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1.
J Photochem Photobiol B ; 201: 111624, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31722283

RESUMO

Biosynthesis of Zinc oxide nanoparticles (ZnONPs) from natural plants stands as a promising nanodrug delivery system in cancer therapeutics. Marsdenia tenacissima (M.t), a Chinese medicinal plant has been extensively used as clinical remedy for treating several types of cancer. In this present study, ZnONPs were synthesized from Marsdenia tenacissima and its anti cancer potency was assessed against in vitro laryngeal cancer cell line Hep-2. The biosynthesized Marsdenia tenacissima Zinc Oxide Nanoparticles [M.t-ZnONPs] was characterized using UV-visible Spec, SEM, TEM and EDAX analysis. The cytotoxic and apoptotic inducing potential of M.t-ZnONPs was assessed by MTT assay and staining such as DCFH-DA, AO/EtBr, Rhodamine 123, DAPI and comet assay. The anticancer potential of M.t-ZnONPs was analysed by Real time PCR analysis of proapoptotic, antiapoptotic and caspases proteins. Our present findings showed characteristic and morphological representation of synthesized M.t-ZnONPs by UV-visible Spec, SEM, TEM and EDAX analysis. M.t-ZnONPs exhibits its cytotoxicity by inhibiting the viability of Hep-2 cells and IC50 value was obtained by MTT assay. The results of apoptotic staining techniques in M.t-ZnONPs treated Hep-2 cells confirm with excess ROS generation, disruption of mitochondrial membrane potential and nuclear damage. The apoptotic inducing potential of M.t-ZnONPs was also evidenced by upregulation of proapoptotic proteins Bax, Caspase 3 & 9 and downregultion of antiapoptotic protein Bcl-2 by RT-PCR analysis. Finally, these results suggested that biosynthesized M.t-ZnONPs is an effective anticancer agent which induces apoptosis in Hep-2 laryngeal cell line and thus conclude that M.t-ZnONPs, a valid anticancer strategy in treating various cancer.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Marsdenia/química , Nanopartículas Metálicas/toxicidade , Óxido de Zinco/química , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Química Verde , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Marsdenia/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas Metálicas/química , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
Artif Cells Nanomed Biotechnol ; 47(1): 3029-3036, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31328556

RESUMO

Nowadays, the synthesis and characterization of gold nanoparticles (AuNPs) from plant based extracts and effects of their anticancer have concerned an important interest. Marsdenia tenacissima (MT), a conventional Chinese herbal medicine, has long been used for thousands of years to treat tracheitis, asthma, rheumatism, etc. In this present study, we optimize the reaction of parameters to manage the nanoparticle size, which was categorized by high-resolution transmission electron microscopy (HR-TEM). A different characterization method, for example, UV-visible spectroscopy (UV-vis), fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) were performed to consider the synthesized AuNPs getting from the MT leaf extract. The MT-AuNPs were analyzed for their cytotoxicity property against HepG2 cells by MTT analysis. The apoptosis was evaluated by using reactive oxygen species (ROS), migration assay, mitochondrial membrane potential (MMP) and apoptotic protein expression. Interestingly, the findings of our study observed the cytotoxicity effect of synthesized MT-AuNPs at a concentration of 59.62 ± 4.37 µg after 24 hrs treatment. Apoptosis was induced by the MT-AuNPs with enhanced ROS, changed MMP and inhibit the migration assay. Finally, the apoptosis was confirmed by the considerable up-regulation of Bax, caspase-9 and caspase-3, while the anti-apoptotic protein expressions of Bcl-2 and Bcl-XL were down-regulated. Although, in this studies, we evaluated the characterization, synthesis and anticancer action of gold nanoparticles from MT (MT-AuNPS) helpful for liver cancer therapeutics.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Ouro/química , Ouro/farmacologia , Neoplasias Hepáticas/patologia , Marsdenia/química , Nanopartículas Metálicas/química , Antineoplásicos/síntese química , Técnicas de Química Sintética , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanotecnologia , Extratos Vegetais/química
3.
Biomed Chromatogr ; 33(9): e4569, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31050008

