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1.
Chin J Nat Med ; 20(8): 580-588, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36031230

RESUMO

Male infertility has evolved from a common reproductive system disease to a major social issue. Youjing granule (YG) is a Chinese medicinal material used as a therapy method for tonifying the kidneys and removing dampness due to its pathogenic characteristics. YG has been shown to regulate sperm quality in clinical trials, but the underlying mechanism is not fully understood. The present study was aimed to explore the protective effects and mechanism of action of YG on male reproductive system damage caused by methyl methane sulfonate (MMS). We first established an infertility model of rats through oral administration of MMS and then treated with YG. To determine the effect of YG, spermatogenesis, microvascular density, and secretory function of Leydig cells and Sertoli cells in rats were assessed. Spermatogonial stem cells (SSCs) were co-cultured with mouse embryo fibroblast (MEF) cells as an in vitro cell model before exposure to serum containing YG. Furthermore, the proliferation and apoptosis of SSCs were measured. Results indicated that YG increased the expression of self-renewal and proliferation-related molecules such as glial cell line derived neurotrophic factor (GDNF) and fibroblast growth factor-2 (FGF2), and improved the quality of sperm and the proliferation of SSCs. In conclusion, YG may protect spermatogenetic function of rats through regulating the proliferation and self-renewal of SSCs.


Assuntos
Espermatogônias , Células-Tronco , Animais , Proliferação de Células , Masculino , Camundongos , Ratos , Sêmen , Espermatogênese
2.
Front Pharmacol ; 13: 812587, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185568

RESUMO

Kangfuxiaoyan suppository (KFXYS) is a commonly used traditional Chinese medicine (TCM) preparation for the treatment of chronic pelvic inflammatory disease (CPID) clinically, and its safety and effectiveness have been well verified. However, the potential mechanism remains unclear. The integrated strategy of metabolomics and network pharmacology was employed in the study to reveal the potential mechanism of KFXYS in the treatment of CPID. Our research consists of five steps. First, the effect of KFXYS in reversing uterine inflammation indexes was verified. Second, based on the comprehensive characterization of 123 chemical ingredients of KFXYS, the ingredients of KFXYS absorbed into blood were identified by UPLC-Q-TOF/MS, then ADME research was carried out on the main ingredients. Third, the differential metabolites with significant correlation to inflammatory indexes were discovered by metabolomics and correlation analysis. Fourth, the potential targets and pathways of KFXYS in treating CPID were predicted by network pharmacology based on the ingredients which had good ADME behavior. Fifth, the proteins in common pathways of metabolomics and network pharmacology were used to screen the key targets from the potential targets of network pharmacology, and the potential mechanism of KFXYS in treating CPID was clarified. As a result, KFXYS significantly reversed the uterine inflammation indexes, including IL-1 and IL-6. The ingredients absorbed into blood including matrine, sophocarpine, aloin, esculetin-O-glucuronide, 7,4'-dihydroxyisoflavone-O-glucuronide, and 4'-methoxyisoflavone-7-O-glucuronide had good ADME behavior in vivo. Among the differential metabolites, Leukotriene A4, 5-Hydroxyindoleacetic acid, Ornithine, Arginine, and PC (20:1 (11Z)/20:4 (8Z,11Z,14Z,17Z)) were significant correlation to inflammation indexes. The integration analysis of metabolomics and network pharmacology shows that KFXYS may regulate the key targets including ARG1, NOS2, NOS3, etc. We speculate that ingredients of KFXYS, such as matrine, sophocarpine, aloin etc. act on the key proteins including ARG1, NOS2, and NOS3, to exert anti-inflammatory effect.

