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1.
Protein Cell ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635907

RESUMO

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease (GD) and Parkinson's disease (PD). Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

2.
Zhongguo Zhong Yao Za Zhi ; 48(4): 985-992, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872269

RESUMO

The present study investigated the chemical constituents in the aerial part of Cannabis sativa. The chemical constituents were isolated and purified by silica gel column chromatography and HPLC and identified according to their spectral data and physicochemical properties. Thirteen compounds were isolated from the acetic ether extract of C. sativa and identified as 3',5',4″,2-tetrahydroxy-4'-methoxy-3-methyl-3″-butenyl p-disubstituted benzene ethane(1), 16R-hydroxyoctadeca-9Z,12Z,14E-trienoic acid methyl ester(2),(1'R,2'R)-2'-(2-hydroxypropan-2-yl)-5'-methyl-4-pentyl-1',2',3',4'-tetrahydro-(1,1'-biphenyl)-2,6-diol(3), ß-sitosteryl-3-O-ß-D-glucopyranosyl-6'-O-palmitate(4), 9S,12S,13S-trihydroxy-10-octadecenoate methyl ester(5), benzyloxy-1-O-ß-D-glucopyranoside(6), phenylethyl-O-ß-D-glucopyranoside(7), 3Z-enol glucoside(8), α-cannabispiranol-4'-O-ß-D-glucopyranose(9), 9S,12S,13S-trihydroxyoctadeca-10E,15Z-dienoic acid(10), uracil(11), o-hydroxybenzoic acid(12), and 2'-O-methyladenosine(13). Compound 1 is a new compound, compound 3 is a new natural product, and compounds 2, 4-8, 10, and 13 were isolated from Cannabis plant for the first time.


Assuntos
Produtos Biológicos , Cannabis , Di-Hidroestilbenoides , Ésteres , Componentes Aéreos da Planta
3.
Biotechnol Adv ; 64: 108107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36758651

RESUMO

Lignin is the most affluent natural aromatic biopolymer on the earth, which is the promising renewable source for valuable products to promote the sustainability of biorefinery. Flavonoids are a class of plant polyphenolic secondary metabolites containing the benzene ring structure with various biological activities, which are largely applied in health food, pharmaceutical, and medical fields. Due to the aromatic similarity, microbial conversion of lignin derived aromatics to flavonoids could facilitate flavonoid biosynthesis and promote the lignin valorization. This review thereby prospects a novel valorization route of lignin to high-value natural products and demonstrates the potential advantages of microbial bioconversion of lignin to flavonoids. The biodegradation of lignin polymers is summarized to identify aromatic monomers as momentous precursors for flavonoid synthesis. The biosynthesis pathways of flavonoids in both plants and strains are introduced and compared. After that, the key branch points and important intermediates are clearly discussed in the biosynthesis pathways of flavonoids. Moreover, the most significant enzyme reactions including Claisen condensation, cyclization and hydroxylation are demonstrated in the biosynthesis pathways of flavonoids. Finally, current challenges and potential future strategies are also discussed for transforming lignin into various flavonoids. The holistic microbial conversion routes of lignin to flavonoids could make a sustainable production of flavonoids and improve the feasibility of lignin valorization.


Assuntos
Flavonoides , Lignina , Lignina/química , Biodegradação Ambiental
4.
J Ethnopharmacol ; 301: 115834, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36270558

