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1.
Asian J Pharm Sci ; 19(2): 100891, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584690

RESUMO

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvß3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

2.
J Hazard Mater ; 469: 133894, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38452668

RESUMO

Exposure to different types of nanoparticles (NPs) results in their deposition in human bodies. While most studies have examined the cellular uptake of only one type of NP at a time, how the dynamics of NP uptake may change in the presence of other types of NPs remains unclear. We therefore investigated the interplay of two differently sized SiO2 NPs during their uptake by A549 human lung carcinoma cells. Both NPs contained a CdSeTe core, which was labeled with different Cd isotopes to differentiate between them. Our study showed that the uptake of one size of SiO2 NPs either increased or decreased with the concentration of the other size of SiO2 NPs. This variation in uptake was attributable to the concentration-dependent aggregation of SiO2 NPs, as determined by the amount of cell-excreted proteins adsorbed on the NP surface. Further, the effects of the protein corona on the attachment of SiO2 NPs to the cell surface and uptake competition between differently sized SiO2 NPs also played important roles. Cell-excreted proteins were then analyzed by proteomics. Overall, the complex interactions between coexisting NPs of different physicochemical properties and cell-excreted proteins should be considered during bio-applications and bio-safety evaluations of NPs.


Assuntos
Nanopartículas , Dióxido de Silício , Humanos , Dióxido de Silício/química , Proteínas/metabolismo , Nanopartículas/química , Linhagem Celular , Membrana Celular/metabolismo
3.
Front Biosci (Landmark Ed) ; 29(2): 70, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38420793

RESUMO

BACKGROUND: The number of older people in the world is increasing year by year; studies have shown that more than 90% of cardiovascular disease occurs in the older people population, indicating that aging is one of the major risks involved in the development of cardiovascular disease. Therefore, retarding the development of cardiac aging is an important strategy to prevent aging-related cardiovascular diseases. METHODS: In the current study, we examined the anti-cardiovascular aging potential of canthaxanthin in vitro and in vivo experiments. For this, a model of cardiomyocyte senescence induced by D-galactose was established, which was used to investigate the canthaxanthin's effect on cardiac premature aging. RESULTS: We found that canthaxanthin obviously mitigated the cardiomyocyte senescence in vitro. Further mechanistic studies revealed that canthaxanthin seems to alleviate cardiomyocyte senescence by regulating the autophagy process. Furthermore, the effects of canthaxanthin on cardiovascular senescence were further evaluated. We also observed that canthaxanthin mitigated cardiac aging and fibrosis in the aged mice model. CONCLUSIONS: To sum up, the current work showed that canthaxanthin could obviously alleviate cardiac premature aging, indicating that canthaxanthin could be used as a biologically active molecule for the treatment of cardiac aging and fibrosis.


Assuntos
Senilidade Prematura , Doenças Cardiovasculares , Humanos , Animais , Camundongos , Idoso , Cantaxantina/farmacologia , Senilidade Prematura/patologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/patologia , Envelhecimento , Miócitos Cardíacos , Fibrose , Senescência Celular
4.
Environ Sci Technol ; 58(1): 751-759, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38113379

RESUMO

Aquatic environments are complicated systems that contain different types of nanoparticles (NPs). Nevertheless, recent studies of NP toxicity, and especially those that have focused on bioaccumulation have mostly investigated only a single type of NPs. Assessments of the environmental risks of NPs that do not consider co-exposure regimes may lead to inaccurate conclusions and ineffective environmental regulation. Thus, the present study examined the effects of differently sized silica NPs (SiO2 NPs) on the uptake of iron oxide NPs (Fe2O3 NPs) by the zooplankton Daphnia magna. Both SiO2 NPs and Fe2O3 NPs were well dispersed in the experimental medium without significant heteroaggregation. Although all three sizes of SiO2 NPs inhibited the uptake of Fe2O3 NPs, the underlying mechanisms differed. SiO2 NPs smaller than the average mesh size (∼200 nm) of the filtering apparatus of D. magna reduced the accumulation of Fe2O3 NPs through uptake competition, whereas larger SiO2 NPs inhibited the uptake of Fe2O3 NPs mainly by reducing the water filtration rate of the daphnids. Overall, in evaluations of the risks of NPs in the natural environment, the different mechanisms underlying the effects of NPs of different sizes on the uptake of dissimilar NPs should be considered.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Daphnia magna , Daphnia , Dióxido de Silício/farmacologia , Nanopartículas/toxicidade , Nanopartículas Magnéticas de Óxido de Ferro , Poluentes Químicos da Água/toxicidade
5.
Biochem Biophys Res Commun ; 680: 135-140, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37738903

