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1.
Org Lett ; 22(9): 3449-3453, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32293190

RESUMO

Two naphthoquinone-derived heterodimers with unprecedented carbon skeletons, eleucanainones A (1) and B (2), were isolated from the bulbs of Eleutherine americana. Their structures were elucidated by comprehensive spectroscopic methods. The structures of 1 and 2 were determined to be the first examples of dibenzofuran- and naphthalenone-containing naphthoquinone dimers. Compound 1 exhibited significant anti-MRSA activity in vitro with minimum inhibitory concentration (MIC) values of 0.78 µg/mL by downregulation of basal expression of agrA, cidA, icaA and sarA in methicillin-resistant S. aureus (MRSA).

2.
Pediatr Cardiol ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32006083

RESUMO

Transcatheter closure of large atrial septal defects (ASDs) remains controversial. The aim of this study was to evaluate the feasibility and safety of transthoracic echocardiography (TTE)-guided transcatheter closure of large ASDs. Patients with large secundum ASDs (≥ 30 mm) who underwent device closure were retrospectively reviewed. TTE was performed to guide ASD occluder positioning and assess the immediate and long-term outcomes. A total of 60 patients (median age 43.5 years, range 15-78 years) were enrolled in the study. The median ASD size was 35 mm (range 30-42 mm). Mild to moderate pulmonary hypertension was observed in 36 patients (60%). Thirty-one patients (51.7%) had one short rim, and 18 patients (30.0%) had two deficient rims. Placement of the device was successful in 57 patients (95%), and the median device size was 42 mm (range 40-50 mm). Dislodgement of the device occurred in three patients with two deficient rims: a larger device was redeployed in one case, and two patients required surgical repair. During a median follow-up of 37 months (range 6-83 months), no residual shunts, erosion, or embolization were noted, and pulmonary hypertension resolved in 75% of the patients. Thus t vast majority (95%) of large ASDs can be successfully closed percutaneously using the Chinese-made Shanghai Shape Memory Alloy (SHSMA) occluder under TTE guidance. Long-term follow-up showed that transcatheter closure could become a safe and effective alternative to surgery in select large ASDs.

3.
Aging (Albany NY) ; 12(2): 1704-1724, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31986489

RESUMO

Atherosclerosis-related cardiovascular disease is still the predominant cause of death worldwide. Araloside C (AsC), a natural saponin, exerts extensive anti-inflammatory properties. In this study, we explored the protective effects and mechanism of AsC on macrophage polarization in atherosclerosis in vivo and in vitro. Using a high-fat diet (HFD)-fed ApoE-/- mouse model and RAW264.7 macrophages exposed to ox-LDL, AsC was evaluated for its effects on polarization and autophagy. AsC significantly reduced the plaque area in atherosclerotic mice and lipid accumulation in ox-LDL-treated macrophages, promoted M2 phenotype macrophage polarization, increased the number of autophagosomes and modulated the expression of autophagy-related proteins. Moreover, the autophagy inhibitor 3-methyladenine and BECN1 siRNA obviously abolished the antiatherosclerotic and M2 macrophage polarization effects of AsC. Mechanistically, AsC targeted Sirt1and increased its expression, and this increase in expression was associated with increased autophagy and M2 phenotype polarization. In contrast, the effects of AsC were markedly blocked by EX527 and Sirt1 siRNA. Altogether, AsC attenuates foam cell formation and lessens atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy.

4.
Mol Biol Evol ; 37(3): 849-863, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794607

RESUMO

It is known that adaptive evolution in permanently cold environments drives cold adaptation in enzymes. However, how the relatively high enzyme activities were achieved in cold environments prior to cold adaptation of enzymes is unclear. Here we report that an Antarctic strain of Chlorella vulgaris, called NJ-7, acquired the capability to grow at near 0 °C temperatures and greatly enhanced freezing tolerance after systematic increases in abundance of enzymes/proteins and positive selection of certain genes. Having diverged from the temperate strain UTEX259 of the same species 2.5 (1.1-4.1) to 2.6 (1.0-4.5) Ma, NJ-7 retained the basic mesophilic characteristics and genome structures. Nitrate reductases in the two strains are highly similar in amino acid sequence and optimal temperature, but the NJ-7 one showed significantly higher abundance and activity. Quantitative proteomic analyses indicated that several cryoprotective proteins (LEA), many enzymes involved in carbon metabolism and a large number of other enzymes/proteins, were more abundant in NJ-7 than in UTEX259. Like nitrate reductase, most of these enzymes were not upregulated in response to cold stress. Thus, compensation of low specific activities by increased enzyme abundance appears to be an important strategy for early stage cold adaptation to Antarctica, but such enzymes are mostly not involved in cold acclimation upon transfer from favorable temperatures to near 0 °C temperatures.