RESUMO

Marsdenia tenacissima, or Tongguanteng in Chinese, is a traditional Chinese herb and has a broad application in clinical practice for its pharmacological effects of treating asthma, pneumonia, tonsillitis, pharyngitis tumors, etc. However, few studies have reported the screening of the active components of this medicine for tumor therapy. In this work, a two-dimensional analytical system was developed to screen antagonists of epidermal growth factor receptor (EGFR) from M. tenacissima. A fraction was retained on the EGFR cell membrane chromatography (CMC) column, separated and identified as tenacissoside G (TG), tenacissoside H (TH) and tenacissoside I (TI) by two-dimensional HPLC-IT-TOF-MS. Molecular docking and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay were carried out to assess the activity of TS (including TG, TH and TI). Molecular docking results showed that the binding mode of TS on EGFR is similar to that of gefitinib. The MTT assay demonstrated that gefitinib and TS (especially TI) could inhibit the growth of EGFR highly expressed cell lines in a dose-dependent manner in the range of 5-50 µmol/L. In conclusion, the two-dimensional EGFR/CMC-HPLC-IT-TOF-MS system could be a useful approach in drug discovery from traditional Chinese medicines for searching for potential antitumor candidates.


Assuntos
Membrana Celular/metabolismo , Cromatografia de Afinidade/métodos , Medicamentos de Ervas Chinesas , Receptores ErbB/antagonistas & inibidores , Marsdenia/química , Células A549 , Cromatografia Líquida de Alta Pressão/métodos , Descoberta de Drogas , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/metabolismo , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular
4.
J Ethnopharmacol ; 235: 309-319, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30772481

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima (Roxb.) Wight et Arn is a vine distributed in southwest area of China and used in folk medicine for treatment of tumors. Recent decades of studies on this plant reveal its synergistic effects with certain anticancer drugs in cancer therapy. In our previous study, an extract ETA which contains total aglycones made from M. tenacissima significantly enhanced antitumor activity of paclitaxel in tumor-bearing mice. However, the effective constituents in ETA and the underlying mechanisms remain unclear. AIM OF THE STUDY: Reveal the active components in ETA as well as the molecular mechanism in enhancing antitumor efficacy of paclitaxel. MATERIAL AND METHODS: Main constituents in ETA were purified by chemical methods. Effects of the purified constituents on metabolic activity of CYP450 enzymes were evaluated in human liver microsomes. Ability of the constituents to enhance antitumor activity of paclitaxel were investigated in nude mice bearing HeLa tumors. Pharmacokinetic study was performed in SD rats. Molecular docking was carried out for investigation of drug-protein interactions. RESULTS: Three main C21 steroidal aglycones, 11α-O-tigloyl-12ß-O-acetyl-tenacigenin B (MT1), 11α-O-2-methylbutanoyl-12ß-O-tigloyl-tenacigenin B (MT2) and 11α-O-2-methylbutanoyl-12ß-O-acetyl-tenacigenin B (MT3), together with tenacigenin B (MT4) was prepared from ETA. Among them, MT1, MT2 and MT3 strongly inhibit the metabolic activity of CYP3A4. MT2 also showed inhibitory effects on CYP2C8, CYP2B6 and CYP2C19. In HeLa tumor xenografts, MT1, MT2 and MT3 (30 mg/kg) did not affect tumor growth themselves, but significantly enhanced paclitaxel-induced growth inhibition. In addition, coadministration of MT2 with paclitaxel resulted in significant reduction of liver CYP2C8. In pharmacokinetic study, MT2 significantly increased the blood concentration of paclitaxel with increased AUC value by 2.2-5.3 folds. Molecular docking analysis suggested hydrophobic interaction modes of tenacigenin B derivatives with CYP3A4, and also the essential roles of the C-11 and C-12 ester groups for effective interaction with CYP3A4. CONCLUSION: Our study proves that, 11α-O-tigloyl-12ß-O-acetyl-tenacigenin B, 11α-O-2-methylbutanoyl-12ß-O-tigloyl-tenacigenin B and 11α-O-2-methylbutanoyl-12ß-O-acetyl-tenacigenin B, which are the main constituents of ETA, are active inhibitors of CYP3A4 with potential to increase therapeutic efficacy of anticancer drugs that are substrates of CYP3A4. Tenacigenin B derivatives with C-11 and C-12 ester group substitutions, or at least a large part of them, are active components in ETA and M. tenacissima to enhance in vivo antitumor efficacies of paclitaxel.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Marsdenia/química , Paclitaxel/farmacologia , Esteroides/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Citocromo P-450 CYP3A/efeitos dos fármacos , Citocromo P-450 CYP3A/metabolismo , Sinergismo Farmacológico , Ésteres/química , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Simulação de Acoplamento Molecular , Paclitaxel/administração & dosagem , Ratos , Ratos Sprague-Dawley , Esteroides/química , Esteroides/isolamento & purificação , Ensaios Antitumorais Modelo de Xenoenxerto
5.
J Nat Med ; 73(1): 93-103, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30251034