3.
Theranostics ; 11(4): 1953-1969, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408791

RESUMO

Photodynamic therapy (PDT) efficacy in cancer cells is affected by sub-physiological hypoxia caused by dysregulated and "chaotic" tumor microvasculature. However, current traditional O2-replenishing strategies are undergoing their own intrinsic deficiencies. In addition, resistance mechanisms activated during PDT also lead the present situation far from satisfactory. Methods: We propose a nitric oxide (NO)-based theranostic nanoplatform by using biocompatible poly-lactic-co-glycolic acid nanoparticles (PLGA NPs) as carriers, in which the outer polymeric layer embeds chlorin e6 (Ce6) and incorporates L-Arginine (L-Arg). This nanoplatform (L-Arg@Ce6@P NPs) can reduce hyperactive O2 metabolism of tumor cells by NO-mediated mitochondrial respiration inhibition, which should raise endogenous O2 tension to counteract hypoxia. Furthermore, NO can also hinder oxidative phosphorylation (OXPHOS) which should cause intracellular adenosine triphosphate (ATP) depletion, inhibiting tumor cells proliferation and turning cells more sensitive to PDT. Results: When the L-Arg@Ce6@P NPs accumulate in solid tumors by the enhanced permeability and retention (EPR) effect, locally released L-Arg is oxidized by the abundant H2O2 to produce NO. In vitro experiments suggest that NO can retard hypoactive O2 metabolism and save intracellular O2 for enhancing PDT efficacy under NIR light irradiation. Also, lower intracellular ATP hinders proliferation of DNA, improving PDT sensitization. PDT phototherapeutic efficacy increased by combining these two complementary strategies in vitro/in vivo. Conclusion: We show that this NO-based nanoplatform can be potentially used to alleviate hypoxia and sensitize tumor cells to amplify the efficacy of phototherapy guided by photoacoustic (PA) imaging.


Assuntos
Trifosfato de Adenosina/metabolismo , Neoplasias da Mama/tratamento farmacológico , Nanopartículas/administração & dosagem , Óxido Nítrico/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Poliésteres/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Biomater Sci ; 8(23): 6561-6578, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33231593

RESUMO

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has shown great promise for cancer treatment in many preclinical studies. This study reports a nanoreactor designed for an enhanced mild temperature phototherapy which utilizes multiple mechanisms including simultaneous glucose consumption, oxygen supply, glutathione (GSH) depletion and heat-resistance relief. The nanoreactor is prepared using an Fe-doped polydiaminopyridine (Fe-PDAP) nanozyme with an intrinsic catalase-like activity coloaded with glucose oxidase (GOx) and indocyanine green (ICG). Evidence shows that glucose plays a vital role in tumor progression. Initiated by the breakdown of glucose into gluconic acid and H2O2 by GOx, Fe-PDAP promotes reoxygenation by catalyzing the reaction-supplied and tumor cell-supplied H2O2 into O2, which then enhances the O2-dependent PDT. Moreover, Fe-PDAP depletes GSH in tumor cells for more efficient reactive oxygen species (ROS) production. Meanwhile, the heat resistance of tumor cells is relieved by GOx-induced glucose exhaustion and heat shock protein (HSP) reduction, improving the efficiency of PTT. In particular, the nanoreactor also serves as a contrast agent for fluorescence, photoacoustic, and magnetic resonance multimodal imaging. Consequently, this nanoreactor efficiently inhibits tumor growth through mild temperature phototherapy under multimodal imaging guidance, resulting in successful tumor ablation with minimal systemic toxicity.


Assuntos
Peróxido de Hidrogênio , Nanotecnologia , Fototerapia , Animais , Linhagem Celular Tumoral , Imagem Multimodal , Temperatura
5.
ACS Nano ; 14(10): 12652-12667, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32986406

RESUMO

Organic-inorganic hybrid materials have drawn increasing attention as photothermal agents in tumor therapy due to the advantages of green synthesis, high loading efficiency of hydrophobic drugs, facile incorporation of theranostic iron, and excellent photothermal efficiency without inert components or additives. Herein, we proposed a strategy for biomimetic engineering-mediated enhancement of photothermal performance in the tumor microenvironment (TME). This strategy is based on the specific characteristics of organic-inorganic hybrid materials and endows these materials with homologous targeting ability and photothermal stability in the TME. The hybrid materials perform the functions of cancer cells to target homolytic tumors (acting as "artificial nanotargeted cells (ANTC)"). Inspired by the pH-dependent disassembly behaviors of tannic acid (TA) and ferric ion (FeIII) and subsequent attenuation of photothermal performance, cancer cell membranes were self-deposited onto the surfaces of protoporphyrin-encapsulated TA and FeIII nanoparticles to achieve ANTC with TME-stable photothermal performance and tumor-specific phototherapy. The resulting ANTC can be used as contrast agents for concurrent photoacoustic imaging, magnetic resonance imaging, and photothermal imaging to guide the treatment. Importantly, the high loading efficiency of protoporphyrin enables the initiation of photodynamic therapy to enhance photothermal therapeutic efficiency, providing antitumor function with minimal side effects.