5.
Fish Shellfish Immunol ; 97: 351-358, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31874297

RESUMO

This study was conducted to investigate the effect of dietary Scenedesmus ovalternus on the growth and disease resistance of gibel carp (Carassius gibelio) during overwintering. Gibel carp (initial body weight: 90.39 ± 0.33 g) were fed with diets containing 0% or 4% Scenedesmus ovalternus (DS0 and DS4) for 4 weeks during the early overwintering period, and then all fish were left unfed during the late overwintering period. A bacterial challenge test using Aeromonas hydrophila was subsequently conducted. The 4% Scenedesmus ovalternus diet had no effect on the growth of gibel carp (P > 0.05), but did improve the survival rate after the challenge (P ≤ 0.05). In the DS0 group, the bacterial challenge decreased the contents of complement 3 (C3), immunoglobulin M (IgM), interleukin 2 (IL2) and tumor necrosis factor α (TNFα) in fish (P < 0.05); in the DS4 group, the challenge increased total antioxidant capacity (T-AOC) and myeloperoxidase (MPO) activity but decreased IL2 and TNFα contents (P < 0.05). The activities of MPO and contents of C3, IgM and TNFα were higher in the DS4 group than that fed the DS0 diet after bacterial challenge (P < 0.05). Compared to pre challenge, the expression levels of toll like receptor 2 (TLR2), toll like receptor 3 (TLR3), toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), Toll/IL-1 receptor domain-containing adaptor protein (TIRAP), TIR-domain-containing adapter-inducing interferon ß (TRIF), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα), transforming growth factor ß (TGFß), interleukin 1ß (IL1ß), tumor necrosis factor α1 (TNFα1) and interleukin 10 (IL10) in the head kidney of gibel carp were induced after challenge (P < 0.05). Gibel carp fed the DS4 diet showed lower expression of TGFß in head kidney before the challenge and lower expression of TLR2, TLR3, TLR4, TIRAP, TRIF, IκBα, TNFα1, IL10 and TGFß after the challenge than that fed the DS0 diet (P < 0.05). Overall, Scenedesmus ovalternus supplement enhanced the resistances of gibel carp against A. hydrophila after overwintering via the TLR signaling pathway.

6.
Opt Express ; 27(26): 38493-38508, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31878615

RESUMO

The stability of Cr/C multilayer during irradiation or thermal annealing was investigated using grazing incidence X-ray reflectivity measurement, X-ray photoelectron spectroscopy, X-ray diffraction analysis, small-angle X-ray scattering analysis, and soft X-ray reflectivity measurement. One sample was irradiated with a white beam of synchrotron radiation and five other samples were annealed at various temperatures. The 18-h irradiation treatment caused local surface contaminants but did not affect the buried stacks. The annealing treatment resulted in increased reflectivity at approximately 1.2 keV, and the multilayer remained stable for temperature up to 700 °C. Thus, the Cr/C multilayers exhibited excellent stability during irradiation and thermal treatments and can be used for the mirrors and multilayer gratings of third-generation synchrotron radiation systems.

7.
Fitoterapia ; 139: 104404, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31676394

RESUMO

Five new cucurbitane-type triterpenoid saponins Xuedanosides A-E (1-5) were isolated from the medicinal plant Hemsleya amabilis Diels by silica gel column, octadecylsilyl (ODS) column, and pre-HPLC techniques. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Separated compounds were evaluated for their cytotoxic activity in HeLa, HCT-8, MCF-7 and HepG2 human cancer cell lines, and compounds 1 and 2 showed significant effects against HeLa cells with IC50 values of 3.21 and 8.57 µM, respectively.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cucurbitaceae/química , Tubérculos/química , Saponinas/farmacologia , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , China , Glicosídeos , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação
8.
Am J Transl Res ; 11(10): 6577-6584, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737209