RESUMO

Seven new pregnane glycosides (1-7) and eight known compounds (8-15) were isolated from the bark of Marsdenia cundurango (Asclepiadaceae). The structures of 1-7 were determined by spectroscopic analysis, including two-dimension NMR spectroscopy, chemical transformations, and chromatographic analysis of the hydrolyzed products. The isolated compounds 1-15 were evaluated for their cytotoxic activity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, and TIG-3 normal human lung cells, including apoptosis-inducing activity of a representative pregnane glycoside in HL-60 cells.


Assuntos
Citotoxinas/uso terapêutico , Glicosídeos/química , Células HL-60/metabolismo , Marsdenia/química , Casca de Planta/química , Pregnanos/química , Citotoxinas/farmacologia , Humanos
6.
PLoS One ; 13(4): e0195240, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29624609

RESUMO

The accurate identification and quality evaluation of herbal medical plants is highly necessary to ensure their safety and efficacy. In present study, a new strategy combining DNA barcoding techniques with thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) was proposed to facilitate the identification and quality control of M. tenacissima. In present work, the internal transcribed spacer 2 (ITS2) barcode was successfully used to identify 58 M. tenacissima samples and its adulterants. TLC successfully identified the other three M. tenacissima samples that failed to produce ITS2 regions. An adulterant was found in all the 62 samples. Moreover, the content of active medicinal ingredients is important for herbal plants quality. The content of tenacissoside H (TS-H) of M. tenacissima samples was determined by HPLC to range from 0.39% to 1.09%, which meets the criterion of the Chinese Pharmacopoeia. Thus, DNA barcoding coupled with TLC and HPLC is very promising to identify and evaluate the quality of M. tenacissima in the medicine market.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/normas , Marsdenia/química , Plantas Medicinais/química , China , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Delgada , Código de Barras de DNA Taxonômico , DNA de Plantas/genética , Contaminação de Medicamentos , Humanos , Marsdenia/genética , Plantas Medicinais/genética , Controle de Qualidade
7.
J Nat Med ; 72(1): 166-180, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28914410

RESUMO

Twenty-three new C21 steroidal glycosides, marstenacissides C1-C10 (1-10), D1-D7 (11-17) and E1-E6 (18-23), and four new C21 steroids, 11α,12ß-O-ditigloyl-tenacigenin C (24), 11α-O-benzoyl-12ß-O-tigloyl-tenacigenin C (25), 11α-O-tigloyl-12ß-O-benzoyl-tenacigenin C (26) and 11α-O-tigloyl-12ß-O-benzoyl-marsdenin (27), were isolated from the Dai herbal medicine Dai-Bai-Jie, derived from the roots of Marsdenia tenacissima. The chemical structures of all compounds were established by spectroscopic techniques, including high-resolution mass spectrometry and NMR spectroscopy, as well as by comparison with reported spectral data. The anti-HIV activities of these compounds were screened, and the compounds obtained displayed inhibitory effects against HIV-1 with inhibition rates of 36.4-81.3% at 30 µM.


Assuntos
Infecções por HIV/tratamento farmacológico , Medicina Herbária/métodos , Marsdenia/química , Fitoterapia/métodos , Raízes de Plantas/química , Plantas Medicinais/química
8.
J Zhejiang Univ Sci B ; 18(7): 597-604, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28681584

RESUMO

Marsdeniae tenacissimae extract (MTE) has been used as an adjuvant medicine for cancer therapy for a long time. Although massive studies demonstrated its considerable anti-cancer effect, there is no research on its influence on erythrocytes, which are firstly interacted with MTE in the circulation. To investigate the influence of MTE on erythrocytes, we used a flow cytometer to detect the MTE-treated alternations of morphology, calcium concentration, and reactive oxygen species (ROS) level in erythrocytes. We used hemolysis under different osmotic solutions to evaluate the fragility of erythrocytes. Data showed that MTE treatment dose-dependently increased the ratio of erythrocyte fragmentation (P<0.001) and shrinking, and elevated the forward scatter (FSC) value (P<0.001) and calcium accumulation (P<0.001). MTE induced ROS production of erythrocytes under the high glucose condition (P<0.01) and consequently caused a rise in fragility (P<0.05). These results suggest that MTE induces cytotoxicity and aging in erythrocytes in a dose-dependent manner, and presents the possibility of impairment on cancer patients' circulating erythrocytes when MTE is used as an anti-cancer adjuvant medicine.