Assuntos
Hipertermia Induzida , Nanopartículas , Animais , Linhagem Celular Tumoral , Compostos Férricos , Camundongos , Camundongos Endogâmicos BALB C , Imagem Multimodal , Fototerapia , Nanomedicina Teranóstica
6.
Int J Nanomedicine ; 15: 5927-5949, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848397

RESUMO

PURPOSE: A multi-functional nanoplatform with diagnostic imaging and targeted treatment functions has aroused much interest in the nanomedical research field and has been paid more attention in the field of tumor diagnosis and treatment. However, some existing nano-contrast agents have encountered difficulties in different aspects during clinical promotion, such as complicated preparation process and low specificity. Therefore, it is urgent to find a nanocomplex with good targeting effect, high biocompatibility and significant therapeutic effect for the integration of diagnosis and treatment and clinical transformation. MATERIALS AND METHODS: Nanoparticles (NPs) targeting breast cancer were synthesized by phacoemulsification which had liquid fluorocarbon perfluoropentane(PFP) in the core and were loaded with Iron(II) phthalocyanine (FePc) on the shell. The aptamer (APT) AS1411 was outside the shell used as a molecular probe. Basic characterization and targeting abilities of the NPs were tested, and their cytotoxicity and biological safety in vivo were evaluated through CCK-8 assay and blood bio-chemical analysis. The photoacoustic (PA) and ultrasound (US) imaging system were used to assess the effects of AS1411-PLGA@FePc@PFP (A-FP NPs) as dual modal contrast agent in vitro and in vivo. The effects of photothermal therapy (PTT) in vitro and in vivo were evaluated through MCF-7 cells and tumor-bearing nude mouse models. RESULTS: A-FP NPs, with good stability, great biocompatibility and low toxicity, were of 201.87 ± 1.60 nm in diameter, and have an active targeting effect on breast cancer cells and tissues. With the help of PA/US imaging, it was proved to be an excellent dual modal contrast agent for diagnosis and guidance of targeted therapy. Meanwhile, it can heat up under near-infrared (NIR) laser irradiation and has achieved obvious antitumor effect both in vitro and in vivo experiments. CONCLUSION: As a kind of nanomedicine, A-FP NPs can be used in the integration of diagnosis and treatment. The treatment effects and biocompatibility in vivo may provide new thoughts in the clinical transformation of nanomedicine and early diagnosis and treatment of breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Indóis/química , Nanopartículas Multifuncionais/química , Oligodesoxirribonucleotídeos/farmacologia , Animais , Aptâmeros de Nucleotídeos/administração & dosagem , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , Neoplasias da Mama/patologia , Meios de Contraste/química , Feminino , Fluorocarbonos/química , Humanos , Ferro/química , Isoindóis , Células MCF-7 , Camundongos Endogâmicos BALB C , Nanopartículas Multifuncionais/administração & dosagem , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/química , Fototerapia/métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ultrassonografia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Mater Sci Eng C Mater Biol Appl ; 108: 110460, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923975

RESUMO

Myelosuppression, gastrointestinal toxicity and hypersensitivities always accompany chemotherapy of osteosarcoma (OS). In addition, the intricate karyotype of OS, the lack of targeted antitumor drugs and the bone microenvironment that provides a protective alcove for tumor cells reduce the therapeutic efficacy of chemotherapy. Here, we developed a multifunctional bone cement loaded with Fe3O4 nanoparticles and the antitumor drug doxorubicin (DOX/Fe3O4@PMMA) for synergistic MH ablation and chemotherapy of OS. The localized intratumorally administered DOX/Fe3O4@PMMA can change from liquid into solid at the tumor site via a polyreaction. The designed multifunctional bone cement was constructed with Fe3O4 nanoparticles, PMMA, and an antitumor drug approved by the U.S. Food and Drug administration (FDA). The injectability, magnetic hyperthermia (MH) performance, controlled drug release profile, and synergistic therapeutic effect of DOX/Fe3O4@PMMA in vitro were investigated in detail. Furthermore, the designed DOX/Fe3O4@PMMA controlled the release of DOX, enhanced the apoptosis of OS tissue, and inhibited the proliferation of tumor cells, demonstrating synergistic MH ablation and chemotherapy of OS in vivo. The biosafety of DOX/Fe3O4@PMMA was also evaluated in detail. This strategy significantly reduced surgical time, avoided operative wounds and prevented patient pain, showing a great clinical translational potential for OS treatment.


