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1.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2947-2952, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602838

RESUMO

The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1ß) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1ß and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Citocinas/metabolismo , Eleutherococcus/química , Polissacarídeos/farmacologia , Animais , Fígado/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Peptídeos Cíclicos , Distribuição Aleatória , Transdução de Sinais
2.
Artif Cells Nanomed Biotechnol ; 47(1): 3297-3305, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31379212

RESUMO

Siberian ginseng, perennial herb belongs to Araliaceae family used in traditional medicines to treat hypertension, thrombus, inflammation and cancer. In the present study, we biosynthesized goldnanoparticles using Siberian ginseng aqeous extract in a cost effective manner. The synthesized Siberian ginseng gold nanoparticle (SG-GNPs) were characterized using UV-Vis spec, HR-TEM, XRD, FTIR, SAED analysis. UV-Vis spectroscopic analysis showed a surface Plasmon resonance peak at 538 nm which does not reduce till 30 days of incubation. The results of HR-TEM, XRD and SAED confirm the spherical shape, crystalline nature and the size of the synthesized gold nanoparticles. The FTIR results prove that the biological components present in the Siberian ginseng had reduced the gold ions to synthesis gold nanoparticles. After characterization, the efficacy of SG-GNPS against the melanoma, a deadliest skin carcinoma, was assessed in vitro using B16 murine melanoma cells. The CC50 dose of SG-GNPs against B16 cells were assessed with MTT assay and the anticancer activity was evaluated using Rhodamine 123, H2DCFDA and dual staining techniques. The induction of apoptosis by SG-GNPs against melanoma cells were confirmed with q-PCR analysis. The results of staining techniques prove that SG-GNPs increase the reactive oxygen species and decreased the mitochondrial membrane potential. It is further confirmed by the results of q-PCR analysis which shows increased apoptotic Bid, Bad, Casp3, Casp 9 genes and decreased antiapoptotic Bcl2 gene expression in SG-GNPs treated cells. Our results authentically prove the biosynthesized SG-GNPs induces apoptosis in melanoma cells and it possesses anticancer property.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Eleutherococcus/química , Ouro/química , Ouro/farmacologia , Melanoma Experimental/patologia , Nanopartículas Metálicas , Animais , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ouro/metabolismo , Química Verde , Metaloproteinases da Matriz/metabolismo , Camundongos , Extratos Vegetais/metabolismo , Espécies Reativas de Oxigênio/metabolismo
3.
Planta Med ; 85(13): 1080-1087, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31342475

RESUMO

Although Acanthopanax senticosus root extract (ASRE), a functional food used in Japan, improves peripheral blood circulation and exerts vasorelaxant effects in rats under healthy conditions, the underlying mechanisms currently remain unclear. Therefore, we investigated the mechanisms responsible for ASRE-induced relaxation in isolated thoracic aortas using organ bath techniques and examined whether ASRE affects systemic and peripheral circulation using a photoplethysmographic tail-cuff system and noncontact laser tissue blood flow meter in Wistar rats. Similar to acetylcholine (ACh), ASRE induced dose-dependent relaxation in aortas pre-contracted with phenylephrine; however, in contrast to ACh, ASRE-induced relaxation was partially inhibited by treatments with antagonists of nitric oxide (NO) synthase and soluble guanylyl cyclase as well as by endothelium removal. Contractile responses to phenylephrine or potassium chloride were observed in the presence of ASRE. The oral administration of ASRE (900 mg/kg/d for 1 wk) decreased systolic blood pressure in rats 3 h after the treatment and did not affect heart rate, tail blood flow, mass, or velocity; this decreasing effect was not observed on day 2. A 1-wk treatment with ASRE did not affect vasorelaxation in response to ASRE. These results demonstrate that ASRE induces vasorelaxation via endothelial NO production and an NO-independent pathway in rats. Based on these findings, positive impacts of ASRE on blood pressure and peripheral blood circulation cannot be expected under healthy conditions as the systemic effects of ASRE are temporary. Instead, caution is needed to prevent the occurrence of side effects (i.e., orthostatic dizziness) at the beginning of ASRE dosing.


Assuntos
Eleutherococcus/química , Endotélio Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Aorta Torácica , Relação Dose-Resposta a Droga , Masculino , Óxido Nítrico Sintase Tipo III/fisiologia , Raízes de Plantas/química , Ratos , Ratos Wistar
4.
Nutrients ; 11(5)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121888

RESUMO

The pharmacological properties of Eleutherococcus senticosus leaf have not been clarified although it is taken as a food item. In this study, the effects of water extract of Eleutherococcus senticosus leaves on memory function were investigated in normal mice. Oral administration of the extract for 17 days significantly enhanced object recognition memory. Compounds absorbed in blood and the brain after oral administration of the leaf extract were detected by LC-MS/MS analyses. Primarily detected compounds in plasma and the cerebral cortex were ciwujianoside C3, eleutheroside M, ciwujianoside B, and ciwujianoside A1. Pure compounds except for ciwujianoside A1 were administered orally for 17 days to normal mice. Ciwujianoside C3, eleutheroside M, and ciwujianoside B significantly enhanced object recognition memory. These results demonstrated that oral administration of the leaf extract of E. senticosus enhances memory function, and that active ingredients in the extract, such as ciwujianoside C3, eleutheroside M, and ciwujianoside B, were able to penetrate and work in the brain. Those three compounds as well as the leaf extract had dendrite extension activity against primary cultured cortical neurons. The effect might relate to memory enhancement.