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mume Fructus (MF) is processed from the near-ripe fruit of Prunus mume (Siebold) Siebold & Zucc by drying at low temperature until the color turns black. MF is often used in Chinese medicine for the treatment of chronic diarrhea and dysentery. Previous studies have shown that the active components of MF against Crohn's disease (CD) are mainly citrate and hydroxycinnamate derivatives, which can alleviate the CD-induced inflammatory response and intestinal barrier damage. However, their molecular mechanisms on CD still need further elucidation. AIM OF THE STUDY: To investigate the protective effects and underlying mechanisms of citrate and hydroxycinnamate derivatives in MF on intestinal epithelial injury. MATERIALS AND METHODS: Network pharmacology technology was used to predict the anti-CD targets and molecular mechanisms of 4 citrate and 11 hydroxycinnamate derivative prototypes and 5 hydroxycinnamate derivative metabolites in the 40% ethanol fraction of MF (MFE40), the active anti-CD ingredient group of MF. Lipopolysaccharide (LPS)-treated IEC-6 cells were used to investigate the effects of the above components on the proliferation of damaged IEC-6 cells and to verify the molecular mechanism of their regulation on the FAK/PI3K/AKT signaling pathways for the promotion of the proliferation of IEC-6 cells. RESULTS: A "compound-target-pathway" network was constructed based on network pharmacology analysis, including 20 citrate and hydroxycinnamate derivatives that target 316 core proteins and 36 CD-related pathways, of which PI3K-AKT pathway and focal adhesion were the most enriched pathways. Further cell validation experiments showed that 1 citric acid (CA) compound and 10 hydroxycinnamate derivatives, including 3-O-caffeoylquinic acid (3CQA), 4-O-caffeoylquinic acid (4CQA), 5-O-caffeoylquinic acid (5CQA), caffeic acid (CFA), p-coumaric acid (PCMA), m-coumaric acid (MCMA), ferulic acid (FUA), isoferulic acid (IFUA), 3-hydroxyphenylpropionic acid (3HPPA) and hippuric acid (HPP), could promote the proliferation of IEC-6 cells and inhibit the damage of LPS to IEC-6 cells. Ethyl caffeate (ECFA), a hydroxycinnamic acid derivative, had no effect on promoting the proliferation of IEC-6 cells and was weak in inhibiting the damage of IEC-6 cells caused by LPS. Further mechanistic verification experiments showed that 7 citrate and hydroxycinnamate derivatives (CA, CFA, 3CQA, MCMA, FUA, 3HPPA, and HPP) could upregulate the expression of p-FAK, p-PI3K, and p-AKT proteins. Among them, CA had the better effect on activating the FAK-PI3K-AKT signaling pathway. CONCLUSIONS: Citrate and hydroxycinnamate derivatives in MF can ameliorate LPS-induced intestinal epithelial cell injury to demonstrate potential for Crohn's disease alleviation. This protective effect can be achieved by upregulating FAK/PI3K/AKT pathway.


Assuntos
Doença de Crohn , Lipopolissacarídeos , Lipopolissacarídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Frutas/metabolismo , Ácido Cítrico , Doença de Crohn/metabolismo , Doença de Crohn/terapia , Transdução de Sinais , Células Epiteliais
5.
Int J Biol Sci ; 18(11): 4469-4481, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35864969

RESUMO

Our study is to explore the key molecular of Low-density lipoprotein receptor-related protein 6 (LRP6) and the related Wnt/ß-catenin pathway regulated by LRP6 during the intestinal barrier dysfunction. Colorectal protein profile analysis showed that LRP6 expression was decreased in dextran sulfate sodium (DSS)-induced colitis mice, and mice received fecal bacteria transplantation from stroke patients. Mice with intestinal hypoxia and intestinal epithelial cells cultured in hypoxia showed decreased expression of LRP6. Overexpression of LPR6 or its N-terminus rescued the Wnt/ß-catenin signaling pathway which was inhibited by hypoxia and endoplasmic reticulum stress. In mice overexpressing of LRP6, the expression of ß-catenin and DKK1 increased, Bcl2 decreased, and Bax increased. Mice with LRP6 knockout showed an opposite trend, and the expression of Claudin2, Occludin and ZO-1 decreased. Two drugs, curcumin and auranofin could alleviate intestinal barrier damage in DSS-induced colitis mice by targeting LRP-6. Therefore, gut microbiota dysbiosis and hypoxia can inhibit the LRP6 and Wnt/ß-catenin pathway, and drugs targeting LRP6 can protect the intestinal barrier.


Assuntos
Colite , Microbioma Gastrointestinal , Via de Sinalização Wnt , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Hipóxia , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos , beta Catenina/genética , beta Catenina/metabolismo
6.
J Ethnopharmacol ; 296: 115465, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35718051

