Nutrient scavenging-fueled growth in pancreatic cancer depends on caveolae-mediated endocytosis under nutrient-deprived conditions.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its nutrient-scavenging ability, crucial for tumor progression. Here, we investigated the roles of caveolae-mediated endocytosis (CME) in PDAC progression. Analysis of patient data across diverse datasets revealed a strong association of high caveolin-1 (Cav-1) expression with higher histologic grade, the most aggressive PDAC molecular subtypes, and worse clinical outcomes. Cav-1 loss markedly promoted longer overall and tumor-free survival in a genetically engineered mouse model. Cav-1-deficient tumor cell lines exhibited significantly reduced proliferation, particularly under low nutrient conditions. Supplementing cells with albumin rescued the growth of Cav-1-proficient PDAC cells, but not in Cav-1-deficient PDAC cells under low glutamine conditions. In addition, Cav-1 depletion led to significant metabolic defects, including decreased glycolytic and mitochondrial metabolism, and downstream protein translation signaling pathways. These findings highlight the crucial role of Cav-1 and CME in fueling pancreatic tumorigenesis, sustaining tumor growth, and promoting survival through nutrient scavenging.

JNTX-101, a novel albumin-encapsulated gemcitabine prodrug, is efficacious and operates via caveolin-1-mediated endocytosis.

Albumin is an attractive candidate carrier for the development of novel therapeutic drugs. Gemcitabine has been FDA approved for the treatment of solid tumors; however, new drugs that optimize gemcitabine delivery are not available for clinical use. The aim of this study was to test the efficacy of a novel albumin-encapsulated gemcitabine prodrug, JNTX-101, and investigate whether Cav-1 expression predicts the therapeutic efficacy of JNTX-101. We first determined the treatment efficacy of JNTX-101 in a panel of pancreatic/lung cancer cell lines and found that increases in Cav-1 expression resulted in higher uptake of albumin, while Cav-1 depletion attenuated the sensitivity of cells to JNTX-101. In addition, decreased Cav-1 expression markedly reduced JNTX-101-induced apoptotic cell death in a panel of cells, particularly in low-serum conditions. Furthermore, we tested the therapeutic efficacy of JNTX-101 in xenograft models and the role of Cav-1 in JNTX-101 sensitivity using a Tet-on-inducible tumor model in vivo. Our data suggest that JNTX-101 effectively inhibits cell viability and tumor growth, and that Cav-1 expression dictates optimal sensitivity to JNTX-101. These data indicate that Cav-1 correlates with JNTX-101 sensitivity, especially under nutrient-deprived conditions, and supports a role for Cav-1 as a predictive biomarker for albumin-encapsulated therapeutics such as JNTX-101.

Inhibition of RRM2 radiosensitizes glioblastoma and uncovers synthetic lethality in combination with targeting CHK1.

Glioblastoma (GBM) is an aggressive malignant primary brain tumor. Radioresistance largely contributes to poor clinical outcomes in GBM patients. We targeted ribonucleotide reductase subunit 2 (RRM2) with triapine to radiosensitize GBM. We found RRM2 is associated with increasing tumor grade, is overexpressed in GBM over lower grade gliomas and normal tissue, and is associated with worse survival. We found silencing or inhibition of RRM2 by siRNA or triapine sensitized GBM cells to ionizing radiation (IR) and delayed resolution of IR-induced γ-H2AX nuclear foci. In vivo, triapine and IR reduced tumor growth and increased mouse survival. Intriguingly, triapine led to RRM2 upregulation and CHK1 activation, suggesting a CHK1-dependent RRM2 upregulation following RRM2 inhibition. Consistently, silencing or inhibition of CHK1 with rabusertib abolished the triapine-induced RRM2 upregulation. Accordingly, combining rabusertib and triapine resulted in synthetic lethality in GBM cells. Collectively, our results suggest RRM2 is a promising therapeutic target for GBM, and targeting RRM2 with triapine sensitizes GBM cells to radiation and independently induces synthetic lethality of GBM cells with CHK1 inhibition. Our findings suggest combining triapine with radiation or rabusertib may improve therapeutic outcomes in GBM.

