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1.
Acta Pharmacol Sin ; 43(7): 1843-1856, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34845369

RESUMO

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.


Assuntos
Antineoplásicos , Neoplasias da Mama , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Farneseno Álcool/análogos & derivados , Farneseno Álcool/farmacologia , Farneseno Álcool/uso terapêutico , Feminino , Humanos , Camundongos , Salicilatos , Proteínas ras/metabolismo , Proteínas ras/uso terapêutico
2.
Math Biosci Eng ; 17(3): 2003-2015, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-32233520

RESUMO

The continuous predator-prey model is one of the main models studied in recent years. The dynamical properties of these models are so complex that it is an urgent topic to be studied. In this paper, we transformed a continuous predator-prey model with modified Leslie-Gower and Hollingtype III schemes into a discrete mode by using Euler approximation method. The existence and stability of fixed points for this discrete model were investigated. Flip bifurcation analyses of this discrete model was carried out and corresponding bifurcation conditions were obtained. Provided with these bifurcation conditions, an example was given to carry out numerical simulations, which shows that the discrete model undergoes flip bifurcation around the stable fixed point. In addition, compared with previous studies on the continuous predator-prey model, our discrete model shows more irregular and complex dynamic characteristics. The present research can be regarded as the continuation and development of the former studies.


Assuntos
Cadeia Alimentar , Modelos Biológicos , Comportamento Predatório , Animais , Simulação por Computador , Conceitos Matemáticos , Biologia de Sistemas
3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(4): 656-659, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30378324

RESUMO

OBJECTIVE: To determine the effect of implant position on clinical crown length and papilla fills in implant-supported maxillary central incisors. METHODS: One implant replacing the 11th or 21st tooth was given to 158 patients who lost a maxillary central incisor after trauma. The contra-lateral central incisors were used as controls. The three-dimensional positional parameters were estimated using standardized photographs of the cast models, clinical photographs and peri-apical radiographs. Paired t tests were performed to examine the differences between the implants and the control teeth in clinical crown length, papilla fills, proximal bone crest levels, and the horizontal implant-teeth distance at the mesial and distal implant. Pearson correlations were used to identify the implant positional parameters associated with crown length and papilla fills. RESULTS: The implant-supported crowns were statistically longer than the controls [(10.9±1.1) mm vs. (10.4±0.8) mm, P<0.05]. Greater papilla fills were found in the mesial implants and distal contra-lateral teeth compared with the distal implants (P<0.000 1). The implants had higher levels of mesial proximal bone crest than the distal [(2.2±1.4) mm vs. (1.2±1.5) mm, P<0.05]. The oro-facial position of the implants was associated with the crown length (R=0.602, P=0.001). But the crown length was not correlated with the sagital angulation of the implants or the vertical distance from the implant fixture to the soft tissue margin. The proximal bone crest level was correlated with the papilla fill height (R=0.400, P=0.001). CONCLUSION: An implant positioned buccally results in longer crown length. Minor buccal angulations of the implant do not necessarily result in increased crown length. Appropriate position and input depth may help avoid bone absorption and papilla shrinkage.


Assuntos
Coroas , Implantes Dentários para Um Único Dente , Incisivo , Humanos , Maxila
4.
Cell Death Discov ; 4: 105, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30479839

RESUMO

Triple-negative breast cancer (TNBC) remains a clinical challenge because of the absence of effective therapeutic targets. In TNBC, overexpression of YAP and TAZ correlates with bioactivities of cancer stem cells (CSCs), high histological grade, resistance to chemotherapy, and metastasis. Thus, YAP/TAZ may serve as potential therapeutic targets in TNBC. To identify YAP/TAZ inhibitors, in previous experiments, we screened a library of natural compounds by using YAP/TAZ luciferase reporter assay and identified apigenin as a potential inhibitor. In this study, we demonstrated that apigenin significantly suppressed the proliferation and migration of TNBC cells. Furthermore, we demonstrated that apigenin inhibited stemness features of TNBC cells in both in vitro and in vivo assays. Our mechanism study demonstrated that apigenin decreased YAP/TAZ activity and the expression of target genes, such as CTGF and CYR61, in TNBC cells. We also showed that apigenin disrupted the YAP/TAZ-TEADs protein-protein interaction and decreased expression of TAZ sensitized TNBC cells to apigenin treatment. Collectively, our studies suggest that apigenin is a promising therapeutic agent for the treatment of TNBC patients with high YAP/TAZ activity.

