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1.
Biotechnol Appl Biochem ; 63(1): 92-100, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25643814

RESUMO

The biosynthesis of medium-chain-length poly-3-hydroxyalkanoates by Pseudomonas putida Bet001 cultivated on mixed carbon sources was investigated. The mixed carbon sources consisted of heptanoic acid (HA) and oleic acid (OA). A relatively low PHA content at 1.2% (w/w) and 11.4% (w/w) was obtained when HA or OA was used as the sole carbon source. When these fatty acids were supplied as a mixture, PHA content increased threefold. Interestingly, the mixture-derived PHA composed of both odd and even monomer units, namely. 3-hydroxyheptanoate, 3-hydroxyoctanoate, 3-hydroxydecanoate, and 3-hydroxydodecanoate and no unsaturated monomer was detected. It is hypothesized that the even-numbered monomers were derived primarily from OA, whereas the odd-numbered monomer was derived from HA. This also points out to an efficient and yet distinct fatty acids metabolism that fed the PHA biosynthesis machinery of this particular microorganism. PHA obtained was elastomeric because melting temperature (Tm ) and crystallinity were absent. It showed good thermal stability with degradation temperature (Td ) ranging from 275.96 to 283.05 °C.


Assuntos
Ácidos Graxos/metabolismo , Poli-Hidroxialcanoatos/metabolismo , Pseudomonas putida/metabolismo , Ácidos Heptanoicos/metabolismo , Ácido Oleico/metabolismo , Poli-Hidroxialcanoatos/química , Pseudomonas putida/química , Pseudomonas putida/crescimento & desenvolvimento , Águas Residuárias/microbiologia
2.
PeerJ ; 3: e1376, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26539336

RESUMO

Lactobacillus plantarum BET003 isolated from Momordica charantia fruit was used to ferment its juice. Momordica charantia fresh juice was able to support good growth of the lactic acid bacterium. High growth rate and cell viability were obtained without further nutrient supplementation. In stirred tank reactor batch fermentation, agitation rate showed significant effect on specific growth rate of the bacterium in the fruit juice. After the fermentation, initially abundant momordicoside 23-O-ß-Allopyranosyle-cucurbita-5,24-dien-7α,3ß,22(R),23(S)-tetraol-3-O-ß-allopyranoside was transformed into its corresponding aglycone in addition to the emergence of new metabolites. The fermented M. charantia juice consistently reduced glucose production by 27.2%, 14.5%, 17.1% and 19.2% at 15-minute intervals respectively, when compared against the negative control. This putative anti-diabetic activity can be attributed to the increase in availability and concentration of aglycones as well as other phenolic compounds resulting from degradation of glycosidic momordicoside. Biotransformation of M. charantia fruit juice via lactic acid bacterium fermentation reduced its bitterness, reduced its sugar content, produced aglycones and other metabolites as well as improved its inhibition of α-glucosidase activity compared with the fresh, non-fermented juice.

3.
Mar Drugs ; 13(8): 5447-91, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26308010

RESUMO

Diabetes mellitus is a group of metabolic disorders of the endocrine system characterised by hyperglycaemia. Type II diabetes mellitus (T2DM) constitutes the majority of diabetes cases around the world and are due to unhealthy diet, sedentary lifestyle, as well as rise of obesity in the population, which warrants the search for new preventive and treatment strategies. Improved comprehension of T2DM pathophysiology provided various new agents and approaches against T2DM including via nutritional and lifestyle interventions. Seaweeds are rich in dietary fibres, unsaturated fatty acids, and polyphenolic compounds. Many of these seaweed compositions have been reported to be beneficial to human health including in managing diabetes. In this review, we discussed the diversity of seaweed composition and bioactive compounds which are potentially useful in preventing or managing T2DM by targeting various pharmacologically relevant routes including inhibition of enzymes such as α-glucosidase, α-amylase, lipase, aldose reductase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl-peptidase-4 (DPP-4). Other mechanisms of action identified, such as anti-inflammatory, induction of hepatic antioxidant enzymes' activities, stimulation of glucose transport and incretin hormones release, as well as ß-cell cytoprotection, were also discussed by taking into consideration numerous in vitro, in vivo, and human studies involving seaweed and seaweed-derived agents.


Assuntos
Fatores Biológicos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Alga Marinha/metabolismo , Animais , Humanos
4.
Chem Biol Drug Des ; 82(1): 1-11, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23421589

RESUMO

Various works have been carried out in developing therapeutics against dengue. However, to date, no effective vaccine or anti-dengue agent has yet been discovered. The development of protease inhibitors is considered as a promising option, but most previous works have involved competitive inhibition. In this study, we focused on rational discovery of potential anti-dengue agents based on non-competitive inhibition of DEN-2 NS2B/NS3 protease. A homology model of the DEN-2 NS2B/NS3 protease (using West Nile Virus NS2B/NS3 protease complex, 2FP7, as the template) was used as the target, and pinostrobin, a flavanone, was used as the standard ligand. Virtual screening was performed involving a total of 13 341 small compounds, with the backbone structures of chalcone, flavanone, and flavone, available in the ZINC database. Ranking of the resulting compounds yielded compounds with higher binding affinities compared with the standard ligand. Inhibition assay of the selected top-ranking compounds against DEN-2 NS2B/NS3 proteolytic activity resulted in significantly better inhibition compared with the standard and correlated well with in silico results. In conclusion, via this rational discovery technique, better inhibitors were identified. This method can be used in further work to discover lead compounds for anti-dengue agents.


Assuntos
Vírus da Dengue/enzimologia , Flavonas/química , Inibidores de Proteases/química , Tetrazóis/química , Proteínas não Estruturais Virais/antagonistas & inibidores , Regulação Alostérica , Sítios de Ligação , Dengue/tratamento farmacológico , Flavonas/farmacologia , Flavonas/uso terapêutico , Humanos , Cinética , Simulação de Acoplamento Molecular , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico , Estrutura Terciária de Proteína , RNA Helicases/antagonistas & inibidores , RNA Helicases/genética , RNA Helicases/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Termodinâmica , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
5.
Food Chem Toxicol ; 50(5): 1393-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22326971

RESUMO

Andrographolide is a major phytoconstituent present in Andrographis paniculata, a plant used in traditional medicines in Asia for various ailments. This tropical shrub was reported to possess various pharmacological activities and has been marketed around the world including Europe, however the toxicological data especially potential genotoxicity assessment on the phytocompound is still lacking. This study was performed to assess the ability of andrographolide to induce chromosomal changes using the in vitro cytokinesis-blocked micronucleus assay with immunofluorescent labelling of kinetochores in metabolically-competent AHH-1 and MCL-5 human lymphoblastoid cell lines. Various cytotoxicity endpoints were also evaluated in this study. Andrographolide was found to cause a weak increase in micronuclei induction at 10-50 µM in both AHH-1 and MCL-5 cell lines, respectively which were within the historical range. Kinetochore analysis revealed that the micronuclei induced in MCL-5 cells due to andrographolide exposure originated via an aneugenic mechanism that was indicated by the relatively higher but non-significant percentage of kinetochore positive micronuclei compared to negative control. Andrographolide also elicited a dose-dependent cellular cytotoxicity, with cells dying primarily via necrosis compared to apoptosis. Here we report that andrographolide was not genotoxic at the doses tested and it induces dose-dependent necrosis in vitro.


Assuntos
Carcinógenos/toxicidade , Diterpenos/toxicidade , Mutagênicos/toxicidade , Linhagem Celular , Imunofluorescência , Humanos , Técnicas In Vitro , Cinetocoros , Testes para Micronúcleos
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