Preparation of Polyethylene Glycol-Ginsenoside Rh1 and Rh2 Conjugates and Their Efficacy against Lung Cancer and Inflammation.

Low solubility and tumor-targeted delivery of ginsenosides to avoid off-target cytotoxicity are challenges for clinical trials. In the present study, we report on a methodology for the synthesis of polyethylene glycol (PEG)-ginsenoside conjugates through a hydrolysable ester bond using the hydrophilic polymer polyethylene glycol with the hydrophobic ginsenosides Rh1 and Rh2 to enhance water solubility and passive targeted delivery. The resulting conjugates were characterized by 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FT-IR). 1H NMR revealed that the C-6 and C-3 sugar hydroxyl groups of Rh1 and Rh2 were esterified. The conjugates showed spherical shapes that were monitored by field-emission transmission electron microscopy (FE-TEM), and the average sizes of the particles were 62 ± 5.72 nm and 134 ± 8.75 nm for PEG-Rh1and PEG-Rh2, respectively (measured using a particle size analyzer). Owing to the hydrophilic enhancing properties of PEG, PEG-Rh1 and PEG-Rh2 solubility was greatly enhanced compared to Rh1 and Rh2 alone. The release rates of Rh1 and Rh2 were increased in lower pH conditions (pH 5.0), that for pathophysiological sites as well as for intracellular endosomes and lysosomes, compared to normal-cell pH conditions (pH 7.4). In vitro cytotoxicity assays showed that the PEG-Rh1conjugates had greater anticancer activity in a human non-small cell lung cancer cell line (A549) compared to Rh1 alone, whereas PEG-Rh2 showed lower cytotoxicity in lung cancer cells. On the other hand, both PEG-Rh1 and PEG-Rh2 showed non-cytotoxicity in a nondiseased murine macrophage cell line (RAW 264.7) compared to free Rh1 and Rh2, but PEG-Rh2 exhibited increased efficacy against inflammation by greatly inhibiting nitric oxide production. Thus, the overall conclusion of our study is that PEG conjugation promotes the properties of Rh1 for anticancer and Rh2 for inflammation treatments. Depends on the disease models, they could be potential drug candidates for further studies.

Photoluminescent And Self-Assembled Hyaluronic Acid-Zinc Oxide-Ginsenoside Rh2 Nanoparticles And Their Potential Caspase-9 Apoptotic Mechanism Towards Cancer Cell Lines.

BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are used in modern cancer therapy based on their specific target, efficacy, low toxicity and biocompatibility. The photocatalytic performance of Zinc oxide (ZnO) nanocomposites with hyaluronic acid (HA) was used to study anticancer properties against various human cancer cell lines. METHODS: Zinc oxide (ZnO) nanocomposites functionalized by hyaluronic acid (HA) were prepared by a co-precipitation method (HA-ZnONcs). The submicron-flower-shaped nanocomposites were further functionalized with ginsenoside Rh2 by a cleavable ester bond via carbodiimide chemistry to form Rh2HAZnO. The physicochemical behaviors of the synthesized ZnO nanocomposites were characterized by various analytical and spectroscopic techniques. We carried out 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the toxicity of Rh2HAZnO in various human cancer cells (A549, MCF-7, and HT29). Furthermore, to confirm the apoptotic effects of Rh2HAZnO and to determine the role of the Caspase-9/p38 MAPK pathways by various molecular techniques such as RT-PCR and Western blotting. Furthermore, Rh2HAZnO induced morphological changes of these cell lines, mainly intracellular reactive oxygen species (ROS) were observed by ROS staining and nucleus by Hoechst staining. RESULTS: We confirmed that Rh2HAZnO exhibits the anti-cancer effects on A549 lung cancer, HT29 colon cancer, and MCF7 breast cancer cells. Moreover, intracellular reactive oxygen species (ROS) were observed in three cancer cell lines. Rh2HAZnO induced apoptotic process through p53-mediated pathway by upregulating p53 and BAX and downregulating BCL2. Specifically, Rh2HAZnO induced activation of cleaved PARP (Asp214) in A549 lung cancer cells and upregulated Caspase-9/phosphorylation of p38 MAPK in other cell lines (HT29 and MCF-7). Furthermore, Rh2HAZnO induced morphological changes in the nucleus of these cell lines. CONCLUSION: These results suggest that the potential anticancer activity of novel Rh2HAZnO nanoparticles might be linked to induction of apoptosis through the generation of ROS by activation of the Caspase-9/p38 MAPK pathway.