5.
Int J Mol Sci ; 19(3)2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-29495545

RESUMO

Hepatic fibrosis is the main pathological basis for chronic cirrhosis, and activated hepatic stellate cells (HSCs) are the primary cells involved in liver fibrosis. Our study analyzed anti-fibrosis long noncoding RNAs (lncRNAs) in activated human HSCs (hHSCs). We performed RNA sequencing (RNA-seq) and bioinformatics analysis to determine whether lncRNA expression profile changes between hHSCs activation and quiescence. Eight differentially expressed (DE) lncRNAs and three pairs of co-expression lncRNAs-mRNAs were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). A total of 34146 DE lncRNAs were identified in this study. Via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we found several DE lncRNAs regulated hHSC activation by participating in DNA bending/packaging complex, growth factor binding and the Hippo signaling pathway (p < 0.05). With lncRNA-mRNA co-expression analysis, three lncRNAs were identified to be associated with connective tissue growth factor (CTGF), fibroblast growth factor 2 (FGF2) and netrin-4 (NTN4). The quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results of the eight DE lncRNAs and three pairs of co-expression lncRNAs-mRNAs were consistent with the RNA-seq data and previous reports. Several lncRNAs may serve as potential targets to reverse the progression of liver fibrosis. This study provides a first insight into lncRNA expression profile changes associated with activated human HSCs.


Assuntos
Células Estreladas do Fígado/metabolismo , Cirrose Hepática/genética , RNA Longo não Codificante/genética , Transcriptoma , Biomarcadores , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Células Estreladas do Fígado/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunofenotipagem , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Fenótipo , Interferência de RNA , RNA Mensageiro/genética , Reprodutibilidade dos Testes , Análise de Sequência de RNA , Ácido Valproico/análogos & derivados , Ácido Valproico/farmacologia
6.
Arch Virol ; 162(6): 1661-1669, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28243801

RESUMO

Ribavirin is a broad-spectrum antiviral agent that is used against RNA and DNA viruses and has been reported to inhibit infection by influenza A and B virus in vitro and in vivo. Studies have shown that ribavirin can lower convalescent antibody titers in young children hospitalized with influenza. Here, we report that ribavirin administration in juvenile mice significantly attenuated respiratory immune responses, production of total IgA and hemagglutinin (HA)-specific secretory IgA responses on the mucosal surface. In contrast, systemic IgG and IgA responses were not affected. Ribavirin significantly suppressed toll-like receptor 2 and 4 expression in the lung and decreased the level of IL-1ß, IL-6, TNF-α, and IFN-γ in lung tissues of mice infected with influenza virus. Our findings suggest ribavirin appears to be able to inhibit viral replication and, as a result, TLR and cytokine expression are not up-regulated, attenuating inflammation as well as the respiratory tract's immune response.


Assuntos
Antivirais/administração & dosagem , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/imunologia , Sistema Respiratório/efeitos dos fármacos , Ribavirina/administração & dosagem , Replicação Viral/efeitos dos fármacos , Animais , Feminino , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/fisiologia , Interferon gama/genética , Interleucina-1beta/genética , Interleucina-6/genética , Pulmão/imunologia , Pulmão/virologia , Camundongos , Sistema Respiratório/imunologia , Receptor 2 Toll-Like/efeitos dos fármacos , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética
7.
J Med Virol ; 89(7): 1158-1167, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27966790