Assuntos
Encéfalo/efeitos dos fármacos , Eleutherococcus/química , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Células Cultivadas , Córtex Cerebral/química , Córtex Cerebral/embriologia , Córtex Cerebral/ultraestrutura , Dendritos/efeitos dos fármacos , Dendritos/fisiologia , Glicosídeos/análise , Glicosídeos/farmacocinética , Glicosídeos/farmacologia , Masculino , Camundongos , Extratos Vegetais/análise , Extratos Vegetais/farmacocinética , Saponinas/análise , Saponinas/farmacocinética , Saponinas/farmacologia
5.
Neoplasma ; 66(4): 555-563, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30943746

RESUMO

Lung cancer (LC) is the highest lethality in all tumors. Non-small cell lung cancer (NSCLC) accounts for about 80% of all LC. Acanthopanax senticosus polysaccharide (ASPS) is extracted from the root of Acanthopanax senticosus (AS). Herein, we examined the effect and molecular mechanism of ASPS on NSCLC. The proliferation, invasion and migration of NCI-H520 cells were detected by cell counting kit-8 (CCK-8), transwell assay and wound healing assay, respectively. The epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathway-related factors were evaluated using quantitative real-time PCR (QRT-PCR) and western blot assay. Our results observed that ASPS significantly decreased the proliferation of cells at 24 and 48 h. Moreover, ASPS markedly repressed the invasion and migration capacities of cells in a concentration-dependent manner. Besides, ASPS obviously down-regulated the levels of matrix metalloproteinase-2 (MMP-2), MMP-9, fibronectin 1 (FN1), vimentin, wnt3a, phosphorylated-glycogen synthase kinase 3ß (p-GSK3ß) and cyclin D1, whereas, up-regulating E-cadherin level. The level of GSK3ß was not changed in the different groups. ASPS conspicuously inhibited the abilities of proliferation and metastasis in human non-small cell lung cancer cell line NCI-H520 possibly by suppressing Wnt/ß-catenin pathway mediated-EMT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Eleutherococcus/química , Neoplasias Pulmonares , Polissacarídeos/farmacologia , Via de Sinalização Wnt , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Humanos
6.
Phytomedicine ; 60: 152881, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30987861

RESUMO

INTRODUCTION: The adaptogens modulate expression of genes playing key roles in development of aging-related disorders, which are considered as low-grade systemic inflammatory conditions characterized by an imbalance between pro-and anti-inflammatory eicosanoids. AIM OF THE STUDY: We compared the effects of anti-inflammatory and adaptogenic plant extracts on the expression of genes involved in biosynthesis of eicosanoids with the purpose to find those plants, which selectively upregulated the expression of anti-inflammatory lipoxins signaling pathways and inhibited pro-inflammatory signaling pathways associated with biosynthesis of leukotrienes, prostaglandins and thromboxanes. MATERIALS AND METHODS: We conducted transcriptome-wide RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of plant extract and analyzed the relevance of deregulated genes to eicosanoids signaling pathways using in silico models. RESULTS: For the first time, we demonstrated that Rhodiola rosea, Withania somnifera and Eleutherococcus senticosus downregulate the expression of key genes (ALOX5AP, DPEP2, LTC4S) involved biosynthesis of leukotrienes A, B, C, D and E, resulting in inhibition of leukotriene signaling pathway suggesting their potential benefits in Alzheimer disease. The common feature for all tested anti-inflammatory plants extracts was related to downregulation of ALOX12, which was also associated with neuroprotective action of these medicinal plants as well as their potential benefits in neurodegenerative diseases. None of tested anti-inflammatory and adaptogenic plants selectively activated the ALOX15-mediated signaling pathway, which is associated with generation anti-inflammatory lipoxins. Almost all tested plants upregulated the expression of the prostaglandin E receptor 3 gene (PTGER3) suggesting their potential benefits in the treatment of cancer. CONCLUSION: Every single plant tested in this study revealed a specific "signature" on eicosanoid signaling-related gene expression, regardless of their common features as anti-inflammatory or adaptogenic activity. Further studies of the combination of Rhodiola with Withania (Adaptra) for the treatment of Alzheimer disease are required.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Eicosanoides/biossíntese , Eleutherococcus/química , Extratos Vegetais/farmacologia , Rhodiola/química , Withania/química , Anti-Inflamatórios/química , Eicosanoides/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Leucotrienos/biossíntese , Leucotrienos/genética , Neuroglia/efeitos dos fármacos , Extratos Vegetais/química , Plantas Medicinais , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos
7.
Oxid Med Cell Longev ; 2019: 8673521, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984341