Assuntos
Cimentos Ósseos , Neoplasias Ósseas/terapia , Hipertermia Induzida , Nanopartículas de Magnetita , Osteossarcoma/terapia , Animais , Cimentos Ósseos/química , Cimentos Ósseos/farmacologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Zhonghua Nan Ke Xue ; 25(9): 828-832, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32233211

RESUMO

OBJECTIVE: To investigate the effect and action mechanism of Yu Si Granules (YSG) in the treatment methyl methanesulphonate (MMS)-induced oligoasthenozoospermia (OAZ) in mice. METHODS: Thirty adult male mice were randomly divided into three groups of equal number, normal control, OAZ model control and YSG intervention. The OAZ model was established by oral administration of MMS and the model mice in the YSG intervention group were treated intragastrically with YSG suspension at 0.144 g/100 g of the body weight per day for 48 successive days. Then, all the mice were sacrificed and their epididymides harvested for detection of the sperm count and motility, observation of the morphology of the seminiferous tubules by HE staining, determination of the expressions of the germ cell-, sperm cell-, spermatocyte-, Sertoli cell- and blood-testis barrier-related genes by RT-PCR, and measurement of the levels of oxidative stress in the blood. RESULTS: Compared with the normal control, the OAZ model mice showed significantly decreased sperm count (ï¼»49.2 ± 0.7ï¼½ vs ï¼»23.6 ± 0.4ï¼½ ×107/ml/g, P < 0.05) and sperm motility (ï¼»76.3 ± 0.7ï¼½% vs ï¼»5.0 ± 5.8ï¼½%, P < 0.05), which were both remarkably increased after YSG intervention (ï¼»38.4 ± 0.5ï¼½ ×107/ml/g and ï¼»71.5 ± 0.5ï¼½%) (P < 0.05). The OAZ model mice also exhibited degenerated and atrophic seminiferous tubules, thinner seminiferous epithelia, disorderly arranged cells at different levels, reduced number of sperm in the lumen and unclear layers of germ cells in the epididymis, while those after YSG intervention manifested regularly organized seminiferous tubules with orderly arrangement and clear layers. The expressions of the Vasa, Dazl and Snd1 genes were significantly decreased (P < 0.05), but not those of Gfra, Plzf, Stra8, Spo11, Sycp3, Sox9 and Vim (P > 0.05) in the OAZ model and YSG intervention groups as compared with those in the normal control group. The superoxide dismutase (SOD) activity in the serum was markedly reduced in the OAZ model mice as compared with that in the normal controls (P < 0.05) and increased again after YSP intervention (P < 0.05), but the opposite was the case with the expression of the superoxide anion. CONCLUSIONS: YSG can significantly reduce MMS-induced OAZ in mice, which may be associated with oxidative stress.


Assuntos
Astenozoospermia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Epididimo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Astenozoospermia/induzido quimicamente , Masculino , Metanossulfonato de Metila , Camundongos , Estresse Oxidativo , Distribuição Aleatória , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides
9.
Chin J Nat Med ; 15(5): 355-362, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28558871

RESUMO

Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu (DSS), palmitoyl Danshensu (PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL-1, its solubility in FaSSIF and FeSSIF reached 4.68 and 9.08 mg·mL-1, respectively. Octanol-water partition coefficient (log P) was increased from -2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. Cmax was 1.67 ± 0.11 µg·mL-1 for PDSS and 0.81 ± 0.06 µg·mL-1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug.


Assuntos
Composição de Medicamentos/métodos , Lactatos/química , Pró-Fármacos/química , Salvia miltiorrhiza/química , Animais , Disponibilidade Biológica , Avaliação Pré-Clínica de Medicamentos , Concentração de Íons de Hidrogênio , Lactatos/farmacocinética , Masculino , Pró-Fármacos/farmacocinética , Ratos , Ratos Sprague-Dawley , Solubilidade
10.
Environ Sci Pollut Res Int ; 24(9): 8336-8351, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28168564