Assuntos
Antineoplásicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Eritrócitos/efeitos dos fármacos , Marsdenia/química , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Senescência Celular , Quimioterapia Adjuvante , Relação Dose-Resposta a Droga , Eritrócitos/citologia , Citometria de Fluxo , Glucose/análise , Hemólise , Humanos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Espalhamento de Radiação
9.
J Ethnopharmacol ; 203: 110-119, 2017 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-28363522

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Multidrug resistance (MDR) of cancer is often associated with the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP or ABCG2), in cancer cells, which facilitates the active efflux of a wide variety of chemotherapeutic drugs out of the cells. Marsdenia tenacissima is a traditional Chinese medicinal herb that has long been clinically used for treatment of cancers, particularly in combinational use with anticancer drugs. Polyoxypregnanes (POPs) are identified as main constituents of this herb, and three of them have been reported to exhibit P-gp modulatory effect and thus reverse MDR. Therefore, it is of great necessity to investigate more POPs that have potential to reverse transporters-mediated MDR. AIM OF THE STUDY: We aimed to identify POPs as the chemical basis responsible for circumventing ABC transporters-mediated MDR by M. tenacissima. MATERIALS AND METHODS: The MDR reversal effects of M. tenacissima crude extract together with a series of isolated POPs were evaluated on several MDR cancer cell lines that overexpress P-gp, MRP1 or ABCG2. The activities of P-gp, MRP1 and ABCG2 were determined by the flow cytometry-based substrate efflux assay. Molecular docking of POPs to a three-dimensional human P-gp homology structure was also performed. RESULTS: The crude extract of M. tenacissima was firstly found to circumvent P-gp-mediated MDR. Then, 11 polyoxypregnane compounds (POPs) isolated from this herb were found to overcome P-gp-, MRP1- and/or ABCG2-mediated MDR. Further mechanistic study delineated that the reversal of MDR by these POPs was due to significant increase in the intracellular concentrations of the substrate anticancer drugs via their inhibition of different ABC transporter-mediated efflux activities. Furthermore, molecular docking revealed that POPs with P-gp modulatory effect bound to P-gp and fitted well into the cavity between the alpha and beta subunit of P-gp via forming hydrogen bonds. In addition, several key structural determinants for inhibition of P-gp, MRP1 or ABCG2 by POPs were illustrated. CONCLUSIONS: Our findings advocated the rational use of M. tenacissima to enhance efficacies of conventional anticancer drugs in tumors with ABC drug transporters-mediated MDR. Furthermore, 11 POPs were found to contribute to MDR reversal effect of M. tenacissima via inhibition of different ABC efflux transporters.


Assuntos
Antineoplásicos/farmacologia , Marsdenia/química , Extratos Vegetais/farmacologia , Pregnanos/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Simulação de Acoplamento Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Pregnanos/isolamento & purificação
10.
Int J Biol Macromol ; 96: 743-753, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28057569

RESUMO

An antifungal class III peroxidase was purified from Marsdenia megalantha latex (named Mo-POX) using DEAE-cellulose and gel filtration chromatography on a Superose 12 HR 10/30 column. Mm-POX has an apparent molecular mass of 67.0kDa and a pI of 5.2, shares identity with other peroxidases, and follows Michaelis-Menten kinetics. It has a high affinity for guaiacol and hydrogen peroxide. The pH and temperature optima for Mm-POX were 5.0-7.0 and 60°C, respectively. The catalytic activity of Mm-POX was decreased in the presence of classic peroxidase inhibitors including azide, dithiothreitol, ethylenediamine tetraacetic acid, and sodium metabisulfite and high concentrations of Na+, Mn+, and salicylic acid. In contrast, Ca+ and Mg+, even at low concentrations, enhanced the Mm-POX enzymatic activity. This protein inhibited the germination of the conidia of the phytopathogenic fungi Fusarium oxysporum and Fusarium solani by acting through a membrane permeabilization mechanism. Mm-POX also induced oxidative stress in F. solani. Mm-POX is the first enzyme to be isolated from the M. megalantha species and it has potential use in the control of plant disease caused by important phytopathogenic fungi. This adds biotechnological value to this enzyme.