RESUMO

It is need for development of new means against influenza virus due to the lack of efficacy of available therapeutic strategies. In previous research, 1,8-cineol exert its inhibition of nuclear factor (NF)-κB, the main regulator of cytokine and chemokine production in influenza, and anti-inflammatory activity. These fact supports and helps establish the hypothesis that 1,8-cineol may have synergism with an antiviral on influenza virus infection. The combined effect of 1,8-cineol with oseltamivir in a mouse type A influenza virus (Victoria/3/75,H3N2) model were examined. We initially tested combinations of 1,8-cineol (30, 60, and 120 mg/kg/day) and oseltamivir (0.1, 0.2, and 0.4 mg/kg/day). In addition, the 0.4 mg/kg/day of oseltamivir combined with 120 mg/kg of 1,8-cineol was selected for further combination studies. Oseltamivir was 30%, 40%, and 60% protective at 0.1, 0.2, and 0.4 mg/kg/d. Combinations of 1,8-cineol (30, 60, and 120 mg/kg/d) and oseltamivir (0.1, 0.2, and 0.4 mg/kg/d) increased the number of survivors and mean survival time (MST) following combination treatment was greater than monotherapy alone. Three dimensional analysis of drug interactions using the MacSynergy method showed a strong synergistic effect of these drug combinations. Survival, MST, lung parameters (lung index, viral titers, and pathology), and cytokines (IL-10, TNF-α, IL-1ß, and IFN-γ) expression in lung demonstrated the high effectiveness of the combination. Combined treatment was associated with longer MST and more reduced cytokine levels than oseltamivir alone. These data demonstrate that combinations of 1,8-cineol and oseltamivir have synergistic effect against influenza A virus (H3N2) infection.


Assuntos
Antivirais/uso terapêutico , Cicloexanóis/uso terapêutico , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Monoterpenos/uso terapêutico , Oseltamivir/uso terapêutico , Animais , Antivirais/administração & dosagem , Cicloexanóis/administração & dosagem , Citocinas/efeitos dos fármacos , Citocinas/genética , Citocinas/imunologia , Sinergismo Farmacológico , Quimioterapia Combinada , Eucaliptol , Humanos , Influenza Humana/virologia , Interleucina-10/genética , Interleucina-10/imunologia , Pulmão/imunologia , Pulmão/virologia , Camundongos , Monoterpenos/administração & dosagem , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Oseltamivir/administração & dosagem , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
8.
Chin J Integr Med ; 22(10): 768-73, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27146049

RESUMO

OBJECTIVE: To evaluate the effect of Chinese medicine Haoqin Qingdan Decoction (, HQD) for febrile disease dampness-heat syndrome (FDDHS). METHODS: Forty mice were divided into four groups, including normal control, FDDHS (induced by Radix et Rhizoma Rhei recipe and influenza virus A1 FM1 model), HQD, and the ribavirin groups (10 in each). The normal control and FDDHS groups were administered normal saline. HQD and the ribavirin groups were administered HQD and ribavirin intragastrically once daily at a dose of 64 g/(kg d) and 0.07 g/(kg d), respectively for 7 days. Lethargy, rough hair, diarrhea, tongue color and sole color were evaluated for pathological changes in morphology. The tongue and lung tissues were collected for histology. The CD14 and toll-like receptor 4 (TLR4) expression levels were measured using real-time quantitative polymerase chain reaction. RESULTS: More than 80% of the FDDHS mice showed hypokinesia and lethargy, and pathological changes associated with rough hair, diarrhea, tongue color and sole color. With advanced treatment for 7 days, the thick greasy tongue fur of the HQD and ribavirin groups were thinner than that of the FDDHS group (P<0.05), and it was the thinnest in the ribavirin group as compared with that in other groups (P<0.05). The CD14 and TLR4 expression levels in the lung tissues of HQD and ribavirin groups significantly delined compared with the model group (P<0.05 or P<0.01). CD14 was down-regulated more remarkably in the HQD group compared with the ribavirin group (P<0.05), whereas the converse was true with TLR4 (P<0.05). CONCLUSIONS: We established a FDDHS mouse model showing systemic clinical symptoms. Both HQD and ribavirin can inhibit the expression of CD14 and TLR4 in FDDHS mice, while the effect of ribavirin might be much more violent. The expression changes of CD14 and TLR4 consistently refers to lipopolysaccharide, the commonly and hotly inducing factor in FDDHS.


Assuntos
Regulação para Baixo , Medicamentos de Ervas Chinesas/uso terapêutico , Febre/tratamento farmacológico , Ribavirina/uso terapêutico , Receptor 4 Toll-Like/genética , Animais , Comportamento Animal , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Febre/patologia , Perfilação da Expressão Gênica , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos BALB C , Ribavirina/farmacologia , Síndrome , Receptor 4 Toll-Like/metabolismo
9.
J Ethnopharmacol ; 179: 128-36, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26190352

