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Responsive heat resistance (by heat shock protein upregulation) and spontaneous reactive oxygen species (ROS) detoxification have been regarded as the major obstacles for photothermal/photodynamic therapy of cancer. To overcome the thermal resistance and improve ROS susceptibility in breast cancer therapy, Au ion-crosslinked hydrogels including indocyanine green (ICG) and polyphenol are devised. Au ion has been introduced for gel crosslinking (by catechol-Au3+ coordination), cellular glutathione depletion, and O2 production from cellular H2O2. ICG can generate singlet oxygen from O2 (for photodynamic therapy) and induce hyperthermia (for photothermal therapy) under the near-infrared laser exposure. (-)-Epigallocatechin gallate downregulates heat shock protein to overcome heat resistance during hyperthermia and exerts multiple anticancer functions in spite of its ironical antioxidant features. Those molecules are concinnously engaged in the hydrogel structure to offer fast gel transformation, syringe injection, self-restoration, and rheological tuning for augmented photo/chemotherapy of cancer. Intratumoral injection of multifunctional hydrogel efficiently suppressed the growth of primary breast cancer and completely eliminated the residual tumor mass. Proposed hydrogel system can be applied to tumor size reduction prior to surgery of breast cancer and the complete remission after its surgery.
Assuntos
Neoplasias da Mama , Hipertermia Induzida , Fotoquimioterapia , Humanos , Feminino , Espécies Reativas de Oxigênio/metabolismo , Hidrogéis/uso terapêutico , Peróxido de Hidrogênio , Verde de Indocianina/uso terapêutico , Verde de Indocianina/química , Neoplasias da Mama/tratamento farmacológico , Proteínas de Choque TérmicoRESUMO
Alum-crosslinked hyaluronic acid-dopamine (HD) hydrogel containing indocyanine green (ICG) with anti-programmed cell death-1 (PD-1) antibody (Ab) administration was developed for immunophoto therapy of cancer. Alum modulates the rheological characteristics of hydrogel for enabling syringe injection, shear-thinning feature, and slower biodegradation. In addition, alum in HD-based hydrogel provided CD8+ T cell-mediated immune responses for cancer therapy. ICG in the hydrogel under near-infrared (NIR) light exposure may induce hyperthermia and generate singlet oxygen for selective cancer cell killing. HD/alum/ICG hydrogel injection with NIR laser irradiation elevated PD-1 level in CD8+ T cells. Administration of PD-1 Ab aiming at highly expressed PD-1 in T cells may amplify the anticancer efficacies of HD/alum/ICG hydrogel along with NIR laser. HD/alum/ICG hydrogel with NIR light may have both CD8+ T cell-linked immune responses and ICG-related photodynamic/photothermal effects. Additional injection of immune checkpoint inhibitor can ultimately suppress primary and distant tumor growth by combination with those therapeutic actions.
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Three new compounds, (3S)-dihydrobonducellin 8-O-ß-D-glucopyranoside (1), 3',5'-dimethoxy-jezonolid (2), and latisilinoid (3), along with 16 known compounds, were isolated from the twigs of Caesalpinia latisiliqua (Leguminosae). The known compounds were identified as flavonoids, stilbenes, and phenolics as determined by extensive spectroscopic methods, including 1D and 2D NMR. All the isolated compounds were evaluated for their antiviral activity in HRV1B-, CVB3-, and EV71-infected cells. Among the tested compounds, three flavonoids (4-6) and two stilbenes (12 and 14) exhibited significant antiviral activity. This is the first phytochemical investigation of C. latisiliqua twigs.
