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1.
In Vitro Cell Dev Biol Anim ; 55(9): 766-775, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31529418

RESUMO

Bioreactor-cultured adventitious roots (ARs) of the endangered medicinal plant Oplopanax elatus Nakai is a novel alternative plant material. To utilize ARs in the product production, the present study investigated the anti-inflammatory effect of O. elatus ARs. In the in vivo experiment, lipopolysaccharide (LPS)-induced acute lung injury disease model was established and several inflammatory indexes were determined. For the LPS-stimulated mice, after pretreatment of AR crude extract (200 mg/kg), cell infiltration in lungs was decreased, the production of proinflammatory mediators, including nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6, and 1ß in the bronchoalveolar lavage fluid was evidently reduced, which indicated that O. elatus ARs had an anti-inflammatory effect. In the in vitro experiment, ethyl acetate (EtOAc) fractions (12.5, 25, and 50 µg/mL) were used to treat LPS-induced peritoneal macrophages (PMs) of mice. The production of NO, prostaglandin E2, TNF-α, IL-6, and IL-1ß in LPS-stimulated PMs was obviously inhibited (p < 0.05) after pretreatment with EtOAc fractions, and the expression of the inducible nitric oxide synthase and cyclooxygenase were also suppressed. To clarify the anti-inflammatory mechanism, effects of EtOAc fraction on changes of proteins related to the pathways of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) were investigated. The phosphorylation of extracellular regulated protein kinases, c-jun n-terminal kinase, and p38 MAPK in LPS-induced PMs was inhibited after pretreatment of EtOAc fractions. In addition, EtOAc fractions enhanced inhibitor of nuclear factor-kappa B-α expression and decreased nuclear translocation of p65 NF-κB. Thus, EtOAc from O. elatus ARs is involved in regulating MAKP and NF-κB signaling pathways to inhibit LPS-induced inflammation.


Assuntos
Inflamação/tratamento farmacológico , Oplopanax/química , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , NF-kappa B/genética , Extratos Vegetais/química , Raízes de Plantas/química
2.
Am J Chin Med ; 47(6): 1381-1404, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31488036

RESUMO

Oplopanax elatus (Nakai) Nakai is an oriental herb, the polyyne-enriched fraction of which (PEFO) showed anticolorectal cancer (anti-CRC) effects. Other concomitant components, which are inevitably bio-transformed by gut microbiota after oral administration, might be interfere with the pharmacodynamics of polyynes. However, the influence of human gut microbiota on molecules from O. elatus possessing anticancer activity are yet unknown. In this study, the compounds in PEFO and PEFO incubated with human gut microbiota were analyzed and tentatively identified by HPLC-DAD-QTOF-MS. Two main polyynes ((3S,8S)-falcarindiol and oplopandiol) were not significantly decomposed, but some new unknown molecules were discovered during incubation. However, the antiproliferative effects of PEFO incubated with human gut microbiota for 72 h (PEFO I) were much lower than that of PEFO on HCT-116, SW-480, and HT-29 cells. Furthermore, PEFO possessed better anti-CRC activity in vivo, and significantly induced apoptosis of the CRC cells, which was associated with activation of caspase-3 according to the Western-blot results (P<0.05). These results suggest anticolorectal cancer activity of polyynes might be antagonized by some bio-converted metabolites after incubation with human gut microbiota. Therefore, it might be better for CRC prevention if the polyynes could be orally administrated as purified compounds.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Di-Inos/metabolismo , Álcoois Graxos/metabolismo , Microbioma Gastrointestinal/fisiologia , Oplopanax/química , Administração Oral , Animais , Antineoplásicos Fitogênicos , Apoptose/efeitos dos fármacos , Biotransformação , Caspase 3/metabolismo , Cromatografia Líquida de Alta Pressão , Di-Inos/administração & dosagem , Di-Inos/isolamento & purificação , Di-Inos/farmacologia , Álcoois Graxos/administração & dosagem , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/farmacologia , Células HT29 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Espectrometria de Massas em Tandem , Células Tumorais Cultivadas
3.
Nutr Cancer ; 71(3): 472-482, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30372160