RESUMO

Venous malformations are a vascular disorder. Currently, the use of chemical sclerosing agents is a common clinical approach for the treatment of venous malformations. However, the effectiveness of existing sclerosing agents is unsatisfactory and often accompanied by severe side effects. In this study, we have developed a novel cationic surfactant-based sclerosing agent (POL-TA) by conjugating the plasmin inhibitor tranexamic acid (TA) with a nonionic surfactant polidocanol (POL) through an ester bond. POL-TA induces endothelial cell damage, triggering the coagulation cascade and thrombus formation. Moreover, it releases TA in vivo, which inhibits plasmin activity and the activation of matrix metalloproteinase (MMPs), thereby stabilizing the fibrin network of the thrombus and promoting vascular fibrosis. We have established a cell model using venous malformation endothelial cells and assessed the cellular damage and underlying mechanisms of POL-TA. The inhibitory effects of POL-TA on the plasmin-MMPs system were evaluated using MMP-9 activity assay kit. Additionally, the mice tail vein model was employed to investigate the vascular sclerosing effects and mechanisms of POL-TA.

6.
Mol Ther Nucleic Acids ; 32: 729-742, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37234746

RESUMO

A large proportion of patients with chronic myeloid leukemia (CML; 20%-50%) develop resistance to imatinib in a BCR-ABL1-independent manner. Therefore, new therapeutic strategies for use in this subset of imatinib-resistant CML patients are urgently needed. In this study, we used a multi-omics approach to show that PPFIA1 was targeted by miR-181a. We demonstrate that both miR-181a and PPFIA1-siRNA reduced the cell viability and proliferative capacity of CML cells in vitro, as well as prolonged the survival of B-NDG mice harboring human BCR-ABL1-independent imatinib-resistant CML cells. Furthermore, treatment with miR-181a mimic and PPFIA1-siRNA inhibited the self-renewal of c-kit+ and CD34+ leukemic stem cells and promoted their apoptosis. Small activating (sa)RNAs targeting the promoter of miR-181a increased the expression of endogenous primitive miR-181a (pri-miR-181a). Transfection with saRNA 1-3 inhibited the proliferation of imatinib-sensitive and -resistant CML cells. However, only saRNA-3 showed a stronger and more sustained inhibitory effect than the miR-181a mimic. Collectively, these results show that miR-181a and PPFIA1-siRNA may overcome the imatinib resistance of BCR-ABL1-independent CML, partially by inhibiting the self-renewal of leukemia stem cells and promoting their apoptosis. Moreover, exogenous saRNAs represent promising therapeutic agents in the treatment of imatinib-resistant BCR-ABL1-independent CML.

