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1.
Bioorg Med Chem ; 78: 117144, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36577328

RESUMO

Novel steroid glycosides, acanthasterosides A1, B1, and B3, have been isolated from the crown-of-thorns starfish Acanthaster planci. Acanthasterosides B1 and B3 having two separated xyloses induced neurite outgrowth as like as nerve growth factor (NGF) in the rat pheochromocytoma cell line PC12, whereas acanthasteroside A1, having one xylose, did not induce neurite outgrowth. The acanthasteroside B3 induced neuritogenesis via the significant activation of p38 mitogen-activated protein kinase after the activation of the small G-protein Cdc42 rather than via Ras-MEK-ERK pathway that is predominantly activated by NGF. Following subcutaneous administration, acanthasteroside B3 attenuated cognitive impairment of senescence-accelerated mice (SAMP8) in two different cognitive tests. Liquid chromatography-mass spectrometry-assisted quantitative analysis demonstrated that acanthasteroside B3 could be transported into the brain via the circulatory system in mice. Thus, acanthasteroside B3 (and possibly B1) are a novel class of potential drug candidates for neurodegenerative diseases.


Assuntos
Disfunção Cognitiva , Proteína Quinase 14 Ativada por Mitógeno , Camundongos , Ratos , Animais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Neuritos/metabolismo , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/farmacologia , Células PC12 , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Disfunção Cognitiva/metabolismo , Estrelas-do-Mar/metabolismo , Esteroides
2.
Plant Dis ; 2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36774577

RESUMO

Jujube (Zizyphus jujuba Mill.), a native small deciduous tree of China, is widely cultivated in China, Korea, India, Japan, Europe, and the United States (Chen et al. 2020). The fruit have been commonly consumed as healthy food supplements and traditional Chinese medicine for over 2000 years (Li et al. 2007). In August 2019, anthracnose-like leaf spot symptoms were observed on jujube plants in Xiaomenya Village, Jinan City, Shandong Province, China (36°27'39″N, 117°3'13″E), with over 30% leaf disease incidence. The spots were circular, sunken, brown in the center and with dark brown edges. As the spots enlarged and coalesced, it resulted in leaf perforation and early defoliation. Sometimes acervuli were observed on the lesions (Fig. S1a, b). To identify the causal agent, 20 diseased leaves were sampled, the margins of the lesions were cut into pieces (5 × 5 mm), sterilized and cultured following the protocol described previously (Wan et al. 2020) at 25 ℃ for 5 days. Twelve monospore isolates showing identical colony morphology were obtained. Three representative isolates, JNZG11, JNZG311, JNZG313, were used for further study. When grown on PDA the colony color was initially white and then turned pale-gray to gray in 5-day-old cultures. On the reverse, colonies were brown-black with an orange pigmentation near the center. Aerial mycelium was cottony, dense, white to pale-gray. Conidia were hyaline, 1-celled, smooth-walled, subcylindrical, oblong, attenuated with slightly rounded ends, (11.1-) 12.7-13.3 (-17.8) ×(-4.4) 5.2-5.5 (-6.3) µm (n=50). Appressoria were dark-brown, oval or irregular, (7.3-) 8.6-9.2 (-9.8) ×(-5.1) 5.8-6.9 (-7.0) µm (n=50) (Fig. S1c-g). The morphology resembled those of Colletotrichum gloeosporioides species complex (Cannon et al. 2012). For accurate identification, the sequences of the ribosomal internal transcribed spacer (ITS), actin (ACT), ß-tub2 (TUB2), calmodulin (CAL), chitin synthase (CHS-1), and glyceraldehyde-3phosphate dehydrogenase (GAPDH) of the 3 isolates were sequenced (Weir et al. 2012), and deposited into GenBank (Accession Nos. see Table 1). The six loci (ITS, GAPDH, ACT, CHS-1, CAL, and TUB2) were concatenated and the aligned sequences (1904 bp) were 99.7% homologous to ex-type C. siamense ICMP18578. The sequences of 38 Colletotrichum species (44 isolates) were downloaded from GenBank for phylogenetic analyses. In the maximum likelihood phylogenetic tree generated, the highest log likelihood was -8798.90 and the three isolates were all in the C. siamense clade (bootstrap support 94 %) (Fig. S2). To complete Koch's postulates, 60 healthy, mature jujube leaves on 12 branches (5 leaves per branch) (variety 'Zhongqiuhong') were inoculated with 20 µL of spore suspension (106 conidia/mL) or sterile water as a control. The branches were placed in sterile beakers containing a small amount of sterile water sealed with plastic wrap and maintained at 28 °C, 12 h light/dark. Five days after inoculation, all treated leaves showed the typical anthracnose symptom, similar to that observed in the field (Fig. S1h). The same fungus was re-isolated from the margins of the lesions using the aforementioned methods. Whereas no fungus were isolated from the controls. Previously, C. siamense has been reported to infect Z. mauritiana in China (Shu et al. 2020). To our knowledge, this is the first report of C. siamense causing anthracnose on Z. jujuba in China. This finding provides crucial information for the effective management of this disease.