RESUMO

Secondary metabolites of the roots of Eleutherococcus spp. cultivated in Poland, or the bioactivity, are not fully known. The 75% methanol extracts of five Eleutherococcus spp. (E. senticosus, E. divaricatus, E. sessiliflorus, E. gracilistylus, and E. henryi) were examined for the content of polyphenols and phenolic acids as well as for antiacetylcholinesterase, antihyaluronidase, anti-DPPH∗, and cytotoxic activities. The richest in polyphenols were the roots of E. henryi (10.4 mg/g DW), while in flavonoids the roots of E. divaricatus (6.5 mg/g DW). The richest in phenolic acids occurred the roots of E. henryi [protocatechuic acid (1865 µg/g DE), caffeic acid (244 µg/g DE), and p-coumaric and ferulic acids (55 µg/g DE)]. The highest inhibition of AChE was observed for E. gracilistylus and E. sessiliflorus (32%), at the concentration of 100 µg/0.19 mL of the reaction mixture, while that of Hyal for the roots of E. henryi (40.7%), at the concentration of 100 µg/0.16 mL of the reaction mixture. Among five species tested, the E. henryi extract exhibited the strongest HL-60 cell line growth's inhibition (IC50 270 µg/mL). The extracts reduced DPPH∗ in a time-dependent mode, at the concentration of 0.8 mg/mL. After 90 min from 14.7 to 26.2%, DPPH∗was reduced. A phytochemical composition and activity of the Eleutherococcus species, cultivated in Poland, are still under research; however, on the basis of the results obtained, it may be concluded that they may become a source of phytochemicals and be useful for Europe's citizens.


Assuntos
Eleutherococcus/química , Extratos Vegetais/química , Folhas de Planta/química , Antioxidantes , Europa (Continente)
8.
Phytomedicine ; 58: 152743, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30901664

RESUMO

BACKGROUND: Cancer chemotherapy-induced cognitive impairments are apparently associated with harmful effects on physiological functions of brain cells. Adaptogens, are known to exhibit neuroprotective effects and to increase cognitive functions in clinical studies. In our previous study (Seo et al., 2018), we demonstrated that selected adaptogenic extracts significantly attenuate cytostatic-induced regulation of more than 100 genes involved in the activation of neuronal death and inhibiting neurogenesis. Neuroprotective and cytoprotective activities of adaptogens rise the question about their possible impact on cytostatic effects of a chemotherapeutic combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC). AIM: The aim of this study was to assess the effects of selected adaptogenic herbal extracts, namely of andrographolide (AND), Herba Andrographidis (AP), Radix Eleutherococci (ES) genuine extracts, their fixed combination (AE), and the combination of three adaptogenic herbs, Rhodiola Radix, Shisandra Fructus and Eleutherococci Radix (RSE) on the cytotoxicity of a fixed combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) on neuroglia cells. METHODS: Cytotoxicity of FEC, adaptogenic extracts and their combination with FEC was tested on isolated T98G cells in a wide range of concentrations of all tested compounds. RESULTS: FEC reproducibly inhibited the proliferation of T98G cells by 50% at concentrations of 5 × 10-1 µg/ml epirubicin, 500 × 10-1 µg/ml 5-fluorouracil and 20 × 10-1 µg/ml 4-hydroperoxycyclophosphamide after 24 h incubation of cells. These concentrations were subsequently used for experiments with adaptogenic extracts. The cytotoxic activity of FEC was not significantly changed in the presence of AND, ES and AE. Furthermore, it was potentiated by AP extract and RSE in concentrations of 0.06-6 µg/ml and 17.6-26.4 µg/ml. CONCLUSION: The neuroprotective effect of adaptogens did not attenuate the cytotoxic activity of FEC. Application of cytostatic drugs in combination with adaptogenic plant extracts likely have no impact in cytotoxic effect of FEC. Furthermore, AP and RSE potentiated the cytotoxic effects of FEC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neuroglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Andrographis/química , Linhagem Celular , Ciclofosfamida/administração & dosagem , Ciclofosfamida/análogos & derivados , Relação Dose-Resposta a Droga , Eleutherococcus/química , Epirubicina/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Neuroglia/patologia , Fármacos Neuroprotetores/administração & dosagem , Rhodiola/química
9.
J Pharm Biomed Anal ; 170: 68-82, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30909056