RESUMO

OBJECTIVES: This study aims to investigate influence of colonic dialysis using Chinese medicine on creatinine decomposition by intestinal bacteria in uremia rats. METHODS: Healthy male Sprague Dawley (SD) rats were randomly divided into three groups, including uremic group, sham group and Chinese medicinal group. Uremic model was established in uremic group and Chinese medicinal groupby 5/6 nephrectomy, while sham group did not undergo nephrectomy. All rats were sacrificed at the end of ten weeks. Serum creatinine was examined. Histopathological changes of rat kidney were observed by hematoxylin-eosin staining. The numbers of Bifidobacterium, Lactobacillus and E.coli in the intestinal tract were quantitatively determined by real-time fluorescent quantitative PCR with 16S RNA. RESULTS: Compared with sham group, the number of E.coli in the jejunum increased significantly, while that of Bifidobacterium and Lactobaeillus in the ileum decreased. The number of Bifidobacterium and Lactobaeillus was decreased in the colon whereas that of E.coli increased. CONCLUSION: Our findings revealed that Influence of colonic dialysis using Chinese medicine on creatinine decomposition by intestinal bacteria in uremia rats.

9.
Nat Prod Res ; : 1-7, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31625773

RESUMO

Three new triterpenoids, 2α, 3α, 20ß, 23-tetrahydroxyurs-13 (18)-en-28-oic-acid (1) (Figure 1), 2ß, 3α, 20ß, 23-tetrahydroxyurs-13(18)-en-28-oic-acid (2), and 2α, 3α-dihydroxyurs-12(13), 18(19)-dien-28-oic-acid (3) were isolated from the roots of R. cymosa. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and IR spectroscopic analyses data. All the isolates were evaluated for their α-glucosidase inhibitory and anti-inflammatory activities in vitro. The results showed that compound 2 displayed moderate anti-inflammatory activity with IC50 value of 9.4 µM.

10.
Sci Rep ; 9(1): 11835, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413307

RESUMO

Ten new cucurbitane triterpenoids, hemsleyacins A-J (1-10), together with three known cucurbitane triterpenoids, dihydrocucurbitacin F (11), scandenogenin D (12), and jinfushanencin F (13), were separated from ethanolic tuber extracts of Hemsleya penxianensis. The absolute configurations of the new compounds were established based on NMR, HRESIMS, and CD spectra. Compounds 7 and 10-12 were evaluated in terms of their antifeedant activity against Plutella xylostella larvae. The result showed that compound 10 exhibited potent antifeedant activity against P. xylostella larvae after 48 h of treatment. Furthermore, the MTT test showed that compound 11 exhibited potent inhibition toward the UMUC-3 and T24 cell lines with IC50 values of 29.12 and 35.62 µM, respectively, compared to the positive control cisplatin IC50 values of 8.27 and 13.72 µM. Western blot analysis revealed that compound 11 treatments substantially inhibited the phosphorylation of IκBα.

11.
Molecules ; 24(16)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412677

RESUMO

Five new cucurbitane-typetriterpenoid glycosides, named Xuedanoside F-J (1-5), were obtained from the rhizomes of Hemsleya penxianensis (Xue dan), which belongs to the family of Cucurbitaceae. These new compounds were elucidated byspectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS spectra. Additionally, all the isolates were evaluated for cytotoxicity against three human cancer cell lines (Hela, MCF-7, and A-549) with the IC50 ranging from 2.25 to 49.44 µM in vitro with treatment 48 h and showed low cytotoxicity in human normal liver L-02 cells (IC50 > 50 µM). Compound 5 showed the most significant cytotoxic activity with the IC50 value of 2.25, 4.72, and 5.33 µM in 48 h, respectively.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cucurbitaceae/química , Glicosídeos/química , Glicosídeos/farmacologia , Rizoma/química , Triterpenos/química , Triterpenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia
12.
J Med Internet Res ; 21(5): e13168, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31344676

RESUMO

BACKGROUND: Renal anemia is one of the most important complications in patients on maintenance hemodialysis (MHD). Telehealth-based dialysis registration systems have the advantage of real-time monitoring and have gradually been applied to the management of chronic diseases. OBJECTIVE: The objective of our study was to evaluate the impact of a telehealth-based dialysis registration system on patients on MHD in terms of renal anemia control. METHODS: The Red China project aimed to develop a dialysis registration system based on the WeChat mobile platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, and baseline creatinine levels were recorded using this system. In addition, the hemoglobin and hematocrit levels were recorded monthly. The platform then generated a hemoglobin and hematocrit statistics report for each hemodialysis center monthly, including the detection rate, target rate, and distribution of hemoglobin and released it to physicians via the WeChat mobile phone app. The physicians were then able to treat the individual's anemia appropriately by changing the doses of erythropoiesis-stimulating agents or iron use on the basis of this report. We analyzed the demographic and baseline laboratory parameters, detection rate, target rate, and average level and distribution of hemoglobin 28 months after the launch of the project. RESULTS: A total of 8392 patients on MHD from 28 hemodialysis centers in Shanghai were enrolled from June 2015 to October 2017. The detection rate of hemoglobin increased from 54.18% to 73.61% (P<.001), the target rate of hemoglobin increased from 47.55% to 56.07% (P<.001), and the mean level of hemoglobin increased from 10.83 (SD 1. 60) g/dL to 11.07 (SD 1.60) g/dL (P<.001). In addition, the proportion of patients with hemoglobin levels ≥11 g/dL but <13 g/dL increased from 40.40% to 47.48%. CONCLUSIONS: This telehealth-based dialysis registration system can provide timely reporting of the anemia status in patients on MHD, which may improve the awareness of anemia and the attention to and compliance with anemia monitoring.