7.
Int J Biol Sci ; 19(4): 1211-1227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923939

RESUMO

BCR-ABL oncogene-mediated Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) is suggested to originate from leukemic stem cells (LSCs); however, factors regulating self-renewal of LSC and normal hematopoietic stem cells (HSCs) are largely unclear. Here, we show that RalA, a small GTPase in the Ras downstream signaling pathway, has a critical effect on regulating the self-renewal of LSCs and HSCs. A RalA knock-in mouse model (RalARosa26-Tg/+) was initially constructed on the basis of the Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR/Cas9) assay to analyze normal hematopoietic differentiation frequency using single-cell resolution and flow cytometry. RalA overexpression promoted cell cycle progression and increased the frequency of granulocyte-monocyte progenitors (GMPs), HSCs and multipotent progenitors (MPPs). The uniform manifold approximation and projection (UMAP) plot revealed heterogeneities in HSCs and progenitor cells (HSPCs) and identified the subclusters of HSCs and GMPs with a distinct molecular signature. RalA also promoted BCR-ABL-induced leukemogenesis and self-renewal of primary LSCs and shortened the survival of leukemic mice. RalA knockdown prolonged survival and promoted sensitivity to imatinib in a patient-derived tumor xenograft model. Immunoprecipitation plus single-cell RNA sequencing of the GMP population confirmed that RalA induced this effect by interacting with RAC1. RAC1 inhibition by azathioprine effectively reduced the self-renewal, colony formation ability of LSCs and prolonged the survival in BCR-ABL1-driven RalA overexpression CML mice. Collectively, RalA was detected to be a vital factor that regulates the abilities of HSCs and LSCs, thus facilitating BCR-ABL-triggered leukemia in mice. RalA inhibition serves as the therapeutic approach to eradicate LSCs in CML.


Assuntos
Sistemas CRISPR-Cas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Camundongos , Animais , GTP Fosfo-Hidrolases/metabolismo , Edição de Genes , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Carcinogênese/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas ral de Ligação ao GTP/genética , Proteínas ral de Ligação ao GTP/metabolismo
8.
Front Biosci (Landmark Ed) ; 28(12): 367, 2023 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-38179737

RESUMO

BACKGROUND: Vascular endothelial dysfunction is an early phenotype of aging-related vascular dysfunction. Delaying vascular aging and preventing cardiovascular disease are major public health problems that urgently need to be solved. Scientists have studied various drugs to prevent the occurrence and progress of cardiovascular disease, but progress has been slow. Here, the antisenescence and anti-endothelial damage of canthaxanthin (CX, which is an active molecule from food) has been studied. METHODS: This study was performed by adding CX to a model of cell senescence and oxidative damage induced by hydrogen peroxide. Cellular senescence markers (e.g., p16, p21, and p53) and oxidative damage markers (e.g., reactive oxygen species, nitric oxide, malondialdehyde, superoxide dismutase) were evaluated by the enzyme-linked immunosorbent assay, laser scanning confocal microscopy, and Western blotting. RESULTS: We found that CX downregulated the expression level of senescence-associated molecules, and significantly reduced the oxidative damage of vascular endothelial cells. These observations showed that CX effectively alleviated the senescence of vascular endothelial cells. Furthermore, CX treatment reduced the expression levels of interleukin-6 (IL-6), tumor necrosis factor alpha, and IL-1ß. Finally, in vivo, CX significantly alleviated vascular senescence. CONCLUSIONS: The current study shows that CX has potential application value for treating vascular aging or endothelial cell senescence.


Assuntos
Cantaxantina , Doenças Cardiovasculares , Camundongos , Animais , Cantaxantina/farmacologia , Células Endoteliais , Envelhecimento , Senescência Celular/genética , Estresse Oxidativo , Inflamação
9.
Mol Ther Oncolytics ; 23: 560-570, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34938856