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ligustrum purpurascens Y.C. Yang (Oleaceae) is traditionally recorded as "Ku Ding Cha", a kind of functional tea in southern China for about two thousand years, which has been reported with sore throat alleviating and pathogenic heat expelling effects. However, there are no scientific studies demonstrating its antiviral activity. THE AIM OF THE STUDY: This study is aimed at investigating the anti-influenza virus effects of phenylethanoid glycosides isolated from L. purpurascens (LPG) as well as its corresponding mechanisms. MATERIALS AND METHODS: In vitro, hemagglutination assay was employed to detect the influenza virus titer; In vivo, C57BL/6J mice were given oral administration of LPG (100mg/kg, 300mg/kg, 900mg/kg) or ribavirin (100mg/kg) once daily for 5 successive days. Meanwhile, on the second day, mice were infected intranasally (i.n.) with A/FM/1/47 H1N1 virus. Mice survival rate and other clinical index were monitored for 15 days. Infected mice were sacrificed to measure the lung lesion and stained with hematoxylin-eosin. Flow cytometry analyses spleen lymphocytes and interferon-γ (IFN-γ) level. The IFN-γ knockout mice (IFN-γ(-/-) mice, C57BL/6J) which had been verified lacking IFN-γ through Western Blot, were applied in the death-protection test to identify the role of IFN-γ played in LPG antiviral effect. RESULTS: In vitro, LPG at 0.5mg/ml inhibited Influenza A Virus H1N1 type (H1N1) infection of MDCK cells. In vivo, LPG at 300 and 900mg/kg significantly decreased the mouse lung index (p<0.05), alleviated influenza-induced lethality and clinical symptoms, and therefore enhanced mouse survival (p<0.05). More detailed experiments demonstrated that antiviral cytokine IFN-γ was involved in the antiviral effect of LPG. Flow cytometric analysis revealed that LPG (900mg/kg) significantly induced secretion of IFN-γ by splenic CD4(+) and CD8(+) cells (p<0.05). Moreover, LPG (900mg/kg) protected wild-type C57BL/6J mice from H1N1 injury, whereas LPG-mediated survival protection disappeared in IFN-γ(-/-) mice. CONCLUSION: These results suggest that up-regulating endogenous IFN-γ by LPG may represent a novel therapeutic approach for H1N1 infection.


Assuntos
Antivirais/farmacologia , Glicosídeos/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Indutores de Interferon/farmacologia , Interferon gama/biossíntese , Ligustrum/química , Animais , Antivirais/toxicidade , Citocinas/metabolismo , Cães , Feminino , Humanos , Influenza Humana/virologia , Interferon gama/genética , Ligustrum/toxicidade , Pulmão/virologia , Contagem de Linfócitos , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/patologia , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Análise de Sobrevida
10.
Molecules ; 20(5): 8791-9, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25988610

RESUMO

An approach for molecular similarity/substructure searching based on structural hierarchy matching is proposed. In this approach, small molecules are divided into two categories, acyclic and cyclic forms. The latter are further divided into three structural hierarchies, namely, framework, complicated-, and mono-rings. During searching, the similarity coefficients of a structural query and each retrieved molecule are calculated using the hierarchy of the query as the reference. A total of 13,911 chemicals were involved in this work, from which the minimal cyclic and acyclic substructures are extracted, and further processed into fuzzy structural fingerprints. Subsequently, the fingerprints are used as the searching indices for molecular similarity or substructure searching. The tests show that this approach can give user options to choose between one-substructure and multi-substructure searching with sorted results. Moreover, this algorithm has the potential to be developed for molecular similarity searching and substructure analysis.


Assuntos
Algoritmos , Bases de Dados de Compostos Químicos , Estrutura Molecular , Relação Estrutura-Atividade
11.
J Ethnopharmacol ; 155(3): 1575-82, 2014 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-25102242

