RESUMO
Oplopanax elatus is a valuable medicinal plant, but its plant resource is lacking. Adventitious root (AR) culture of O. elatus is an effective way for the production of plant materials. Salicylic acid (SA) exerts enhancement effect on metabolite synthesis in some plant cell/organ culture systems. To clarify the elicitation effect of SA on fed-batch cultured O. elatus ARs, this study investigated the effects of SA concentration, and elicitation time and duration. Results showed that flavonoid and phenolic contents, and antioxidant enzyme activity obviously increased when the fed-batch cultured ARs were treated with 100 µM SA for 4 days starting on day 35. Under this elicitation condition, total flavonoid and phenolic contents reached 387 rutin mg/g DW and 128 gallic acid mg/g DW, respectively, which were significantly (p < 0.05) higher than those in the SA-untreated control. In addition, DPPH scavenging and ABTS+ scavenging rates, and Fe2+ chelating rate also greatly increased after SA treatment, and their EC50 values were 0.0117, 0.61, and 3.34 mg/L, respectively, indicating the high antioxidant activity. The findings of the present study revealed that SA could be used as an elicitor to improve the flavonoid and phenolic production in fed-batch O. elatus AR culture.
Assuntos
Flavonoides , Oplopanax , Oplopanax/química , Oplopanax/metabolismo , Ácido Salicílico/farmacologia , Antioxidantes/metabolismo , Fenóis/químicaRESUMO
25 phenolic acids, including four new isolates, eurylophenosides A-D (1-4) and 21 known ones (5-25) were isolated and identified from the stems of Oplopanax elatus Nakai. Among the known compounds 5-9, 11-13, 16, 18-25 were isolated from the genus for the first time; 17 was first obtained from the plant; and the NMR data of 22 was reported here first. Meanwhile, the UVB-induced photodamage model of HaCaT cells was used to study the prevent-photodamage abilities of compounds 1-2, 4-8, 11-13 and 15-25 with a nontoxic concentration at 50 µM. Moreover, a dose-dependent experiment was conducted for active compounds at the concentration of 10, 25, and 50 µM, respectively. Consequently, pretreatment with compounds 1, 16, 17, 19, 20, 22, 24 and 25 could suppress the cell viability decreasing induced by UVB irradiation in a concentration-dependent manner. These results indicated that phenolic acids were one kind of material basis with prevent-photodamage activity of O. elatus.
Assuntos
OplopanaxRESUMO
Oplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome-derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.
Assuntos
Microbioma Gastrointestinal/fisiologia , Oplopanax/química , Extratos Vegetais , Adulto , Biotransformação , Cromatografia Líquida de Alta Pressão/métodos , Fezes/microbiologia , Humanos , Masculino , Espectrometria de Massas/métodos , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Poli-Inos/análise , Poli-Inos/metabolismo , Sesquiterpenos/análise , Sesquiterpenos/metabolismoRESUMO
Oplopanax horridus and Panax ginseng are members of the plant family Araliaceae, which is rich in structurally diverse polyacetylenes. In this work, we isolated and determined structures of 23 aliphatic C17 and C18 polyacetylenes, of which five are new compounds. Polyacetylenes have a suitable scaffold for binding to PPARγ, a ligand-activated transcription factor involved in metabolic regulation. Using a reporter gene assay, their potential was investigated to activate PPARγ. The majority of the polyacetylenes showed at least some PPARγ activity, among which oplopantriol B 18-acetate (1) and oplopantriol B (2) were the most potent partial PPARγ activators. By employing in silico molecular docking and comparing the activities of structural analogues, features are described that are involved in PPARγ activation, as well as in cytotoxicity. It was found that the type of C-1 to C-2 bond, the polarity of the terminal alkyl chain, and the backbone flexibility can impact bioactivity of polyacetylenes, while diol structures with a C-1 to C-2 double bond showed enhanced cytotoxicity. Since PPARγ activators have antidiabetic and anti-inflammatory properties, the present results may help explain some of the beneficial effects observed in the traditional use of O. horridus extracts. Additionally, they might guide the polyacetylene-based design of future PPARγ partial agonists.