Role of p53 isoforms in the DNA damage response during Drosophila oogenesis.

The tumor suppressor p53 is involved in the DNA damage response and induces cell cycle arrest or apoptosis upon DNA damage. Drosophila p53 encodes two isoforms, p53A and p53B, that induce apoptosis in somatic cells. To investigate the roles of Drosophila p53 isoforms in female germline cells, the DNA damage response was analyzed in the adult ovary. Early oogenesis was sensitive to irradiation and lok-, p53-, and hid-dependent cell death occurred rapidly after both low- and high-dose irradiation. Both p53 isoforms were responsible for this cell death. On the other hand, delayed cell death in mid-oogenesis was induced at a low level only after high-dose irradiation in a p53-independent manner. The daily egg production, which did not change after low-dose irradiation, was severely reduced after high-dose irradiation in p53 mutant females due to the loss of germline stem cells. When the p53A or p53B isoform was expressed in the germline cells in the p53 mutant females at levels that do not affect normal oogenesis, p53A, but not p53B, restored the fertility of the irradiated female. In summary, moderate expression of p53A is critical to maintain the function of germline stem cells during normal oogenesis as well as after high-dose irradiation.

Development of Lactobacillus kimchicus DCY51T-mediated gold nanoparticles for delivery of ginsenoside compound K: in vitro photothermal effects and apoptosis detection in cancer cells.

We report a non-covalent loading of ginsenoside compound K (CK) onto our previously reported gold nanoparticles (DCY51T-AuCKNps) through one-pot biosynthesis using a probiotic Lactobacillus kimchicus DCY51T isolated from Korean kimchi. The ginsenoside-loaded gold nanoparticles were characterized by various analytical and spectroscopic techniques such as field emission transmission electron microscopy (FE-TEM), energy-dispersive X-ray (EDX) spectroscopy, elemental mapping, X-ray powder diffraction (XRD), selected area electron diffraction (SAED), Fourier-transform infrared (FTIR) spectroscopy and dynamic light scattering (DLS). Furthermore, drug loading was also determined by liquid chromatography-mass spectrometry (LC-MS). In addition, DCY51T-AuNps and DCY51T-AuCKNps were resistant to aggregation caused by pH variation or a high ionic strength environment. Cell-based study confirmed that DCY51T-AuCKNps exhibited slightly higher cytotoxicity compared to ginsenoside CK treatment in A549 cells (human lung adenocarcinoma cell line) and HT29 (human colorectal adenocarcinoma cell line). Upon laser treatment, DCY51T-AuCKNps showed enhanced cell apoptosis in A549, HT29 and AGS cells (human stomach gastric adenocarcinoma cell line) compared with only DCY51T-AuCKNps treated cells. In conclusion, this preliminary study identified that DCY51T-AuCKNps act as a potent photothermal therapy agents with synergistic chemotherapeutic effects for the treatment of cancer.

Gold Nanoparticles Synthesized with Fresh Panax ginseng Leaf Extract Suppress Adipogenesis by Downregulating PPARγ/CEBPα Signaling in 3T3-L1 Mature Adipocytes.