Assuntos
Permeabilidade da Membrana Celular/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Látex/química , Marsdenia/química , Peroxidase/isolamento & purificação , Peroxidase/farmacologia , Plantas/microbiologia , Sequência de Aminoácidos , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Inibidores Enzimáticos/farmacologia , Estabilidade Enzimática , Fusarium/citologia , Fusarium/metabolismo , Fusarium/fisiologia , Concentração de Íons de Hidrogênio , Cinética , Metais/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Peso Molecular , Peroxidase/antagonistas & inibidores , Peroxidase/química , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/farmacologia , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/crescimento & desenvolvimento , Especificidade por Substrato , Temperatura Ambiente
11.
Planta Med ; 83(1-02): 126-134, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27272399

RESUMO

A continuous phytochemical study on the roots of Marsdenia tenacissima led to the isolation and identification of 13 new polyoxypregnane glycosides named marstenacissides B10-B17 (1, 2, 4, 7, 8, 11, 12, and 14) and marstenacissides A8-A12 (3, 9, 10, 13, and 15) in addition to two known polyoxypregnane glycosides marsdenosides M and L (5 and 6). Their structures were established by spectroscopic techniques and by comparison with the reported data in the literature. Moreover, the anti-HIV activities of these isolates and the previous isolated marstenacissides A1-A7 and B1-B9 were assessed, some of which exhibited slight or negligible effects against HIV-1.


Assuntos
Fármacos Anti-HIV/farmacologia , Medicamentos de Ervas Chinesas/química , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Marsdenia/química , Saponinas/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Infecções por HIV/virologia , Medicina Tradicional Chinesa , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Caules de Planta/química , Saponinas/química , Saponinas/isolamento & purificação
12.
Nat Prod Res ; 31(7): 749-757, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27756147

RESUMO

Two new compounds 1 (Methyl 26-di-deoxy-6-methyl-ß-D-allohexopyranoside) and 3 (3, 11, 12, 20 tetra-O-acetyl-pregn-5-ene-14ß-ol) have been isolated from the chloroform-soluble extract of the whole plant of Marsdenia roylei (family: Asclepiadaceae) and their structures were determined by 1D, 2D NMR and ESI-MS as well as by chemical modification. We have calculated the molecular geometries, local reactivity descriptors by the density functional theory with B3LYP functional with basis set 6-311G+(d,2p) of 1, 3 and 4 (deacylated 3). The 1H and 13C NMR chemical shifts of 1, 3 and 4 were calculated using Gauge-Including Atomic Orbital approach and these values are correlated with the experimental observations.


Assuntos
Marsdenia/química , Acilação , Clorofórmio/química , Glucosídeos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Extratos Vegetais/química , Pregnenos , Teoria Quântica , Espectrometria de Massas por Ionização por Electrospray
13.
Oncotarget ; 7(50): 82851-82863, 2016 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-27756877

RESUMO

Marsdenia tenacissimae extraction (MTE) as a traditional Chinese herb has long been used to treat some diseases such as tumors in China. However, the potential effectiveness of MTE in leukemia has not yet been fully understood, and the related molecular mechanism is still unknown. In the present study, we aimed to evaluate the effects of MTE on the proliferation and apoptosis of Jurkat cells (T-ALL lines) and lymphocytes from T-ALL (T-cell acute lymphoblastic leukemia) patients. Firstly, CCK8 assays and flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of Jurkat cells by arresting cell cycle at S phase. Secondly, Annexin V-FITC/PI-stained flow cytometry and TUNEL staining assays showed that MTE promoted the apoptosis of Jurkat cells. Mechanistically, MTE enhanced PTEN (phosphatases and tensin homolog) level and inactivated PI3K/AKT/mTOR signaling pathway in Jurkat cells, which mediated the inhibition of cell proliferation by MTE and MTE-induced apoptosis. Finally, MTE significantly inhibited the proliferation and promoted the apoptosis of lymphocytes from T-ALL patients, compared with lymphocytes from healthy peoples. Taken together, these results reveal an unrecognized function of MTE in inhibiting the proliferation and inducing the apoptosis of T-ALL cells, and identify a pathway of PTEN/PI3K/AKT/mTOR for the effects of MTE on leukemia therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Marsdenia , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Extratos Vegetais/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Células Jurkat , Marsdenia/química , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Leucemia-Linfoma Linfoblástico de Células T Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Fatores de Tempo , Células Tumorais Cultivadas
14.
J Tradit Chin Med ; 36(3): 261-70, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27468539