RESUMO

This paper focused on untargeted MSAll, also called MSE, and sequential window acquisition of all theoretical fragment-ion spectra (SWATH) fragmentations for comprehensive structural characterization of triterpene saponins (TSs) in leaves of Acanthopanax senticosus through ultra-high performance liquid chromatography electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF). [M+H]+, [M + NH4]+ and [M + Na]+ precursor ions and the corresponding fragment ions were collected simultaneously in energy-resolved MSAll. SWATH fragmentation was applied as a comparable and complementary method for resolving co-eluting species. A workflow based on MSAll and SWATH fragmentations was constructed for comprehensive structural characterization and rapid discovery of TSs in leaves of A. senticosus. As a result, 89 TSs, along with 14 sapogenins, were unambiguously characterized or tentatively identified. Of these, 33 compounds were characterized as potentially new compounds, including the first report of malonyl-saponin in genus Acanthopanax. This study aimed to systematically analyze TSs in leaves of A. senticosus, and the results are significant for the utilization of A. senticosus leaves.


Assuntos
Eleutherococcus/química , Folhas de Planta/química , Saponinas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Triterpenos/química , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química
10.
Photodiagnosis Photodyn Ther ; 26: 142-149, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30836210

RESUMO

OBJECTIVES: The aim of this study was to develop a novel photosensitizer from traditional plant extracts and to investigate the photodynamic therapy (PDT) effect and mechanism of action of the novel photosensitizer on KB and Hep-2 cells. METHODS: Fluorescence emission, cell viability, and intracellular distribution of candidates were analyzed to screen potential photosensitizers from traditional plant extracts. Cellular reactive oxygen species (ROS) quantification, Annexin V-FITC/PI staining, and western blotting were performed to explore the mechanism of cell death in KB and Hep-2 cells. RESULT: Of 289 traditional plant extracts, 13 plant extracts with strong fluorescence were initially screened by fluorescence emission analysis. The cell viability assay and intracellular distribution of candidates showed that Acanthopanacis Cortex (AC) extract is a potential photosensitizer. Under optimal PDT conditions, high levels of ROS were produced in KB and Hep-2 cells, followed by cell death. However, there was no significant damage to HaCaT cells. Moreover, apoptosis induced by AC extract with 625 nm irradiation (IR) down-regulated the expression of Bcl-2 protein and up-regulated the expression of Bax protein, as well as that of cleaved PARP-1 protein in both KB and Hep-2 cells. CONCLUSION: The fluorescence intensity of AC extract at 420 nm is similar to that of the commercial Hematoporphyrin (HP). AC extract with 625 nm IR could enhance the PDT effect, induce ROS generation, and trigger apoptotic pathways in KB and Hep-2 cells. Therefore, we suggest that AC is a potential novel photosensitizer for PDT in head and neck squamous cell carcinoma.


Assuntos
Eleutherococcus/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Extratos Vegetais/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio , Células Tumorais Cultivadas
11.
Int J Mol Sci ; 20(5)2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871109

RESUMO

Eleutherococcus extract mixture (EEM) is an herbal mixture of dried stem of Eleutherococcus sessiliflorus and germinated barley, which has been highly effective, in previous screening and among the traditional medicines to tonify innate qi and acquired qi, respectively. In this study, we investigate the effects of EEM on endochondral bone formation. Female adolescent rats were given EEM, growth hormone or vehicle for 10 days. Tetracycline was intraperitoneally injected to light the fluorescent band 72 h before sacrifice to determine endochondral bone formation. In order to evaluate endocrine or paracrine/autocrine mechanisms, expressions of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), or bone morphogenetic protein 2 (BMP2) were evaluated after EEM administration in liver or growth plate (GP). EEM oral administration significantly increased endochondral bone formation and proliferative and hypertrophic zonal heights of tibial GP. EEM also upregulated hepatic IGF1 and IGFBP3 mRNA expressions, and IGF1 and BMP2 expressions in GP. Taken together, EEM increases endochondral bone formation through stimulating proliferation and hypertrophy with upregulation of hepatic IGF1 and IGFBP3 expressions. Considering immunohistochemical studies, the effect of EEM may be due to increased local IGF1 and BMP2 expression in GP, which may be considered growth hormone (GH)-dependent endocrine and autocrine/paracrine pathways.


Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Eleutherococcus/química , Osteogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tíbia/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/metabolismo , Proliferação de Células/efeitos dos fármacos , Condrócitos/metabolismo , Feminino , Hormônio do Crescimento/metabolismo , Lâmina de Crescimento/efeitos dos fármacos , Lâmina de Crescimento/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Tíbia/metabolismo
12.
Phytomedicine ; 56: 246-260, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30668345

RESUMO

BACKGROUND: Toxicity of chemotherapeutics is a serious problem in cancer therapy. Adaptogens are known to increase adaptability and survival organisms. AIM: The aim of this study was to assess the effects of selected adaptogenic herbal extracts on FEC (fixed combination of 5-fluorouracil, epirubicin and cyclophosphamide) induced changes in transcriptome-wide microarray profiles of neuroglia cells. Another task of the study was to identify those genes, which are associated with FEC-induced hepato-, cardio- and nephrotoxicity to predict potential effects of andrographolide (AND), Andrographis herb, Eleutherococcus roots genuine extracts (ES), their fixed combination (AE) and the combination of Rhodiola roots, Schisandra berries and Eleutherococcus roots (RSE) on the organismal level. METHODS: Gene expression profiling was performed by transcriptome-wide mRNA microarray in the human T98G neuroglia cells after treatment with adaptogens. Interactive pathways downstream analysis was performed with data sets of significantly up- or down-regulated genes and predicted effects on cellular functions and diseases were identified by Ingenuity IPA database software. RESULT: Significant differences of transcriptome-wide microarray profiles were observed after treatment of T98G cells with FEC and after co-incubation with adaptogens. FEC induced deregulation of certain genes with suggested toxicity associated with liver fibroses, necrosis and congenital heart diseases. Co-incubation of AE with FEC prevented FEC-induced deregulation of 66 genes increasing organismal death, 37 genes decreasing cell survival, 37 genes decreasing DNA repair, 37 genes decreasing viral infection and some other functions, indicating on potential beneficial effects of AE. Furthermore, FEC-induced hepato-, nephro- and cardiotoxicity related to deregulation of genes was predictably attenuated by AE. Moreover, co-incubation of AE with FEC caused differential expression of genes, which presumably are beneficial for an organism during chemotherapy. They include predicted activation of DNA repair, activation of movement of antigen presenting cells and inhibition of muscle cells death. The main active constituent of AE is AND. Co-incubation of FEC only with AND results in deregulation of 10 genes causing death of breast cancer cells, decrease of liver toxicity and attenuation of organismal death. Co-incubation of ES extract with FEC showed that ES suppressed FEC-induced deregulation of genes, which inhibit organismal death and fertility. Co-incubation of FEC with RSE indicated potential hepatoprotective effect against FEC-induced apoptosis of liver cells presumably due to suppression of FEC-induced expressions of genes, which increased liver cell apoptosis. Simultaneously, RSE activated expression of genes inhibiting tumor growth. Though, microarray analysis did not provide final proof that the genes induced by the AE, AP and ES are responsible for the physiological effects observed in human patients following their oral administration, it provided insights into putative genes and directions for future research and possible implementation into practice. CONCLUSION: Application of cytostatic drugs in combination with adaptogenic plant extracts induced significant changes in transcriptome-wide microarray profiles of neuroglial cells. These changes indicate on potential beneficial effects of adaptogens on FEC induced adverse events in cancer chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Antitoxinas/farmacologia , Eleutherococcus/química , Extratos Vegetais/farmacologia , Rhodiola/química , Schisandra/química , Transcriptoma/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Células Cultivadas , Ciclofosfamida/administração & dosagem , Fluoruracila/administração & dosagem , Frutas/química , Perfilação da Expressão Gênica , Humanos , Análise em Microsséries , Neuroglia/efeitos dos fármacos , Raízes de Plantas/química
13.
Int J Mol Sci ; 20(3)2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30678313

RESUMO

Eleutherococcus senticosus Maxim. belongs to the Araliaceae family. Phytochemical studies reveal that E. senticosus leaves contain triterpene glycosides along with organic acid derivatives and flavonoid compounds. It is believed that E. senticosus is similar to ginseng because they come from same family and both contain triterpene saponins. E. senticosus leaves have been developed as a functional beverage called ci-wu-jia tea in recent years. Triterpene glycosides are difficult to identify by ultraviolet (UV) detection and contents of these compounds are low in E. senticosus leaves. In this study, a sensitive ultra-high performance liquid chromatographic (UHPLC) method combining UV and tandem mass spectrometry (MS/MS) was developed to characterize the triterpene glycosides from E. senticosus leaves and related commercial products. Fragmentation patterns of three sub-groups of triterpene glycosides in E. senticosus leaves were investigated. Additionally, fragmentation pathways and UV characteristics of organic acid derivatives and flavonoids were also characterized. A compound screening library, including 241 compounds reported in the literature, was created and used to confirm the compounds in the samples. In this study, a total of 24 samples, including 13 plant samples of E. senticosus and 11 ci-wu-jia tea products, were analyzed. Out of the 11 commercial products, three products were discovered to contain green tea (Camellia sinensis) that was considered to be an adulterant since it was not an ingredient on the labels. The developed UHPLC-UV-MS/MS analytical method combined with the UNIFI processing method can simultaneously characterize organic acid derivatives, flavonoids, and triterpene saponins from E. senticosus. It provides a simple and sensitive way to perform quality control of E. senticosus and related ci-wu-jia tea products.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Eleutherococcus/química , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodos , Flavonoides/química , Glicosídeos/química , Ácido Quínico/química , Triterpenos/química
14.
J Sci Food Agric ; 99(7): 3283-3290, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30552777

