RESUMO
From the aerial parts of Eupatorium fortunei, four thymol derivatives (1-4) were isolated and structurally elucidated by NMR and mass spectroscopic methods. Of which, a new dimeric thymol derivative (1) was characterized and its absolute configuration was established by electronic circular dichroism quantum method. In addition, the 1D and 2D NMR as well as HR-ESI mass spectral data of 2 were provided for the first time. Compounds 2-4 were evaluated for their inhibitory activity against α-glucosidase and acetylcholinesterase enzymes. All tested compounds showed weak inhibition at the concentration range of 1-256 µg/mL in both enzymatic assays.
RESUMO
(±)-Patulinervones A (1) and B (2), two diastereomers of spiro-lignans sharing an unprecedented dimethyl-spiro[furan-2,2'-furo[2,3-b]furan] 5/5/5 tricyclic moiety were isolated from the leaves of Melicope patulinervia (Merr. & Chun) C.C. Huang. Their structures were established by extensive spectroscopic data and electronic circular dichroism (ECD) analyses. The racemates (±)-1 and 2 and their enantiomers exhibited α-glucosidase inhibitory effect with IC50 values range of 10.08 ± 1.24 - 25.58 ± 1.97 µM.
RESUMO
In the course of finding new antifungal natural compounds against plant pathogens, the methanol extract of Desmodium triflorum was investigated phytochemically. From n-butanol-soluble fraction, seven compounds (1-7) were isolated and structurally elucidated. Of which, six compounds belong to flavone 6- or 8-C-glycoside class (1-6). Three major compounds (1-3) exhibited moderate in vitro antifungal activity against Sclerotium rolfsii, Fusarium oxysporum f. sp. cubense, and Phytophthora palmivora. Compound 1 (IC50 = 162.1 µg/mL) was most active against S. rolfsii in a dose-dependent manner. At 300 µg/mL, compounds 1 and 2 significantly inhibited P. palmivora, whereas compound 3 lacked effectiveness. In addition, the nanoemulsion of the methanol extract with a droplet size of 12.2 nm displayed an excellent inhibition against S. rolfsii and P. palmivora compared with the normal extract. The presence of 1 (0.846%) and 2 (0.759%) in the methanol extract may attribute to the antifungal activity of D. triflorum. These results proved the potential of D. triflorum and its C-glycoside flavonoids against phytopathogenic fungi for the first time. Besides, an enhancement in the effectiveness of nanoemulsion containing D. triflorum extract against the fungi was confirmed. The structural characteristics of 1 and 2 could be considered to develop new fungicidal substances in the future.
Assuntos
Fungicidas Industriais , Fusarium , Antifúngicos/farmacologia , Metanol , Fungos , Fungicidas Industriais/química , Extratos Vegetais/químicaRESUMO
(1S,2S,3E,7E,11E)-3,7,11,15-cembratetraen-17,2-olide (LS-1), a marine cembrenolide diterpene, has anticancer activity against colon cancer cells such as HT-29, SNU-C5/5-FU (fluorouracil-resistant SNU-C5) and SNU-C5. However, the action mechanism of LS-1 on SNU-C5 human colon cancer cells has not been fully elucidated. In this study, we investigated whether the anticancer effect of LS-1 could result from apoptosis via the modulation of Wnt/β-catenin and the TGF-β pathways. When treated with the LS-1, we could observe the apoptotic characteristics such as apoptotic bodies and the increase of sub-G1 hypodiploid cell population, increase of Bax level, decrease of Bcl-2 expression, cleavage of procaspase-3 and cleavage of poly (ADP-ribose) polymerase in SNU-C5 cells. Furthermore, the apoptosis induction of SNU-C5 cells upon LS-1 treatment was also accompanied by the down-regulation of Wnt/β-catenin signaling pathway via the decrease of GSK-3β phosphorylation followed by the decrease of β-catenin level. In addition, the LS-1 induced the activation of TGF-β signaling pathway with the decrease of carcinoembryonic antigen which leads to decrease of c-Myc, an oncoprotein. These data suggest that the LS-1 could induce the apoptosis via the down-regulation of Wnt/β-catenin pathway and the activation of TGF-β pathway in SNU-C5 human colon cancer cells. The results support that the LS-1 might have potential for the treatment of human colon cancer.