Assuntos
Antivirais/química , Caesalpinia/química , Plantas/químicaRESUMO
Coxsackievirus B3 (CVB3) is an important human pathogen associated with the development of acute pancreatitis, myocarditis, and type 1 diabetes. Currently, no vaccines or antiviral therapeutics are approved for the prevention and treatment of CVB3 infection. We found that Saururus chinensis Baill extract showed critical antiviral activity against CVB3 infection in vitro. Further, manassantin B inhibited replication of CVB3 and suppressed CVB3 VP1 protein expression in vitro. Additionally, oral administration of manassantin B in mice attenuated CVB3 infection-associated symptoms by reducing systemic production of inflammatory cytokines and chemokines including TNF-α, IL-6, IFN-γ, CCL2, and CXCL-1. We found that the antiviral activity of manassantin B is associated with increased levels of mitochondrial ROS (mROS). Inhibition of mROS generation attenuated the antiviral activity of manassantin B in vitro. Interestingly, we found that manassantin B also induced cytosolic release of mitochondrial DNA based on cytochrome C oxidase DNA levels. We further confirmed that STING and IRF-3 expression and STING and TBK-1 phosphorylation were increased by manassantin B treatment in CVB3-infected cells. Collectively, these results suggest that manassantin B exerts antiviral activity against CVB3 through activation of the STING/TKB-1/IRF3 antiviral pathway and increased production of mROS.
Assuntos
Antivirais/farmacologia , Infecções por Coxsackievirus/metabolismo , Infecções por Coxsackievirus/virologia , Enterovirus Humano B/efeitos dos fármacos , Furanos/farmacologia , Fator Regulador 3 de Interferon/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Chlorocebus aethiops , Infecções por Coxsackievirus/tratamento farmacológico , Citocinas/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Mitocôndrias/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células Vero , Replicação Viral/efeitos dos fármacosRESUMO
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major health problem worldwide. Thus, identification of new and more effective drugs to treat emerging multidrug-resistant TB (MDR-TB) and to reduce the side effects of anti-TB drugs, such as liver toxicity and other detrimental changes, is urgently needed. In this study, to develop a novel candidate drug for effective TB treatment with few side effects in the host, we selected pasakbumin A isolated from Eurycoma longifolia (E. longifolia) Jack, which protected host cells against Mtb infection-induced death. Pasakbumin A significantly inhibited intracellular Mtb growth by inducing the autophagy via the ERK1/2-mediated signaling pathway in Mtb-infected macrophages. We further investigated whether pasakbumin A could be used as a potential adjuvant for TB treatment. Treatment with pasakbumin A and anti-TB drug rifampicin (RMP) potently suppressed intracellular Mtb killing by promoting autophagy as well as TNF-α production via the ERK1/2- and NF-κB-mediated signaling pathways in Mtb-infected cells. Our results suggest that pasakbumin A could be developed as a novel anti-TB drug or host-directed therapeutic (HDT) strategy to protect against host cell death and improve host defense mechanisms against Mtb infection in macrophages.
Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Extratos Vegetais/farmacologia , Quassinas/farmacologia , Animais , Antituberculosos/isolamento & purificação , Autofagia/efeitos dos fármacos , Sinergismo Farmacológico , Eurycoma/química , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Extratos Vegetais/isolamento & purificação , Quassinas/isolamento & purificação , Células RAW 264.7 , Rifampina/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Five undescribed cycloartane-type triterpenoids, which were isolated for the first time from the genus, and a flavonoid glycoside together with 11 known compounds were isolated from the burs of Castanea crenata. The structures were elucidated based on the spectroscopic analysis of 1D and 2D NMR and MS data. All isolated compounds were evaluated for antiviral activities against HRV1B-, CVB3-, and PR8-infected cells. Most kaempferol derivatives showed statistically significant antiviral activities against HRV1B-infected cells. Among the tested compounds, kaempferol-3-O-[2â³,6â³-di-O-Z-p-coumaroyl]-ß-d-glucopyranoside exhibited the most consistent and effective antiviral activities against all infections.