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mume Fructus (MF) is a well-known traditional Chinese medicine used to treat chronic cough, prolonged diarrhea, and other inflammation-related diseases. We previously confirmed the anti-colitis effect of its ethanol extract on a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced Crohn's disease (CD) rat model. However, the active ingredients and underlying mechanisms of MF remain unknown. AIM OF THE STUDY: To clarify the material basis and potential mechanism of the ethanol extract of MF (MFE) in alleviating CD and its complications, such as lung injury and intestinal obstruction. MATERIALS AND METHODS: MF was extracted with 80% ethanol aqueous solution and separated with 0, 40, and 100% ethanol aqueous solutions. MFE and its fractions were screened in a TNBS-induced CD rat model. For the bioactive fraction, the chemical composition was identified and quantified using ultrahigh-performance liquid chromatography coupled with diode-array detection and quadrupole time-of-flight tandem mass spectrometry. Interleukin (IL)-1ß, IL-6, IL-17, transforming growth factor (TGF)-ß, and lipopolysaccharide (LPS) levels in the colon, lungs, and/or plasma were detected using enzyme-linked immunosorbent assays. The expression levels of zonula occludens-1 (ZO-1) and occludin in the colon were measured using immunohistochemical staining, and the intestinal microbiota and short-chain fatty acid (SCFA) levels were analyzed using 16S rRNA gene sequencing and gas chromatography/mass spectrometry. RESULTS: The 40% ethanol fraction of MF (MFE40), which mainly contained methyl citrate, ethyl citrate, and caffeoylquinic acid ethyl esters, was identified as the active fraction that could alleviate CD in rats. MFE40 could ameliorate inflammation and fibrosis in the colon and lung tissues by inhibiting the secretion of cytokines, such as IL-1ß, IL-6, IL-17, and TGF-ß, along with intestinal obstruction and lung injury in CD rats. The possible mechanisms of MFE40 were related to increased expression of ZO-1 and occludin in the colon, reduction in plasma LPS levels, and restoration of SCFAs via reduction in the relative abundance of Adlercreutzia, Clostridium_sensu_stricto_1, Erysipelatoclostridium, Faecalibaculum, norank_f_Erysipelotrichaceae, Phascolarctobacterium Coriobacteriaceae_UGG_002, and Allobaculum and increase in the relative abundance of Escherichia shigella, Christensenella, Acetivibrio_ethanolgignens, and Butyricicoccus. MFE40 had no significant influence on the inflammatory factors in healthy rats. CONCLUSIONS: Citrate esters and hydroxycinnamate esters are the main active constituents of MFE40. MFE40 exhibited a remission effect on CD rats and inhibited intestinal obstruction and lung injury via anti-inflammatory effects and regulation of the intestinal microbiota-gut-lung homeostasis.


Assuntos
Doença de Crohn , Obstrução Intestinal , Lesão Pulmonar , Animais , Citratos/metabolismo , Colo , Doença de Crohn/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Etanol/farmacologia , Inflamação/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Obstrução Intestinal/metabolismo , Lipopolissacarídeos/farmacologia , Lesão Pulmonar/metabolismo , Ocludina/metabolismo , RNA Ribossômico 16S , Ratos , Ácido Trinitrobenzenossulfônico/toxicidade
7.
Front Nutr ; 9: 836500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600818

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease. Tianqi Pingchan Granule (TPG) is a clinically effective formula of traditional Chinese medicine to treat PD. However, the therapeutic effect and underlying mechanisms of TPG in PD remain unclear. Based on network pharmacology, the corresponding targets of TPG were identified using the Traditional Chinese Medicine Database and Analysis Platform Database. Differentially expressed genes in PD were obtained from the Therapeutic Target Database, Online Mendelian Inheritance in Man, GeneCards, and DrugBank databases. The protein-protein interaction (PPI) networks of intersected targets were constructed using the STRING database and visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the pathways directly related to the pathogenesis of PD were integrated manually. Furthermore, in vivo studies were carried out based on network pharmacology. The gut microbiota, peripheral inflammatory cytokines, and glia-mediated neuroinflammation in substantia nigra were evaluated. A total of 99 target genes were intersected between targets of TPG and deferentially expressed genes in PD. The PPI network analysis indicated the proinflammatory cytokine as essential targets. GO and KEGG analyses indicated that inflammatory response and its related signaling pathways were closely associated with TPG-mediated PD treatment. In vivo studies revealed that class Negativicutes and order Selenomonadales decreased, whereas class Mollicutes, order Enterobacteriales, and Mycoplasmatales increased in fecal samples of PD rats via 16S rRNA sequence analysis. Furthermore, the function prediction methods purposely revealed that TPG therapy may be involved in flavonoid biosynthesis, which have anti-inflammatory properties. In addition, in vivo studies revealed that TPG exposure was found to not only attenuate the production of peripheral inflammatory cytokines but also inhibit the activation of microglia and astrocytes in substantia nigra of PD rats. Through network pharmacology and in vivo experiment-combined approach, the mechanisms of TPG in the treatment of PD were revealed, and the role of TPG in the regulation of gut microbiota and inflammatory response was confirmed.