Assuntos
Humanos , Apoptose , Antígeno Carcinoembrionário , Caspase 3 , Neoplasias do Colo , Neoplasias Colorretais , Regulação para Baixo , Vesículas Extracelulares , FosforilaçãoRESUMO
Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.
Assuntos
Biflavonoides/farmacologia , Cacau/química , Catequina/farmacologia , HIV-1/efeitos dos fármacos , Proantocianidinas/farmacologia , Provírus/efeitos dos fármacos , Ativação Viral/efeitos dos fármacos , Biflavonoides/química , Biflavonoides/isolamento & purificação , Catequina/química , Catequina/isolamento & purificação , Linhagem Celular , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/genética , HIV-1/fisiologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Indóis/farmacologia , Células Jurkat , Sistema de Sinalização das MAP Quinases , Maleimidas/farmacologia , Testes de Sensibilidade Microbiana , Modelos Biológicos , NF-kappa B/metabolismo , Fitoterapia , Plantas Medicinais/química , Proantocianidinas/química , Proantocianidinas/isolamento & purificação , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Provírus/fisiologia , Latência Viral/efeitos dos fármacosRESUMO
In this study, phytochemical investigation on the aerial parts of Bupleurum falcatum resulted in the isolation of fourteen compounds including three quinic acid derivatives (1 - 3), five flavonoids (4 - 8), three monoterpene glycosides (9 - 11), and three saikosaponins (12 - 14). Compound 1 was first isolated from nature and unambiguously determined to be 3-O-feruloyl 5-O-caffeoylquinic acid on the basis of the extensive spectroscopic evidence. Biological testing revealed that saikosaponin A (12) and saikosaponin D (13) showed moderate antiproliferative effects on HL-60 and HepG2 cancer cell lines.
Assuntos
Bupleurum , Linhagem Celular , Flavonoides , Glicosídeos , Ácido QuínicoRESUMO
Panax ginseng is a medicinal herb that is used worldwide. Its medicinal effects are primarily attributable to ginsenosides located in the root, leaf, seed, and flower. The flower buds of Panax ginseng (FBPG) are rich in various bioactive ginsenosides, which exert immunomodulatory and anti-inflammatory activities. The aim of the present study was to assess the effect of 18 ginsenosides isolated from steamed FBPG on the transcriptional activity of NF-kappaB and the expression of tumor necrosis factor-alpha (TNF-alpha)-stimulated target genes in liver-derived cell lines. Noticeably, the ginsenosides Rk3 and Rs4 exerted the strongest activity, inhibiting NF-kappaB in a dose-dependent manner. SF and Rg6 also showed moderately inhibitory effects. Furthermore, these four compounds inhibited the TNF-alpha-induced expression of IL8, CXCL1, iNOS, and ICAM1 genes. Consequently, ginsenosides purified from steamed FBPG have therapeutic potential in TNF-alpha-mediated diseases such as chronic hepatic inflammation.
Assuntos
Linhagem Celular , Cotilédone , Flores , Ginsenosídeos , Inflamação , Interleucina-8 , NF-kappa B , Panax , Plantas Medicinais , Vapor , Fator de Necrose Tumoral alfaRESUMO
Panax ginseng is a medicinal herb that is used worldwide. Its medicinal effects are primarily attributable to ginsenosides located in the root, leaf, seed, and flower. The flower buds of Panax ginseng (FBPG) are rich in various bioactive ginsenosides, which exert immunomodulatory and anti-inflammatory activities. The aim of the present study was to assess the effect of 18 ginsenosides isolated from steamed FBPG on the transcriptional activity of NF-kappaB and the expression of tumor necrosis factor-alpha (TNF-alpha)-stimulated target genes in liver-derived cell lines. Noticeably, the ginsenosides Rk3 and Rs4 exerted the strongest activity, inhibiting NF-kappaB in a dose-dependent manner. SF and Rg6 also showed moderately inhibitory effects. Furthermore, these four compounds inhibited the TNF-alpha-induced expression of IL8, CXCL1, iNOS, and ICAM1 genes. Consequently, ginsenosides purified from steamed FBPG have therapeutic potential in TNF-alpha-mediated diseases such as chronic hepatic inflammation.
