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1.
Molecules ; 24(20)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623176

RESUMO

Resistance to anti-cancer drugs is one of the main factors of treatment failure resulting in high morbidity. Among the reasons of resistance, overexpression of efflux pumps leading to multidrug resistance is an important issue that needs to be solved. Taiwanofungus camphoratus has been used as a nutritional supplement to treat various cancers. However, its effects on the resistance to chemotherapeutic agents are still unknown. In this study, we report four new chemical constituents of T. camphoratus isolated from an ether extract: camphoratins K (1) and N (2) and benzocamphorins G (3) and I (4). Furthermore, we evaluated zhankuic acids A-C for their P-glycoprotein (P-gp) inhibitory effects. The results showed that zhankuic acid A was the most potent P-gp inhibitor compound and (at 20 µM) could reverse drug resistance in human cancer cells, restoring an IC50 of 78.5 nM for doxorubicin, of 48.5 nM for paclitaxel, and of 321.5 nM for vincristine, indicating a reversal fold of 48, 38, and 45 times, respectively. This study provides support for the use of T. camphoratus in the further development of cancer therapy.

2.
Nat Prod Res ; : 1-8, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31135226

RESUMO

A new dimeric quaternary protoberberine alkaloid, bispalmatrubine (1), and thirteen known compounds (2-14) were purified from the tubers of Tinospora dentata. Their structures were determined by spectroscopic and spectrometric analytical methods. Among the isolates, eight compounds were examined for their in vitro anti-inflammatory potential and several tested alkaloids displayed moderate inhibitory effects of N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release.

3.
Molecules ; 23(11)2018 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-30373325

RESUMO

Fifty-five compounds were isolated from the fresh stems of Cissus assamica, including 14 benzenoids, 11 triterpenes, nine steroids, five tocopherols, five chlorophylls, four flavonoids, two benzoquinones, two tannins, and three other compounds. Their structures were constructed by 1D and 2D nuclear magnetic resonance (NMR) and mass spectral data, and were also identified by a comparison of their spectral data with those reported in the literature. Among these isolates, 1,2-bis-(5--tocopheryl) ethane (51) was reported for the first time from natural sources. Some purified compounds were examined for their anti-inflammatory and anticancer bioactivities. The results indicated that betulinic acid (16) exhibited strong inhibition of superoxide anion generation with IC50 value of 0.2 ± 0.1 µM, while betulinic acid (16) and pheophytin-a (47) inhibited elastase release with IC50 value of 2.7 ± 0.3 and 5.3 ± 1.0 µM, respectively. In addition, betulinic acid (16) and epi-glut-5(6)-en-ol (18) exhibited potential cytotoxicity to non-small-cell lung carcinoma (NCI-H226) and colon cancer (HCT-116) cell lines with IC50 values in the range of 1.6 to 9.1 µM.

4.
J Pharm Pharmacol ; 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30362134

RESUMO

OBJECTIVES: We investigated the apoptotic activities of acrofolione A (1) and B (2) isolated from Acronychia pedunculata against a human pre-B cell leukaemia cell line (NALM-6) to explore the apoptosis-related signalling molecules targeted by 1 and 2. METHODS: The apoptosis effects of 1 and 2 in NALM-6 cells were investigated by TUNEL staining, annexin V, mitochondria membrane potential and caspase 3/7 activity. We carried out a protein array to explore the signalling molecules involved in apoptosis comprehensively. KEY FINDINGS: Acrofolione A (1) suppressed the growth of NALM-6, K562 and HPB-ALL cells (IC50 16.7 ± 1.9, 17.9 ± 0.3 and 10.1 ± 0.2 µm, respectively) more effectively than acrofolione B (2). Both compounds time-dependently increased the number of NALM-6 cells with abnormal nuclei, and increased the number of annexin V-positive cells and decreased the mitochondrial membrane potential of NALM-6 cells. Acrofolione A (1) markedly elevated caspase 3/7 activity and increased the number of TUNEL-positive cells. Cells treated with either compound showed enhanced expression of cleaved PARP and cleaved caspase 3 and 7, and reduced survivin protein levels. CONCLUSIONS: Acrofolione A (1) and B (2) may be useful in the treatment of various types of leukaemia.

