δ-selinene (16.2%), and α-amorphene (14.7%). Bioassays were then performed to evaluate the oil's biological activity. The essential oil exhibited antimicrobial activity against all tested microorganisms (six bacterial strains and one fungal strain) using the minimum inhibitory concentration (MIC) method. Additional cytotoxicity tests were conducted on KB, HepG2, MCF-7, and A549 cancer cell lines using the MTT method. The essential oil exhibited strong cytotoxic effects on all four cell lines, with IC50 values ranging from 1.37 ± 0.05 μg/mL (KB) to 2.40 ± 0.06 μg/mL (A549).

Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo.

Cucurbitacin B (CuB) is a natural triterpenoid with diverse pharmacological effects including potent anticancer activity. However, its oral bioavailability is hampered by limited metabolism in vivo. We characterized CuB's in vivo metabolism in rats to uncover bioactive metabolites retaining therapeutic potential, using a robust UHPLC-Q-TOF-MS/MS workflow. This workflow combined molecular networking, fragmentation filtering, and mass defect filtering to identify CuB metabolites in rat urine, plasma, and feces following oral administration. Thirteen metabolites were identified and seven were confirmed. Major phase I transformations involved hydrolysis, reduction, epoxidation, and amination. Phase II conjugation included cysteine, glutathione, glucuronide, and gluconic acid conjugates. Notably, one of the main metabolites formed was the cysteine conjugate CuB-Cys. CuB-Cys maintained similar in vitro antiproliferative activity to CuB on HepG2, MCF-7, and PANC-1 cancer cell lines. However, it demonstrated lower cytotoxicity towards non-cancerous L02 cells, highlighting improved therapeutic selectivity. Mechanistically, CuB-Cys induced greater apoptotic signaling in HepG2 cells than CuB via enhanced caspase activation and disrupted BAX-Bcl-2 balance. This represents the first systematic characterization of CuB's in vivo metabolic pathway. The identification and confirmation of CuB-Cys provide insight for drug development efforts aiming to maintain therapeutic efficacy while reducing toxicity, via metabolite-based approaches. Our findings shed light on strategies for improving CuB's clinical potential.