3.
Int J Mol Sci ; 24(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38069009

RESUMO

Metabolic-dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD) is a global chronic liver disease, and no licensed drugs are currently available for its treatment. The incidence of MASLD is increasing, which could lead to a huge clinical and economic burden. As a multifactorial disease, MASLD involves a complex set of metabolic changes, and many monotherapies for it are not clinically effective. Therefore, combination therapies using multiple drugs are emerging, with the advantages of improving drug efficacy and reducing side effects. Peanut skin extract (PSE), geniposide (GEN), and isoquercitrin (IQ) are three natural antiaging components or compounds. In this study, the preventive effects of individual PSE, GEN, and IQ in comparison with the effects of their mixture (MPGI) were examined in a mouse model of high-fat-feed-induced MASLD. The results showed that MPGI could significantly reduce the body and liver weights of mice and improve hepatic steatosis and liver function indicators. Further mechanistic studies showed that PSE, GEN, and IQ worked together by reducing inflammation, modulating the intestinal flora, and regulating the TLR4/NF-κB, AMPK/ACC/CPT1, and AMPK/UKL1/LC3B signaling pathways. It is a promising therapeutic method for preventing MASLD.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Proteínas Quinases Ativadas por AMP , Arachis , Homeostase , Lipídeos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Camundongos
4.
Exp Cell Res ; 395(1): 112169, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32653410

RESUMO

It has been reported that cholesterol-lowing agents can ameliorate severity of myocarditis. However, the beneficial effect of the agents has been claimed to be independent of cholesterol reduction as there is no significant change in the plasma cholesterol level in myocarditis. In the present study, using experimental autoimmune myocarditis (EAM) rats as an animal model, we demonstrated that EAM induced elevation of cholesterol level and impaired cholesterol efflux capacity in the cardiac tissue. Moreover, serum high-density lipoprotein (HDL) content was reduced and HDL function associated protein Paraoxonase 1 (PON1) activity was decreased. Besides, the major structural protein within HDL, Apolipoprotein A1 (ApoA1) expression in the cardiac tissues was significantly reduced while the level of serum ApoA1 was not significantly altered. Importantly, cholesterol depleting agent methyl-ß-cyclodextrin (MßCD) alleviated the development of EAM, as monitored by decreased ratio of heart weight to body weight (HW/BW), decreased infiltration of inflammatory cells and collagen deposition, improved cardiac function, reduced expression of apoptosis-related protein Bax, Fas, FasL and caspase-3 and increased level of anti-apoptotic protein Bcl-2. These results suggest that reduction of cholesterol level in cardiac tissue could suppress EAM-induced cardiac apoptosis through both intrinsic and extrinsic apoptotic pathways.