Assuntos
Antivirais/farmacologia , Fagaceae/química , Triterpenos/química , Animais , Antivirais/química , Antivirais/isolamento & purificação , Chlorocebus aethiops , Avaliação Pré-Clínica de Medicamentos/métodos , Enterovirus Humano B/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/farmacologia , Células HeLa , Humanos , Quempferóis/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Células VeroRESUMO
Rhinacanthus nasutus (L.) Kurz (Acanthaceae) is known as traditional medicine for the treatment of fungal and herpes virus infections. A new naphthoquinone racemate, rhinacasutone (1) together with seven known compounds, rhinacanthone (2), rhinacanthins C, D, N, Q, and E (3-7), and heliobuphthalmin (8) were isolated from root of R. nasutus. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-, 2D-NMR and MS data. All the isolated compounds were tested for their antiviral activities against PR8, HRV1B, and CVB3-infected vero cells. Compounds 3-6 exhibited significant antiviral activities with the IC50 value ranging from 0.03 to 23.7 µM in all three infections.
Assuntos
Acanthaceae/química , Antivirais/isolamento & purificação , Naftoquinonas/isolamento & purificação , Animais , Antivirais/química , Antivirais/farmacologia , Benzopiranos/isolamento & purificação , Chlorocebus aethiops , Lignanas/isolamento & purificação , Naftoquinonas/química , Naftoquinonas/farmacologia , Extratos Vegetais/química , Raízes de Plantas/química , Células VeroRESUMO
Lespedeza cuneata (Fabaceae), known as Chinese bushclover, has been used in traditional medicines for the treatment of diseases including diabetes, hematuria, and insomnia. As part of a continuing search for bioactive constituents from Korean medicinal plant sources, phytochemical analysis of the aerial portion of L. cuneata led to the isolation of two new lignan glycosides (1,2) along with three known lignan glycosides (3â»7) and nine known flavonoid glycosides (8â»14). Numerous analysis techniques, including 1D and 2D NMR spectroscopy, CD spectroscopy, HR-MS, and chemical reactions, were utilized for structural elucidation of the new compounds (1,2). The isolated compounds were evaluated for their applicability in medicinal use using cell-based assays. Compounds 1 and 4â»6 exhibited weak cytotoxicity against four human breast cancer cell lines (Bt549, MCF7, MDA-MB-231, and HCC70) (IC50 < 30.0 µM). However, none of the isolated compounds showed significant antiviral activity against PR8, HRV1B, or CVB3. In addition, compound 10 produced fewer lipid droplets in Oil Red O staining of mouse mesenchymal stem cells compared to the untreated negative control without altering the amount of alkaline phosphatase staining.
Assuntos
Flavonoides/química , Glicosídeos/química , Glicosídeos/farmacologia , Lespedeza/química , Lignanas/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Vírus/efeitos dos fármacosRESUMO
Phytochemical investigation of the methanol extract of Vitex limonifolia leaves led to the isolation of three new labdane-type diterpenoids, vitexlimolides A-C (1-3) and eight known compounds, 5,4'-dihydroxy-3,7-dimethoxyflavone (4), vitecetin (5), 5,4'-dihydroxy-7,3'-dimethoxyflavone (6), verrucosin (7), 2α, 3α-dihydroxy-urs-12-en-28-oic acid (8), euscaphlic acid (9), 18,19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11,13(18)-dien-28-oic acid (10), and maslinic acid (11). Their chemical structures were elucidated by physical and chemical methods. All compounds were evaluated for antiviral activities against CVB3, HRV1B, and EV71 viruses. As a result, compounds 4 and 6 showed potent antiviral activity against CVB3 infection with IC50 values of 0.12 ± 0.06 and 1.86 ± 0.18 (µM), respectively.