RESUMO

Although irinotecan is an important anticancer drug for treating colorectal cancer, its dose-dependent side effects limited its clinical application. Thus, it's important to develop low-toxic candidates to enhance the efficacy of irinotecan. Polyynes from genus Oplopanax were reported to possess potential anticancer effects on colorectal cancer. Hereby, we evaluated the synergetic inhibition of human colorectal cancer cells by combining polyyne-enriched fraction from Oplopanax elatus (the dichloromethane fraction of Oplopanax elatus, OED) and irinotecan. The results showed that 5 µg/ml of OED combined with 40 µM of irinotecan possessed significant synergetic inhibition on SW-480 cells with a combination index (CI) of 0.56. Besides, the percentage of apoptotic cells was significantly increased from 69.57% (40 µM of irinotecan) or 72.7% (5 µg/ml of OED) to 95.6% after treatment of OED combined with irinotecan (OCI), suggesting OED and irinotecan possess the synergistic apoptotic effect (P < 0.01). Furthermore, Caspase-3 was significantly activated in OCI group (P < 0.05). Besides, the percentage of apoptotic cells of OED or/and irinotecan significantly decreased after inhibition of caspase-3. These data indicated that OED could enhance antiproliferative effects of irinotecan on colorectal cancer cells, which was related with induction of apoptosis and regulations of activity of caspase-3.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Colorretais/patologia , Irinotecano/administração & dosagem , Oplopanax/química , Extratos Vegetais/administração & dosagem , Poli-Inos/administração & dosagem , Apoptose/efeitos dos fármacos , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Sinergismo Farmacológico , Células HCT116 , Humanos , Casca de Planta/química , Extratos Vegetais/química , Poli-Inos/análise
4.
Curr Pharm Biotechnol ; 19(3): 258-264, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29766799

RESUMO

BACKGROUND AND METHODS: Oplopanax elatus (Nakai) Nakai is used in folk medicine in China. In this study, the antiproliferative activity of an O. elatus fraction extracted by ethyl acetate (EF) was tested on human breast cancer MCF-7 cells, human colon cancer HCT-116 cells, and human stomach cancer AGS cells. The potential mechanism of antiproliferation was also investigated using an apoptosis assay. RESULTS: The results showed that the EF remarkably suppressed proliferation of human breast, stomach, and colon cancer cells. Further apoptosis tests by flow cytometry and immunoblot analyses showed the EF inhibited HCT-116 cell proliferation by inducing apoptosis. The bioassay-monitored fractionation of the EF resulted in the isolation of two polyacetylenes, falcarindiol (compound 1) and oplopandiol (compound 2), with falcarindiol possessing the strongest antiproliferative activity in colon cancer cells. CONCLUSION: Together, this study evaluated the anticancer activity of an O. elatus extract against human cancer cells, and provided the basis for further development of this herbal extract for the treatment of cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Oplopanax , Extratos Vegetais/farmacologia , Poli-Inos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , China , Neoplasias do Colo/tratamento farmacológico , Feminino , Células HCT116 , Humanos , Células MCF-7 , Medicina Tradicional , Caules de Planta , Poli-Inos/isolamento & purificação , Neoplasias Gástricas/tratamento farmacológico
5.
Planta Med ; 84(1): 42-48, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28701020