5.
Molecules ; 23(10)2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30301176

RESUMO

Fifty-seven compounds were purified from the stems of Tinospora sinensis, including three new compounds characterized as a lignan (1), a pyrrole alkaloid (11), and a benzenoid (17), respectively. Their structures were elucidated and established by various spectroscopic and spectrometric analytical methods. Among the isolates, fifteen compounds were examined for their anti-inflammatory potential in vitro. The results showed that several compounds displayed moderate inhibition of N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release.

6.
J Food Drug Anal ; 26(3): 1105-1112, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29976403

RESUMO

Lycii Fructus, a solanaceous drug, is widely used as functional foods and in Traditional Chinese Medicine. Samples collected from different regions of China have been found to be not identical in chemical compositions which might affect the biological activities. Although many chromatographic and spectrometric methods have been reported to determine the concentration of betaine and other bioactive amino acids, disturbance resulted from other polar substances with low UV-absorbance and expensive mass facilities reduced the applicability of these techniques. In the present study, the strong cation exchange solid phase extraction procedure incorporated with 1H NMR was successfully developed as a rapid and reliable method that can simultaneously determine betaine, citric acid, threonine, alanine, and proline in various Lycii Fructus. In addition, ERETIC 2 method based on PULCON principle was also applied and compared with conventional method. This feasible and practical method offers a very powerful tool for the quality control of commercial Lycii Fructus from different sources.

7.
Bioorg Med Chem ; 26(14): 3909-3916, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-29908756

RESUMO

The aim of this study was to develop a new drug substance with low toxicity and effective inhibitory activity against cisplatin-resistant oral cancer. The naturally produced pterostilbene was selected as the lead compound for design and synthesis of a series of bis(hydroxymethyl)propionate-based prodrugs. All derivatives were screened for antiproliferative effects against the cisplatin-resistant oral squamous (CAR) cell line and the results indicated that several compounds demonstrated superior inhibitory activity compared with pterostilbene and resveratrol. Among them, the most promising compound, 12, was evaluated for in vivo antitumor activity in a CAR xenograft nude mouse model. Obvious antitumor activity was observed at the lowest oral dose (25 mg/kg/day). Increasing the dose of 12 to 100 mg/kg/day reduced the tumor size to 22% of the control group. Based on these findings as well as the extremely low toxicity seen in the in vivo studies, we believe that compound 12 could serve as a new lead for further development.

8.
Mol Med Rep ; 18(2): 2043-2051, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29916544

RESUMO

3­(5­hydroxymethyl­2­furyl)­1­benzyl­indazole (YC­1) is understood to protect against ischemic stroke, but the molecular basis for its neuroprotection remains to be fully characterized. The present study investigated the influence of YC­1 on inflammatory responses following experimental stroke. Previous studies indicated that nuclear factor (NF)­κB­driven signals serve a pivotal role in mediating inflammatory responses following stroke. Ischemic stroke results in activation of NF­κB to induce gene expression of factors including inducible nitric oxide synthase, interleukin (IL)­1ß, IL­6 and matrix metalloproteinases (MMPs). The results of the present study demonstrated that YC­1 effectively reduced brain infarction and brain edema, and improved blood­brain barrier leakage. Additionally, animals treated with YC­1 exhibited significant reductions in neutrophil and macrophage infiltration into the ischemic brain. Furthermore, YC­1 effectively inhibited NF­κB translocation and binding activity, and the activity and expression of MMP­9 following ischemic stroke. In conclusion, YC­1 may effectively attenuate NF­κB­induced inflammatory damage following cerebral ischemia­reperfusion.


Assuntos
Edema Encefálico/metabolismo , NF-kappa B/metabolismo , Traumatismo por Reperfusão/metabolismo , Acidente Vascular Cerebral/metabolismo , Animais , Edema Encefálico/patologia , Isquemia Encefálica/patologia , Indazóis , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Acidente Vascular Cerebral/patologia
9.
Eur J Pharmacol ; 829: 141-150, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29665367