RESUMO

Resistance to the BCR-ABL inhibitor imatinib mesylate poses a major problem for the treatment of chronic myeloid leukemia. Imatinib resistance often results from a secondary mutation in BCR-ABL that interferes with drug binding. However, sometimes there is no mutation in BCR-ABL, and the basis of such BCR-ABL-independent imatinib mesylate resistance remains to be elucidated. SOS1, a guanine nucleotide exchange factor for Ras protein, affects drug sensitivity and resistance to imatinib. The depletion of SOS1 markedly inhibits cell growth either in vitro or in vivo and significantly increases the sensitivity of chronic myeloid leukemia cells to imatinib. Furthermore, LC-MS/MS and RNA-seq assays reveal that SOS1 negatively regulates the expression of SLC22A4, a member of the carnitine/organic cation transporter family, which mediates the active uptake of imatinib into chronic myeloid leukemia cells. HPLC assay confirms that intracellular accumulation of imatinib is accompanied by upregulation of SLC22A4 through SOS1 inhibition in both sensitive and resistant chronic myeloid leukemia cells. BAY-293, an inhibitor of SOS1/Ras, was found to depress proliferation and colony formation in chronic myeloid leukemia cells with resistance and BCR-ABL independence. Altogether these findings indicate that targeting SOS1 inhibition promotes imatinib sensitivity and overcomes resistance with BCR-ABL independence by SLC22A4-mediated uptake transport.

10.
Anal Chem ; 93(12): 5005-5008, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33724781

RESUMO

We used online secondary electrospray ionization mass spectrometry to measure venlafaxine (VEN), a nonvolatile drug, in the exhaled air of mice intraperitoneally treated with VEN. The breath pharmacokinetic (PK) profile of VEN was recorded, which was in good agreement with that of the blood. Combined with online collection of exhaled breath particles (EBPs), it was shown that VEN existed as part of EBPs rather than gas molecules in the breath. Linear free-energy relationship analysis confirmed that almost completely ionized VEN at physiological conditions unlikely partition from the lung lining fluid (LLF) into breath air. This implies that the occurrence of VEN in exhaled air accompanies the formation of EBPs from the LLF. By comparison with the low breath signals of VEN metabolites, passive membrane permeability and lung/blood partition coefficient are suggested as the main influencing factors for the levels of drugs in the breath. This study advances our knowledge on the mechanism by which nonvolatile drugs are transferred from blood into exhaled breath, providing guidance for breath test-based therapeutic drug monitoring.


Assuntos
Expiração , Preparações Farmacêuticas , Animais , Testes Respiratórios , Monitoramento de Medicamentos , Camundongos , Espectrometria de Massas por Ionização por Electrospray
11.
Int J Nanomedicine ; 15: 2859-2872, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368058

RESUMO

PURPOSE: The topical application of exosomes secreted by mesenchymal stem cells (MSC-Exos) on the skin is a very new and interesting topic in the medical field. In this study, we aimed to investigate whether marine sponge Haliclona sp. spicules (SHSs) could effectively enhance the skin delivery of human umbilical cord-derived MSC-Exos (hucMSC-Exos), and further evaluate the topical application of hucMSC-Exos combined with SHSs in rejuvenating photoaged mouse skin. MATERIALS AND METHODS: SHSs were isolated from the explants of sponge Haliclona sp. with our proprietary method, and hucMSC-Exos were prepared from the conditioned medium of hucMSCs using ultracentrifugation. The effects of SHSs on the skin penetration of fluorescently labeled hucMSC-Exos were determined using confocal microscopy in vitro (porcine skin) and in vivo (mouse skin). The therapeutic effects of hucMSC-Exos coupled with SHSs against UV-induced photoaging in mice were assessed by using microwrinkles analysis, pathohistological examination and real-time RT-PCR. We also tested the skin irritation caused by the combination of hucMSC-Exos and SHSs in guinea pigs. RESULTS: In vitro results showed that hucMSC-Exos could not readily penetrate through porcine skin by themselves. However, SHSs increased the skin absorption of exosomes by a factor of 5.87 through creating microchannels. Similar penetration enhancement of hucMSC-Exos was observed after SHSs treatment in mice. The combined use of hucMSC-Exos and SHSs showed significant anti-photoaging effects in mice, including reducing microwrinkles, alleviating histopathological changes, and promoting the expression of extracellular matrix constituents, whereas hucMSC-Exos alone produced considerably weaker effects. Skin irritation test showed that the combination of hucMSC-Exos and SHSs caused slight irritation, and the skin recovered shortly. CONCLUSION: SHSs provide a safe and effective way to enhance the skin delivery of MSC-Exos. Moreover, the combination of MSC-Exos and SHSs may be of much use in the treatment of photoaging.