RESUMO

The genetic barcode ITS2 (ITS: internal transcribed spacer) and pollen morphology were used for the identification of the pharmacologically valuable wild Araliaceae species Panax ginseng, Oplopanax elatus, Aralia elata, Aralia continentalis, Eleutherococcus senticosus, and Eleutherococcus sessiliflorus inhabiting the natural forests of Primorye, Russia. The ITS2 locus successfully identified all six species, which supports the use of ITS2 as a standard barcode for medicinal plants. However, the ITS2 locus was insufficient for intra-specific discrimination in these species, neither within Primorye nor from other world representatives within GenBank. Araliaceae pollen was confirmed to undergo size-reducing metamorphosis. The final morphotypes were species-specific for each of the six species but could not discriminate intra-species geographic localities within Primorye. The morphologies of the final pollen morphotypes from homologous species inhabiting other parts of the world are not yet known. Therefore, whether pollen is applicable for Araliaceae intra-species discrimination between Primorye and other world localities could not be established. Based on these findings, we propose that the ITS2 genetic barcode and the final pollen morphotypes are suitable for the identification of Araliaceae species. However, further studies will be needed to determine the suitability of genetic and pollen traits for Araliaceae geographic authentication.


Assuntos
Araliaceae/genética , Código de Barras de DNA Taxonômico/métodos , Pólen/ultraestrutura , Aralia/genética , Aralia/ultraestrutura , Araliaceae/ultraestrutura , DNA Espaçador Ribossômico/genética , Eleutherococcus/genética , Eleutherococcus/ultraestrutura , Oplopanax/genética , Oplopanax/ultraestrutura , Panax/genética , Panax/ultraestrutura , Filogenia , Especificidade da Espécie
6.
Molecules ; 22(10)2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28937627

RESUMO

Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO) on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet) for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of ß-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of ß-catenin, cyclinD1, c-myc and p-GSK-3ß in HCT116 and SW480 cells at 25 µM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Oplopanax/química , Extratos Vegetais/uso terapêutico , Poli-Inos/química , Animais , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Extratos Vegetais/química , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
7.
Chin J Nat Med ; 14(9): 714-720, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27667518

RESUMO

Polyynes, such as facarindiol (FAD) and oplopandiol (OPD), are responsible for anticancer activities of Oplopanax elatus (O. elatus). A novel approach to pharmacokinetics determination of the two natural polyynes in rats was developed and validated using a liquid chromatography-electrospray ionization-mass spectrometry (LC-MS) method. Biosamples were prepared by liquid-liquid extraction using ethyl acetate/n-hexane (V : V = 9 : 1) and the analytes were eluted on an Agilent ZORBAX Eclipse Plus C18 threaded column (4.6 mm × 50 mm, 1.8 µm) with the mobile phase of acetonitrile-0.1% aqueous formic acid at a flow-rate of 0.5 mL·min(-1) within a total run time of 11 min. All analytes were simultaneously monitored in a single-quadrupole mass spectrometer in the selected ion monitoring (SIM) mode using electrospray source in positive mode. The method was demonstrated to be rapid, sensitive, and reliable, and it was successfully applied to the pharmacokinetic studies of the two polyynes in rat plasma after oral administration of polyynes extract of O. elatus.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Di-Inos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Álcoois Graxos/farmacocinética , Naftóis/farmacocinética , Oplopanax/química , Poli-Inos/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos , Administração Oral , Animais , Di-Inos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Álcoois Graxos/administração & dosagem , Masculino , Naftóis/administração & dosagem , Poli-Inos/administração & dosagem , Ratos , Ratos Sprague-Dawley
8.
J Sep Sci ; 39(22): 4269-4280, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27624907

RESUMO

The root of Oplopanax elatus (Nakai) Nakai has a well-known history of use for the treatment of diseases such as neurasthenia, cardiovascular disorders, and cancer by the native people in northeast China. It is important to screen and identify the bioactive molecules from its root rapidly. Hereby, an off-line two-dimensional high performance liquid chromatography coupled with diode array detection and tandem time-of-flight mass spectrometry together with 2,2'-diphenyl-1-picrylhydrazyl was established to screen antioxidants from the root of O. elatus. A Waters cyanogen column (150 × 3.9 mm, id, 4 µm) was used for the first dimensional liquid chromatography, while a Hypersil BDS-C18 column (250 × 4.6 mm, id, 5 µm) was installed for the second dimension liquid chromatographic analysis. Twenty-eight compounds had been tentatively identified from the methanol extract of the air-dried root of O. elatus including six polyynes and eight phenolic derivatives were screened with antioxidant activity. The developed method could be expedient for screening and identifying antioxidants from O. elatus.