Assuntos
Antivirais/isolamento & purificação , Diterpenos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Vitex/química , Animais , Antivirais/química , Antivirais/farmacologia , Chlorocebus aethiops , Diterpenos/química , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Enterovirus Humano A/efeitos dos fármacos , Enterovirus Humano B/efeitos dos fármacos , Células HeLa , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Rhinovirus/efeitos dos fármacos , Triterpenos , Células VeroRESUMO
Codonopsis lanceolata (C. lanceolata) is a traditional medicinal plant used for the treatment of certain inflammatory diseases such as asthma, tonsillitis, and pharyngitis. We evaluated whether steamed and fermented C. lanceolata (SFC) extract improves amyloid-ß- (Aß-) induced learning and memory impairment in mice. The Morris water maze and passive avoidance tests were used to evaluate the effect of SFC extract. Moreover, we investigated acetylcholinesterase (AChE) activity and brain-derived neurotrophic factor (BDNF), cyclic AMP response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK) signaling in the hippocampus of mice to determine a possible mechanism for the cognitive-enhancing effect. Saponin compounds in SFC were identified by Ultra Performance Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS). SFC extract ameliorated amyloid-ß-induced memory impairment in the Morris water maze and passive avoidance tests. SFC extract inhibited AChE activity and also significantly increased the level of CREB phosphorylation, BDNF expression, and ERK activation in hippocampal tissue of amyloid-ß-treated mice. Lancemasides A, B, C, D, E, and G and foetidissimoside A compounds present in SFC were determined by UPLC-Q-TOF-MS. These results indicate that SFC extract improves Aß-induced memory deficits and that AChE inhibition and CREB/BDNF/ERK expression is important for the effect of the SFC extract. In addition, lancemaside A specifically may be responsible for efficacious effect of SFC.
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Adjuvant systems based on oil-in-water (o/w) microemulsions (MEs) for vaccination via intranasal administration were prepared and evaluated. A ready-to-use blank ME system composed of mineral oil (oil), Labrasol (surfactant), Tween 80 (cosurfactant), and water was prepared and blended with antigen (Ag) solution prior to use. The o/w ME system developed exhibited nano-size droplets within the tested range of Ag concentrations and dilution factors. The maintenance of primary, secondary, and tertiary structural stability of ovalbumin (OVA) in ME, compared with OVA in solution, was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), and fluorescence intensity measurements, respectively. The uptake efficiency in RAW 264.7 cells, evaluated by flow cytometry, of OVA in the ME group was significantly higher than that of the OVA solution group (p<0.05). In an intranasal immunization study with OVA ME in mice, elevated adjuvant effects in terms of mucosal immunization and Th1-dominant cell-mediated immune responses were identified. Given the convenience of use (simply mixing with Ag solution prior to use) and the adjuvant effects after intranasal immunization, the new o/w ME may be a practical and efficient adjuvant system for intranasal vaccination.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Administração Intranasal , Animais , Linhagem Celular , Coloides/química , Portadores de Fármacos/química , Feminino , Glicerídeos/química , Imunidade nas Mucosas , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Óleo Mineral/química , Ovalbumina/química , Tamanho da Partícula , Polissorbatos/química , Propriedades de Superfície , Tensoativos/química , Água/químicaRESUMO
Several anti-influenza drugs that reduce disease manifestation exist, and although these drugs provide clinical benefits in infected patients, their efficacy is limited by the emergence of drug-resistant influenza viruses. In the current study, we assessed the therapeutic strategy of enhancing the antiviral efficacy of an existing neuraminidase inhibitor, oseltamivir, by coadministering with the leaf extract from Hedera helix L, commonly known as ivy. Ivy extract has anti-inflammatory, antibacterial, antifungal, and antihelminthic properties. In the present study, we investigated its potential antiviral properties against influenza A/PR/8 (PR8) virus in a mouse model with suboptimal oseltamivir that mimics a poor clinical response to antiviral drug treatment. Suboptimal oseltamivir resulted in insufficient protection against PR8 infection. Oral administration of ivy extract with suboptimal oseltamivir increased the antiviral activity of oseltamivir. Ivy extract and its compounds, particularly hedrasaponin F, significantly reduced the cytopathic effect in PR8-infected A549 cells in the presence of oseltamivir. Compared with oseltamivir treatment alone, coadministration of the fraction of ivy extract that contained the highest proportion of hedrasaponin F with oseltamivir decreased pulmonary inflammation in PR8-infected mice. Inflammatory cytokines and chemokines, including tumor necrosis factor-alpha and chemokine (C-C motif) ligand 2, were reduced by treatment with oseltamivir and the fraction of ivy extract. Analysis of inflammatory cell infiltration in the bronchial alveolar of PR8-infected mice revealed that CD11b+Ly6G+ and CD11b+Ly6Cint cells were recruited after virus infection; coadministration of the ivy extract fraction with oseltamivir reduced infiltration of these inflammatory cells. In a model of suboptimal oseltamivir treatment, coadministration of ivy extract fraction that includes hedrasaponin F increased protection against PR8 infection that could be explained by its antiviral and anti-inflammatory activities.