Assuntos
Apoptose/fisiologia , Doenças Autoimunes/imunologia , Colesterol/metabolismo , Hipercolesterolemia/metabolismo , Miocardite/metabolismo , Animais , Caspase 3/metabolismo , Colesterol/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Miocardite/imunologia , Miocárdio/metabolismo , Ratos
5.
J Cell Mol Med ; 23(9): 6283-6294, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31257716

RESUMO

Cucurbitacin B (CuB) isolated from Cucumis melo by using a PC12 cell bioassay system exhibited significant nerve growth factor (NGF)-mimic or NGF-enhancing activity in PC12 and primary neuron cells. It was also demonstrated pro-neurogenesis effects in ICR and APP/PS1 mice and improved memory deficit of APP/PS1 mice. Its possible mechanism includes significant induction of the phosphorylation of glucocorticoid receptor (GR), protein kinase C (PKC), phospholipase C (PLC) and inhibition of cofilin. ChemProteoBase profiling, binding assay and cellular thermal shift assay (CETSA) were used to determine the target protein. Results revealed that CuB could affect actin dynamics as an actin inhibitor but did not bind with GR. The protein level of cofilin in PC12 cells after treating 0.3 µM and different temperatures was significantly higher than that of control group. Other neurotrophic signalling pathways, such as TrkA/TrkB, were analysed with specific inhibitors and Western blot. The inhibitors of TrkA, PLC, PKC, Ras, Raf and ERK1/2 significantly decreased the percentage of PC12 cells with neurite outgrowth and shortened the length of neurite outgrowth induced by CuB. CuB significantly induced the phosphorylation of TrkA, ERK and CREB. The phosphorylation of these proteins was obviously decreased by their specific inhibitors. These results suggest that cofilin is a candidate target protein of CuB in PC12 cells and that the GR/PLC/PKC and TrkA/Ras/Raf/ERK signalling pathways play important roles in the neuroprotective effect of CuB.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Memória/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Crescimento Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oligopeptídeos/metabolismo , Triterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Camundongos , Camundongos Endogâmicos ICR , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células PC12 , Ratos , Transdução de Sinais/efeitos dos fármacos
6.
Biochem Biophys Res Commun ; 516(3): 747-752, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31253404

RESUMO

Both mitogen-activated protein kinase (MAPK) cascades and reactive oxygen species (ROS) are critical to signaling in eukaryotes. Cadmium induces MAPK activation and ROS production in plants. This study aims to identify specific MAPKs activated by CdCl2 in maize roots, and examine the relationship between MAPK activation and ROS production under CdCl2 treatment. Using in-gel kinase assays, immunoprecipitation, and immunoblot analysis, we identified 43 and 45 kDa ERK-like MAPKs in response to CdCl2. Further analysis revealed that ZmMPK3-1 and ZmMPK6-1 correspond to the 43 and 45 kDa MAPKs, respectively. In addition, CdCl2 induced ROS production prior to the activation of ZmMPK3-1 and ZmMPK6-1. Inhibition of ROS attenuated Cd-activation of ZmMPK3-1 and ZmMPK6-1, whereas inhibition of MAPK signaling did not disturb Cd-induced ROS production. Collectively, these results indicate that, in maize roots, cadmium stress activates ZmMPK3-1 and ZmMPK6-1 via ROS induction.


Assuntos
Cádmio/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Zea mays/metabolismo , Cloreto de Cádmio/farmacologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Immunoblotting , Isoenzimas/genética , Isoenzimas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas de Plantas/genética , Raízes de Plantas/genética , Zea mays/genética
7.
Mol Pharm ; 16(4): 1423-1432, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30763105