8.
Phytomedicine ; 99: 154002, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35231824

RESUMO

BACKGROUND: Mume Fructus (MF) is used in traditional Chinese herbal medicine (TCM) to treat chronic cough, prolonged diarrhea, and other inflammation-related diseases. It is processed from Prunus mume fruit (PM) by drying at low temperature according to the Chinese Pharmacopoeia. The standard quality control method includes measurement of citric acid content, which is not sufficient to determine its clinical efficacy. In addition, the quality markers, that would ensure consistent drug composition and stability during extraction and processing of the drug, are currently not available. PURPOSE: This study sought to determine and analyze the bioactive compounds in MF and to establish the quality maker evaluation system, which would enable accurate assessment of different processing and extraction approaches for MF preparation. STUDY DESIGN AND METHODS: First, a UPLC-QTOF-MS/MS method was established to identify the chemical constituents of PM and MF. Second, the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-treated rats were used to assess anti-inflammatory activity of water and ethanol extracts of PM and MF. Third, correlation analysis and multivariate statistical analysis was used to seek the candidate quality markers of MF. Fourth, molecular docking was used to predict the potential mechanism of identified compounds for the anti-inflammatory activity. Finally, a UPLC method was established to quantify the selected quality markers in MF products, that were prepared by different drying processes. RESULTS: 99 components (28 newly reported) were identified from PM and MF. During the drying process several changes in the composition were observed; caffeoylquinic acids were degraded to p-coumaric acid, caffeic acid, protocatechuic acid, or p-hydroxybenzoic acid; multi-acetyl p-coumaroyl sucroses were degraded to mumeose R and p-coumaroyl-3-O-sucrose. On the other hand, contents of mumefural and amygdalin increased after drying process. In colitis rats, MF reduced more NO levels to greater extent in comparison to PM, which could be attributed to the presence of caffeic acid, p-coumaric acid, protocatechuic acid, p-hydroxybenzoic acid, mumefural, p-coumaroyl-3-O-sucrose, mumeose R, and amygdalin in MF. Moreover, water extracts were better than ethanol extracts in alleviating the IL-1ß, IL-6, and IL-17 levels, possibly on account of citric acid and caffeoylquinic acids. The predicted mechanism of action could be through inhibition of the production of NLRP3, TLR4, and NF-κB proteins. Finally, 7 compounds (citric acid, 3-O-caffeoylquinic acid, 5-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, caffeic acid, protocatechuic acid, and p-coumaric acid) were selected as quality markers of MF that could be used for the process quality control. CONCLUSION: This study revealed the material basis of PM and MF for anti-colitis activity and discovered the quality markers of MF which could reflect the anti-inflammatory activity and the processing process of MF.

9.
Biol Trace Elem Res ; 200(4): 1956-1964, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34275097

RESUMO

Ramulus Mori alkaloids, also known as SangZhi alkaloids (SZ-A), is a natural medicine used for the treatment of type 2 diabetes mellitus in China. SZ-A is extracted from Morus alba L., which grows in the natural environment and may be contaminated by heavy metals and harmful elements. These contaminants can enter SZ-A products during the extraction of M. alba, thereby posing a threat to patient health. Therefore, it is necessary to formulate scientific and reasonable limits to ensure patient safety. For this purpose, in this study, we used the extraction process of SZ-A as the object of investigation and determined the content of five harmful elements: Cd, Pb, As, Hg, and Cu in the herb raw material, SZ-A product, and its intermediates obtained in different extraction steps. Next, the transfer rate of harmful elements in the extraction process was used as an indicator to evaluate the ability of different operations to remove harmful elements. Subsequently, the health risks of heavy metals and harmful elements in SZ-A were assessed. Our results demonstrated that M. alba has little risk of contamination by Hg. The cation and anion resin refining processes are the best effective method to remove Cd, Pb, and Cu from the products. However, As is not easily eliminated during the water extraction. There is as much as 87% of As transferred from the herb raw material to the water-extracted intermediate, while Cd, Pb, and Cu are rarely transferred (6% to 17%) under the same conditions. Overall, the results indicate that the regulatory standard limits for Cd, Pb, As, Hg, and Cu contained in natural medicine Ramulus Mori alkaloids are set to 1, 5, 2, 0.2, and 20 µg/g, respectively, which is the most scientific and it can guarantee the safety of patients.