Assuntos
Antivirais/administração & dosagem , Hedera , Vírus da Influenza A/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Oseltamivir/administração & dosagem , Fitoterapia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/metabolismo , Efeito Citopatogênico Viral/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Técnicas In Vitro , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Vírus da Influenza A/patogenicidade , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neuraminidase/antagonistas & inibidores , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Extratos Vegetais/administração & dosagem , Saponinas/administração & dosagemRESUMO
Oral solid formulations based on Angelica gigas Nakai (AGN) and Soluplus were prepared by the hot-melting extrusion (HME) method. AGN was pulverized into coarse and ultrafine particles, and their particle size and morphology were investigated. Ultrafine AGN particles were used in the HME process with high shear to produce AGN-based formulations. In simulated gastrointestinal fluids (pH 1.2 and pH 6.8) and water, significantly higher amounts of the major active components of AGN, decursin (D) and decursinol angelate (DA), were extracted from the HME-processed AGN/Soluplus (F8) group than the AGN EtOH extract (ext) group (p < 0.05). Based on an in vivo pharmacokinetic study in rats, the relative oral bioavailability of decursinol (DOH), a hepatic metabolite of D and DA, in F8-administered mice was 8.75-fold higher than in AGN EtOH ext-treated group. In scopolamine-induced memory-impaired mice, F8 exhibited a more potent cognitive enhancing effect than AGN EtOH ext in both a Morris water maze test and a passive avoidance test. These findings suggest that HME-processed AGN/Soluplus formulation (F8) could be a promising therapeutic candidate for memory impairment.
Assuntos
Angelica/química , Química Farmacêutica , Memória/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Administração Oral , Animais , Disponibilidade Biológica , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Camundongos , Tamanho da Partícula , Extratos Vegetais/administração & dosagem , RatosRESUMO
OBJECTIVES: Coxsackievirus A group 16 strain (CVA16) is one of the predominant causative agents of hand, foot, and mouth disease (HFMD). METHODS: Using a specimen from a male patient with HFMD, we isolated and performed sequencing of the Korean CVA16 strain and compared it with a G10 reference strain. Also, we were investigated the effects of medicinal plant extract on the cytopathic effects (CPE) by CPE reduction assay against Korean CVA16. RESULTS: Phylogenetic analysis showed that the Korean CVA16 isolate belonged to cluster B-1 and was closely related to the strain PM-15765-00 isolated in Malaysia in 2000. The Korean CVA16 isolate showed 73.2% nucleotide identity to the G10 prototype strain and 98.7% nucleotide identity to PM-15765-00. Next, we assessed whether the Korean CVA16 isolate could be used for in vitro screening of antiviral agents to treat HFMD infection. Vero cells infected with the Korean CVA16 isolate showed a cytopathic effect 2 days after the infection, and the treatment of cells with Cornus officinalis, Acer triflorum, Pulsatilla koreana, and Clematis heracleifolia var. davidiana Hemsl extracts exhibited strong antiviral activity against CVA16. CONCLUSION: Collectively, our work provides potential candidates for the development of vaccine and novel drugs to treat the CVA16 strain isolated from a Korean patient.