Assuntos
Exossomos , Poríferos/anatomia & histologia , Envelhecimento da Pele/efeitos dos fármacos , Cordão Umbilical/citologia , Administração Tópica , Animais , Exossomos/metabolismo , Feminino , Cobaias , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Envelhecimento da Pele/fisiologia , Testes de Irritação da Pele/métodos , Suínos
12.
Data Brief ; 24: 103908, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31061856

RESUMO

The data presented in this article are associated with the research article entitled " Meroterpenoids isolated from Arnebia euchroma (Royle) Johnst. and their cytotoxic activity in human hepatocellular carcinoma cells " [1]. The aim of this data was to provide the 1D-NMR spectrum of novel meroterpenoids from Arnebia euchroma (Royle) Johnst.

13.
Biomater Sci ; 7(4): 1299-1310, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30821312

RESUMO

We demonstrated that the topical combined use of sponge Haliclona sp. spicules (SHS) and flexible liposomes (FL), referred to as SFLS (SHS-Flexible Liposomes combined System), can result in synergy to improve the skin absorption and deposition of hyaluronic acid (HA), especially in deep skin layers, both in vitro and in vivo. SHS treatment can result in skin micro-channels which are continuous, deep enough (48.6 ± 13.5 µm) and available in large quantities (850 ± 125 micro-channels per mm2). These micro-channels gradually closed up in 120 h and also allowed the intact vesicles of flexible liposomes and vesicle-bound or vesicle-encapsulated HA to penetrate into the skin-deep layers under the driving force of transdermal osmotic gradients. Specifically, SFLS topical application enhanced the penetration of FITC-HA (MW: 250 kDa) into porcine skin in vitro up to 23.2 ± 3.7%, which is 19.4 ± 3.1-fold (p < 0.001) that of a Phosphate Buffered Saline (PBS) group, 3.4 ± 0.5-fold (p < 0.01) that of an SHS group and 3.6 ± 0.6-fold (p < 0.01) that from the combined use of a Dermaroller and flexible liposomes. Moreover, SFLS can lead to significantly enhanced skin deposition of HA in all skin layers, especially in deep skin layers: up to 86.8 ± 4.1% of HA absorbed by skin was accumulated in deep skin layers. The effectiveness of SFLS topical application was also confirmed in vivo by using BALB/c mice. In addition, a skin irritation and toxicity study showed that the SFLS treatment may cause very minimal redness and the skin can recover in a short time. In sum, the combined use of SHS and FL (SFLS) offers a promising strategy to safely and effectively improve the skin delivery of hydrophilic biomacromolecules such as HA.


Assuntos
Ácido Hialurônico/química , Poríferos/química , Pele/química , Animais , Feminino , Cabelo/química , Cabelo/citologia , Ácido Hialurônico/administração & dosagem , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Pele/citologia , Absorção Cutânea , Suínos
14.
Phytomedicine ; 57: 282-291, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30802714