Assuntos
Diabetes Mellitus Tipo 2 , Metais Pesados , China , Contaminação de Medicamentos , Monitoramento Ambiental , Humanos , Medicina Tradicional Chinesa , Metais Pesados/análise , Medição de Risco
10.
Rapid Commun Mass Spectrom ; 35(6): e9012, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33238063

RESUMO

RATIONALE: Flavones are significant indicators of quality in traditional Chinese medicines (TCMs) and thus play a significant role in the quality control of TCMs in the pharmaceutical industry. Most flavones in Dendrobium nobile Lindl, a TCM with a long cultivation history and rich sources, have not been identified. This study was aimed at identifying the flavones in D. nobile from various habitats. METHODS: High-performance liquid chromatography (HPLC) coupled with diode-array detection and HPLC multiple-stage tandem mass spectrometry was used to identify the chemical constituents of D. nobile from various habitats, and a method was established to determine the content of vicenin II, violanthin and isoviolanthin. Hierarchical cluster analysis, principal component analysis and orthogonal partial least-squares discriminant analysis were used to analyze the variations among 26 batches from different habitats. RESULTS: A total of 33 flavones were tentatively identified. Twenty-five flavones, previously undescribed in D. nobile, were acylated by p-coumaroyl, feruloyl, sinapoyl or 3-hydroxy-3-methylglutaryl. The D. nobile habitats were distinguished by significant differences in their flavone content. The C-glycosyl flavones were demonstrated to be characteristic compounds for evaluating D. nobile from various habitats. In particular, flavones acylated with 3-hydroxy-3-methylglutaryl were specific compounds that were only detected in samples from Yunnan. CONCLUSIONS: The results of this study could be used to improve the quality control of D. nobile and could provide references for the identification of acylated C-glycosyl flavones in other natural products.


Assuntos
Medicamentos de Ervas Chinesas/química , Flavonas/química , China , Cromatografia Líquida de Alta Pressão , Dendrobium/química , Estrutura Molecular , Controle de Qualidade , Espectrometria de Massas em Tandem
11.
Theranostics ; 10(8): 3594-3611, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32206110

RESUMO

Background: Accumulating evidences indicate that nanomedicines greatly decrease the side effects and enhance the efficacy of colorectal cancer (CRC) treatment. In particular, the use of rectal delivery of nanomedicines, with advantages such as fast therapeutic effects and a diminishing hepatic first-pass effect, is currently emerging. Method: We established a CRC targeted delivery system, in which α-lactalbumin peptosomes (PSs) co-loaded with a microRNA (miR)-31 inhibitor (miR-31i) and curcumin (Cur) were encapsuslated in thiolated TEMPO oxidized Konjac glucomannan (sOKGM) microspheres, referred as sOKGM-PS-miR-31i/Cur. The CRC targeting capability, drug release profiles, mucoadhesive-to-penetrating properties and therapeutic efficacy of sOKGM-PS-miR-31i/Cur delivery system were evaluated in colorectal cancer cells and azoxymethane-dextran sodium (AOM-DSS) induced tumor models. Results: sOKGM-PS-miR-31i/Cur delivery system were stable in the harsh gastrointestinal environment after rectal or oral administration; and were also mucoadhesive due to disulfide bond interactions with the colonic mucus layer, resulting in an enhanced drug retention and local bioavailability in the colon. Concomitantly, the released PS-miR-31i/Cur PSs from the microsphere was mucus-penetrating, efficiently passing through the colonic mucus layer, and allowed Cur and miR-31i specifically target to colon tumor cells with the guide of CD133 targeting peptides. Consequently, rectal delivery of sOKGM-PS-miR-31i/Cur microspheres suppressed tumor growth in an azoxymethane-dextran sodium sulfate (AOM-DSS)-induced tumor model. Conclusion: sOKGM-PS-miR-31i/Cur microspheres are effective rectal delivery system with combined advantages of mucoadhesive and mucus-penetrating properties, representing a potent and viable therapeutic approach for CRC.