RESUMO
Human enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are major causative agents of hand, foot, and mouth disease (HFMD) especially in infants and children under 5 years of age. Despite recent outbreaks of HFMD, there are no approved therapeutics against EV71 and CA16 infection. Moreover, in a small percentage of cases, the disease progression can lead to serious complications of the central nervous system. In this study, we investigated the antiviral effect of corilagin and Phyllanthus urinaria extract, which contains corilagin as a major component, on EV71 and CA16 infection in vitro. Our results indicate that corilagin reduces the cytotoxicity induced by EV71 or CA16 on Vero cells with and IC50 value of 5.6 and 32.33 µg/mL, respectively. We confirmed the presence of corilagin in EtOAc and BuOH fractions from P. urinaria extract and this correlated with antiviral activity of the fractions against EV71 or CA16. Future studies will be required to confirm the antiviral activity of corilagin and P. urinaria extract in vivo. Challenging a model with a lethal dose of viral infection will be required to test this. Collectively, our work provides potential candidates for the development of novel drugs to treat HFMD.
Assuntos
Antivirais/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Phyllanthus/química , Extratos Vegetais/farmacologia , Animais , Antivirais/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Efeito Citopatogênico Viral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Enterovirus Humano A/patogenicidade , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Epiteliais/virologia , Glucosídeos/isolamento & purificação , Taninos Hidrolisáveis/isolamento & purificação , Componentes Aéreos da Planta/química , Extratos Vegetais/isolamento & purificação , Células VeroRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment. Codonopsis lanceolata (C. lanceolata) has been employed clinically for lung inflammatory diseases such as asthma, tonsillitis, and pharyngitis. The present study was undertaken to evaluate the effect of fermented C. lanceolata (300, 500, and 800 mg/kg) on learning and memory impairment induced by scopolamine by using the Morris water maze and passive avoidance tests. To elucidate possible mechanism of cognitive-enhancing activity, we measured acetylcholinesterase (AchE) activity, brain-derived neurotrophic factor (BDNF), and cyclic AMP response element-binding protein (CREB) expression in the brain of mice. Administration of fermented C. lanceolata (800 mg/kg) led to reduced scopolamine-induced memory impairment in the Morris water maze and passive avoidance tests. Accordingly, the administration of fermented C. lanceolata inhibited AchE activity. Interestingly, the level of CREB phosphorylation and BDNF expression in hippocampal tissue of scopolamine-treated mice was significantly increased by the administration of fermented C. lanceolata. These results indicate that fermented C. lanceolata can ameliorate scopolamine-induced memory deficits in mouse and may be an alternative agent for the treatment of AD.
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Using a combination of chromatographic methods, one new flavonol glycoside, myricetin 3,7-di-O-alpha-L-rhamnopyranoside (1), and nine known compounds myricitrin (2), quercetin 3,7-di-O-alpha-L-rhamnopyranoside (3), quercitrin (4), desmanthin-l (5), myricetin 3-O-(3"-O-galloyl)-alpha-L-rhamnopyranoside (6), (+)-catechin (7), benzyl O-1-D-glucopyranoside (8), 2-phenylethyl O-beta-D-glucopyranoside (9), and corilagin (10) were isolated from the leaves of Ardisia splendens Pit. Based on an in vitro test against Coxsackie viruses A16 by SRB assay, only compounds 2, 5, and 10 exhibited activity against Coxsackie viruses A16 with IC50 values of 40.1, 32.2, and 30.5 microM, respectively. This result suggested that compounds 2, 5, and 10 might be potential agents for treating hand, foot and mouth diseases.