RESUMO

OBJECTIVE: To investigate the clinical efficacy and safety of Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract combined with chemotherapy in the treatment of advanced non-small cell lung cancer (NCSLC) compared with chemotherapy alone. METHODS: Databases including Chinese National Knowledge Infrastructure, China Biology Medicine Disc, Wanfang, and MEDLINE were searched until April 1, 2014. Two assessors independently reviewed each trial. The primary outcome was the effective rate (ER) of Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract combined with chemotherapy. The secondary outcomes included quality of life improvement rate (QOLIR) and adverse reactions. Statistical calculations were performed by using Cochrane Collaboration Review Manager 5.2. RESULTS: A total of 888 patients from 15 studies, 13 randomized controlled trials (RCT) and two controlled clinical trials, were included. Compared with chemotherapy alone, Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract plus chemotherapy significantly improved ER [Risk ratio (RR) = 1.32, 95% CI, (1.14, 1.54)] (based on 15 studies) and QOLIR [RR = 2.04, 95% CI, (1.69, 2.47)] (based on 13 studies). Compared with chemotherapy alone, Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract plus chemotherapy significantly inhibited chemotherapy-induced white blood cell decline [RR = 0.79, 95% CI, (0.70, 0.90) (based on 10 studies), chemotherapy-induced platelet decline [RR = 0.77, 95% CI, (0.60, 0.98)] (based on 8 studies), and significantly alleviated nausea and vomiting (NV) [RR = 0.83, 95% CI, (0.71, 0.97)] (based on 7 studies). There was no significant difference in hemoglobin decline between the two therapies [RR = 0.88, 95% CI, (0.70, 1.09)] (based on 6 studies). CONCLUSION: This Meta-analysis suggests that Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract combined with chemotherapy may be more efficacious in the treatment of advanced NSCLC than chemotherapy alone. This effect includes enhancing ER and QOLIR, and weakening chemotherapy toxicity. However, large-scale RCTs are required to further investigate the short- and long-term effects of Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Marsdenia/química , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Biomed Chromatogr ; 30(11): 1757-1765, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27106066

RESUMO

Marsdenia tenacissima, which is widely used as an anticancer herb in traditional Chinese medicine, has been shown to possess anticancer activity. However, its metabolic profile is poorly investigated. Tenacigenin B is the major steroidal skeleton of C-21 steroids in M. tenacissima. Tenacissoside H and Tenacissoside I are detected at relatively high levels in M. tenacissima. Therefore, we studied their metabolic characteristics in human liver microsomes by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. Fourteen metabolites were tentatively identified by accurate mass measurement and MS/MS fragmentation behavior. It was found that hydroxylation reactions were the major metabolic pathway of Tenacissoside H and Tenacissoside I in human liver microsomes, whereas the metabolic pathway of Tenacigenin B involved dehydrogenation reactions. This is the first time that the metabolic profile of C-21 steroids from M. tenacissima has been explored in human liver microsomes, which is of great significance for subsequent pharmacokinetic and interaction research. Biotransformation in vivo or in vitro may influence the structure of a compound and change its activity. Identification of their fragmentation behaviors and metabolites provides valuable and new information for further understanding the anti-tumor activity of M. tenacissima. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Microssomos Hepáticos/metabolismo , Fitosteróis/metabolismo , Saponinas/metabolismo , Esteroides/metabolismo , Antineoplásicos Fitogênicos/química , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Marsdenia/química , Redes e Vias Metabólicas , Metabolômica/métodos , Fitosteróis/química , Saponinas/química , Esteroides/química , Espectrometria de Massas em Tandem/métodos
16.
Chin J Nat Med ; 14(3): 203-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27025367