Assuntos
Antagomirs/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Curcumina/administração & dosagem , MicroRNAs/antagonistas & inibidores , Animais , Antagomirs/administração & dosagem , Disponibilidade Biológica , Moléculas de Adesão Celular/metabolismo , Curcumina/farmacocinética , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Quimioterapia Combinada , Molécula de Adesão da Célula Epitelial/administração & dosagem , Molécula de Adesão da Célula Epitelial/farmacocinética , Molécula de Adesão da Célula Epitelial/uso terapêutico , Lactalbumina/farmacocinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microesferas , Nanomedicina/métodos , Nanomedicina/estatística & dados numéricos , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/farmacocinética , Absorção Retal/fisiologia
12.
Chemosphere ; 243: 125428, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995880

RESUMO

Toxic elements exposure disturbs the homeostasis of essential elements in organisms, but the mechanism remains elusive. In this study, we demonstrated that Drosophila melanogaster exposed to Lead (Pb, a pervasive environmental threat to human health) exhibited various health defects, including retarded development, decreased survival rate, impaired mobility and reduced egg production. These phenotypes could be significantly modulated by either intervention of dietary iron levels or altering expression of genes involved in iron metabolism. Further study revealed that Pb exposure leads to systemic iron deficiency. Strikingly, reactive oxygen species (ROS) clearance significantly increased iron uptake by restoring the expression of iron metabolism genes in the midgut and subsequently attenuated Pb toxicity. This study highlights the role of ROS in Pb induced iron dyshomeostasis and provides unique insights into understanding the mechanism of Pb toxicity and suggests ideal ways to attenuate Pb toxicity by iron supplementation therapy or ROS clearance.


Assuntos
Anemia Ferropriva/etiologia , Drosophila melanogaster/metabolismo , Chumbo/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Anemia Ferropriva/induzido quimicamente , Animais , Dieta , Drosophila melanogaster/efeitos dos fármacos , Homeostase , Humanos , Ferro/metabolismo , Chumbo/metabolismo , Espécies Reativas de Oxigênio/metabolismo
13.
Glob Chang Biol ; 26(2): 682-696, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31596019

RESUMO

Arctic and boreal ecosystems play an important role in the global carbon (C) budget, and whether they act as a future net C sink or source depends on climate and environmental change. Here, we used complementary in situ measurements, model simulations, and satellite observations to investigate the net carbon dioxide (CO2 ) seasonal cycle and its climatic and environmental controls across Alaska and northwestern Canada during the anomalously warm winter to spring conditions of 2015 and 2016 (relative to 2010-2014). In the warm spring, we found that photosynthesis was enhanced more than respiration, leading to greater CO2 uptake. However, photosynthetic enhancement from spring warming was partially offset by greater ecosystem respiration during the preceding anomalously warm winter, resulting in nearly neutral effects on the annual net CO2 balance. Eddy covariance CO2 flux measurements showed that air temperature has a primary influence on net CO2 exchange in winter and spring, while soil moisture has a primary control on net CO2 exchange in the fall. The net CO2 exchange was generally more moisture limited in the boreal region than in the Arctic tundra. Our analysis indicates complex seasonal interactions of underlying C cycle processes in response to changing climate and hydrology that may not manifest in changes in net annual CO2 exchange. Therefore, a better understanding of the seasonal response of C cycle processes may provide important insights for predicting future carbon-climate feedbacks and their consequences on atmospheric CO2 dynamics in the northern high latitudes.


Assuntos
Ecossistema , Fotossíntese , Alaska , Regiões Árticas , Canadá , Ciclo do Carbono , Dióxido de Carbono , Mudança Climática , Estações do Ano
14.
J Cancer ; 10(24): 5986-5991, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31762808

RESUMO

Background: This study sought to evaluate the efficacy of a novel intraoperative chemotherapy (IOC) regimen that consists of hydroxycamptothecin, tumor necrosis factor (TNF), 5-fluorouracil (5-FU), and calcium folinate (CF) on the outcomes of colorectal cancer (CRC). Methods: In total, 551 CRC patients who had undergone surgical resection were evaluated. Among these patients, 247 were treated with postoperative adjuvant chemotherapy, and 193 were treated with intraoperative chemotherapy. Of the CRC patients who underwent chemotherapy, 52 were treated with both postoperative adjuvant chemotherapy and intraoperative chemotherapy. Patients' characteristics, including age, sex, stage, differentiation, lymph node metastasis, surgical-pathological staging, tumor location, tumor size, and relapse-free survival, were collected. Results: IOC for CRC therapy was associated with a more favorable survival prognosis (HR, 0.30, 95%CI, 0.19-0.48, P<0.001) independent of other clinical covariates. CRC patients treated with IOC survived longer than patients who were not treated with IOC did during surgery (P<0.0001, Kaplan-Meier log rank). Meanwhile, a Kaplan-Meier analysis demonstrated that individuals who received both IOC and POC survived longer than patients who received only POC: for stage II and stage III patients (P=0.0001, Kaplan-Meier log rank), stage II patients alone (P=0.02, Kaplan-Meier log rank), and stage III patients alone (P=0.046, Kaplan-Meier log rank). Conclusions: The therapeutic effects of colorectal cancer by intraoperative chemotherapy with a novel regimen were enhanced, which improved the prognosis of patients with CRC.