The obesity rate has been increasing worldwide, which is important because obesity has been linked to the development of various metabolic disorders, such as type 2 diabetes, hypertension, cancer, and stroke. Nanomedicine offers a new approach for treating many diseases, including metabolic disorders such as obesity. In this study, we explored the anti-adipogenic effects of spherical gold nanoparticles synthesized with fresh Panax ginseng leaves (P.g AuNPS) in vitro using 3T3-L1 mature adipocytes. Cell viability was assessed by quantitating preadipocyte growth at different time points. Furthermore, to assess the anti-adipogenic effects of P.g AuNPS, intracellular lipid accumulation was investigated in mature adipocytes. To this end, cells were observed under a microscope and OD measurements were taken after Oil Red O staining. In addition, transcriptional gene regulation was examined by performing real time PCR to assess the levels of adipogenic genes such as PPARγ, CEBPα, CEBPß, Jak2, STAT3, FAS, SREBP-1, and ap2. Moreover, protein levels were evaluated by immunoblotting. Altogether, these results confirm that P.g AuNPS exhibit anti-adipogenic effects at a concentration of 100 µg/ml and that these effects are mediated by the downregulation of PPARγ/CEBPα (major transcription factors) signaling in 3T3-L1 mature adipocytes.

Rhizome of Anemarrhena asphodeloides as mediators of the eco-friendly synthesis of silver and gold spherical, face-centred cubic nanocrystals and its anti-migratory and cytotoxic potential in normal and cancer cell lines.

The water extract of Anemarrhena asphodeloides, the traditional oriental medicinal plant, mediated the eco-friendly synthesis of silver nanoparticles (Aa-AgNPs) and gold nanoparticles (Aa-AuNPs). First, its therapeutic rhizome was powdered prior to water extraction and then silver, gold nanoparticles were synthesized. Aa-AgNPs and Aa-AuNPs were found to be spherical, face-centred cubic nanocrystals with a Z-average hydrodynamic diameter of 190 and 258 nm, respectively. In addition, proteins and aromatic biomolecules were the plausible players associated with the production and stabilization of Aa-AgNPs; instead, phenolic compounds were responsible for the synthesis and stability of Aa-AuNPs. In vitro cytotoxic analysis revealed that up to 50 µg.mL-1 concentration Aa-AuNPs did not exhibit any toxicity on 3T3-L1, HT29 and MCF7 cell lines, while being specifically cytotoxic to A549 cell line. On the contrary, Aa-AgNPs displayed a significantly higher toxicity in comparison to Aa-AuNPs in all cell lines specially MCF7 cell line. Since cancer cells were more sensitive to Aa-Au/AgNPs treatments, further evaluation was done in order to determine their anticancer potential. Reactive oxygen species (ROS) generation was not affected by Aa-AuNPs, on the other hand, Aa-AgNPs treatment exhibited a higher potential to induce oxidative stress in A549 cells than HT29 and MCF7 cells. In addition, Aa-Ag/AuNPs reduced cell migration in A549 cells at 10 and 50 µg.mL-1, respectively. So far, this is the only report uncovering the ability of A. asphodeloides to synthesize silver and gold nanoparticles with anticancer potential and also indirectly enabling its large-scale utilization with value addition.

Caspase-3/MAPK pathways as main regulators of the apoptotic effect of the phyto-mediated synthesized silver nanoparticle from dried stem of Eleutherococcus senticosus in human cancer cells.