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the root of Ilex asprella (Hook. & Arn.) Champ. ex Benth. (IA) has been widely used to treat influenza, lung abscess and other diseases in South China for many years. The present study is aimed at investigating the treatment effect of IA on acute respiratory distress syndrome (ARDS) induced by the H1N1 virus in mice. MATERIALS AND METHODS: After being inoculated with several viral doses of influenza A/FM/1/47 H1N1 virus, mice were given oral administration of IA extract (500 mg/kg or 12 5mg/kg per day) for five or 10 consecutive days, respectively. Mice survival rate and clinical condition were observed for 15 days after inoculation. Lung weight, pathological analysis and arterial blood gas analysis were assessed. Lung viral load was quantified by RT-PCR. Moreover, immunological analysis was measured by leukocyte counts and the levels of inflammatory cytokines, including IL-6, IL-10, TNF-α, IFN-γ, MCP-1 and IL-12p 70 in serum of mice. RESULTS: We found that the extract of Ilex asprella at dosages of 500 mg/kg could effectively diminish mortality rate, and ameliorate lung edema and inflammation. Administration of IA extract significantly depressed the expression of IL-6, TNF-α and MCP-1, and significantly increased the expression of IL-10 and IFN-γ in serum. Simultaneously, the extract was also found to reduce the lung viral load and improve pulmonary ventilation. CONCLUSION: The present study shows that the extract of IA has the potential to treat ARDS, due to its abilities of attenuation of systemic and pulmonary inflammatory responses and inhibition of viral replication.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Ilex , Vírus da Influenza A Subtipo H1N1 , Pneumopatias/tratamento farmacológico , Infecções por Orthomyxoviridae/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Citocinas/sangue , Feminino , Contagem de Leucócitos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Pneumopatias/sangue , Pneumopatias/patologia , Pneumopatias/virologia , Masculino , Camundongos , Infecções por Orthomyxoviridae/sangue , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Fitoterapia , Extratos Vegetais/farmacologia , Raízes de Plantas , Carga Viral/efeitos dos fármacos
12.
Yi Chuan ; 35(10): 1217-25, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24459895

RESUMO

MYB-type transcription factor is one of the largest families in plants, which plays important roles in accepting stress signals from environment and regulating the expression of stress-tolerant genes. In this paper, using homologous cloning and RACE technology, a MYB-type transcription factor, designated PeMYB2, was cloned from Phyllostachys edulis. The results of bioinformatics showed that PeMYB2 is a typical R2R3-MYB. It contained two tandem repeats in its N-terminus, and a membrane protein DUF3651 in its C-terminus. In addition, phylogenetic analysis indicated that PeMYB2 shared the highest homology with 85.98% to OsMYB18 protein from Oryza sativa spp. Japonica. In addition, a yeast one-hybrid assay showed that PeMYB2 could activate the expression of downstream genes. After PeMYB2 was transformed into Arabidopsis thaliana, seven PeMYB2 transgenic Arabidopsis lines were obtained. Phenotypic analysis of the transgenic and wild-type Arabidopsis showed that over-expression of PeMYB2 caused delayed flower or dwarfism in transgenic Arabidopsis. Under the abiotic stress conditions, such as salt and cold stresses, the over-expression of PeMYB2 in Arabidopsis had higher survival rate than the wild-type Arabidopsis. Expression analysis of saline stress response marker genes in the transgenic and wild-type plants under the salt stress condition showed that PeMYB2 regulated the expression of NXH1, SOS1, RD29A, and COR15A. As the result, PeMYB2 might play an important role in various responses to abiotic stresses in P. edulis.


Assuntos
Clonagem de Organismos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poaceae/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Filogenia , Poaceae/classificação , Poaceae/metabolismo
13.
Int Immunopharmacol ; 12(1): 294-301, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22193241

RESUMO

Seasonal influenza A infection results in considerable morbidity and mortality. The limited efficacy of available therapeutic strategies stresses the need for development and study of new molecules against influenza virus (IFV). Patchouli alcohol (PA), the major chemical constituent of Pogostemonis Herba, was previously found to strongly inhibit influenza H1N1 replication in vitro. In the present study, the in vivo anti-IFV effect of PA was investigated. In a mouse model infected with lethal levels of FM1, oral administration of PA (20 mg/kg to 80 mg/kg) for 7 d post IFV infection significantly increased the survival rate and survival time. For IFV infection at nonlethal levels, the quantity of IFV in the lungs 5 d after infection was significantly reduced after PA (20 mg/kg to 80 mg/kg) administration. Anti-IFV IgA, IgM, and IgG titers in serum on day 6 were significantly higher in the PA-treated group than the IFV-control group. Anti-IFV immune response augmentation was further confirmed by the elevated production of CD3+, CD4+, and CD8+ T cell levels in blood. Furthermore, the levels of inflammatory cytokines, including TNF-alpha, IL-10 and IFN-gamma in serum of mice, were regulated. Lung inflammation was reduced significantly after PA administration, and the effect may be mediated, at least in part, by regulating the lung levels of inflammatory cytokines. Thus, oral administration of PA appears to be able to augment protection against IFV infection in mice via enhancement of host immune responses, and attenuation of systemic and pulmonary inflammatory responses.