RESUMO

Marsdenia tenacissima, a traditional Chinese medicine, is long been used to treat various diseases including asthma, cancer, trachitis, tonsillitis, pharyngitis, cystitis, and pneumonia. Although Marsdenia tenacissima has been demonstrated to have strong anti-tumor effects against primary tumors, its effect on cancer metastasis remains to be defined, and the molecular mechanism underlying the anti-metastatic effect is unknown. In the present study, we investigated the effects of XAP (an extract of Marsdenia tenacissima) on A549 lung cancer cell migration and explored the role of CCR5-CCL5 axis in the anti-metastatic effects of XAP. Our resutls showed that XAP inhibited A549 lung cancer cell migration and invasion in a dose-dependent manner. The protein levels of CCR5, but not CCR9 and CXCR4, were decreased by XAP. The secretion of CCL5, the ligand of CCR5, was reduced by XAP. XAP down-regulated Rho C expression and FAK phosphorylation. In conclusion, XAP inhibited A549 cell migration and invasion through down-regulation of CCR5-CCL5 axis, Rho C, and FAK.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Movimento Celular/efeitos dos fármacos , Quimiocina CCL5/metabolismo , Marsdenia/química , Extratos Vegetais/farmacologia , Receptores CCR5/metabolismo , Células A549 , Linhagem Celular Tumoral , Quinase 1 de Adesão Focal/metabolismo , Humanos , Neoplasias Pulmonares , Fosforilação , Proteínas rho de Ligação ao GTP/metabolismo , Proteína de Ligação a GTP rhoC
17.
Chin J Nat Med ; 14(12): 922-930, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28262119

RESUMO

Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 µL·L-1) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC Δ and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCΔ-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Marsdenia/química , Extratos Vegetais/farmacologia , Transdução de Sinais , Ciclo Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-26233789

RESUMO

A combination of Fourier transform infrared spectroscopy with chemometrics tools provided an approach for studying Marsdenia tenacissima according to its geographical origin. A total of 128 M. tenacissima samples from four provinces in China were analyzed with FTIR spectroscopy. Six pattern recognition methods were used to construct the discrimination models: support vector machine-genetic algorithms, support vector machine-particle swarm optimization, K-nearest neighbors, radial basis function neural network, random forest and support vector machine-grid search. Experimental results showed that K-nearest neighbors was superior to other mathematical algorithms after data were preprocessed with wavelet de-noising, with a discrimination rate of 100% in both the training and prediction sets. This study demonstrated that FTIR spectroscopy coupled with K-nearest neighbors could be successfully applied to determine the geographical origins of M. tenacissima samples, thereby providing reliable authentication in a rapid, cheap and noninvasive way.


Assuntos
Marsdenia/química , Reconhecimento Automatizado de Padrão/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Algoritmos , China , Geografia , Marsdenia/classificação , Análise de Componente Principal , Máquina de Vetores de Suporte
19.
Nat Prod Res ; 30(13): 1532-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26618710

RESUMO

Marsdenia tinctoria is an indigo producing plant commonly found in Borneo, Malaysia. In this present study, one new flavone kapitone (1) and three known compounds, that is 3,2'-dihydroxyflavone (2), 1-methylcyclobutene (3) and dimethyl isatoate (4) were isolated from the Malaysia Borneo M. tinctoria R. Br. (Apocynaceae). These compounds were isolated and characterised using extensive chromatographic and spectroscopic methods.


Assuntos
Flavonas/isolamento & purificação , Marsdenia/química , Bornéu , Flavonas/química
20.
Carbohydr Polym ; 137: 52-58, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26686104

RESUMO

One water-soluble polysaccharide (Marsdenia tenacissima polysaccharide, MTP), with an average molecular weight of 4.9 × 10(4) Da, was isolated from the dried rattan of M. tenacissima. MTP contained 93.8% carbohydrates, 5.6% proteins and 21.3% uronic acid, and were composed of arabinose, mannose, galactose, xylose, glucuronic acid at a molar ratio of 9.1, 17.7, 30.2, 22.4 and 20.6. The experiments on the animals showed that MTP could increase the serum hemolysin, promote the formation of antibody-forming cells and improve the phagocytosis of mononuclear macrophage in normal mice. Meanwhile, MTP could also inhibit the growth of tumor in H22 tumor-bearing mice dose-dependently, and increase the spleen index, thymus index and serum albumin level in the mice. In addition, MTP could elevate the serum level of TNF-α and IL-2, increase the activity of GSH-Px, CAT and SOD in the liver tissue, and reduce the content of VEGF and MDA. These results suggest that MTP can regulate the immune function in mice and suppress the growth of tumor in H22 tumor-bearing mice, and its antitumor activity may be related to its antioxidant and immunomodulatory effects.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Marsdenia/química , Extratos Vegetais/uso terapêutico , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Animais , Antineoplásicos/química , Catalase/metabolismo , Glutationa/metabolismo , Interleucina-2/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Camundongos , Extratos Vegetais/química , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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