15.
Steroids ; 150: 108424, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31201842

RESUMO

Nicandra physaloides is a medicinal and edible plant and has been used as traditionally herbal medicine to treat various diseases in folk. Its characteristic withanolides, a kind of ergostane-type steroids, are reported to display plentiful biological activities that many explain the effect of N. physaloides to some extent. Thus, to further find bioactive steroids, the stems and leaves of N. physaloides were investigated and three new C23 steroids, nic-physatones I-J (1-2), and nic-physatone S (3), together with a known C25 steroid, nic 17 (4), were isolated. Their structures were elucidated by extensive 1D NMR and 2D NMR (HSQC, HMBC, 1H-1H COSY, and ROESY), UV and MS analyses. Compounds 1-3 possess a rare C23 steroid skeleton. Among them, compound 3 represented the first example of a C23 steroid featuring a benzene ring (D ring). The isolated compounds showed no cytotoxic activity.


Assuntos
Antineoplásicos/química , Neoplasias/tratamento farmacológico , Solanaceae/química , Esteroides/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/química , Esteroides/isolamento & purificação , Esteroides/farmacologia
16.
Chemosphere ; 215: 163-172, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30316158

RESUMO

Spent coffee grounds (SCG-1 and SCG-2) were used to study the adsorption of tetracycline (TC) antibiotics and the effects of adsorption time, initial pH, amount of adsorbent and ionic strength were detected. The TC adsorption isotherm on SCG-1 was compared with SCG-2. The results showed that the removal efficiencies of TC (50 mg/L) of SCG-1 and SCG-2 were 83.1% and 97.2%, respectively, shake for 2 h. The probability of adsorption is high and balances in about 20 min. The estimate of parameters got for TC from the Langmuir isotherm saturated adsorption quantity and adsorption balance constant were 64.89 mg/g, 0.0557 L/mg, respectively for SCG-1 and 123.46 mg/g, 0.4735 L/mg, respectively for SCG-2. The adsorption mechanism might be a π-π interaction that occurs in the interface by hydrogen bonding and the between the TC molecular and the SCGs. At last, we found that SCG has a high adsorption size for TC.


Assuntos
Antibacterianos/isolamento & purificação , Café/química , Tetraciclina/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Adsorção , Antibacterianos/química , Tetraciclina/química , Poluentes Químicos da Água/química
17.
Nat Prod Res ; 31(23): 2730-2736, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28326801

RESUMO

Three new isobenzofurans (1-3), together with four known phenylpropanoids (4-7) were isolated from the roots of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1-6 were tested for their anti-tobacco mosaic virus (anti-TMV) activities and cytotoxicity activities. The results showed that compounds 5 and 6 exhibited high anti-TMV activities with inhibition rates of 35.1 and 33.4%, respectively. The cytotoxicities of compounds 1-7 against five human tumor cell lines (NB4, A549, SHSY5Y, PC3 were also tested. Compounds 1-7 showed weak inhibitory activities against some tested human tumor cell lines with IC50 values in the range of 3.8-9.6 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antivirais/farmacologia , Benzofuranos/química , Nicotiana/química , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antivirais/química , Benzofuranos/farmacologia , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Raízes de Plantas/química
18.
Eur Spine J ; 26(7): 1961-1968, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28283839