Assuntos
Alphainfluenzavirus/imunologia , Medicamentos de Ervas Chinesas/uso terapêutico , Infecções por Orthomyxoviridae/prevenção & controle , Fitoterapia , Sesquiterpenos/uso terapêutico , Administração Oral , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Citocinas/sangue , Feminino , Alphainfluenzavirus/genética , Alphainfluenzavirus/patogenicidade , Lamiaceae , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , RNA Viral/análise
14.
Molecules ; 16(9): 8076-82, 2011 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-21934645

RESUMO

Two new 13,28-epoxy oleanane-type triterpenoids, namely heterogenoside E and F, were isolated from Lysimachia heterogenea Klatt, together with the eight known compounds: palmitic acid, ß-stigmasterol, kaempferol, quercetin, hyperin, isorhamnetin, isorhamnetin-3-O-galactopyranoside and anagallisin C. Heterogenoside F possesses acetoxyl groups at the unusual C-21 and C-22 positions of its oleanane skeleton. The cytotoxic activities of anagallisin C, heterogenoside E and F were weak.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Primulaceae/química , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triterpenos/química , Triterpenos/farmacologia
15.
Bioorg Med Chem Lett ; 18(16): 4647-50, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18644720

RESUMO

A series of alisol A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. The preliminary investigation demonstrates that simple modifications of the parent structure of alisol A can produce a number of potentially important derivatives against HBV. The most active anti-HBV compound 6a showed high activities against the secretion of HBV surface antigen (IC(50)=0.024 mM), HBV e antigen (IC(50)=0.028 mM) and remarkable selective indices (SI(HBsAg)>108, SI(HBeAg)>93), which was selected for further evaluation as a novel HBV inhibitor.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Química Farmacêutica/métodos , Colestenonas/síntese química , Vírus da Hepatite B/metabolismo , Hepatite B/tratamento farmacológico , Antígenos Virais/química , Colestenonas/química , DNA Viral , Desenho de Fármacos , Antígenos da Hepatite B/imunologia , Humanos , Radical Hidroxila , Concentração Inibidora 50 , Modelos Químicos , Replicação Viral/efeitos dos fármacos
16.
Bioorg Med Chem Lett ; 18(13): 3787-9, 2008 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-18524583

RESUMO

A series of 4-aryl-6-chloro-quinolin-2-ones and 5-aryl-7-chloro-1,4-benzodiazepine were synthesized and assayed for their in vitro anti-hepatitis B virus activities and cytotoxicities for the first time. Some of the tested compounds were active against HBsAg and HBeAg secretion in Hep G2.2.15 cells. Compound 5c showed IC(50) of 0.074 and 0.449 mM on HBsAg and HBeAg secretions, respectively, which were 10 times higher than that of its analog 4c and led to better selective index (SI) values (SI=23.2 and 3.4, respectively).


Assuntos
Antivirais/síntese química , Benzodiazepinas/química , Química Farmacêutica/métodos , Cloro/química , Vírus da Hepatite B/metabolismo , Hepatite B/prevenção & controle , Antivirais/química , Benzodiazepinas/síntese química , Linhagem Celular Tumoral , Desenho de Fármacos , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B/química , Humanos , Técnicas In Vitro , Concentração Inibidora 50 , Modelos Químicos , Conformação Molecular , Estrutura Molecular , Relação Estrutura-Atividade
17.
J Nat Prod ; 71(5): 760-3, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18396905