Assuntos
Antioxidantes/análise , Medicamentos de Ervas Chinesas/análise , Oplopanax/química , Raízes de Plantas/química , Compostos de Bifenilo , Cromatografia Líquida de Alta Pressão , Picratos , Espectrometria de Massas em Tandem
9.
Nutr Cancer ; 67(6): 954-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26221768

RESUMO

Devil's club Oplopanax horridus (DC) is a close relative of ginseng; its inner root and stem bark extract showed antiproliferation activity on human leukemia, ovarian, breast and colon cancer cells. We study here the effects of DC 70% ethanol extract alone, or in combination with cisplatin, gemcitabine, and paclitaxel on pancreatic endocrine HP62 and pancreatic ductal carcinoma PANC-1 and BxPC-3 cells. Antiproliferation activity assay, cell cycle analysis by flow cytometry, apoptosis-related markers by antibody array, and RT-PCR assay were used for this study. DC extract inhibited proliferation of HP62 with IC50 (50% inhibition concentration) at 0.037±0.002% (v/v), PANC-1 at 0.0058 ± 0.0004% and BxPC-3 at 0.021 ± 0.003%. DC at 0.0033% combined with 1 nM of paclitaxel showed inhibition synergy on PANC-1 cells with a combination index of 0.44. Apoptosis focused antibody array profile indicated upregulation of cytochrome C, claspin, cIAP-2 and HTRA2/Omi apoptosis-related markers in DC-treated HP62 and PANC-1. Our data suggest that DC acts through targeting the intrinsic mitochondrial apoptosis pathway in the pancreatic cancer cells. The high antiproliferation potency of DC on PANC-1 is potentially useful as an adjunct therapy for treating pancreatic cancer, which is known for developing resistance to conventional chemotherapeutics.


Assuntos
Proliferação de Células/efeitos dos fármacos , Oplopanax/química , Poli-Inos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Humanos , Concentração Inibidora 50 , Paclitaxel/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Transdução de Sinais
10.
Int J Mycobacteriol ; 4(3): 165-83, 2015 09.
Artigo em Inglês | MEDLINE | ID: mdl-27649863

RESUMO

Currently, one third of the world's population is latently infected with Mycobacterium tuberculosis (MTB), while 8.9-9.9 million new and relapse cases of tuberculosis (TB) are reported yearly. The renewed research interests in natural products in the hope of discovering new and novel antitubercular leads have been driven partly by the increased incidence of multidrug-resistant strains of MTB and the adverse effects associated with the first- and second-line antitubercular drugs. Natural products have been, and will continue to be a rich source of new drugs against many diseases. The depth and breadth of therapeutic agents that have their origins in the secondary metabolites produced by living organisms cannot be compared with any other source of therapeutic agents. Discovery of new chemical molecules against active and latent TB from natural products requires an interdisciplinary approach, which is a major challenge facing scientists in this field. In order to overcome this challenge, cutting edge techniques in mycobacteriology and innovative natural product chemistry tools need to be developed and used in tandem. The present review provides a cross-linkage to the most recent literature in both fields and their potential to impact the early phase of drug discovery against TB if seamlessly combined.