Assuntos
Oplopanax/química , PPAR gama/agonistas , Panax/química , Poli-Inos/química , Poli-Inos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Células HEK293 , Humanos , Hipoglicemiantes/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To study the anti-inflammatory action and cellular mechanism of Oplopanax elatus. METHODS: A hot water extract of OE (WOE) was prepared and a major constituent, syringin, was successfully isolated. Its content in WOE was found to be 214.0 µg/g dried plant (w/w). Their anti-inflammatory activities were examined using RAW 264.7 macrophages and a mouse model of croton oil-induced ear edema. RESULTS: In lipopolysaccharide (LPS)-treated RAW 264.7 cells, a mouse macrophage cell line, WOE was found to significantly and strongly inhibit cyclooxygenase-2 (COX-2)-induced prostaglandin E2 (PGE2) production [half maximal inhibitory concentration (IC50)=135.2 µg/mL] and inducible nitric oxide synthase (iNOS)-induced NO production (IC50=242.9 µg/mL). In the same condition, WOE was revealed to inhibit NO production by down-regulating iNOS expression, mainly by interrupting mitogen activated protein kinases (MAPKs)/activator protein-1 (AP-1) pathway. The activation of all three major MAPKs, p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase, was inhibited by WOE (50-300 µg/mL). On the other hand, WOE reduced PGE2 production by inhibiting COX-2 enzyme activity, but did not affect COX-2 expression levels. In addition, WOE inhibited the production of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. In croton oil-induced ear edema in mice, oral administration of WOE (50-300 mg/kg) dose-dependently inhibited edematic inflammation. CONCLUSION: Water extract of OE exhibited multiple anti-inflammatory action mechanisms and may have potential for treating inflammatory disorders.
Assuntos
Inflamação/prevenção & controle , Macrófagos/efeitos dos fármacos , Oplopanax/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Macrófagos/fisiologia , Camundongos , Extratos Vegetais/química , Células RAW 264.7 , Água/químicaRESUMO
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/químicaRESUMO
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 CultivadasRESUMO
Natural falcarinol-type (FC-type) polyacetylenes are known to show anticancer activities. We studied the bioactivity of synthetic FC, 1,2-dihydrofalcarinol (FCH) and 3-acetoxyfalcarinol (FCA) and compared them with the natural bioactive polyacetylene [9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate] (DCA) isolated from Devil's club (DC) Oplopanax horridus. Antiproliferation activity of these polyacetylenes, along with DC inner stem bark 70% ethanol and water extracts, was tested on human pancreatic ductal adenocarcinoma cell lines PANC-1 and BxPC-3. Chemically synthesized FC and FCA showed consistent IC50 (50% inhibition concentration) and higher potency than DCA. FC and DCA's mechanism of action investigated by antibody array on apoptosis-associated genes, and cellular features confirmed by microscopy demonstrated that both compounds modulated genes related to pro-apoptosis, antiapoptosis, apoptosis, cell cycle, stress related, and death receptors. FC-type polyacetylenes with a terminal double bond (FC, FCA, and DCA) are potent inhibitors of pancreatic cancer cell proliferation compared to FCH with a terminal single bond. Liquid chromatography mass spectrometry confirmed the presence of FC and FCH in the inner stem bark of DC. For potential applications of FC-type polyacetylenes as anticancer agents, preparing them by chemical synthesis may provide an advantage over the labor intensive extraction process from raw plant material.
Assuntos
Carcinoma Ductal Pancreático/tratamento farmacológico , Di-Inos/farmacologia , Álcoois Graxos/farmacologia , Oplopanax/química , Neoplasias Pancreáticas/tratamento farmacológico , Polímero Poliacetilênico/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pancreáticas/patologia , Casca de Planta/química , Extratos Vegetais/farmacologiaRESUMO
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/análiseRESUMO
The stems of Oplopanax elatus (OE) have long been used to treat inflammatory disorders in herbal medicine, and in the previous investigation, OE was found to possess anti-inflammatory activity in lipopolysaccharide-treated macrophages, RAW 264.7 cell. OE reduces inducible nitric oxide (NO) synthase-induced NO production, and interferes with mitogen-activated protein kinase activation pathways. In the present study, the pharmacological action of the water extract of OE was examined to establish anti-arthritic action, using a rat model of adjuvant-induced arthritis (AIA). The water extract of OE administered orally inhibited AIA-induced arthritis at (100 – 300) mg/kg/day. The paw edema was significantly decreased, in combination with reduced production of pro-inflammatory cytokines. The action mechanism includes an inhibition of MAPKs/nuclear transcription factor-κB activation. These new findings strongly suggest that OE possesses anti-arthritic action, and may be used as a therapeutic agent in inflammation-related disorders, particularly in arthritic condition.
Assuntos
Animais , Ratos , Artrite , Artrite Reumatoide , Citocinas , Edema , Medicina Herbária , Macrófagos , Modelos Animais , Óxido Nítrico , Oplopanax , Proteínas Quinases , ÁguaRESUMO
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 farmacológicoRESUMO
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 EspécieRESUMO
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/metabolismoRESUMO
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-DawleyRESUMO
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 TandemRESUMO
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
Animais , Masculino , Ratos , Administração Oral , Cromatografia Líquida de Alta Pressão , Métodos , Di-Inos , Farmacocinética , Medicamentos de Ervas Chinesas , Farmacocinética , Álcoois Graxos , Farmacocinética , Naftóis , Farmacocinética , Oplopanax , Química , Poli-Inos , Farmacocinética , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray , MétodosRESUMO
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 , GencitabinaRESUMO
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/microbiologiaRESUMO
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 adversosRESUMO
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.