RESUMO

Four new hasubanane-type alkaloids, periglaucines A-D (1-4), and three known alkaloids, norruffscine (5), (-)-8-oxotetrahydropalmatine (6), and (-)-8-oxocanadine (7), were isolated from the aerial parts of Pericampylus glaucus. Their structures were elucidated on the basis of extensive NMR and EIMS data, and that of periglaucine A (1) was confirmed by single-crystal X-ray diffraction. Alkaloids 1-4 inhibited hepatitis B virus (HBV) surface antigen (HBsAg) secretion in Hep G2.2.15 cells. (-)-8-Oxotetrahydropalmatine (6) possessed a high selectivity index (SI = 22.4) for HBsAg secretion of the Hep G2.2.15 cell line with an IC(50) value of 0.14 mM. Norruffscine (5) and (-)-8-oxotetrahydropalmatine (6) exhibited inhibitory activity against human immunodeficiency virus (HIV-1) with EC(50) values of 10.9 and 14.1 microM in C8166 cells (SI = 45.7 and 18.8), respectively.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Antivirais/isolamento & purificação , Antivirais/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Menispermaceae/química , Plantas Medicinais/química , Alcaloides/química , Fármacos Anti-HIV/química , Antivirais/química , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , HIV-1/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Conformação Molecular , Estrutura Molecular
18.
Zhong Yao Cai ; 31(9): 1388-90, 2008 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19180966

RESUMO

OBJECTIVE: To observe the cytopathogenic inhibitory effect of resveratrol on vary respiroviruses and explore the mechanism of resveratrol against viruses. METHODS: MDCK, A549, HEp-2 cell and MRC-5 were infected with Influenza virus type A FM1 strain, rhinovirus type R14, RS virus, AD virus type 7 separately, and the antiviral activity of resveratrol were observed. RESULTS: Resveratrol significantly inhibited cytopathogenic effect of AD virus type 7 at the concentration 120 microg/ml. No significant cytopathogenic effect of Resveratrol inhibiting Influenza virus type A FM1 strain, Rhinovirus type R14, RS virus on separate cells was observed. CONCLUSION: It is concluded that resveratrol is effective on inhibiting AD virus type 7 in vitro, however, its mechanism is needed for further study.


Assuntos
Adenovírus Humanos/efeitos dos fármacos , Antivirais/farmacologia , Plantas Medicinais/química , Vírus de RNA/efeitos dos fármacos , Alcaloides de Veratrum/farmacologia , Linhagem Celular Tumoral , Efeito Citopatogênico Viral , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Vírus da Influenza A/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Rhinovirus/efeitos dos fármacos
19.
Bioorg Med Chem Lett ; 17(19): 5316-20, 2007 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-17723297

RESUMO

Two new alkaloids, hypserpanines A and B (1, 11), together with eleven known compounds, phenolbetain (2), acutumine (3), acutumidine (4), dechloroacutumine (5), dauricumine (6), dauricumidine (7), pronuciferine (8), glaziovine (9), S-reticuline (10), magnoflorine (12) and laurifoline(13), were isolated from Hypserpa nitida Miers. (Menispermaceae) and chemically elucidated through spectral analyses. All the isolated alkaloids were evaluated for their anti-HBV activities in vitro using the HBV transfected Hep G2.2.15 cell line. The most active compound, dauricumidine (7), exhibited an IC(50) value of 0.450 mM (SI=4.13) on hepatitis B virus (HBV) surface antigen (HBsAg) secretion of the Hep G2.2.15 cell line.


Assuntos
Alcaloides/farmacologia , Antivirais/farmacologia , Dietilaminas/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Menispermaceae/química , Compostos de Espiro/farmacologia , Alcaloides/química , Antivirais/química , Linhagem Celular , Cromatografia por Troca Iônica , Dietilaminas/química , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Compostos Heterocíclicos com 3 Anéis/química , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Espectrometria de Massas por Ionização por Electrospray , Compostos de Espiro/química
20.
Zhong Yao Cai ; 30(3): 342-5, 2007 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-17634047

RESUMO

OBJECTIVE: To prepare the Zedoary Turmeric Oil spray and investigate its anti-virus effects. METHODS: According to the Zedoray Turmeric Oil and Glucose Injection, the new dosage of Zedoray Turmeric Oil spray was studied. Antiviral effects of the Zedoary Turmeric Oil spray in the respiratory tract were studied both in vivo and in vitro. RESULTS: The quality of the Zedoary Turmeric Oil spray was controlled. The influenza virus, parainfluenza Virus I, III, RS virus and AD virus 3,7 could be inhibited slightly, but the parainfluenza Virus II could be obviously inhibited by the Zedoary Turmeric Oil spray. CONCLUSION: The Zedoary Turmeric Oil spray's formula is simple, useful and safe.


Assuntos
Antivirais/farmacologia , Curcuma/química , Óleos/química
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