Siberian ginseng (Eleutherococcus senticosus) was used for the synthesis of an ecofriendly silver nanoparticle (Sg-AgNP), which has exhibited antibacterial, antioxidant effect and lower cytotoxicity to normal cells in comparison to human cancer cells. Although, the potential anticancer activity of Sg-AgNP has not been determined. In this study, two cancer cell lines were used to evaluate the cytotoxicity and apoptotic effect of Sg-AgNP along with the determination of the role of the Caspase-3 / p38 MAPK pathways. Results shown that Sg-AgNP reduced the cell viability of colon cancer cells HT29 and lung cancer cells A549. The cytotoxic effect was higher than the effect exhibited by a commercial silver nanoparticle and Cisplatin. Reactive oxygen species were observed to be superior in both cell lines in the presence of Sg-AgNPs than c-AgNPs and Cisplatin. It was observed an activation of MAPK14 gene and phosphorylation of p38 MAPK protein in both cell lines induced by Sg-AgNPs treatment. Furthermore, induction of morphological changes in the nucleus was done by Sg-AgNPs at 10 µg/mL in both cell lines. On the other hands, the activation of CASP3 gene and Caspase-3 protein was observed in HT29 cells but only at protein level in A549 cells. These results, suggest that Sg-AgNPs anticancer potential activity might be linked to the induction of apoptosis though the generation of ROS by activation of the Caspase-3/p38 MAPK pathway.

Gold nanoflowers synthesized using Acanthopanacis cortex extract inhibit inflammatory mediators in LPS-induced RAW264.7 macrophages via NF-κB and AP-1 pathways.

We reported the rapid synthesis (<8s) of gold nanoparticles at room temperature using Acanthopanacis cortex extract (A-AuNPs). We characterized the A-AuNPs using several analytical techniques and found that nano-flower type A-AuNPs, which are known to possess a coarse surface with a high surface to volume ratio, conferring these particles with high binding capacity for various biological molecules. After confirming the stability of the nanoparticles, we investigated the anti-inflammatory effect of A-AuNPs in LPS-stimulated RAW264.7 cells. These nanoparticles inhibited LPS-induced iNOS and COX-2 protein as well as gene expression level, along with reduction of NO and PGE2 production. Furthermore, we observed that the A-AuNPs inhibited translocation of NF-κB and AP-1 through phosphorylation of MAPK signaling by western blot analysis. In summary, we synthesized gold nanoflowers in an economical and eco-friendly way using Acanthopanacis cortex extract and the resultant flower-like A-AuNPs had anti-inflammatory activity, highlighting their potential as therapeutic candidates for suppression of inflammatory-mediated diseases.

Biosynthesized gold and silver nanoparticles by aqueous fruit extract of Chaenomeles sinensis and screening of their biomedical activities.

The design of mild and non-toxic synthesis of metallic nanoparticles is a topical subject in the nanotechnology field. The objective of this present study is to screen the bioactivity of biosynthesized nanoparticles by aqueous fruit extract of Chaenomeles sinensis. The reducing and stabilizing ability of C. sinensis to fabricate gold (Cs-AuNps) and silver (Cs-AgNps) nanoparticles was confirmed by UV-visible (UV-Vis) spectroscopy at 562 nm and 477 nm, respectively. The field-emission transmission electron microscopy (FE-TEM) and X-ray diffraction analysis (XRD) verify the nano-scale morphology and crystallinity of Cs-AuNps (20-40 nm) and Cs-AgNps (5-20 nm). Furthermore, we evaluated the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging capacity, antimicrobial activity against Staphylococcus aureus and Escherichia coli and cytotoxicity against breast cancer cells. The results showed that Cs-AuNps (IC50: 725.93 µg/mL) displayed superior inhibitory activities on DPPH than Cs-AuNps. The biosynthesized Cs-AuNps successfully inhibited the growth of pathogenic bacteria S. aureus (ATCC 6538) and E. coli (BL21). The cytotoxic effect of Cs-AuNps and Cs-AgNps was evaluated in murine macrophage (RAW264.7) and human breast cancer cell lines (MCF7) by MTT assay. Thus, the present study explores the biomedical applications of gold and silver nanoparticles synthesized by C. sinensis.

Cardamom fruits as a green resource for facile synthesis of gold and silver nanoparticles and their biological applications.