RESUMO

Targeting cell cycle regulators has been a suggested mechanism for therapeutic cancer strategies. We report here that the bichalcone analog TSWU-CD4 induces S phase arrest of human cancer cells by inhibiting the formation of cyclin A-phospho (p)-cyclin-dependent kinase 2 (CDK2, threonine [Thr] 39) complexes, independent of mutant p53 expression. Ectopic expression of CDK2 (T39E), which mimics phosphorylation of the Thr 39 residue of CDK2, partially rescues the cells from TSWU-CD4-induced S phase arrest, whereas phosphorylation-deficient CDK2 (T39A) expression regulates cell growth with significant S phase arrest and enhances TSWU-CD4-triggered S phase arrest. Decreased histone deacetylase 3 (HDAC3) expression after TSWU-CD4 treatment was demonstrated, and TSWU-CD4 induced S phase arrest and inhibitory effects on cyclin A expression and CDK2 Thr 39 phosphorylation, while cyclin A-p-CDK2 (Thr 39) complex formation was suppressed by ectopic wild-type HDAC3 expression. The co-transfection of CDK2 (T39E) along with HDAC3 completely restored cyclin A expression, Thr 39-phosphorylated CDK2, cyclin A-p-CDK2 (Thr 39) complex formation, and the S phase population to normal levels. Protein kinase B (Akt) inactivation was required for TSWU-CD4-induced S phase cell cycle arrest, because constitutively active Akt1 blocks the induction of S phase arrest and the suppression of cyclin A and HDAC3 expression, CDK2 Thr 39 phosphorylation, and cyclin A-p-CDK2 (Thr 39) complex formation by TSWU-CD4. Taken together, our results indicate that TSWU-CD4 induces S phase arrest by inhibiting Akt-mediated HDAC3 expression and CDK2 Thr 39 phosphorylation to suppress the formation of cyclin A-p-CDK2 (Thr 39) complexes.


Assuntos
Chalcona/química , Chalcona/farmacologia , Quinase 2 Dependente de Ciclina/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histona Desacetilases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Quinase 2 Dependente de Ciclina/química , Histona Desacetilases/química , Humanos , Fosforilação/efeitos dos fármacos , Treonina/metabolismo
10.
Mol Med Rep ; 17(5): 6490-6496, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29512783

RESUMO

3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), has been demonstrated to inhibit platelet aggregation, vascular contraction and hypoxia­inducible factor 1 activity in vitro and in vivo. The present study investigated the neuroprotective efficacy of YC­1 in cultured neurons exposed to glutamate­induced excitotoxicity and in an animal model of stroke. In a cortical neuronal culture model, YC­1 demonstrated neurotoxicity at a concentration >100 µM, and YC­1 (10­30 µM) achieved potent cytoprotection against glutamate­induced neuronal damage. Additionally, YC­1 (30 µM) effectively attenuated the increase in intracellular Ca2+ levels. Delayed treatment of YC­1 (30 µM) also protected against glutamate­induced neuronal damage and cell swelling in cultured neurons, though only at 4 h post­treatment. In addition, immediate treatment of YC­1 (30 µM) following the exposure of cortical neurons to glutamate (300 µM) produced a marked reduction in intracellular pH. Delayed treatment of YC­1 (25 mg/kg) protected against ischemic brain damage in vivo, though only when administered at 3 h post­insult. Thus, YC­1 exhibited neuroprotection against glutamate-induced neuronal damage and in mice subjected to transient focal cerebral ischemia. This neuroprotection may be mediated via its ability to limit the glutamate­induced excitotoxicity. However, the neuroprotective therapeutic window of YC­1 is only at 3 h in vivo and 4 h in vitro, which may, at least in part, be attributed to its ability to reduce the intracellular pH in the early phase of ischemic stroke. Although YC­1 provided the potential for clinical therapy, the treatment time point must be carefully evaluated following ischemia.


Assuntos
Isquemia Encefálica , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Ácido Glutâmico/efeitos adversos , Indazóis/farmacologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Citoproteção/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Camundongos , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley
11.
Nat Prod Res ; 32(20): 2392-2397, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29232973

RESUMO

A new tirucallane-type triterpenoid igniarine (1), and four known compounds meshimakobnol A (2), meshimakobnol B (3), ergosterol (4) and ergosterol peroxide (5), were purified from the methanol extracts of the fruiting bodies of Phellinus igniarius (DC. ex Fr.) Quél. The structure of 1 was elucidated using a combination of 1D and 2D NMR techniques and HR-ESI-MS analyses. In addition, the isolated compounds were examined for their cytotoxicity against several tumour cell lines and part of the tested compounds demonstrated weak cytotoxicity.