RESUMO

Nonpoint storm runoff remains a major threat to surface water quality in China. As a paddy matures, numerous fertilizers are needed, especially in the rainy seasons; the concentration of nitrogen and phosphorus in rainfall runoff from farmland is much higher than at other times, and this poses a great threat to water bodies and is the main reason for water eutrophication, especially in high concentration drainages. To date, most studies regarding the characteristics of pollutants in rainfall runoff have mainly been concentrated on urban runoff and watershed runoff; therefore, it is particularly important to investigate the characteristics of nitrogen and phosphorus loss in rainfall runoff from paddy fields. To study the characteristics of nitrogen and phosphorus loss and whether the first flush effect exists, continuous monitoring of the rainfall runoff process of six rainfall events was conducted in 2013, of which four rainfall events during storm, high, middle, and low intensity rainfalls were analyzed, and runoff and quality parameters, such as suspended solids (SS), total nitrogen (TN), ammonium nitrogen (NH4+-N), nitrate nitrogen (NO3--N), total phosphorus (TP), and phosphate (PO43--P), were analyzed to determine the relationship between runoff and water quality. The paddy field is located north of Wuxi Lake Basin along the Hejia River upstream in Zhoutie town, Yixing city. An analysis of the load distribution during rainfall runoff was conducted. Event mean concentration (EMC) was used to evaluate the pollution situation of the paddy field's rainfall runoff. A curve of the dimensionless normalized cumulative load (L) vs. normalized cumulative flow (F) (L-F curve), the probability of the mass first flush (MFFn), and the pollutants carried by the initial 25% of runoff (FF25) were used to analyze the first flush effect of the paddy field runoff, and different contaminants show different results: the concentration of nitrogen and phosphorus fluctuate and follow a similar trend as runoff changes, NO3--N concentration is lower in the early part of runoff and higher in the later, and TP mainly occurs in the particle state in storm runoff and mainly in the dissolved state when the rainfall intensity is smaller. Nitrogen and phosphorus losses from paddy fields are closely related to the average rainfall intensity and the max rainfall intensity, and the runoff loss of nitrogen and phosphorus is more severe when the rainfall intensity is large. Based on an analysis of multiple methodologies, TN and NH4+-N show a certain degree of a first flush effect, whereas the first flush effect of TP is not obvious. The first flush effect of SS is obvious in larger intensity rainfall and shows a slight secondary flush effect in smaller rainfall events.


Assuntos
Fertilizantes , Chuva , Poluentes Químicos da Água/análise , Poluição da Água/análise , China , Cidades , Monitoramento Ambiental , Eutrofização , Lagos , Nitratos/análise , Nitrogênio/análise , Fosfatos/análise , Fósforo/análise , Água/análise , Movimentos da Água , Qualidade da Água
11.
Oncotarget ; 8(69): 113614-113621, 2017 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-29371933

RESUMO

Oral carcinoma (OC) remains one of the most difficult malignancies to cure. selenium (Se) is an essential trace mineral for human and animals, but high concentrations of Se induce apoptosis and oxidative effects. Although cell apoptosis has been evidenced as a critical mechanism mediating the anticancer activity of Se, the underlying molecular mechanisms remain elusive. To explore the role of Se in rat OC, we examined the weather the oxidative stress-mediated apoptotic pathway induced by Se was involved in the development of OC. In this study, we successfully constructed the OC rat model by 4-Nitroquinoline-1-oxide (4-NQO) exposure which reflected from histopathological observations. Se-induced the productions of methane dicarboxylic aldehyde (MDA) and reactive oxygen species (ROS), which was accompanied by the inhibition of superoxide dismutase (SOD) both in vivo and vitro. The anti-apoptotic gene (Bcl-2) was down-regulated and pro-apoptosis members (Bax, Bak, Cyt-c, caspase9 and caspase3) were up-regulated by Se in OC cells. Meanwhile, we also found that Se could strongly inhibited the cell proliferation of OC lines in vitro. These results suggested that excessive Se could effectively cause oxidative stress and induce apoptosis in OC cells, as a result the OC was also inhibited to some extent. Therefore, the information presented in this study is believed to be helpful in supplementing data for further therapy of OC.