Assuntos
Antituberculosos/farmacologia , Produtos Biológicos/farmacologia , Descoberta de Drogas , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Berberis/química , Bioensaio , Descoberta de Drogas/tendências , Humanos , Oplopanax/química , Extratos Vegetais/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
11.
Molecules ; 19(12): 19708-17, 2014 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-25438081

RESUMO

Volatile oil from the root bark of Oplopanax horridus is regarded to be responsible for the clinical uses of the title plant as a respiratory stimulant and expectorant. Therefore, a supercritical fluid extraction method was first employed to extract the volatile oil from the roots bark of O. horridus, which was subsequently analyzed by GC/MS. Forty-eight volatile compounds were identified by GC/MS analysis, including (S,E)-nerolidol (52.5%), τ-cadinol (21.6%) and S-falcarinol (3.6%). Accordingly, the volatile oil (100 g) was subjected to chromatographic separation and purification. As a result, the three compounds, (E)-nerolidol (2 g), τ-cadinol (62 mg) and S-falcarinol (21 mg), were isolated and purified from the volatile oil, the structures of which were unambiguously elucidated by detailed spectroscopic analysis including 1D- and 2D-NMR techniques.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Óleos Voláteis/isolamento & purificação , Oplopanax/química , Casca de Planta/química , Raízes de Plantas/química , Espectrometria de Massas em Tandem/métodos , Óleos Voláteis/química , Pressão , Reprodutibilidade dos Testes , Temperatura , Fatores de Tempo
12.
Chin J Nat Med ; 12(10): 721-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25443364

RESUMO

Oplopanax elatus (Nakai) Nakai, a member of the ancient angiosperm plant family Araliaceae, is used for the treatment of different disorders in the medicine systems of China, Russia, and Korea, and was designated in Russia as a classical adaptogen. Despite extensive studies of classical adaptogens, there are comparatively few reports concerning the chemical composition and pharmacological effects of O. elatus in English. The plant is a potential source of saponins, flavonoids, anthraquinones, terpenes, and other active compounds. Experimental studies and clinical applications have indicated that O. elatus possesses a number of pharmacological activities, including adaptogenic, anti-convulsant, anti-diabetic, anti-fungal, anti-inflammatory, anti-oxidant, blood pressure modulating, and reproductive function effects. In this review, the chemistry, safety, and therapeutic potential of O. elatus are summarized and highlighted to encourage the further development of this plant.


Assuntos
Oplopanax/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Humanos , Medicina Tradicional , Fitoterapia , Extratos Vegetais/efeitos adversos
13.
Zhongguo Zhong Yao Za Zhi ; 39(10): 1852-7, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-25282894

RESUMO

The chemical constituents were isolated and purified by various chromatographic techniques indluding silica gel, reverse phase silica gel, sephadex LH-20 and pre-HPLC and identified by their physicochemical properties and spectral data. Sixteen phenolic compounds had been isolated and n-butanol extracts which were fractionated from the ethanol extract of Oplopanax horridus roots bark. Their structures were identified as below, including 7 phenylpropanoid compounds, ferulic acid (1), 3-acetylcaffeic acid (2), caffeic acid (3), homovanillyl alcohol 4-O-beta-D-glucopyranoside (4), 3-hydroxyphenethyl alcohol 4-O-beta-D-glucopyranoside (5), 3, 5-dimethoxycinnamyl alcohol 4-O-beta-D-glucopyranoside (6), and 3-dimethoxycinnamyl alcohol 4-O-beta-D-glucopyranoside (7). Three coumarins, scopoletin (8), esculetin (9) and 3'-angeloyl-4'-acetyl-cis-knellactone (10). And 6 lignan compounds, (+)-isolaricires-inol-9'-O-beta-D-glucopyranoside (11), 3, 3'-dimethoxy-4, 9, 9'-trihydroxy-4', 7-epoxy-5', 8-lignan-4, 9-bis-O-beta-D-glucopyranoside (12), (+)-5, 5'-dimethoxylariciresinol 4'-O-beta-D-glucopyranoside (13), (-)-5,5'-dimethoxylariciresinol 4'-O-beta-D-glucopyranoside (14), (-)-pinoresinol 4'-O-beta-D-glucopyranoside (15), and (+)-5, 5'-dimethoxylariciresinol 9'-O-beta-D-glucopyranoside (16). All compounds were isolated and identified for the first time from this plant All the constituents except compounds 4, 6, 12 and 13 were obtained for the first time from the genus Oplopanax.