RESUMO

BACKGROUND: In our previous work, we purified a novel biflavonoid named Japoflavone D (JFD) from Lonicera japonica flower buds. Biflavonoids are chemical compounds characterized by their high levels of antioxidative activity. PURPOSE: The present study aimed to investigate the function and molecular mechanism of JFD under different oxidative conditions in hepatoma cells. METHODS: MTT assay and apoptosis assay were used to evaluate the cytotoxic effect of JFD. The activities of SOD and CAT were detected to evaluate the oxidative level. Oxidative stress was induced by H2O2 stimulation. The molecular mechanism of JFD was investigated by analyzing relative signaling pathway. RESULTS: JFD inhibited cell viability in all hepatoma cell lines we examined. Under quiescent conditions, JFD treatment of SMMC-7721 cells resulted in upregulation of AKT/mTOR signal pathway and ERK activities and downregulation of KEAP1/NRF2/ARE signaling axis, together with apoptosis. However, under oxidative stress, JFD played a quite different role. Treatment of JFD suppressed the activation of ERK and mTOR and activated the KEAP1/NRF2/ARE signaling axis, which is a predominant regulator of cytoprotective responses to oxidative stress, thereby lessening the damage caused by excess reactive oxygen species (ROS). A molecular docking analysis suggested that JFD may interrupt the interaction between KEAP1 and NRF2 by competitively anchoring to the NRF2 binding site on KEAP1. CONCLUSION: The results indicate that JFD functions as a potent antioxidant and plays dual roles in modulating apoptosis under different oxidative conditions. JFD has the potential to be developed as a protective drug for diseases related with excess ROS.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Biflavonoides/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Lonicera/química , Antineoplásicos Fitogênicos/química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Biflavonoides/química , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Flores/química , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/química , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
15.
RSC Adv ; 9(40): 22921-22930, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35514508

RESUMO

Astilbin is a dihydroflavonol natural product isolated from a variety of food and medicinal herbs (e.g. Smilax glabra Roxb.), and its mechanism of action in vascular pharmacology remains unclear. The aim of this study was to investigate the pro-angiogenic effects of astilbin and its putative mechanism of action. Briefly, our in vitro studies showed a dose-dependent ability of astilbin to increase the ability of HUVECs to proliferate and migrate, and undergo cell invasion and tube formation. Moreover, astilbin significantly increased the expression levels of several major proteins involved in the angiogenesis pathway, e.g. PI3K, Akt, p38 and ERK1/2. Our in vivo studies demonstrated the ability of astilbin to significantly restore the blood vessel loss induced by VRI in a VRI-induced vascular insufficiency zebrafish model. In conclusion, in this study we first demonstrate that astilbin exhibits pro-angiogenic activity in HUVECs and VRI-induced vascular insufficient zebrafish, possibly through the activation of the PI3K/Akt and MAPK/ERK dependent signaling pathways. These findings suggest that astilbin could be further developed as a potential agent in the prevention or treatment of insufficient angiogenesis related diseases in the future.

16.
Data Brief ; 21: 2192-2207, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30555857

RESUMO

The data presented in this article are associated with the research article entitled " Novel flavonoids from Lonicera japonica flower buds and validation of their anti-hepatoma and hepatoprotective activity in vitro studies " (Ge et al., 2018) [1]. The aim of this data was to provide the NMR spectrum of novel flavonoids from Lonicera japonica flower buds. Samples were isolated from EtOAc fraction of Lonicera japonica flower buds extracts, then dissolved in DMSO-d6 before NMR testing.

17.
Fitoterapia ; 131: 236-244, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30414877

RESUMO

Six previously undescribed naturally occurring meroterpenoids (2, 5-9) together with seven known meroterpenoids (1, 3, 4, 10-13) were isolated from the root plant of Arnebia euchroma. Their structures and absolute configurations were determined by extensive 1D (1H NMR, 13C NMR) and 2D NMR (1H1H COSY, DEPT, HMQC, HMBC, NOESY) spectroscopic methods, spectroscopy high resolution mass spectrometry, as well as DFT and MM2 force-field calculations. Meroterpenoids 1-13 were evaluated for their cytotoxicities against human liver cancer cell lines SMMC-7721, HepG2, QGY-7703 and HepG2/ADM. Meroterpenoid 5 exhibited the most potent activity with IC50 values of 6.40 ±â€¯0.51, 3.86 ±â€¯0.28, 3.43 ±â€¯0.27 and 11.31 ±â€¯0.67 µM, respectively. Meroterpenoid 4 exhibited significant growth inhibitory effects against HepG2/ADM with IC50 at 18.77 ±â€¯1.23 µM, and meroterpenoid 8 with IC50 at 5.41 ±â€¯0.51 and 6.18 ±â€¯0.47 µM against HepG2 and QGY-7703, respectively. These were more potent than the positive drug, Cisplatin.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Boraginaceae/química , Terpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , China , Células Hep G2 , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Terpenos/isolamento & purificação
18.
Sci Rep ; 8(1): 13152, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-30177727