Assuntos
Linhagem Celular , Cotilédone , Flores , Ginsenosídeos , Inflamação , Interleucina-8 , NF-kappa B , Panax , Plantas Medicinais , Vapor , Fator de Necrose Tumoral alfaRESUMO
Ten oleanane-type saponins (1-10), including three new compounds, namely bifinosides A-C (1-3), were isolated from the roots of Panax bipinnatifidus SEEM. Their structures were elucidated on the basis of chemical and spectroscopic methods.
Assuntos
Ácido Oleanólico/química , Panax/química , Saponinas/química , Triterpenos/química , Espectroscopia de Ressonância Magnética , Conformação Molecular , Raízes de Plantas/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificaçãoRESUMO
One newly (1) and 10 known oleanane-type triterpenoids (2-11) were isolated from the methanol extract of Panax stipuleanatus rhizomes. Based on their spectroscopic data, these compounds were identified as spinasaponin A methyl ester (1), pesudoginsenoside RP(1) methyl ester (2), spinasaponin A 28-O-glucoside (3), pseudoginsenoside RT(1) methyl ester (4), pseudoginsenoside RT(1) (5), stipuleanoside R(2) methyl ester (6), stipuleanoside R(2) (7), araloside A methyl ester (8), 3-O-ß-D-glucopyranosyl (1â3)-ß-D-glucuronopyranoside-28-O-ß-D-glucopyranosyl oleanolic acid methyl ester (9), 3-O-ß-D-xylopyranosyl (1â2)-ß-D-glucopyranosyl-28-O-ß-D-glucopyranosyl oleanolic acid (10), and chikusetsusaponin IVa (11). When the cytotoxic activities of the isolated compounds were evaluated, compound 1 exhibited significant cytotoxic activity with IC(50) values of 4.44 and 0.63 µM against HL-60 (leukemia) and HCT-116 (colon cancer) cell lines, respectively. Compound 2 showed potent cytotoxicity with an IC(50) of 6.50 µM against HCT-116, whereas it was less cytotoxic against HL-60 (IC(50)=41.45 µM). After HL-60 and HCT-116 were treated with compounds 1 and 2, increased production of apoptotic bodies was observed. Furthermore, compounds 1 and 2 in HCT-116 cells activated intrinsic and extrinsic apoptosis pathways by upregulating DR-5 and Bax, downregulating Bcl-2, activating caspase-9, and cleaving poly-ADP-ribose polymerase (PARP). We also observed the activation of ERK1/2 MAPK by both compounds in the HCT-116 cells. Together, compounds 1 and 2 might induce intrinsic and extrinsic apoptosis pathways through the activation of the ERK1/2 MAPK pathway in HCT-116 colon cancer cells. Structure-activity relationship analysis indicated that a carboxyl group at position-28 is potentially responsible for the cytotoxic effects.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Ácido Oleanólico/análogos & derivados , Panax/química , Triterpenos/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Células HCT116 , Células HL-60 , Humanos , Concentração Inibidora 50 , Camundongos , Ácido Oleanólico/química , Extratos Vegetais , Transdução de Sinais/efeitos dos fármacos , Análise Espectral , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Chromatographic separation resulted in the identification of one new squalene derivative, named lobophytene (1), three cembranoid diterpenes (2-4), and two sterols (5 and 6) from the Vietnamese marine soft coral Lobophytum sp. Their structures were identified on the basis of extensive spectroscopic data and comparison of those with reported data. Compounds 1 and 2 showed significant cytotoxic activities against lung (A549) and colon (HT-29) cell lines with IC(50) values of 8.2 and 5.6 microM for 1; 5.1 and 1.8 microM for 2, respectively.