Gold (FA-AuNps) and silver (FA-AgNps) nanoparticles were synthesized at room temperature by aqueous extract of dried fruits of Amomum villosum, also known as Fructus Amomi (cardamom), in order to confer antioxidant, catalytic, antimicrobial activities and treatment effect against breast cancer cells. Fruit extracts served as both reducing agents and stabilizers in lieu of chemical agents. Ultra-violet visible (UV-Vis) spectroscopy, field emission transmission electron microscopy (FE-TEM), energy-dispersive X-ray (EDX) spectroscopy, elemental mapping, X-ray powder diffraction (XRD), selected area electron diffraction (SAED), dynamic light scattering (DLS) and Fourier transform infrared (FTIR) spectroscopy were employed to characterize the biosynthesized nanoparticles. Both FA-AuNps and FA-AgNps exhibited free radical scavenging activity against 2,2-diphenyl-1-picrylhydrzyl (DPPH). Additionally, biosynthesized nanoparticles successfully reduced methylene blue, a well-known redox indicator. FA-AgNps showed zones of inhibition against pathogenic Staphylococcus aureus and Escherichia coli. Finally, the biological activities and cytotoxicity of nanoparticles were subsequently investigated in vitro. FA-AuNps demonstrated a potential cytotoxic agent against breast cancer cells as evaluated by MTT assay. The study highlights a rapid synthesis of FA-AuNps and FA-AgNps by dried Fructus Amomi aqueous extract and evaluates their potential biological applications on medical platforms.

Biological synthesis of gold and silver chloride nanoparticles by Glycyrrhiza uralensis and in vitro applications.

The current study highlights the rapid biosynthesis of gold nanoparticles (Gu-AuNps) and silver chloride nanoparticles (Gu-AgClNps) by aqueous root extract of Glycyrrhiza uralensis, a medicinal plant. G. uralensis has been reported for anticancer and hepatoprotective effects. The reduction of chloroauric acid and silver nitrate by the Glycyrrhiza root extract prompted the formation of Gu-AuNps and Gu-AgClNps within 4 and 40 min at 80 °C, respectively. The complete reaction did not require supplemental reducing and stabilizing agents, which demonstrated green synthesis. Field emission transmission electron microscopy (FE-TEM) revealed the spherical shape of Gu-AuNps and Gu-AgClNps. X-ray diffraction (XRD) showed face-centred cubic structure of Gu-AuNps and Gu-AgClNps with average crystallite size 12.25 nm and 8.01 nm, respectively. The biosynthesized Gu-AgClNps served as competent antimicrobial agent against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella enterica. Additionally, Gu-AuNps and Gu-AgClNps were analyzed for their catalytic ability to reduce methylene blue as model test pollutant. Likewise, both nanoparticles possessed free radical scavenging activity against 2,2-diphenyl-1-picrylhydrzyl (DPPH). Moreover, in vitro cytotoxicity in murine macrophage (RAW264.7) and human breast cancer (MCF7) cells were evaluated. Thus, the study proposes a green synthesis of Gu-AuNps and Gu-AgClNps by G. uralensis extract and in vitro biological applications. [Formula: see text].

Gold nanoflowers synthesized using Acanthopanacis cortex extract inhibit inflammatory mediators in LPS-induced RAW264.7 macrophages via NF-κB and AP-1 pathways.

We reported the rapid synthesis (<8s) of gold nanoparticles at room temperature using Acanthopanacis cortex extract (A-AuNPs). We characterized the A-AuNPs using several analytical techniques and found that nano-flower type A-AuNPs, which are known to possess a coarse surface with a high surface to volume ratio, conferring these particles with high binding capacity for various biological molecules. After confirming the stability of the nanoparticles, we investigated the anti-inflammatory effect of A-AuNPs in LPS-stimulated RAW264.7 cells. These nanoparticles inhibited LPS-induced iNOS and COX-2 protein as well as gene expression level, along with reduction of NO and PGE2 production. Furthermore, we observed that the A-AuNPs inhibited translocation of NF-κB and AP-1 through phosphorylation of MAPK signaling by western blot analysis. In summary, we synthesized gold nanoflowers in an economical and eco-friendly way using Acanthopanacis cortex extract and the resultant flower-like A-AuNPs had anti-inflammatory activity, highlighting their potential as therapeutic candidates for suppression of inflammatory-mediated diseases.