RESUMO

3ß,23,28-Trihydroxy-12-oleanene 3ß-caffeate (compound 1) is a neuritogenic pentacyclic triterpenoid, which was isolated from Desmodium sambuense based on a PC12 cell bioassay system. Compound 1 induced neurite outgrowth dose-dependently in PC12 cells and primary cortical neurons at doses of 0.1, 0.3, and 1 µM. The potential target of compound 1 was predicted by ChemProteoBase profiling, and the mechanism of action was investigated using specific inhibitors, Western blot analysis, and PC12 [rasN17] and PC12 [mtGAP] mutants. Compound 1 activates endoplasmic reticulum (ER) as an ER stress inducer, and the maker of ER stress GRP78 protein significantly increased after treatment with compound 1. The inhibitors of tyrosine kinase B (TrkB), insulin-like growth factor 1 receptor (IGF-1R), mitogen-activated protein kinase (MEK), and phosphatidylinositol 3 kinase (PI3K) significantly decreased the neurite outgrowth induced by compound 1. Furthermore, the increases of phosphorylation of TrkB, IGF-1R, extracellular signal-regulated kinase (ERK), and protein kinase B (AKT) were observed in the compound 1-treated group, and the phosphorylation of these proteins was diminished by corresponding inhibitors. Thus, the compound-1-induced neuritogenic activity depended on the activation of slight ER stress and associated BDNF-TrkB/Ras/Raf/ERK and IGF-1R/PI3K/AKT signaling pathways in PC12 cells.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ácidos Cafeicos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fabaceae/química , Regulação da Expressão Gênica/efeitos dos fármacos , Neurônios/citologia , Ácido Oleanólico/farmacologia , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/farmacologia , Receptor trkB/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Ácidos Cafeicos/química , Chaperona BiP do Retículo Endoplasmático , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ácido Oleanólico/análogos & derivados , Células PC12 , Triterpenos Pentacíclicos/química , Fosforilação , Ratos , Receptor trkB/genética , Transdução de Sinais
8.
Molecules ; 24(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30978970

RESUMO

The aim of this study was to investigate anti-aging molecules from Onosma bracteatum Wall, a traditional medicinal plant used in the Unani and Ayurvedic systems of medicine. During bioassay-guided isolation, two known benzoquinones, allomicrophyllone (1) and ehretiquinone (2) along with three novel benzoquinones designated as ehretiquinones B-D (3-5) were isolated from O. bracteatum. Their structures were characterized by spectroscopic analysis through 1D and 2D NMR, by MS spectroscopic analysis and comparing with those reported in the literatures. The anti-aging potential of the isolated benzoquinones was evaluated through a yeast lifespan assay, and the results indicated that 1, 2, 4 and 5 significantly extended the replicative lifespan of K6001 yeast, indicating that these benzoquinones obtained from O. brateatum have the ability to be employed as a potential therapeutic agent against age-related diseases.


Assuntos
Envelhecimento/efeitos dos fármacos , Benzoquinonas/química , Boraginaceae/química , Longevidade/efeitos dos fármacos , Envelhecimento/fisiologia , Benzoquinonas/isolamento & purificação , Humanos , Ayurveda , Estrutura Molecular , Plantas Medicinais/química , Saccharomyces cerevisiae/efeitos dos fármacos
9.
Water Sci Technol ; 78(3-4): 868-877, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30252664

RESUMO

The shells of Chinese chestnuts (Castanea mollissima) are an agricultural residue. This work aimed to evaluate this feasibility of using steam explosion to modify this residue for Cu(II) biosorption from aqueous solutions. Equilibrium, kinetic and thermodynamic parameters were evaluated. The steam-explosion pretreatment increased the surface area of the chestnut shell and exposed more hydroxyl and carboxyl groups, which are binding sites for Cu(II). It changed the sorption from a spontaneous process driven by enthalpy to a nonspontaneous one driven by entropy. It increased the Cu(II) sorption capacity at higher temperatures while it decreased the capacity at lower ones. Compared with untreated chestnut shell, the steam-exploded shell is preferable for Cu(II) sorption at higher temperatures.


Assuntos
Explosões , Vapor , Adsorção , Cobre , Concentração de Íons de Hidrogênio , Cinética , Termodinâmica
10.
Angew Chem Int Ed Engl ; 57(27): 8100-8104, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29729060

RESUMO

Asexual and sexual reproduction are the most important biological events in the life cycle of phytopathogenic and toxigenic Fusarium and are responsible for disease epidemics. However, the signaling molecules which induce the asexual reproduction of Fusarium are unknown. Herein we describe the structure elucidation, including the absolute configuration, of Fusarium asexual reproduction inducer (FARI), a new sesquiterpene derivative, by spectroscopic analysis, total synthesis, and conidium-inducing assays of synthetic isomers. We have also uncovered the universality of FARI among Fusarium species. Moreover, a mechanism-of-action study suggested that the Gpmk1 and LaeA signaling pathways are required for conidium formation induced by FARI; conversely, the Mgv1 of mitogen-activated protein kinase is not involved in conidium formation. FARI exhibited conidium-inducing activity at an extremely low dose and high stereoselectivity, which may suggest the presence of a stereospecific target.