Assuntos
Anemia/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Telemedicina/métodos , Anemia/terapia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Biomed Res Int ; 2019: 4878240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236407

RESUMO

Objectives: To evaluate the performance of Xpert MTB/RIF for lymph node tuberculosis (LNTB). Methods: We searched databases for published reports. We reviewed the studies and identified the performance of Xpert MTB/RIF with respect to a composite reference standard (CRS) and culture. We used a bivariate random-effects model to perform meta-analyses and used metaregression to analyze sources of heterogeneity. Results: 15 independent studies compared Xpert MTB/RIF with CRS while 21 comparing it with culture were included. The pooled sensitivity and specificity of Xpert MTB/RIF were 79% and 98% compared to that of CRS, respectively, and 84% and 91% compared to that of culture, respectively. The pooled sensitivity and specificity using fine needle aspiration (FNA) samples versus CRS were 80% and 96%, whereas those against culture were 90% and 89%, respectively. The percentages while working with tissue samples versus CRS were 76% and 100%, respectively, whereas those against culture were 76% and 92%, respectively. There was no significant difference in diagnostic efficiency among the types of specimen. Conclusions: Xpert MTB/RIF demonstrates good diagnostic efficiency for LNTB and is not related to the type of specimen, obtained via different routes.


Assuntos
Linfonodos/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/diagnóstico , Bioensaio/métodos , Humanos , Linfonodos/patologia , Mycobacterium tuberculosis/patogenicidade , Padrões de Referência , Rifampina/química , Tuberculose/microbiologia
14.
J Cardiovasc Pharmacol ; 73(6): 373-382, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31162246

RESUMO

Puerarin is used to treat cardiovascular diseases due to its anti-inflammatory and antifibrotic effects. However, its mechanism of action in atrial fibroblasts is unknown. In this study, we investigated the autophagy pathway and molecular changes in angiotensin II (AngII)-stimulated atrial fibroblasts in response to puerarin treatment. Atrial fibroblasts were cultured and then subjected to stimulation with AngII and puerarin or other chemical drugs (3-MA, CQ, and SP600125). Quantitative real-time polymerase chain reaction and Western blot experiments were used to quantify the expression levels of mRNA and protein. mCherry-GFP-LC3 adenovirus was applied to reflect the autophagic flux. The results showed aggravating levels of autophagy and collagen deposit in the presence of AngII. Puerarin inhibited autophagy and decreased collagen secretion in a dose-dependent manner in atrial fibroblasts. Furthermore, phosphorylation of JNK was down-regulated in response to puerarin, whereas phosphorylation of Akt and mammalian target of rapamycin (mTOR) was upregulated. Interestingly, reduced autophagy and collagen secretion were observed when the JNK signaling pathway was blocked using SP600125. We also observed upregulation of Akt and mTOR phosphorylation in the presence of SP600125. These results suggest that puerarin exerts its antifibrotic effect in atrial fibroblasts partly through the inhibition of autophagy. Furthermore, the mechanism of action of puerarin in fibroblast autophagy seems to be mediated partly through JNK-Akt-mTOR signaling.

15.
Molecules ; 24(5)2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30857274

RESUMO

A series of novel caffeoylquinic acid derivatives of chlorogenic acid have been designed and synthesized. Biological evaluation indicated that several synthesized derivatives exhibited moderate to good lipid-lowering effects on oleic acid-elicited lipid accumulation in HepG2 liver cells. Particularly, derivatives 3d, 3g, 4c and 4d exhibited more potential lipid-lowering effect than the positive control simvastatin and chlorogenic acid. Further studies on the mechanism of 3d, 3g, 4c and 4d revealed that the lipid-lowering effects were related to their regulation of TG levels and merit further investigation.