Assuntos
Antivirais/isolamento & purificação , Ardisia/química , Enterovirus/efeitos dos fármacos , Antivirais/química , Antivirais/farmacologia , Espectroscopia de Ressonância Magnética , Folhas de Planta/químicaRESUMO
Codonopsis lanceolata has been used as an herbal medicine for several lung inflammatory diseases, such as asthma, tonsillitis, and pharyngitis. Previously, we showed the neuroprotective effect of steamed and fermented C. lanceolata (SFC) in vitro and in vivo. In the current study, the treatment of HT22 cells with SFC decreased glutamate-induced cell death, suggesting that SFC protected HT22 cells from glutamate-induced cytotoxicity. Based on these, we sought to elucidate the mechanisms of the neuro-protective effect of SFC by measuring the oxidative stress parameters and the expression of Bax and caspase-3 in HT22 cells. SFC reduced contents of ROS, Ca(2+) and NO. Moreover, SFC restored contents of glutathione and glutathione reductase as well as inhibited Bax and caspase-3 activity in HT22 cells. These results indicate that steamed and fermented C. lanceolata (SFC) extract protected HT22 cells by anti-oxidative effect and inhibition of the expression of Bax and caspase-3.
RESUMO
One new flavonol glycoside, 4'-O-methylmyricitrin 3'-O-beta-D-glucopyranoside (1), one new sesquiterpene, reynoudiol (11), as well as the 12 known compounds (2-10, 12-14) quercetin 3-O-methyl ether (2), quercitrin (3), isorhamnetin 3-alpha-L-rhamnopyranoside (4), tamarixetin 3-alpha-L-rhamnopyranoside (5), myricitrin (6), 4'-O-methylmyricitrin (7), isorhamnetin 3-O-beta-D-xylopyranosyl (1-2)-O-beta- D-glucopyranoside (8), isorhamnetin 3-O-beta- D-apiofuranosyl(1-2)-O-beta- D-glucopyranoside (9), (+)-catechin (10), 7-drimene-3,11,12-triol (12), clovane-2 beta,9 alpha-diol (13), and a-cadinol (14), were isolated from the methanol extract of Reynoutria japonica roots. Based on in vitro screening of the anti-influenza activity of the isolated compounds, reynoudiol showed significantly higher activity than that of oseltamivir phosphate at the same concentration, and did not induce any detectable cytopathic effect in MDCK cells. The CC50 of reynoudiol was above 50 micro M and could inhibit influenza virus infection with an IC50 of 0.29 +/- 0.01 microM. The therapeutic index (TI) of reynoudiol against influenza infection was 172.4, and thus, this compound can be potentially used to treat oseltamivir-resistant influenza virus infection.
Assuntos
Antivirais/isolamento & purificação , Polygonaceae/química , Sesquiterpenos/isolamento & purificação , Animais , Cães , Vírus da Influenza A/efeitos dos fármacos , Células Madin Darby de Rim Canino , Testes de Sensibilidade Microbiana , Oseltamivir , Raízes de Plantas/química , Plantas Medicinais/química , Sesquiterpenos/farmacologia , Testes de ToxicidadeRESUMO
DNA-based vaccines generate potent cellular immunity as well as humoral immunity. It seems evident that cytokines play a crucial role in generation of effector T cell subsets and in determining the magnitude of the response by DNA vaccines. In this study, we compared the effects of several TH1 cytokine genes as adjuvant in DNA vaccination using mycobacterial Hsp65 as a model antigen. Our results demonstrated that although the overall immune response to Hsp65 was enhanced by co-injection of Hsp65 DNA with cytokine genes, each cytokine gene was shown to affect different immune response elements. Co-injection of Hsp65 DNA with IL-12 or GM-CSF led to an increase in IFN-gamma production and represented potent protections against Mycobacterium tuberculosis challenge, while that with Eta-1, IL-12 or IL-18 gene led to an elevated IgG2a/IgG1 ratio. Interestingly, co-administration of Flt3L gene was shown to enhance the Ag-specific CTL response. These results show that the direction and magnitude of immune response in DNA vaccination against Hsp65 of M. tuberculosis could be modulated in different ways by co-injection of an appropriate cytokine gene as adjuvant.