Assuntos
Fusarium/fisiologia , Reprodução Assexuada/fisiologia , Sesquiterpenos/metabolismo , Proteínas Fúngicas/metabolismo , Fusarium/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Reprodução Assexuada/efeitos dos fármacos , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Transdução de Sinais , Esporos Fúngicos/efeitos dos fármacos , Estereoisomerismo
11.
Biosci Biotechnol Biochem ; 81(8): 1586-1590, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28585468

RESUMO

One new (1, SZMT01) and one known (2) anti-aging substances were isolated from Shenzhou honey peach fruit. Their structures were elucidated by spectroscopic methods and chemical derivatization, and the result reveals that these two compounds are sesquiterpene glucosides. SZMT01 possesses a new glycosylation with an ester linkage at one terminal in an acyclic sesquiterpenoid which is the end of a double bond at another terminal. Both compounds extend the replicative lifespan of K6001 yeast strain at doses of 7.5 and 25 µM. Then, to understand the action mechanism involved, we performed an anti-oxidative experiment on SZMT01. The result revealed that treatment with SZMT01 increased the survival rate of yeast under oxidative stress. Moreover, the lifespans of sod1 and sod2 mutant yeast strains with a K6001 background were not affected by SZMT01. These results demonstrate that anti-oxidative stress performs important roles in anti-aging effects of SZMT01.


Assuntos
Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Glucosídeos/farmacologia , Prunus persica/química , Saccharomyces cerevisiae/efeitos dos fármacos , Sesquiterpenos/farmacologia , Antioxidantes/isolamento & purificação , Frutas/química , Expressão Gênica , Glucosídeos/isolamento & purificação , Glicosilação , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Sesquiterpenos/isolamento & purificação , Superóxido Dismutase/deficiência , Superóxido Dismutase/genética , Superóxido Dismutase-1/deficiência , Superóxido Dismutase-1/genética
12.
Chem Pharm Bull (Tokyo) ; 64(2): 161-70, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26833444

RESUMO

Tetradecyl 2,3-dihydroxybenzoate (ABG-001) has been designed and synthesised as a lead compound to treat Alzheimer's disease, based on structure-activity relationships of gentisides. In this paper, the alkyl chain and ester linkage group of ABG-001 were modified. Consequently, several series of novel gentiside derivatives were designed and synthesised, and their neuritogenic activity was evaluated in PC12 cells. Among all the tested compounds, S-dodecyl 2,3-dihydroxybenzothioate (15d, named as ABG-199) was the most potent; the compound induced significant neurite outgrowth at 0.1 µM, which was comparable to that of nerve growth factor at the optimal concentration of 40 ng/mL and ABG-001 at 1 µM. A brief study on the mechanism of action of ABG-199 revealed that extracellular signal-regulated kinase phosphorylation was involved in ABG-199-induced neurite outgrowth in PC12 cells.


Assuntos
Hidroxibenzoatos/síntese química , Hidroxibenzoatos/farmacologia , Neuritos/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Hidroxibenzoatos/química , Estrutura Molecular , Neuritos/patologia , Células PC12 , Ratos , Relação Estrutura-Atividade
13.
Molecules ; 21(4): 487, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27110763