12.
Sci Rep ; 6: 33237, 2016 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-27616058

RESUMO

Transcriptomic analysis of cultured fungi suggests that many genes for secondary metabolite synthesis are presumably silent under standard laboratory condition. In order to investigate the expression of silent genes in symbiotic systems, 136 fungi-fungi symbiotic systems were built up by co-culturing seventeen basidiomycetes, among which the co-culture of Trametes versicolor and Ganoderma applanatum demonstrated the strongest coloration of confrontation zones. Metabolomics study of this co-culture discovered that sixty-two features were either newly synthesized or highly produced in the co-culture compared with individual cultures. Molecular network analysis highlighted a subnetwork including two novel xylosides (compounds 2 and 3). Compound 2 was further identified as N-(4-methoxyphenyl)formamide 2-O-ß-D-xyloside and was revealed to have the potential to enhance the cell viability of human immortalized bronchial epithelial cell line of Beas-2B. Moreover, bioinformatics and transcriptional analysis of T. versicolor revealed a potential candidate gene (GI: 636605689) encoding xylosyltransferases for xylosylation. Additionally, 3-phenyllactic acid and orsellinic acid were detected for the first time in G. applanatum, which may be ascribed to response against T.versicolor stress. In general, the described co-culture platform provides a powerful tool to discover novel metabolites and help gain insights into the mechanism of silent gene activation in fungal defense.


Assuntos
Ganoderma/metabolismo , Glicosídeos/metabolismo , Trametes/metabolismo , Sequência de Aminoácidos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Sequência Conservada , Avaliação Pré-Clínica de Medicamentos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ganoderma/genética , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Metabolômica , Interações Microbianas , Pentosiltransferases/genética , Pentosiltransferases/metabolismo , Filogenia , Trametes/genética , UDP Xilose-Proteína Xilosiltransferase
13.
Nat Prod Commun ; 8(8): 1129-34, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24079186

RESUMO

We investigated the fingerprints of 48 batches of turmeric total extracts (TTE) by HPLC-MS-MS and GC-MS analyses and 43 characteristic peaks (22 constituents from HPLC-MS-MS; 21 from GC-MS) were analyzed qualitatively and quantitatively. An MTT {3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide} assay was implemented to measure the cytotoxicity of the TTE against HeLa cells. Then we utilized orthogonal partial least squares analysis, which correlated the chemical composition of the TTE to its cytotoxic activity, to identify potential cytotoxic constituents from turmeric. The result showed that 19 constituents contributed significantly to the cytotoxicity. The obtained result was verified by canonical correlation analysis. Comparison with previous reports also indicated some interaction between the curcuminoids and sesquiterpenoids in turmeric.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Curcuma/química , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Células HeLa , Humanos , Extratos Vegetais/química , Plantas Medicinais/química , Estatística como Assunto
14.
Kaohsiung J Med Sci ; 29(5): 239-45, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23639509

RESUMO

Adenoid cystic carcinoma (ACC) is characterized by intensive local invasion and high incidence of distant metastases. Conventional chemotherapy for ACC produces a poor result. We aimed to evaluate the effect of apple polyphenols (APs), a novel nutraceutical agent, on the proliferation and apoptosis levels in a metastatic oral ACC cell line. A metastatic ACC (ACC-M) cell line and control cells (MRC-5 cells derived from normal lung tissue) were treated with APs at different concentrations. MTT assay was used to determine the in vitro cytotoxicity. The cell cycle distribution and apoptosis levels were measured by flow cytometry. To evaluate the mechanism of APs, vascular endothelial growth factor receptor-2 (VEGFR-2) and caspase-3 messenger ribonucleic acid (mRNA) and protein levels were evaluated by reverse transcription-polymerase chain reaction and Western blots, respectively. After cells were cultured for 24 hours or 48 hours, the critical concentration of cytotoxicity of APs in MRC-5 cells was found to be 250 µg/mL. In contrast, in the concentration range of 100-250 µg/mL, the cytotoxicity of APs in ACC-M cells was time- and dose-dependent: ACC-M cell proliferation declined at 100 µg/mL when cultured for 48 hours, whereas growth was not inhibited at the concentrations of APs below 200 µg/mL when cultured for 24 hours. In selected time and dose patterns (ACC-M cells cultured at the concentrations of 150 and 250 µg/mL for 48 hours), the flow cytometry performance showed that apoptosis and necrosis occurred in APs-treated ACC-M cells. Also, in these patterns, VEGFR-2 mRNA and protein levels decreased whereas the levels of caspase-3 increased. In summary, APs could inhibit proliferation and induce apoptosis in ACC-M cells in vitro. These effects may be related to the downregulation of VEGFR-2 expression and the activation of caspase-3 expression.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Adenoide Cístico/tratamento farmacológico , Malus/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Neoplasias das Glândulas Salivares/tratamento farmacológico , Apoptose/efeitos dos fármacos , Carcinoma Adenoide Cístico/secundário , Caspase 3/genética , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Frutas/química , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias das Glândulas Salivares/patologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
J Pharm Biomed Anal ; 70: 664-70, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22682511

