RESUMO
Stress has been linked to the development of irritable bowel syndrome (IBS), and various methods have been explored to model IBS in combination with other stimuli. However, it remains unclear whether stress alone can induce IBS in animals. This study aimed to investigate the impact of chronic unpredictable mild stress (CUMS) on gastrointestinal sensation and function in mice and assess the potential of CUMS as a modeling approach for IBS. To evaluate the mice's behavior, we conducted open field test, sucrose preference test and weighed the mice, revealing that CUMS indeed induced anxiety and depression in the mice and caused weight loss. Further analyses, including fecal analysis, a total gastrointestinal transport test, and a colon propulsion test, demonstrated that CUMS led to abnormal defecation and disruptions in gastrointestinal motility in the mice. Additionally, the abdominal withdrawal reflex test indicated an increase in visceral sensitivity in CUMS-exposed mice. Histological examination using hematoxylin and eosin staining revealed no significant histological alterations in the colons of CUMS-exposed mice, but it did show a minor degree of inflammatory cell infiltration. In summary, the findings suggest that CUMS can replicate IBS-like symptoms in mice, offering a novel top-down approach to modeling IBS.
Assuntos
Modelos Animais de Doenças , Motilidade Gastrointestinal , Síndrome do Intestino Irritável , Estresse Psicológico , Animais , Estresse Psicológico/fisiopatologia , Estresse Psicológico/complicações , Masculino , Camundongos , Síndrome do Intestino Irritável/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Ansiedade/fisiopatologia , Depressão/fisiopatologia , Camundongos Endogâmicos C57BL , Comportamento Animal , Defecação , Colo/fisiopatologia , Colo/patologiaRESUMO
Four new prenylated 2-arylbenzofurans, namely artopithecins A-D (1-4), together with five known compounds (5-9) were isolated from the twigs of Artocarpus pithecogallus for the first time. Their structures were elucidated based on extensive spectroscopic analysis and in comparison with literature data. All isolates were evaluated for their inhibitory activities against mushroom tyrosinase. Compounds 3 and 4 displayed significant tyrosinase inhibitory activities with IC50 values of 37.09±0.33 and 38.14±0.21 µM, respectively.
Assuntos
Artocarpus/química , Benzofuranos/farmacologia , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Caules de Planta/química , Agaricales/enzimologia , Benzofuranos/química , Benzofuranos/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Prenilação , Relação Estrutura-AtividadeRESUMO
Two new prenylated flavones, artocarnin A (2) and carpachromenol (12), together with 13 known prenylflavonoids (1, 3-11, 13-15) were isolated from the twigs of Artocarpus nigrifolius for the first time. Their structures were elucidated by high resolution-electrospray ionization (HR-ESI)-MS, NMR spectroscopic analysis, and in comparison with the reported data. Compounds 1-15 were evaluated for their antiproliferative effects against SiHa and SGC-7901 human cancer cell lines in vitro. The most active compound, eleocharin A (10), showed significant cytotoxicity on SiHa cells (IC50=0.7±0.1 µM) and inhibitory activity against SGC-7901 cells (IC50=8.3±0.2 µM) and could be considered as potential lead compound for further development of novel anti-tumor agents.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Artocarpus/química , Flavonoides/farmacologia , Casca de Planta/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/química , Flavonoides/isolamento & purificação , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais CultivadasAssuntos
Artocarpus/química , Inibidores Enzimáticos/química , Flavanonas/química , Lignanas/química , Componentes Aéreos da Planta/química , Agaricales/enzimologia , Inibidores Enzimáticos/isolamento & purificação , Flavanonas/isolamento & purificação , Lignanas/isolamento & purificação , Monofenol Mono-Oxigenase/antagonistas & inibidores , EstereoisomerismoRESUMO
Five new α-pyrones, cryptowratones A-E (1-5), and five known congeners (6-10), together with four other known compounds 11-14 were isolated from the twigs of Cryptocarya wrayi. The structures of the new compounds were elucidated on the basis of extensive spectroscopic data analysis and ECD calculations. All α-pyrones except 6 were evaluated for their stimulatory effects on glucose uptake in vitro with CHO-K1/GLUT4 cells. The positive control insulin displayed an approximate 42 ± 0.14% promotion on glucose uptake at 25 µM, compared with the CHO-K1/GLUT4 group. Compounds 1a/2a, 2, 3, and 10 showed a more significant stimulation of glucose uptake than insulin (25 µM) by 36 ± 0.08%, 27 ± 0.12%, 28 ± 0.12%, and 25 ± 0.12% at 1.5 µM, respectively. Immunofluorescence assays indicated the glucose uptake-stimulatory activity of α-pyrones might be correlated with increased GLUT4 translocation.