Assuntos
Hipolipemiantes/síntese química , Hipolipemiantes/farmacologia , Ácido Oleico/farmacologia , Ácido Quínico/análogos & derivados , Ácido Clorogênico/farmacologia , Células Hep G2 , Humanos , Hipolipemiantes/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Ácido Quínico/síntese química , Ácido Quínico/química , Ácido Quínico/farmacologia , Sinvastatina/farmacologia
16.
Pharm Biol ; 57(1): 133-139, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30843752

RESUMO

CONTEXT: Calenduloside E (CE), one of the primary natural products found in Aralia elata (Miq.) Seem. (Araliaceae), possesses prominent anti-apoptotic potential. A previous study found that one of the anti-apoptotic CE targets is heat shock protein 90 AB1 (Hsp90AB1) by probe CE-P, while the other targets of CE still need to be identified with more efficient probes. OBJECTIVE: This study investigates CE analogue (CEA) as one clickable activity-based probe for use in exploring anti-apoptotic CE targets. MATERIALS AND METHODS: Pretreatment of HUVECs with CEA (1.25 µM) for 8 hr, followed by ox-LDL stimulation for 24 h. Flow cytometry analysis and JC-1 staining assays were performed The kinetic constant measurements were tested by the Biacore T200, CM5 Sensor Chip which was activated by using sulpho-NHS/EDC. Ligands were dissolved and injected with a concentration of 12.5, 6.25, 3.125, 1.56, 0.78 and 0 µM. RESULTS: CEA was confirmed to possess an anti-apoptotic effect. The probable targets of CE/CEA were calculated, and as one of the higher scores proteins (Fit values: 0.88/0.86), Hsp90 properly got our attention. Molecular modelling study showed that both CE and CEA could bind to Hsp90 with the similar interaction, and the docking scores (S value) were -7.61 and -7.33. SPR assay provided more evidence to prove that CEA can interact with Hsp90 with the KD value 11.7 µM. DISCUSSION AND CONCLUSIONS: Our results suggest that clickable probe CEA could alleviate ox-LDL induced apoptosis by a similar mechanism of anti-apoptotic CE, and afforded the possibility of identifying additional anti-apoptotic targets of CE.


Assuntos
Apoptose/efeitos dos fármacos , Química Click , Modelos Moleculares , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Relação Dose-Resposta a Droga , Citometria de Fluxo , Proteínas de Choque Térmico HSP90/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Lipoproteínas LDL/metabolismo , Simulação de Acoplamento Molecular , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/farmacologia , Saponinas/administração & dosagem
17.
Front Physiol ; 10: 167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873046

RESUMO

Podocytes, dynamic polarized cells wrapped around glomerular capillaries, are an essential component of the glomerular filtration barrier. BK channels consist of one of the slit diaphragm (SD) proteins in podocytes, interact with the actin cytoskeleton, and play vital roles in glomerular filtration. Mechanistic target of rapamycin (mTOR) complexes regulate expression of SD proteins, as well as cytoskeleton structure, in podocytes. However, whether mTOR complexes regulate podocyte BK channels is still unclear. Here, we investigated the mechanism of mTOR complex regulation of BK channels via real-time PCR, western blot, immunofluorescence, and patch clamping. Inhibiting mTORC1 with rapamycin or downregulating Raptor had no significant effect on BK channel mRNA and protein levels and bioactivity. However, the dual inhibitor of mTORC1 and mTORC2 AZD8055 and short hairpin RNA targeting Rictor downregulated BK channel mRNA and protein levels and bioactivity. In addition, MK2206, GF109203X, and GSK650394, which are inhibitors of Akt, PKCα, and SGK1, respectively, were employed to test the downstream signaling pathway of mTORC2. MK2206 and GF109203X had no effect on BK channel protein levels. MK2206 caused an obvious decrease in the current density of the BK channels. Moreover, GSK650394 downregulated the BK channel protein and mRNA levels. These results indicate mTORC2 not only regulates the distribution of BK channels through Akt, but also modulates BK channel protein expression via SGK1 in podocytes.