RESUMO

Using orthogonal partial least squares (OPLS), based on the Simca-p11.5 software, and canonical correlation analysis (CCA), performed on MatLab r2010 software, the correlation between curcuminoids extracted from Curcuma longa L. and the antitumor activity on HeLa cells was investigated to identify the significantly active constituents. Fingerprints from 31 batches of curcuminoids from C. longa L. were established using high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS), and a total of 26 selected characteristic peaks were quantitatively analyzed. Afterward, the antitumor activities of the curcuminoids on HeLa cells were measured using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. We found that 13 of the curcuminoids (peaks 9, 18, 14, 8, 16, 17, 24, 12, 4, 13, 10, 20 and 11) were significantly correlated with antitumor activity via a Loadings plot and VIP (variable importance in projection) in OPLS and a correlation coefficient in CCA. These results support a method for the discovery of antitumor active constituents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Curcuma/química , Curcumina/farmacologia , Descoberta de Drogas , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Curcumina/química , Curcumina/isolamento & purificação , Descoberta de Drogas/métodos , Células HeLa , Humanos , Análise dos Mínimos Quadrados , Plantas Medicinais , Reprodutibilidade dos Testes , Software , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem
16.
Zhonghua Nan Ke Xue ; 13(5): 471-3, 2007 May.
Artigo em Chinês | MEDLINE | ID: mdl-17569268

RESUMO

OBJECTIVE: To study the anti-inflammatory and analgesic actions of Aike Mixture (AKM). METHODS: A total of 100 male mice were randomly assigned into 5 groups: a normal control group, a drug control group (a hydrocortisone subgroup and an atropine subgroup), a high-dose AKM group, a mid-dose AKM group and a low-dose AKM group. Xylene was spread on the left ear of the experimental mice to induce inflammation, and 1% acetic acid solution injected into the abdominal cavity to produce pain so as to cause the body bend. Different doses of AKM were given and their actions observed. RESULTS: AKM had obvious anti-inflammatory effect on the xylene-induced ear tumefaction and inhibited the pain-caused body bend in the AKM groups, with significant difference from the normal control (P < 0.01). CONCLUSION: AKM has good anti-inflammatory and analgesic effects, which is of clinical significance in the treatment of chronic prostatitis.


Assuntos
Ácido Oleanólico/análogos & derivados , Fitoterapia , Prostatite/tratamento farmacológico , Saponinas/farmacologia , Animais , Doença Crônica , Modelos Animais de Doenças , Combinação de Medicamentos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Saponinas/uso terapêutico
17.
National Journal of Andrology ; (12): 471-473, 2007.
Artigo em Chinês | WPRIM | ID: wpr-297701

RESUMO

<p><b>OBJECTIVE</b>To study the anti-inflammatory and analgesic actions of Aike Mixture (AKM).</p><p><b>METHODS</b>A total of 100 male mice were randomly assigned into 5 groups: a normal control group, a drug control group (a hydrocortisone subgroup and an atropine subgroup), a high-dose AKM group, a mid-dose AKM group and a low-dose AKM group. Xylene was spread on the left ear of the experimental mice to induce inflammation, and 1% acetic acid solution injected into the abdominal cavity to produce pain so as to cause the body bend. Different doses of AKM were given and their actions observed.</p><p><b>RESULTS</b>AKM had obvious anti-inflammatory effect on the xylene-induced ear tumefaction and inhibited the pain-caused body bend in the AKM groups, with significant difference from the normal control (P < 0.01).</p><p><b>CONCLUSION</b>AKM has good anti-inflammatory and analgesic effects, which is of clinical significance in the treatment of chronic prostatitis.</p>


Assuntos
Animais , Masculino , Camundongos , Doença Crônica , Modelos Animais de Doenças , Combinação de Medicamentos , Camundongos Endogâmicos ICR , Ácido Oleanólico , Farmacologia , Usos Terapêuticos , Fitoterapia , Prostatite , Tratamento Farmacológico , Saponinas , Farmacologia , Usos Terapêuticos
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