Assuntos
Antineoplásicos/farmacologia , Basidiomycota/química , Triterpenos/farmacologia , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Ergosterol/análogos & derivados , Ergosterol/isolamento & purificação , Carpóforos/química , Células Hep G2 , Humanos , Células MCF-7 , Estrutura Molecular , Triterpenos/isolamento & purificação , Vietnã
12.
Nat Prod Res ; 32(18): 2127-2132, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28823173

RESUMO

Study of the chemical constituents of the roots of Plumbago zeylanica L. collected in Taiwan led to the isolation and identification of a new naphthoquinone dimer, plumzeylanone (1), along with eight known compounds (2-9). Nine naphthoquinones isolated from this plant were assayed for cell growth inhibition activity using NALM-6 (human B cell precursor leukaemia), A549 (human lung adenocarcinoma), Colo205 (human colorectal adenocarcinoma) and KB (human epidermoid carcinoma). Plumzeylanone (1), a novel plumbagin dimer, suppressed cell proliferation in only NALM-6 cells (IC50 3.98 µM). However, maritinone (9) showed strong inhibition of cell growth in all cell lines tested (0.12 < IC50 < 9.06 µM). This compound appeared to affect the cell cycle.


Assuntos
Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Naftoquinonas/farmacologia , Plumbaginaceae/química , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dimerização , Humanos , Naftoquinonas/química , Naftoquinonas/isolamento & purificação , Raízes de Plantas/química , Taiwan
13.
Molecules ; 22(11)2017 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-29143794

RESUMO

Berberine and the methylenedioxy ring-opening derivatives palmatine and jatrorrhizine are active ingredients in immunomodulatory plants, such as goldenseal. This study aimed to illustrate the effects of protoberberines on aryl hydrocarbon receptor (AhR) activation and cytochrome P450 (CYP) 1 in the estrogen receptor (ER)α(+) MCF-7 breast cancer cells. Among protoberberines at non-cytotoxic concentrations (≤10 µM), berberine had the most potent and statistically significant effects on AhR activation and CYP1A1/1A2/1B1 mRNA induction. The 24-h exposure to 10 µM berberine did not change CYP1A1 mRNA stability, protein level and function. Berberine significantly increased micro RNA (miR)-21-3p by 36% and the transfection of an inhibitor of miR-21-3p restored the induction of CYP1A1 protein with a 50% increase. These findings demonstrate that the ring opening of the methylenedioxyl moiety in berberine decreased AhR activation in MCF-7 cells. While CYP1A1 mRNA was elevated, berberine-induced miR-21-3p suppressed the increase of functional CYP1A1 protein expression.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Berberina/farmacologia , Neoplasias da Mama/metabolismo , Citocromo P-450 CYP1A1/genética , MicroRNAs/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Berberina/análogos & derivados , Berberina/química , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia , Neoplasias da Mama/genética , Citocromo P-450 CYP1A1/metabolismo , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Estrutura Molecular , Receptores de Hidrocarboneto Arílico/genética
14.
Molecules ; 22(9)2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28862688

RESUMO

Investigation of the chemical constituents from the fruits of Citrus medica L. var. sarcodactylis Swingle has led to the characterization of a new sesquiterpene 1 along with thirty-two known compounds. The structure of 1 was established on the basis of 2D NMR spectroscopic and mass spectrometric analyses, and the known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. In addition, most of the isolated compounds were evaluated for the activity assayed by the in vitro inhibition of superoxide anion generation and elastase release by human neutrophils. The results showed that only 6,7-dimethoxycoumarin (5) exhibited significant inhibition of superoxide anion generation, with IC50 value of 3.8 ± 1.4 µM.


Assuntos
Citrus/enzimologia , Cumarínicos/farmacologia , Frutas/enzimologia , Elastase Pancreática/metabolismo , Superóxidos/metabolismo , Adulto , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Humanos , Neutrófilos/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectroscopia de Prótons por Ressonância Magnética , Adulto Jovem
15.
PLoS One ; 12(9): e0185021, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28945763