Assuntos
Antozoários/química , Antineoplásicos , Animais , Antozoários/crescimento & desenvolvimento , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier , VietnãRESUMO
The chemical study of Momordica charantia fruits led to the isolation of three new cucurbitane triterpene glycosides, momordicosides U, V, and W (1-3). The structures of these compounds were determined to be (19R, 23R)-5beta, 19-epoxy-19-methoxycucurbita-6,24-diene-3beta, 23-diol 3-O-beta-D-allopyranoside (1), (23R)-5beta, 19-epoxycucurbita-6,24-diene-3beta, 23-diol 3-O-beta-D-allopyranoside (2), and (19R)-5beta, 19-epoxy-19,25-dihydroxycucurbita-6,23(E)-diene-3beta-ol 3-O-beta-D-glucopyranoside (3), by chemical and spectroscopic methods.
Assuntos
Glicosídeos/isolamento & purificação , Momordica charantia/química , Triterpenos/isolamento & purificação , Configuração de Carboidratos , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Triterpenos/químicaRESUMO
Previous studies have reported that increased high-sensitive C-reactive protein (hs-CRP) levels are associated with an inflammatory state. This study investigated the association among hs-CRP, substrate properties, and long-term clinical outcomes after catheter ablation of atrial fibrillation (AF). A total of 137 patients with AF (54 +/- 13 years) who underwent mapping and catheter ablation were included. The hs-CRP was measured before the first ablation procedure. The substrate properties (initiating triggers, biatrial mean voltage, and high-frequency sites) of the 2 atria and long-term outcome were investigated in patients in the low hs-CRP group (<75%, 2.92 mg/L) and high hs-CRP group (>75%, 2.92 mg/L). Patients with a higher hs-CRP were associated with an increased number of identified nonpulmonary vein ectopies (34.4% vs 17%, p = 0.034), lower mean left atrial (LA) voltage (1.72 +/- 0.73 vs 1.92 +/- 0.72 Hz, p = 0.045), and higher-frequency sites in the left atrium (71% vs 37%, p = 0.027). After a median follow-up period of 15 months, the single-procedure success rate (72% vs 53%, p = 0.008) and final success rate after multiple procedures (94% vs 81%, p = 0.02) were higher in the low hs-CRP group. In a multivariable regression model adjusted for other potential covariates, hs-CRP level (p = 0.021) and LA diameter (p = 0.032) were independent predictors of recurrence. In conclusion, baseline CRP levels before the first AF ablation procedure had an independent prognostic value in predicting long-term recurrence. Patients with a high hs-CRP level were associated with an abnormal LA substrate and high incidence of nonpulmonary vein AF sources.
Assuntos
Fibrilação Atrial/sangue , Fibrilação Atrial/cirurgia , Proteína C-Reativa/metabolismo , Ablação por Cateter , Adulto , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Biomarcadores/sangue , Eletrocardiografia , Feminino , Seguimentos , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Prevenção Secundária , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Three new lupane triterpene glycosides, acankoreosides J-L ( 1- 3), were isolated from the leaves of Acanthopanax koreanum. Based on the spectroscopic data, the chemical structures were determined as 3 alpha-hydroxy-20-oxo-30-norlupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 1); 3 alpha,20,29-trihydroxylupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 2); and (20S)-3 alpha-hydroxy-29,29-dimethoxylupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 3). Compounds 1- 3 were evaluated for their cytotoxicity and showed moderate activity against four cell lines, A549 (lung), HL-60 (leukemia), MCF-7 (breast), and U937 (leukemia), with IC (50) values of 23.4, 36.5, 22.6, and 18.5 microM for 1; 6.8, 18.6, 23.1, and > 100 microM for 2; and 28.9, 21.8, 11.0, and 27.5 microM for 3, respectively.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Eleutherococcus/química , Glicosídeos/uso terapêutico , Neoplasias/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Triterpenos/uso terapêutico , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Six dammarane-type saponins, including three new compounds, floralginsenosides Ta-Tc (1-3), and three known, floralginsenoside Td (4), ginsenoside F(1) (5), and ginsenoside F(5) (6), were isolated from the flower buds of Panax ginseng. Floralginsenoside Td (4) was first isolated from natural plant sources. Their structures were elucidated on the basis of extensive chemical and spectroscopic methods. Compounds 1, 5, and 6 showed cytotoxic activities towards the HL-60 human leukemia cell line with respective IC(50) values of 36.3, 23.2, and 62.4microM. In addition, after the HL-60 cells were treated with these compounds, several apoptosis events, including chromatin condensation and increase in the population of sub-G1 hypodiploid cells, were observed.