Assuntos
Cryptocarya , Cryptocarya/química , Glucose , Estrutura Molecular , Pironas/farmacologiaRESUMO
Two new isoquinoline alkaloids, cryptowrayines A (1) and B (2), along with one known pavine alkaloid (-)-12-hydroxyeschscholtzidine (3), were isolated from the twigs of Cryptocarya wrayi. The structures of new compounds were elucidated by extensive spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Both compounds 1 and 2 exhibited moderate quinone reductase inducing activity in Hepa 1c1c7 cells.
Assuntos
Alcaloides/isolamento & purificação , Cryptocarya/química , Isoquinolinas/isolamento & purificação , Alcaloides/química , Alcaloides/metabolismo , Glucosidases/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/metabolismo , Concentração Inibidora 50 , Isoquinolinas/química , Isoquinolinas/metabolismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , NAD(P)H Desidrogenase (Quinona)/análise , Rotação OcularRESUMO
A new isoiphionane sesquiterpene, named (3S, 5S, 7S, 10R)-3, 11-dihydroxyisoiphion-4-one (1), two new phloroglucinol glycosides, named eucalglobuside A (2) and eucalglobuside B (3), along with 15 known compounds were isolated from the leaves of Eucalyptus globulus. Their structures were elucidated based on extensive spectroscopic analysis and in comparison with literature data. The absolute configuration of compound 1 was determined by ECD calculation. All isolates were evaluated their inhibitory activities against the mushroom tyrosinase. As a result, three sesquiterpenoids, 1, 5ß, 11-dihydroxy-iphionan-4-one (5), and (-)-globulol (8), exhibited the most potent activities with IC50 values of 14.17⯵M, 10.08⯵M and 9.79⯵M, respectively.
Assuntos
Inibidores Enzimáticos/farmacologia , Eucalyptus/química , Glicosídeos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Floroglucinol/farmacologia , Sesquiterpenos/farmacologia , China , Inibidores Enzimáticos/isolamento & purificação , Glicosídeos/isolamento & purificação , Estrutura Molecular , Floroglucinol/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Sesquiterpenos/isolamento & purificaçãoRESUMO
The objective of this study is to design novel dissolution-enhanced microparticles loaded poorly soluble drug nanocrystals used a low viscosity of hydroxypropylcellulose (HPC) as matrix carrier. An interesting approach combined homogenization and the spray-freeze-drying technique was developed. The results demonstrated that the ratio of HPC to drug played an important role in size-reduction efficiency of drug during homogenization. And the formation of cage-like structure of the composite particles depended on ratio of HPC to drug. The spray-freeze-dried composite particles with HPC ratio of 1:2, 1:1 and 2:1 possessed excellent redispersibility, which attributed to its porous matrix and large surface area (3000m2/g). The dissolution of spray-freeze-dried composite particles with higher ratios of HPC (1:2 and 1:1) was significantly enhanced, which attributed to the particle size reduction of drug. The HPC could immobilize drug nanocrystals in its cage-like structure and prevent it from the subsequent agglomeration during storage. In conclusion, the prepared cage-like microparticles is a promising basis for further formulation development.