RESUMO

BACKGROUND: Chemotherapy insensitivity continues to pose significant challenges for treating non-small cell lung cancer (NSCLC). The purposes of this study were to investigate whether 3,6-dimethoxy-1,4,5,8-phenanthrenetetraone (NCKU-21) has potential activity to induce effective toxicological effects in different ethnic NSCLC cell lines, A549 and CL1-5 cells, and to examine its anticancer mechanisms. METHODS: Mitochondrial metabolic activity and the cell-cycle distribution were analyzed using an MTT assay and flow cytometry in NCKU-21-treated cells. NCKU-21-induced cell apoptosis was verified by Annexin V-FITC/propidium iodide (PI) double-staining and measurement of caspase-3 activity. Western blotting and wound-healing assays were applied to respectively evaluate regulation of signaling pathways and cell migration by NCKU-21. Molecular interactions between target proteins and NCKU-21 were predicted and performed by molecular docking. A colorimetric screening assay kit was used to evaluate potential regulation of matrix metalloproteinase-9 (MMP-9) activity by NCKU-21. RESULTS: Results indicated that NCKU-21 markedly induced cytotoxic effects that reduced cell viability via cell apoptosis in tested NSCLC cells. Activation of AMP-activated protein kinase (AMPK) and p53 protein expression also increased in both NSCLC cell lines stimulated with NCKU-21. However, repression of PI3K-AKT activation by NCKU-21 was found in CL1-5 cells but not in A549 cells. In addition, increases in phosphatidylserine externalization and caspase-3 activity also confirmed the apoptotic effect of NCKU-21 in both NSCLC cell lines. Moreover, cell migration and translational levels of the gelatinases, MMP-2 and MMP-9, were obviously reduced in both NSCLC cell lines after incubation with NCKU-21. Experimental data obtained from molecular docking suggested that NCKU-21 can bind to the catalytic pocket of MMP-9. However, the in vitro enzyme activity assay indicated that NCKU-21 has the potential to increase MMP-9 activity. CONCLUSIONS: Our results suggest that NCKU-21 can effectively reduce cell migration and induce apoptosis in A549 and CL1-5 cells, the toxicological effects of which may be partly modulated through PI3K-AKT inhibition, AMPK activation, an increase in the p53 protein, and gelatinase inhibition.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Fenantrenos/uso terapêutico , Células A549 , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Caspase 3/metabolismo , Linhagem Celular Tumoral , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Mitocôndrias/efeitos dos fármacos , Simulação de Acoplamento Molecular
16.
Molecules ; 22(6)2017 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-28598384

RESUMO

A series of chromatographic separations performed on the ethanol extracts of the peels of Citrus grandis has led to the characterization of forty compounds, including seventeen coumarins, eight flavonoids, two triterpenoids, four benzenoids, two steroids, one lignan, one amide, and five other compounds, respectively. The chemical structures of the purified constituents were identified on the basis of spectroscopic elucidation, including 1D- and 2D-NMR, UV, IR, and mass spectrometric analysis. Most of the isolated compounds were examined for their inhibition of superoxide anion generation and elastase release by human neutrophils. Among the isolates, isomeranzin (3), 17,18-dihydroxybergamottin (12), epoxybergamottin (13), rhoifolin (19), vitexicarpin (22) and 4-hydroxybenzaldehyde (29) displayed the most significant inhibition of superoxide anion generation and elastase release with IC50 values ranged from 0.54 to 7.57 µM, and 0.43 to 4.33 µM, respectively. In addition, 7-hydroxy-8-(2'-hydroxy-3'-methylbut-3'-enyl)coumarin (8) and 17,18-dihydroxybergamottin (12) also exhibited the protection of neurons against A-mediated neurotoxicity at 50 µM.


Assuntos
Anti-Inflamatórios/farmacologia , Citrus/química , Cumarínicos/farmacologia , Flavonoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Triterpenos/farmacologia , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/toxicidade , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Morte Celular/efeitos dos fármacos , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Misturas Complexas/química , Cumarínicos/química , Cumarínicos/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Frutas/química , Humanos , Elastase de Leucócito/antagonistas & inibidores , Elastase de Leucócito/metabolismo , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/toxicidade , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , Superóxidos/antagonistas & inibidores , Superóxidos/química , Triterpenos/química , Triterpenos/isolamento & purificação , Resíduos
17.
J Nat Prod ; 80(4): 783-789, 2017 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-28398735