RESUMO

Liver cancer, also known as primary liver cancer, is cancer that starts in the liver. JNU-144, a new meroterpenoid purified from Lithospermum erythrorhizon, has exhibited promising anticancer activity; however, the molecular mechanisms of action of JNU-144 on malignant cells remain unclear. Our studies revealed that JNU-144 suppressed cell viability and proliferation in hepatoma cells by downregulating mTOR activation. Meanwhile, JNU-144 activated the intrinsic apoptosis pathway and subsequently triggered apoptotic cell death in SMMC-7721 cells. We also found that JNU-144 inhibited the epithelial-mesenchymal transition in both SMMC-7721 and HepG2 cells through reprogramming of epithelial-mesenchymal transition (EMT)-related gene expression or regulating protein instability. These findings indicate that JNU-144 exerts potent anticancer activity in hepatoma cells and may be developed as a potential therapeutic drug.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/tratamento farmacológico , Serina-Treonina Quinases TOR/genética , Terpenos/farmacologia , Antígenos CD/genética , Antígenos CD/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Caderinas/genética , Caderinas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Humanos , Lithospermum/química , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Extratos Vegetais/química , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Terpenos/isolamento & purificação , Carga Tumoral/efeitos dos fármacos , Vimentina/genética , Vimentina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
19.
Eur J Pharm Sci ; 123: 524-530, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30107227

RESUMO

The aim of the present work is to evaluate the similarity between PDMS membranes and human skin in vitro in permeation study by linear free energy relationship (LFER) analyses. The values of the permeability coefficient log Kp (cm/s) under reliable experimental conditions were collected from the literature for a set of 94 compounds including both neutral and ionic species, which cover a broad range of structural diversity. The values of log Kp (cm/s) have been correlated with Abraham descriptors to yield an equation with R2 = 0.952 and SD = 0.38 log units. The established LFER model for log Kp (cm/s) across PDMS membranes showed no close analogy with that through human skin in vitro. A further critical analysis of the coefficients of the LFER models confirmed that the PDMS permeation system is a very poor model for human skin permeation.


Assuntos
Dimetilpolisiloxanos/metabolismo , Membranas Artificiais , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Absorção Cutânea , Pele/metabolismo , Administração Cutânea , Humanos , Técnicas In Vitro , Transferência Linear de Energia , Modelos Biológicos , Modelos Químicos , Estrutura Molecular , Permeabilidade , Preparações Farmacêuticas/administração & dosagem , Relação Estrutura-Atividade
20.
RSC Adv ; 8(62): 35374-35385, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35547940

RESUMO

Lonicera japonica Thunb., possesses antiviral and hepatoprotective activities, and is widely used as a health food and in cosmetics. However, its major constituents, caffeoylquinic acid derivatives, and their anti-HBV activity were lacking systematic research. In this study, four novel caffeoylquinic acids, five simple caffeic acids and fourteen known caffeoylquinic acids are isolated and identified from L. japonica. Most caffeoylquinic acids inhibited HBsAg and HBeAg secretion, and HBV DNA replication. In particular, 100 µg ml-1 monocaffeoylquinic acid 9 inhibits HBsAg and HBeAg secretion, and HBV DNA replication by 83.82, 70.76 and 39.36% compared to the control. Unfortunately, 50 µg ml-1 tricaffeoylquinic acid 23 promotes HBsAg and HBeAg secretion, and HBV DNA replication by 172.39, 9.92 and 55.40%. Finally, structure-activity relationships reveal that caffeoylquinic acids containing a caffeoyl group have better inhibitory activities. The results indicate that caffeoylquinic acids from L. japonica could serve as anti-HBV agents for functional food or medicinal use.

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