Assuntos
Medicamentos de Ervas Chinesas/química , Oplopanax/química , Fenóis/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fenóis/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray
14.
Phytother Res ; 28(9): 1308-14, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25340187

RESUMO

Acute myeloid leukemia (AML) is a group of hematological malignancies defined by expanded clonal populations of immature progenitors (blasts) of myeloid phenotype in blood and bone marrow. Given a typical poor prognostic outlook, there is great need for novel agents with anti-AML activity. Devil's club (Oplopanax horridus) is one of the most significant medicinal plants used among the indigenous people of Southeast Alaska and the coastal Pacific Northwest, with different linguistic groups utilizing various parts of the plant to treat many different conditions including cancer. Studies identifying medically relevant components in Devil's club are limited. For this research study, samples were extracted in 70% ethanol before in vitro analysis, to assess effects on AML cell line viability as well as to study regulation of tyrosine phosphorylation and cysteine oxidation. The root extract displayed better in vitro anti-AML efficacy in addition to a noted anti-tyrosine kinase activity independent of an antioxidant effect. In vivo therapeutic studies using an immunocompetent murine model of AML further demonstrated that Devil's club root extract improved the murine survival while decreasing immunosuppressive regulatory T cells and improving CD8+ T-cell functionality. This study defines for the first time an anti-AML efficacy for extracts of Devil's club.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Oplopanax/química , Extratos Vegetais/farmacologia , Animais , Linfócitos T CD8-Positivos/citologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fitoterapia , Plantas Medicinais/química , Transdução de Sinais , Linfócitos T Reguladores/citologia
15.
Electrophoresis ; 35(20): 2959-64, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25070635

RESUMO

A PEG-modified reversed migration MEEKC method was developed for simultaneous determination of six polyynes, including oplopandiol, falcarindiol, oplopandiol acetate, (11S, 16S, 9Z)-9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate, oplopantriol B, and oplopantriol A, in Oplopanax horridus and Oplopanax elatus. The running buffer containing 0.8% v/v ethyl acetate, 3.8% w/v SDS, 6.6% v/v n-butanol in 20 mM phosphate buffer (pH 2.5), followed by mixing with propan-2-ol at 30% v/v and PEG-1000 at 15% w/v, was applied in the analysis. The proposed method was successfully applied to determine the six polyynes in five samples of Oplopanax horridus and one of O. elatus. The result showed that the types and amounts of polyynes present were obviously different when comparing the two herbs. Besides, the developed PEG-modified reversed MEEKC method might be suitable for the analysis of hydrophobic analytes in herbal medicines.


Assuntos
Cromatografia Capilar Eletrocinética Micelar/métodos , Oplopanax/química , Polietilenoglicóis/química , Poli-Inos/análise , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
16.
Nutrients ; 6(7): 2668-80, 2014 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-25045937

RESUMO

Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A) is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01). Next, we characterized the compound's growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01). The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Oplopanax/química , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Planta Med ; 80(8-9): 662-70, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24922275