Pleuropterus multiflorus (Hasuo) mediated straightforward eco-friendly synthesis of silver, gold nanoparticles and evaluation of their anti-cancer activity on A549 lung cancer cell line.

Pleuropterus multiflorus (Hasuo) is a widely used medicinal plant in Korea and China for treating amnesia, isnomia, heart throbbing etc. With the constructive idea of promoting the wide-spread usage of P. multiflorus, we propose its indirect usage in the form of biologically active silver (Pm-AgNPs) and gold nanoparticles (Pm-AuNPs). The synthesized nanoparticles were predominantly spherical, crystalline with the Z-average hydrodynamic diameter of 274.8nm and 104.8nm respectively. Also, proteins and phenols were identified as the major players involved in their synthesis and stability. Further, Pm-AgNPs at 25µg/mL were significantly cytotoxic to lung cancer cells, whereas, Pm-AuNPs were not cytotoxic to both normal keratinocyte and lung cancer cells even at 100µg/mL. In addition, further evaluation of the anti-cancer activity of these new nanoparticles, such as migration and apoptosis, shown that Pm-AgNPs have a potential therapeutic effect on A549 lung cancer cell treatment. To the best of our knowledge, this is the first report dissecting out the ability of the endemic P. multiflorus for the synthesis of bioactive silver and gold nanoparticle which would open up doors for its extensive usage in medicinal field.

In situ preparation of water-soluble ginsenoside Rh2-entrapped bovine serum albumin nanoparticles: in vitro cytocompatibility studies.

The present study investigates a simple and convenient one-step procedure for the preparation of bovine serum albumin (BSA)-Rh2 nanoparticles (NPs) at room temperature. In this work, ginsenoside Rh2 was entrapped within the BSA protein to form BSA-Rh2 NPs to enhance the aqueous solubility, stability, and therapeutic efficacy of Rh2. The physiochemical characterization by high-performance liquid chromatography, nuclear magnetic resonance, Fourier transform infrared spectroscopy, field emission transmission electron microscopy, dynamic light scattering, and thermogravimetric analysis confirmed that the prepared BSA-Rh2 NPs were spherical, highly monodispersed, and stable in aqueous systems. In addition, the stability of NPs in terms of different time intervals, pHs, and temperatures (20°C-700°C) was analyzed. The results obtained with different pHs showed that the synthesized BSA-Rh2 NPs were stable in the physiological buffer (pH 7.4) for up to 8 days, but degraded under acidic conditions (pH 5.0) representing the pH inside tumor cells. Furthermore, comparative analysis of the water solubility of BSA-Rh2 NPs and standard Rh2 showed that the BSA nanocarrier enhanced the water solubility of Rh2. Moreover, in vitro cytotoxicity assays including cell viability assays and morphological analyses revealed that Rh2-entrapped BSA NPs, unlike the free Rh2, demonstrated better in vitro cell viability in HaCaT skin cell lines and that BSA enhanced the anticancer effect of Rh2 in A549 lung cell and HT29 colon cancer cell lines. Additionally, anti-inflammatory assay of BSA-Rh2 NPs and standard Rh2 performed using RAW264.7 cells revealed decreased lipopolysaccharide-induced nitric oxide production by BSA-Rh2 NPs. Collectively, the present study suggests that BSA can significantly enhance the therapeutic behavior of Rh2 by improving its solubility and stability in aqueous systems, and hence, BSA-Rh2 NPs may potentially be used as a ginsenoside delivery vehicle in cancer and inflammatory cell lines.

Pharmacological importance, characterization and applications of gold and silver nanoparticles synthesized by Panax ginseng fresh leaves.