RESUMO

BACKGROUND: In China, Acanthopanax sessiliflorus is a delicious wild vegetable. It is also used to treat inflammation and pain. Chiisanoside (CSS) is the main constituent of the leaf of A. sessiliflorus. Combined use of lipopolysaccharide and d-galactosamine (LPS/D-GalN) can induce acute liver failure in human beings, and there are no reports on the protective effect of CSS against LPS/D-GalN-induced acute liver injury in mice. RESULTS: Chiisanoside pretreatment evidently reduced the activities of alanine transaminase (ALT) and aspartate transaminase (AST) in the changes induced by LPS/D-GalN, and these histopathological changes induced by LPS/GalN were significantly weakened. Catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) activities increased, and malondialdehyde (MDA) activity decreased after CSS treatment compared with LPS/D-GalN treatment. Pretreatment with CSS also inhibited the expression levels of inflammatory factors. The administration of CSS prevented the phosphorylated expression of inhibitor kappa B (IκB) kinase, and led to a significant increase in heme oxygenase-1 (HO-1) expression and nuclear factor erythroid 2-related factor2 (Nrf2) nuclear translocation. CONCLUSION: The protective effects of CSS are attributed to its antioxidative effect and inflammatory suppression in Nuclear factor kappa beta (NF-κB) and Nrf2/HO-1 signaling pathways. Chiisanoside might therefore be a potential ingredient for drug and food development against acute liver injury in the future. © 2018 Society of Chemical Industry.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Medicamentos de Ervas Chinesas/administração & dosagem , Eleutherococcus/química , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Oligossacarídeos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Triterpenos/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Galactosamina/efeitos adversos , Glutationa/metabolismo , Heme Oxigenase-1/genética , Humanos , Lipopolissacarídeos/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
15.
Phytomedicine ; 50: 257-284, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30466987

RESUMO

INTRODUCTION: Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. AIM OF THE STUDY: The aim of this study was to identify key molecular mechanisms of adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola rosea, Eleutherococcus senticosus, Withania somnifera, Rhaponticum carthamoides, and Bryonia alba. MATERIALS AND METHODS: To investigate the underlying molecular mechanisms of adaptogens, we conducted RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of adaptogens and analyzed the relevance of deregulated genes to adaptive stress-response signaling pathways using in silico pathway analysis software. RESULTS AND DISCUSSION: At least 88 of the 3516 genes regulated by adaptogens were closely associated with adaptive stress response and adaptive stress-response signaling pathways (ASRSPs), including neuronal signaling related to corticotropin-releasing hormone, cAMP-mediated, protein kinase A, and CREB; pathways related to signaling involving CXCR4, melatonin, nitric oxide synthase, GP6, Gαs, MAPK, neuroinflammation, neuropathic pain, opioids, renin-angiotensin, AMPK, calcium, and synapses; and pathways associated with dendritic cell maturation and G-coupled protein receptor-mediated nutrient sensing in enteroendocrine cells. All samples tested showed significant effects on the expression of genes encoding neurohormones CRH, GNRH, UCN, G-protein-coupled and other transmembrane receptors TLR9, PRLR, CHRNE, GP1BA, PLXNA4, a ligand-dependent nuclear receptor RORA, transmembrane channels, transcription regulators FOS, FOXO6, SCX, STAT5A, ZFPM2, ZNF396, ZNF467, protein kinases MAPK10, MAPK13, MERTK, FLT1, PRKCH, ROS1, TTN), phosphatases PTPRD, PTPRR, peptidases, metabolic enzymes, a chaperone (HSPA6), and other proteins, all of which modulate numerous life processes, playing key roles in several canonical pathways involved in defense response and regulation of homeostasis in organisms. It is for the first time we report that the molecular mechanism of actions of melatonin and plant adaptogens are alike, all adaptogens tested activated the melatonin signaling pathway by acting through two G-protein-coupled membrane receptors MT1 and MT2 and upregulation of the ligand-specific nuclear receptor RORA, which plays a role in intellectual disability, neurological disorders, retinopathy, hypertension, dyslipidemia, and cancer, which are common in aging. Furthermore, melatonin activated adaptive signaling pathways and upregulated expression of UCN, GNRH1, TLR9, GP1BA, PLXNA4, CHRM4, GPR19, VIPR2, RORA, STAT5A, ZFPM2, ZNF396, FLT1, MAPK10, MERTK, PRKCH, and TTN, which were commonly regulated by all adaptogens tested. We conclude that melatonin is an adaptation hormone playing an important role in regulation of homeostasis. Adaptogens presumably worked as eustressors ("stress-vaccines") to activate the cellular adaptive system by inducing the expression of ASRSPs, which then reciprocally protected cells from damage caused by distress. Functional investigation by interactive pathways analysis demonstrated that adaptogens activated ASRSPs associated with stress-induced and aging-related disorders such as chronic inflammation, cardiovascular health, neurodegenerative cognitive impairment, metabolic disorders, and cancer. CONCLUSION: This study has elucidated the genome-wide effects of several adaptogenic herbal extracts in brain cells culture. These data highlight the consistent activation of ASRSPs by adaptogens in T98G neuroglia cells. The extracts affected many genes playing key roles in modulation of adaptive homeostasis, indicating their ability to modify gene expression to prevent stress-induced and aging-related disorders. Overall, this study provides a comprehensive look at the molecular mechanisms by which adaptogens exerts stress-protective effects.