RESUMO

Four A-type flavan-3-ol-dihydroretrochalcone dimers, dragonins A-D (1-4), were characterized from the traditional Chinese medicine Sanguis Draconis. The structures of 1-4 were elucidated by spectroscopic and spectrometric analyses. Compounds 1 and 2 exhibited significant inhibition of fMLP/CB-induced superoxide anion and elastase. The signaling pathways accounting for the inhibitory effects of compound 2 were also elucidated. These purified A-type flavan-3-ol-dihydroretrochalcones are new potential leads for the development of anti-inflammatory drugs.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Chalconas/isolamento & purificação , Chalconas/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Resinas Vegetais/química , Anti-Inflamatórios/química , Chalconas/química , Flavonoides/química , Humanos , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Ressonância Magnética Nuclear Biomolecular , Elastase Pancreática/antagonistas & inibidores , Superóxidos/antagonistas & inibidores
18.
Bioorg Med Chem Lett ; 27(7): 1547-1550, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28256373

RESUMO

Twenty-one chalcones were prepared via aldol condensation and subsequent reduction of these compound led to the corresponding dihydrochalcone and 1,3-diphenylpropane derivatives. The synthetic products were examined for their effects on NO inhibition in LPS-activated mouse peritoneal macrophages. Among the tested compounds, a 1,3-diarylpropane analog, 2-(3-(3,4-dimethoxyphenyl)propyl)-5-methoxyphenol (3p), displayed the most significant inhibitory effects against NO production. To investigate the mechanism of action, the effects of 3p on iNOS and COX-2 protein expression were studied by immunoblot. The results concluded that 3p is capable of inhibiting iNOS expression in LPS-induced RAW264.7 cells via attenuation of NF-κB signaling by ERK, p38, and JNK.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Chalconas/farmacologia , Fenóis/farmacologia , Propano/análogos & derivados , Propano/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Linhagem Celular , Chalconas/síntese química , Ciclo-Oxigenase 2/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fenóis/síntese química , Fosforilação , Propano/síntese química , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
J Nat Prod ; 80(4): 1055-1064, 2017 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-28218000

RESUMO

Fifty compounds were isolated from the fruits of Forsythia suspensa, including 13 new compounds characterized as eight new diterpenoids (1-8), three new lignans (9-11), a new iridoid (12), and a new triterpenoid (13). Their structures were established on the basis of spectroscopic and spectrometric analysis. Most of the isolated compounds were examined for their anti-inflammatory activity in vitro. The results showed that several compounds displayed significant inhibition of fMLP/CB-induced superoxide anion generation and elastase release, with IC50 values ranging from 0.6 ± 0.1 to 8.6 ± 0.8 µg/mL and from 0.8 ± 0.3 to 7.3 ± 1.1 µg/mL, respectively.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Forsythia/química , Frutas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Anti-Inflamatórios/química , Diterpenos/química , Humanos , Lignanas/química , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Elastase Pancreática/efeitos dos fármacos , Elastase Pancreática/metabolismo , Superóxidos/metabolismo , Taiwan
20.
Bioorg Med Chem Lett ; 27(2): 309-313, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27908762

RESUMO

Two new pyranoflavonoids, morustralins A (1) and B (2), a new natural benzene derivative, one benzenoid (Z)-1-hydroxy-4-(2-nitroethenyl)benzene (3), and thirty known compounds were isolated and characterized from the root bark of Morus australis. The structures of the new compounds were established from spectroscopic and spectrometric analyses. Ten isolates (1-10) were examined for inhibitory effects on adenosine diphosphate (ADP)-, arachidonic acid (AA)-, and platelet-aggregating factor (PAF)-induced platelet aggregation. Among the tested compounds, compound 3 displayed the most significant inhibition of ADP- and AA-induced platelet aggregation with IC50 values of 9.76±5.54 and 9.81±2.7µM, respectively. In addition, eight purified compounds (3-10) were examined for inhibition of nitric oxide (NO) production in RAW 264.7 cells and six compounds (3-8) displayed significant inhibitory effects with IC50 values ranging from 2.1±0.3 to 6.3±0.6µM.


Assuntos
Flavonoides/farmacologia , Morus/química , Óxido Nítrico/antagonistas & inibidores , Raízes de Plantas/química , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Animais , Ácido Araquidônico/antagonistas & inibidores , Ácido Araquidônico/farmacologia , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Fator de Ativação de Plaquetas/antagonistas & inibidores , Fator de Ativação de Plaquetas/farmacologia , Células RAW 264.7 , Coelhos , Relação Estrutura-Atividade
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