Previously, we showed the rapid and eco-friendly synthesis of gold and silver nanoparticles within 3 and 45 min by fresh leaves extract of herbal medicinal plant Panax ginseng. In addition, we characterized the nanoparticles in terms of shape, size, morphology and stability by FE-TEM, EDX, elemental mapping, SEAD, XRD and particles size analysis. In addition of this, we showed their antimicrobial, anti-coagulant, and biofilm inhibition activity of nanoparticles. Continuing our previous study, here we highlight the further characterization and biomedical applications of P. ginseng leaf-mediated gold and silver nanoparticles. We characterized the nanoparticles further in terms of active functional group and capping layer, surface charge, and temperature stability. Based on these factors, we explored the nanoparticles for antioxidant efficacy, biocompatibility in HaCaT cells, 3T3-L1 pre-adipocytes cells, for anticancer efficacy in A549 lung cancer and B16BL6 skin melenoma cancer cell lines and for anti-inflammation efficacy in RAW 264.7 cell lines. Based on our findings, we suggest that the P. ginseng-mediated gold nanoparticles have high antioxidant activity and highly biocompatibility in HaCaT cells, 3T3-L1 pre-adipocytes cells, RAW 264.7 cells lines and could be considered for future drug delivery carriers. The silver nanoparticles also showed high potent antioxidant efficacy, additionally it showed high anticancer effect in A549 lung cancer and B16BL6 skin melenoma cancer cell lines as compared to precursor salts. Moreover, both gold and silver nanoparticles have anti-inflammatory efficacies in RAW 264.7 cells. Thus, the study may provide useful insights of P. ginseng leaves extract-mediated biocompatible gold and silver nanoparticles and improving their applicability in designing nanoparticles carrier systems for drug delivery applications.

Ginsenoside Rg5: Rk1 Exerts an Anti-obesity Effect on 3T3-L1 Cell Line by the Downregulation of PPARγ and CEBPα.

Background: Obesity, a global health problem and a chronic disease, is associated with increased risk of developing type 2 diabetes and coronary heart diseases. A wide variety of natural remedies have been explored for their obesity treatment potential. Objective: The anti-adipogenic effect of ginsenoside Rg5:Rk1 (Rg5:Rk1) on 3T3-L1 mature adipocytes was investigated. Materials and Methods: To elucidate the anti-obesity effect of Rg5:Rk1, a mixture of protopanaxadiol type ginsenosides isolated from Panax ginseng Meyer in a 3T3-L1 adipocytes. In order to determine the anti-obesity effect of Rg5:Rk1, based on oil Red O Staining, triglyceride (TG) content in adipose cells was assessed. Furthermore, to elucidate the possible mechanism of Rg5:RK1 effect on lipid accumulation, mRNA and protein expression analyses of adipocyte markers such as STAT3, PPARγ, CBEPα and ap2 were carried out. Results: Rg5:Rk1 treatment showed an inhibition of lipid droplet accumulation and decrease of TG content. In addition, expression of STAT3, PPARγ, CEBPα and ap2 were decreased in a dose dependent manner. Similarly, the Rg5:Rk1 treatment reduced PPARγ and CEBPα protein expression. Conclusion: Rg5:Rk1 treatment exhibits anti-adipogenic activity by down-regulation of the STAT3/ PPARg/CEBPa signaling pathway in 3T3-L1 adipocyte cell line.

Gold nanoparticles synthesized using Panax ginseng leaves suppress inflammatory - mediators production via blockade of NF-κB activation in macrophages.

In the present study, we report that Gold nanoparticles (AuNPs) synthesized using the leaf extract of Panax ginseng Meyer (P.g AuNPs) exert anti-inflammatory effects through inhibition of downstream NF-κB activation in macrophages. We found that P.g AuNPs reduced the expression of the inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PEG2), interleukin (IL)-6, tumor necrosis factor-α (TNF-α) was attenuated by P.g AuNPs. Furthermore, P.g AuNPs suppressed lipopolysaccharide (LPS)-induced activation of NF-κB signaling pathway via p38 mitogen-activated protein kinase (MAPK) in RAW 264.7 cells. Taken together, our results suggest that P.g AuNPs can be utilized as a novel therapeutic agent for the prevention and cure of inflammation.