Assuntos
Neuroglia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Biologia de Sistemas , Adaptação Fisiológica , Encéfalo/citologia , Bryonia/química , Linhagem Celular Tumoral , Eleutherococcus/química , Glioblastoma , Humanos , Leuzea/química , Longevidade/efeitos dos fármacos , Rhodiola/química , Transdução de Sinais/efeitos dos fármacos , Withania/química
16.
Food Funct ; 9(12): 6555-6565, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30484473

RESUMO

The leaves of Acanthopanax Senticosus Harms (ASL) can be used as a food ingredient and also as raw materials for making tea and wine. As a traditional Chinese medicine (TCM), ASL has demonstrated significant effects in the treatment of ischemic stroke, but the substance basis and the pharmacological mechanism of ASL are unclear. In this study, a sensitive and rapid method was constructed for the separation and identification of the absorbed prototype components and metabolites from ASL in rat plasma and brain using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A database of ASL active ingredients was established, which comprised 27 prototype ingredients and 20 metabolites from the rat plasma and 10 prototype ingredients and 7 metabolites from the rat brain. A comprehensive and effective target-network pharmacological method for tracing co-related targets and pathways between ASL and ischemic stroke was also set up. As a result, 34 targets and 30 pathways were obtained. TNF, NF-κB, IL-6, IL-1B, ICAM, and MMP-9 targets are all critical factors related to ischemic stroke, while the NF-κB signaling pathway, MAPK signaling pathway, TNF signaling pathway, and arachidonic acid metabolism play significant roles in the development of ischemic stroke. The visualized relationship between ASL and ischemic stroke was demonstrated by compound-target networks and compound-target-pathway networks, which revealed the therapeutic targets around the signaling pathways of ASL in the treatment of ischemic stroke. This research method will open a window for the mechanistic studies of TCM in the treatment of diseases.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Eleutherococcus/química , Isquemia/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Espectrometria de Massas em Tandem/métodos , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Isquemia/genética , Isquemia/metabolismo , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/metabolismo
17.
J Oleo Sci ; 67(10): 1235-1246, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30305556

RESUMO

Terpene synthase (TPS) genes were isolated and functionally characterized from three traditional edible plants, Acanthopanax sciadophylloides ("Koshiabura") and Acanthopanax sieboldianus ("Himeukogi"), belonging to the family Araliaceae, and Curcuma zedoaria (zedoary, "Gajutsu"), belonging to the family Zingiberaceae. These plants emit characteristic fragrances and are used for traditional foods and folk medicines. From their fragrant tissues, i.e., sprouts of Araliaceae plants and developing rhizomes of zedoary, total RNAs were extracted and reverse transcribed. The resultant cDNAs were used for degenerate PCR followed by rapid amplification of cDNA ends. From the contig sequences obtained, full-length Tps genes were amplified by PCR with newly synthesized primer sets. The isolated full-length genes were introduced into engineered Escherichia coli cells, which can utilize acetoacetate to synthesize farnesyl diphosphate, the substrate for TPSs, through the mevalonate pathway. TPS products synthesized in the transformed E. coli cells were analysed by gas chromatography-mass spectrometry, nuclear magnetic resonance, and optical rotation. Consequently, the isolated Tps genes were found to encode ß-caryophyllene synthase, germacrene D synthase, linalool/(3S)-(+)-nerolidol synthase, ß-eudesmol synthase, and germacrene B synthase. These results lead us to expect that some of the effective ingredients in folk medicines are volatile terpenes and that intake of traditional foods including these edible plants would have some positive effects on our health.