RESUMO

Chestnut shell melanin can be used as a colorant and antioxidant, and fractionated into three fractions (Fr. 1, Fr. 2, and Fr. 3) with different physicochemical properties. Antioxidant activities of the fractions were comparatively evaluated for the first time. The fractions exhibited different antioxidative potential in different evaluation systems. Fr. 1, which is only soluble in alkaline water, had the strongest peroxidation inhibition and superoxide anion scavenging activity; Fr. 2, which is soluble in alkaline water and hydrophilic organic solvents but insoluble in neutral and acidic water, had the greatest power to chelate ferrous ions; and Fr. 3, which is soluble both in hydrophilic organic solvents and in water at any pH conditions, had the greatest hydroxyl (·OH) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH·) radicals scavenging abilities, reducing power, and phenolic content. The pigment fractions were superior to butylated hydroxytolune (BHT) in ·OH and DPPH· scavenging and to ethylene diamine tetraacetic acid (EDTA) in the Fe(2+)-chelation. They were inferior to BHT in peroxidation inhibition and O2·(-) scavenging and reducing power. However, BHT is a synthetic antioxidant and cannot play the colorant role. The melanin fractions might be used as effective biological antioxidant colorants.


Assuntos
Aesculus/química , Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Melaninas/farmacologia , Quelantes/química , Corantes de Alimentos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Extratos Vegetais/farmacologia
14.
Molecules ; 21(4): 405, 2016 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-27043502

RESUMO

Chestnut shell pigment (CSP) is melanin from an agricultural waste. It has potential as an adsorbent for wastewater treatment but cannot be used in its original state because of its solubility in water. We developed a new method to convert CSP to insolubilized chestnut shell pigment (ICSP) by heating, and the Cu(II) adsorption performance of ICSP was evaluated. The conversion was characterized, and the thermal treatment caused dehydration and loss of carboxyl groups and aliphatic structures in CSP. The kinetic adsorption behavior obeyed the pseudo-second-order rate law, and the equilibrium adsorption data were well described with both the Langmuir and the Freundlich isotherms. ICSP can be used as a renewable, readily-available, easily-producible, environmentally-friendly, inexpensive and effective adsorbent to remove heavy-metal from aquatic environments.


Assuntos
Cobre/química , Cyperaceae/química , Melaninas/química , Metais Pesados/química , Adsorção , Cobre/toxicidade , Cinética , Metais Pesados/toxicidade , Águas Residuárias/química , Águas Residuárias/toxicidade , Água/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Purificação da Água
15.
Mol Pharmacol ; 88(2): 326-34, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26013540

RESUMO

Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from neuritogenic gentisides. In the present study, we investigated the mechanism by which ABG-001 induces neurite outgrowth in a rat adrenal pheochromocytoma cell line (PC12). Inhibitors of insulin-like growth factor 1 (IGF-1) receptor, phosphatidylinositol 3-kinase (PI3K), and extracellular signal-regulated kinase (ERK) 1/2 significantly decreased ABG-001-induced neurite outgrowth. Western blot analysis revealed that ABG-001 significantly induced phosphorylation of IGF-1 receptor, protein kinase B (Akt), ERK, and cAMP responsive element-binding protein (CREB). These effects were markedly reduced by addition of the corresponding inhibitors. We also found that ABG-001-induced neurite outgrowth was reduced by protein kinase C inhibitor as well as small-interfering RNA against the IGF-1 receptor. Furthermore, like ABG-001, IGF-1 also induced neurite outgrowth of PC12 cells, and low-dose nerve growth factor augmented the observed effects of ABG-001 on neurite outgrowth. These results suggest that ABG-001 targets the IGF-1 receptor and activates PI3K, mitogen-activated protein kinase, and their downstream signaling cascades to induce neurite outgrowth.


Assuntos
Hidroxibenzoatos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neuritos/efeitos dos fármacos , Receptor IGF Tipo 1/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Ratos
16.
Biochim Biophys Acta ; 1838(10): 2451-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24946143