RESUMO

PURPOSE: Phosphodiesterase inhibitors possess anti-inflammatory properties. In addition, some studies report that phosphodiesterase 2A (PDE2A) are highly expressed in the dorsal horn of the spinal cord. The present study aimed to investigate whether intrathecal administration of Bay 60-7550, a specific PDE2A inhibitor, could alleviate mechanical allodynia in non-compressive lumbar disc herniation (NCLDH) rats. METHODS: Rat NCLDH models by autologous nucleus pulposus implantation to dorsal root ganglion were established. Vehicle or Bay 60-7550 (0.1, 1.0 mg/kg) was injected by intrathecal catheter at day 1 post-operation. The ipsilateral mechanical withdrawal thresholds were analyzed from the day before surgery to day 7 after surgery. At day 7 post-operation, the ipsilateral lumbar (L4-L6) segments of the spinal dorsal horns were removed, and tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) expressions were measured by ELISA. Furthermore, PDE2A mRNA and protein expressions in spinal cord were measured by Real-Time PCR and Western blot. RESULTS: Intrathecal administration of the PDE2A inhibitor Bay 60-7550, significantly attenuated mechanical allodynia, down-regulated spinal TNF-α, IL-1ß and IL-6 over-expressions, increased the expression of spinal cAMP, as well as cGMP in a more remarkable manner, and decreased the spinal PDE2A expression in NCLDH rats in a dose-dependent manner. CONCLUSIONS: Bay 60-7550 alleviated mechanical allodynia and inflammation in NCLDH rats, which might be associated with increased cAMP and especially cGMP increase. Thus, spinal PDE2A inhibition might represent a potential analgesic strategy for radiculopathy treatment in non-compressive lumbar disc herniation.


Assuntos
Anti-Inflamatórios/uso terapêutico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores , Hiperalgesia/tratamento farmacológico , Imidazóis/uso terapêutico , Deslocamento do Disco Intervertebral/tratamento farmacológico , Triazinas/uso terapêutico , Animais , Biomarcadores/metabolismo , Western Blotting , Ensaio de Imunoadsorção Enzimática , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Injeções Espinhais , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Medula Espinal/metabolismo , Resultado do Tratamento
19.
J Agric Food Chem ; 65(9): 1887-1892, 2017 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-28212012

RESUMO

(+)-Meyeniins A-C (1-3), a novel class of sulfur-containing hexahydroimidazo[1,5-c]thiazole derivatives, were isolated from the tubers of Lepidium meyenii (maca) cultivated in Lijiang, Yunnan province, China. Guided by their biosynthetic hypothesis, a stereocontrolled biomimetic synthesis of meyeniins A-C and their individual enantiomers was efficiently accomplished by a combination of a condensation reaction and Edman degradation. The formation of high-quality crystals for X-ray crystallography occurred much more readily from a racemic mixture of (±)-meyeniin A than with the single enantiomer alone in this case. These extensive strategies, combined with circular dichroism (CD) spectra, allowed the complete structural assignments of (+)-meyeniins A-C. Among them, (+)-meyeniin A showed moderate selective cytotoxicities against the HL-60, A549 and MCF-7 human cell lines with IC50 values of 14.41, 32.22, and 33.14 µM, respectively. To some extent, these findings support traditional applications of maca as healthy nutritional supplements or functional foods for cancer prevention.


Assuntos
Imidazóis/química , Lepidium/química , Extratos Vegetais/química , Tubérculos/química , Tiazóis/química , Biomimética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalização , Cristalografia por Raios X , Humanos , Imidazóis/isolamento & purificação , Imidazóis/farmacologia , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Tiazóis/isolamento & purificação
20.
Molecules ; 22(2)2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28212296

RESUMO

Essential oil extracted from Houttuynia cordata Thunb. (H. cordata) is widely used in traditional Chinese medicine due to its excellent biological activities. However, impurities and deficient preparations of the essential oil limit its safety and effectiveness. Herein, we proposed a strategy to prepare H. cordata essential oil (HEO) safely and effectively by combining the solvent extraction and the macroporous resin purification flexibly, and then encapsulating it using microemulsion. The extraction and purification process were optimized by orthogonal experimental design and adsorption-desorption tests, respectively. The average houttuynin content in pure HEO was then validated at 44.3% ± 2.01%, which presented a great potential for industrial application. Subsequently, pure HEO-loaded microemulsion was prepared by high-pressure homogenization and was then fully characterized. Results showed that the pure HEO-loaded microemulsion was successfully prepared with an average particle size of 179.1 nm and a high encapsulation rate of 94.7%. Furthermore, safety evaluation tests and in vitro antiviral testing indicated that the safety and activity of HEO were significantly improved after purification using D101 resin and were further improved by microemulsion encapsulation. These results demonstrated that the purification of HEO by macroporous resin followed by microemulsion encapsulation would be a promising approach for industrial application of HEO for the antiviral therapies.


Assuntos
Antivirais/química , Antivirais/farmacologia , Houttuynia/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Adsorção , Animais , Composição de Medicamentos , Emulsões , Cromatografia Gasosa-Espectrometria de Massas , Hemólise/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Resinas Vegetais , Solventes , Testes de Toxicidade Aguda
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