Assuntos
Antineoplásicos Fitogênicos/química , Panax/química , Saponinas/química , Triterpenos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Flores/química , Células HL-60 , Humanos , Leucemia/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Conformação Molecular , Saponinas/isolamento & purificação , Saponinas/toxicidade , DamaranosRESUMO
Two new C(29) sterols with a cyclopropane ring at C-25 and C-26, petrosterol-3,6-dione (1) and 5alpha,6alpha-epoxy-petrosterol (2), along with petrosterol (3), were isolated from the Vietnamese marine sponge Ianthella sp. The structures of the new compounds were elucidated by comprehensive spectroscopic analyses. Compounds 1-3 showed cytotoxic activities on A549, HL-60, MCF-7, SK-OV-3, and U937 cancer cell lines with IC(50) in the range of 8.4-22.6 microM, whereas compounds 1-3 exhibited only weak cytotoxic activities on HT-29 cell. After HL-60 cells were treated with the compounds, several apoptosis events like chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. These data supported that the compounds might have potential for leukemia treatment.
Assuntos
Antineoplásicos/química , Poríferos/química , Esteróis/química , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Esteróis/isolamento & purificação , Esteróis/farmacologia , VietnãRESUMO
In our preliminary screening study on the anti-inflammatory activity, eight triterpenes, one sterol, and one chalcone were isolated from the CH(2)Cl(2)-soluble extract of the stems and leaves of Rhus sylvestris Siebold and Zucc (Anacardiaceae). On the basis of their spectroscopic data, these compounds were identified as 10alpha-cucurbitadienol (1), glut-5-en-3-ol (2), beta-amyrin acetate (3), beta-amyrin (4) and lupeol (5), cycloart-24-en-3-one (6), cycloart-25-en-3,24-dione (7), 24-hydroxycycloart-25-en-3-one (8), beta-sitosterol (9), and 2'-hydroxy-4,4'-dimethoxychalcone (10). All of them were isolated from this plant for the first. Furthermore, the compounds in non-cytotoxic concentrations (0-1.0microM) were tested for their ability to block inflammatory cytokine secretion in the presence of LPS in the murine RAW264.7 macrophage cell line. Among the compounds that were tested, compounds 8 and 9 reduced the LPS-induced secretion of IL-6, as well as TNF-alpha, in a mouse RAW264.7 macrophage cell line. Moreover, compounds 2, 3, 7, and 10 specifically diminished only the secretion of TNF-alpha even in 0.01microM concentrations. It is thus suggested that they are potential therapeutics of TNF-alpha-related diseases and conditions, such as transplant rejection, type II diabetes, and atherosclerosis.
Assuntos
Anacardiaceae/química , Anti-Inflamatórios/química , Citocinas/metabolismo , Macrófagos/efeitos dos fármacos , Sitosteroides/química , Triterpenos/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Linhagem Celular , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Camundongos , Folhas de Planta/química , Sitosteroides/isolamento & purificação , Sitosteroides/toxicidade , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Chemical investigation of the stems and leaves of Rhus Sylvestris afforded a new megastigmane glycoside named rhusonoside A ( 1), along with four other known compounds: dihydroquercetin ( 2), astragalin ( 3), hyperin ( 4), and kaempferol-3- O-rutinoside ( 5). Their structures were determined by a combination of spectroscopic analysis and application of the modified Mosher's method. The effect of compounds 1 - 5 on the function of osteoblastic MC3T3-E1 cells was examined by determining cell viability, alkaline phosphatase (ALP) activity, collagen synthesis, and mineralization. Rhusonoside A ( 1) significantly increased the function of osteoblastic MC3T3-E1 cells. Cell viability, ALP activity, and collagen synthesis were increased dose dependently, up to 155.39 %, 171.27 %, and 134.25 %, respectively, of the basal value at 10 muM ( P < 0.05). In addition, 0.1 muM of compound 1 significantly increased mineralization of MC3T3-E1 cells to 142.78 % ( P < 0.05) of the basal value.