18.
Eur J Med Chem ; 166: 159-166, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30703659

RESUMO

In this study, 12 known cycloartane triterpenoids (1-12) with four different skeletons isolated from the roots of Souliea vaginata were screened for the first time for in vitro anti-HIV activity using AZT as a standard. Among the compounds, beesioside I (1) showed the highest potency against HIV-1NL4-3 with an EC50 value of 2.32 µM (CC50 > 40 µM). Preliminary structure-activity relationship (SAR) studies on 1 indicated that simple modification of its aglycone (13) could significantly influence the antiviral activity. Particularly, the introduction of an acyl group at the C-3 position of 13 led to significant improvement in both anti-HIV potency and selectivity index. Among all synthetically modified derivatives, compound 13g was the most potent compound with an EC50 value of 0.025 µM and TI value greater than 800, comparable to those of 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB, bevirimat). Other analogues exhibited strong to weak inhibition of HIV-1 replication in MT-4 cells. The length, carboxylic terminus, and C-3' dimethyl substitution of the C-3 side chain substantially affected the anti-HIV activity. Finally, compound 13g was an effective agent against HIV with high potential for further investigation.


Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Desenho de Fármacos , HIV-1/efeitos dos fármacos , Triterpenos/síntese química , Triterpenos/farmacologia , Fármacos Anti-HIV/química , Técnicas de Química Sintética , HIV-1/fisiologia , Relação Estrutura-Atividade , Triterpenos/química , Replicação Viral/efeitos dos fármacos
19.
Phytomedicine ; 52: 178-186, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599897

RESUMO

BACKGROUND: Protection the heart from ischemia/reperfusion (I/R) injury is an area of intense research, as myocardial infarction is a major cause of mortality and morbidity all around the world. Tournefolic acid B (TAB) is a relative new compound derived from Clinopodium chinense (Benth.) Kuntze (Chinese name: Feng Lun Cai). This traditional Chinese herbal medicine has been used for its activities on anti-inflammatory, lowering blood glucose, antitumor and antiradiation. However, the pharmacological effects of TAB were rarely studied. PURPOSE: Pathways involving phosphoinositide 3-kinase (PI3K) and protein kinase b (Akt) are crucial in regulating the ER stress and associated apoptosis in the process of I/R injury. In the present study, we aim to investigate the cardioprotective effects of tournefolic acid B (TAB) against myocardial I/R injury and explore the molecular mechanisms involved. STUDY DESIGN: H9c2 cadiomyocyte were incubated with TAB for 24 h and then exposed to hypoxia/reoxygenation. Isolated rat hearts were subjected to global ischemia and reperfusion in the absence or presence of TAB. METHODS: The possible mechanisms were investigated in vitro and ex vivo by multiple detection methods including JC-1 staining, ROS detection, activities of caspases detection, TUNEL staining, and Western-blot analysis. RESULTS: We found that TAB significantly improved the hemodynamic parameters (LVeDP, LVSP, + dP/dtmax, - dP/dtmin, and HR) of isolated rat hearts, and depressed the cardiomyocyte apoptosis. Besides, TAB inhibited the oxidative stress by adjusting the activities of antioxidant enzymes (SOD, CAT, and GSH-Px). The I/R injury triggered the endoplasmic reticulum (ER) stress by activating the ER proteins, such as Grp78, ATF6, PERK, and eIf2α. which are all refrained by TAB. TAB also enhanced the phosphorylation of PI3K and AKT, inhibited the expression of CHOP and Caspase-12, reduced the phosphorylation of JNK, and increased Bcl-2/Bax ratio. CONCLUSION: TAB protects against myocardial I/R injury by suppressing PI3K/AKT-mediated ER stress, oxidative stress, and apoptosis, revealing a promising therapeutic agent against ischemic cardiovascular diseases.


Assuntos
Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Lamiaceae/química , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/metabolismo , Linhagem Celular , Fator de Iniciação 2 em Eucariotos/metabolismo , Coração/efeitos dos fármacos , Masculino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
20.
Fitoterapia ; 132: 46-52, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30496808

RESUMO

Seven new naphthoquinone derivatives, named eleutherins A-G (1-7), were isolated from the edible bulbs of Eleutherine americana (Hong-Cong), which belongs to the Iridaceae family. Their structures were elucidated on the basis of spectroscopic analysis including high-resolution-electron spray ionization-mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) techniques. The absolute configurations of compounds 1-4 were determined by experimental and calculated data. Additionally, a hypothetical biosynthetic pathway of 1-7 was postulated. All the isolates were evaluated for their protective effect against the injury of human umbilical vein endothelial cells (HUVECs) in vitro. Eleutherins A and B (1-2) showed a potential protective effect on microvessels.


Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Iridaceae/química , Naftoquinonas/química , Células Cultivadas , China , Humanos , Estrutura Molecular , Naftoquinonas/isolamento & purificação , Raízes de Plantas/química , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação
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