Assuntos
Alquil e Aril Transferases/genética , Alquil e Aril Transferases/isolamento & purificação , Curcuma/enzimologia , Curcuma/genética , Eleutherococcus/enzimologia , Eleutherococcus/genética , Plantas Comestíveis/enzimologia , Plantas Comestíveis/genética , Acetoacetatos/metabolismo , Curcuma/química , DNA Complementar , Eleutherococcus/química , Escherichia coli/metabolismo , Ácido Mevalônico/metabolismo , Plantas Comestíveis/química , Fosfatos de Poli-Isoprenil/metabolismo , Reação em Cadeia da Polimerase , RNA de Plantas/isolamento & purificação , Sesquiterpenos/metabolismo , Terpenos , Compostos Orgânicos Voláteis
18.
Fitoterapia ; 130: 265-271, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30243779

RESUMO

Gracilistones A (1) and B (2), two new eudesmane-type sesquiterpenoids with an unusual tetrahydrofuran-fused 6/6/5 tricyclic ring system, were obtained from Acanthopanax gracilistylus under the guidance of LC-MS investigation. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and quantum calculation methods. Compounds 1 and 2 showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, compared with the positive control L-NMMA. In addition, compounds 1 and 2 were also evaluated for their antioxidant (DPPH• and ABTS•+) and xanthine oxidase (XO) inhibitory activities, and they exhibited weak inhibitory effects at 100 µM.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Eleutherococcus/química , Sesquiterpenos de Eudesmano/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , China , Cromatografia Líquida , Furanos , Espectrometria de Massas , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Células RAW 264.7 , Sesquiterpenos de Eudesmano/isolamento & purificação
19.
Chem Pharm Bull (Tokyo) ; 66(8): 785-793, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30068798

RESUMO

The aim of this study was to investigate and optimize the most important factors affecting the extraction of Acanthopanax giraldii HARMS polysaccharides (AHPs) by ultrasound-assisted extraction (UAE) technology in a systemic manner. The ranges of four factors, including extraction temperature, liquid/solid ratio, extraction time, and ultrasonic power, were first determined by a single-factor experiment, followed by optimization of the UAE conditions using the Box-Behnken design (BBD) for maximum AHPs production. In our study, the models developed from the experimental design predicted the experimental data well and had a high determination coefficient (R2=0.9387). The optimized conditions for AHPs extraction were as follows: extraction temperature, 58°C; liquid/solid ratio, 25 : 1; extraction time, 73 min; and ultrasonic power, 85 W. Under these optimized conditions, the polysaccharide yield was 1.532±0.037% (n=3), being very close to the predicted value of 1.546% by the model. In addition, to investigate whether there was a difference of AHPs content between UAE and traditional hot water extraction (THWE), Fourier-transform (FT) IR spectral analyses was performed. The results showed that the functional groups of the polysaccharides extracted by either UAE or THWE were fundamentally identical. Furthermore, AHPs extracted by UAE could promote macrophage activation, such as enhanced phagocytosis and increased cytokine (interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) secretion in RAW264.7 cells. In conclusion, optimization of the UAE conditions by response surface methodology (RSM) was a promising method to improve the extraction yield of AHPs. AHPs extracted by the optimized UAE method can maintain their polysaccharide structure and biological activity.


Assuntos
Eleutherococcus/química , Polissacarídeos/química , Animais , Fracionamento Químico , Citocinas/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Células RAW 264.7 , Solventes , Temperatura , Ondas Ultrassônicas , Água
20.
Oxid Med Cell Longev ; 2018: 5158243, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29849899

RESUMO

Acanthopanax sessiliflorus (Rupr. & Maxim.) Seem., which belongs to the Araliaceae family, mainly inhabits Korea, China, and Japan. Traditionally, Acanthopanax species have been used as treatment for several diseases such as diabetes, tumors, and rheumatoid arthritis. Especially, its fruits have many biological functions including antitumor, immunostimulating, antithrombosis, and antiplatelet activities. Recently, the extract of A. sessiliflorus fruit has been reported to have antithrombotic and antiplatelet activities related to the alleviation of hypertension. Therefore, we investigated the antihypertensive effect of ethanolic extract from A. sessiliflorus fruits (DHP1501) through in vivo, ex vivo, and in vitro studies. In this study, DHP1501 demonstrated free radical scavenging capacity, enhanced endothelial nitric oxide (NO) production, and inhibited angiotensin-converting enzyme (ACE) activity in spontaneously hypertensive rats (SHRs), resulting in the improvement of vascular relaxation and decrease in blood pressure in the hypertensive animal model. These results suggest that A. sessiliflorus fruit extract may be a promising functional material for the prevention and treatment of hypertension. Furthermore, this study demonstrated the utility of MS-based active compounds for the quality control of DHP1501.


Assuntos
Anti-Hipertensivos/uso terapêutico , Eleutherococcus/química , Frutas/química , Medicina Tradicional do Leste Asiático/métodos , Extratos Vegetais/química , Animais , Anti-Hipertensivos/farmacologia , Humanos , Masculino , Ratos
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