RESUMO

This study was conducted to employ an ovarian cancer Ovcar 10 three-dimensional model to assess the antiproliferation activity of the medicinal plant Devil's club, Oplopanax horridus, and its active compound, alone and in combination, with chemotherapeutic agents compared to Ovcar 10 two-dimensional cells grown as monolayer cells. Ovcar 10 three-dimensional spheroids were prepared with a rotary cell culture system. Cell counting kit-8 assessed the antiproliferation activity. Apoptosis-related gene expression in three-dimensional spheroids and two- dimensional cells was analyzed with an apoptosis antibody array. Flow cytometry was used to analyze the cell cycle. Ovcar 10 cells formed compact three-dimensional spheroids after 5 days of culture in a rotary culture system. Ovcar 10 three-dimensional spheroids were significantly more resistant to killing by Devil's club extract, its active compound alone, gemcitabine, and paclitaxel, but not cisplatin compared to two-dimensional cells, with IC50 levels closer to that observed in vivo. Devil's club extract and its active compound alone significantly enhanced the antiproliferation activity of cisplatin and gemcitabine at some concentrations, but did not affect the activity of paclitaxel. A number of apoptosis-related genes were differentially expressed in three-dimensional spheroids, two-dimensional cells, and cells treated with Devil's club extract compared to untreated controls. In three-dimensional spheroids, the proportion of cells in the G2/M phase was slightly increased and the S phase was slightly decreased compared to two-dimensional cells. Ovcar 10 cells in three-dimensional spheroids altered the expression of multiple apoptosis-related genes, which may have contributed to the increased resistance of the cells to some drugs.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Oplopanax/química , Neoplasias Ovarianas/tratamento farmacológico , Extratos Vegetais/farmacologia , Esferoides Celulares/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Proteoma , Células Tumorais Cultivadas/efeitos dos fármacos
18.
Molecules ; 19(5): 6142-62, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24830715

RESUMO

Six polyynes OH-1~6, some of which are occur naturally in acetylated form, had been isolated and identified from the root bark of Oplopanax horridus (Devil's Club), a natural dietary supplement and medicinal plant in North America. During the evaluation of the polyynes' potential anticancer activities, sixteen more acetylated derivatives OHR-1~16 have synthesized and their anti-proliferation activity on MCF-7, MDA-MB-231, A549, HepG2 and LO2 cells assayed to elucidate their structure-activity relationships. The results showed that OH-1 ((3S, 8S)-falcarindiol) had the most potent anticancer activity, with IC50 values of 15.3, 23.5, 7.7 and 4.7 µM on MCF-7, A549, HepG2 and MDA-MB-231 cells, respectively. For the primary structure-activity relationship, the anticancer activities of polyynes become weaker if their hydroxyl groups are acetylated, the terminal double bonds transformed into single bonds or they contain one more methylene group in the main skeleton chain.


Assuntos
Neoplasias/tratamento farmacológico , Oplopanax/química , Extratos Vegetais/administração & dosagem , Poli-Inos/administração & dosagem , Acetilação/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , América do Norte , Casca de Planta/química , Extratos Vegetais/química , Raízes de Plantas/química , Poli-Inos/química , Poli-Inos/isolamento & purificação , Relação Estrutura-Atividade
20.
Phytomedicine ; 21(4): 506-14, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24215675

RESUMO

Devil's club (DC, Oplopanax horridus) is an important medicinal herb of the Pacific Northwest which has significant antiproliferation activity against a variety of human tumor cell lines in vitro. This study compared the antiproliferation activity of DC extract alone, and in combination with chemotherapeutic agents gemcitabine (GEM), cisplatin (CDDP), and paclitaxel (PTX) on human pancreatic cancer PANC-1 3D spheroids and 2D monolayer cells. 3D tumor spheroids were prepared with a rotary cell culture system. PANC-1 3D spheroids were significantly more resistant to killing by DC extract, GEM and PTX compared to 2D cells, with IC50 levels closer to that observed in vivo. DC extract significantly enhanced the antiproliferation activity of CDDP and GEM at some concentrations. The bioactive compound identified as a polyacetylene showed strong antiproliferation activity against PANC-1 2D cells and 3D spheroids with IC50 at 0.73±0.04 and 3.15±0.16µM, respectively. 3D spheroids and 2D cells differentially expressed a number of apoptosis related genes. Cell cycle analysis showed that the proportion of cells in S phase was increased and in G2/M phase reduced in 3D spheroids compared to 2D cells. DC extract can potentially be used to enhance the activity of chemotherapeutic agents against pancreatic cancer cells. Use of 3D spheroid model for screening of natural products can potentially increase the efficiency in discovering in vivo bioactive compounds.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Oplopanax/química , Neoplasias Pancreáticas/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Plantas Medicinais/química , Proteoma , Esferoides Celulares
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