RESUMO

Our previous study reported that cerebrosides from traditional Chinese medicine Baifuzi directly interact with the STREX domain of BKCa channels, which in turn results in the therapeutic effect of Baifuzi on ischemic stroke. However, it is not known how cerebrosides in the plasma membrane could interact with the STREX domain that is in the cytoplasmic side. Using patch-clamp technique, effects of different cerebrosides on the BKCa channel were studied by measuring single channel currents in CHO cells expressing wild type or mutated BKCa channels. Palmitoylation of the STREX domain was removed either by site-directed mutagenesis or pharmacological inhibition. Removal of palmitoylation sites at C646 and C647 by mutating the residues to Ala abolished the ability of cerebrosides to activate the BKCa channel. In contrast, the mutation neither changed the single channel conductance nor voltage sensitivity of the channel. Both palmitoylation inhibitors tunicamycin and palmitic acid analog 2-bromopalmitate attenuated the activation of the BKCa channel by cerebrosides. Furthermore, confocal images on STREX-EGFP fragments demonstrated that STREX fragments no longer associated with the plasma membrane when the palmitoylation was removed or blocked. These findings suggest that palmitoylation of the STREX domain is necessary for cerebrosides to activate the BKCa channel and provide insight into the mechanism of how Baifuzi could exert therapeutic effect on ischemic stroke.


Assuntos
Proteínas Aviárias/metabolismo , Membrana Celular/metabolismo , Cerebrosídeos/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Lipoilação/fisiologia , Animais , Proteínas Aviárias/química , Proteínas Aviárias/genética , Células CHO , Membrana Celular/química , Membrana Celular/genética , Cerebrosídeos/química , Galinhas , Cricetinae , Cricetulus , Humanos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/química , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Lipoilação/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Mutagênese Sítio-Dirigida , Mutação de Sentido Incorreto , Técnicas de Patch-Clamp , Estrutura Terciária de Proteína , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/metabolismo
17.
Int J Neuropsychopharmacol ; 17(11): 1847-61, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24787365

RESUMO

Tetradecyl 2,3-dihydroxybenzoate, termed ABG001, has been reported to enhance neurite outgrowth of PC12 cells. Herein, we report that oral administration of ABG001 for five days to adult male mice could dose-dependently enhance survival and neurite growth of newborn cells in hippocampal dentate gyrus (DG) without changes in cell proliferation and differentiation of progenitor cells. The ABG001 administration (0.5 mg/kg) enhanced the phosphorylation of tyrosine kinase A (TrkA) receptor, which induced increases in the levels of ERK, Akt and mTOR phosphorylation in hippocampus. The pro-neurogenesis of ABG001 was blocked by the TrkA receptor inhibitor K252a. By contrast, the ERK inhibitor U0126 attenuated only the ABG001-increased number of newborn cells, while the PI3K inhibitor LY294002 prevented mainly the ABG001-enhanced neurite growth. In comparison with control mice, the mice treated with ABG001 showed a more preferential spatial cognitive function as assessed by Morris water maze and Y maze tests, which was sensitive to the blockade of TrkA receptor. In addition, a single injection (i.c.v.) of 'aggregated' Aß 25-35 in adult male mice (Aß 25-35-mice) impaired spatial memory, survival and neurite growth of newborn cells in the DG with reduced phosphorylation of Akt and mTOR. The treatment of Aß 25-35-mice with ABG001 could protect the survival and neurite growth of newborn cells through increasing TrkA receptor-induced phosphorylation of Akt and mTOR, which was accompanied by the improvement of spatial cognitive performance.


Assuntos
Demência/tratamento farmacológico , Hidroxibenzoatos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Receptor trkA/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Bromodesoxiuridina/metabolismo , Demência/induzido quimicamente , Modelos Animais de Doenças , Proteínas do Domínio Duplacortina , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Proteínas Associadas aos Microtúbulos/metabolismo , Neuropeptídeos/metabolismo , Fragmentos de Peptídeos/toxicidade , Fosfopiruvato Hidratase/metabolismo , RNA Mensageiro/metabolismo , Receptor trkA/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo
18.
Int J Mol Sci ; 15(12): 21660-73, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25429428

RESUMO

For screening anti-aging samples from marine natural products, K6001 yeast strain was employed as a bioassay system. The active mussel extract was separated to give an active sterol fraction (SF). SF was further purified, and four sterol compounds were obtained. Their structures were determined to be cholesterol (CHOL), brassicasterol, crinosterol, and 24-methylenecholesterol. All compounds showed similar anti-aging activity. To understand the action mechanism involved, anti-oxidative experiments, reactive oxygen species (ROS) assays, and malondialdehyde (MDA) tests were performed on the most abundant compound, CHOL. Results indicated that treatment with CHOL increases the survival rate of yeast under oxidative stress and decreases ROS and MDA levels. In addition, mutations of uth1, skn7, sod1, and sod2, which feature a K6001 background, were employed and the lifespans of the mutations were not affected by CHOL. These results demonstrate that CHOL exerts anti-aging effects via anti-oxidative stress. Based on the connection between neuroprotection and anti-aging, neuroprotective experiments were performed in PC12 cells. Paraquat was used to induce oxidative stress and the results showed that the CHOL and SF protect the PC12 cells from the injury induced by paraquat. In addition, these substance exhibited nerve growth factor (NGF) mimic activities again confirmed their neuroprotective function.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Mytilidae/química , Fármacos Neuroprotetores/farmacologia , Esteróis/farmacologia , Animais , Antioxidantes/química , Regulação da Expressão Gênica/efeitos dos fármacos , Malondialdeído/metabolismo , Mutação/genética , Fármacos Neuroprotetores/química , Oxirredução/efeitos dos fármacos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Esteróis/química
19.
J Environ Sci (China) ; 26(1): 54-64, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24649691

RESUMO

Dry deposition velocities and fluxes of PM10 during Asian dust events over the Yellow Sea from 2001 to 2007 were investigated using observation data in Qingdao, China and Jeju, Korea. The dry deposition velocities of PM10 during dust events over the Yellow Sea ranged from 0.19 to 8.17 cm/sec, with an average of 3.38 cm/sec. Dry deposition fluxes of PM10 during dust events over the Yellow Sea were in the range of 68.5-2647.1 mg/(m2 x day), with an average of 545.4 mg/(m2 x day), which is 2-10 times higher than those reported by other studies for both dust and non-dust periods. It was estimated that 2.6 x 10(11) -48.7 x 10(11) g dust particles deposit to the Yellow Sea during dust events through dry deposition every year. Compared with the results in previous studies, it was found that the dry deposition of PM10 over the Yellow Sea during dust events in the years with high frequency of dust could account for a large or overwhelming fraction of the annual total dry deposition. Backward air mass trajectory analysis showed that dust events influenced Jeju mainly originated from the desert regions located in Mongolia and Inner Mongolia, China. There were 119 backward trajectories influenced both Qingdao and Jeju during 15 dust events from 2001 to 2007, accounting for 61.3% of the total trajectories of 194, indicating that Qingdao and Jeju were usually on the same pathway of dust transport downwind from source areas.


Assuntos
Poeira/análise , Oceanos e Mares , Algoritmos , China , República da Coreia
20.
Antioxidants (Basel) ; 13(6)2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38929123

RESUMO

Aging is often accompanied by irreversible decline in body function, which causes a large number of age-related diseases and brings a huge economic burden to society and families. Many traditional Chinese medicines have been known to extend lifespan, but it has still been a challenge to isolate a single active molecule from them and verify the mechanism of anti-aging action. Drugs that inhibit senescence-associated secretory phenotypes (SASPs) are called "senomorphics". In this study, arctigenin (ATG), a senomorphic, was screened from the Chinese medicine Fructus arctii using K6001 yeast replicative lifespan. Autophagy, oxidative stress, and telomerase activity are key mechanisms related to aging. We found that ATG may act through multiple mechanisms to become an effective anti-aging molecule. In exploring the effect of ATG on autophagy, it was clearly observed that ATG significantly enhanced autophagy in yeast. We further verified that ATG can enhance autophagy by targeting protein phosphatase 2A (PP2A), leading to an increased lifespan. Meanwhile, we evaluated the antioxidant capacity of ATG and found that ATG increased the activities of the antioxidant enzymes, thereby reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels to improve the survival of yeast under oxidative stress. In addition, ATG was able to increase telomerase activity by enhancing the expression of EST1, EST2, and EST3 genes in yeast. In conclusion, ATG exerts anti-aging effects through induction of autophagy, antioxidative stress, and enhancement of telomerase activity in yeast, which is recognized as a potential molecule with promising anti-aging effects, deserving in-depth research in the future.

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