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1.
Biochem Pharmacol ; 224: 116240, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38679210

RESUMO

Hepatic steatosis is a critical factor in the development of nonalcoholic steatohepatitis (NASH). Sesamin (Ses), a functional lignan isolated from Sesamum indicum, possesses hypolipidemic, liver-protective, anti-hypertensive, and anti-tumor properties. Ses has been found to improve hepatic steatosis, but the exact mechanisms through which Ses achieves this are not well understood. In this study, we observed the anti-hepatic steatosis effects of Ses in palmitate/oleate (PA/OA)-incubated primary mouse hepatocytes, AML12 hepatocytes, and HepG2 cells, as well as in high-fat, high-cholesterol diet-induced NASH mice. RNA sequencing analysis revealed that cluster of differentiation 36 (CD36), a free fatty acid (FA) transport protein, was involved in the Ses-mediated inhibition of hepatic fat accumulation. Moreover, the overexpression of CD36 significantly increased hepatic steatosis in both Ses-treated PA/OA-incubated HepG2 cells and NASH mice. Furthermore, Ses treatment suppressed insulin-induced de novo lipogenesis in HepG2 cells, which was reversed by CD36 overexpression. Mechanistically, we found that Ses ameliorated NASH by inhibiting CD36-mediated FA uptake and upregulation of lipogenic genes, including FA synthase, stearoyl-CoA desaturase 1, and sterol regulatory element-binding protein 1. The findings of our study provide novel insights into the potential therapeutic applications of Ses in the treatment of NASH.


Assuntos
Antígenos CD36 , Dioxóis , Hepatócitos , Lignanas , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Animais , Lignanas/farmacologia , Lignanas/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Camundongos , Humanos , Antígenos CD36/metabolismo , Antígenos CD36/genética , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Células Hep G2 , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Dioxóis/farmacologia , Dioxóis/uso terapêutico , Dieta Hiperlipídica/efeitos adversos
2.
Chin J Integr Med ; 29(4): 333-340, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35089525

RESUMO

OBJECTIVE: To evaluate toxicity of raw extract of Panax notoginseng (rPN) and decocted extract of PN (dPN) by a toxicological assay using zebrafish larvae, and explore the mechanism by RNA sequencing assay. METHODS: Zebrafish larvae was used to evaluate acute toxicity of PN in two forms: rPN and dPN. Three doses (0.5, 1.5, and 5.0 µ g/mL) of dPN were used to treat zebrafishes for evaluating the developmental toxicity. Behavior abnormalities, body weight, body length and number of vertebral roots were used as specific phenotypic endpoints. RNA sequencing (RNA-seq) assay was applied to clarify the mechanism of acute toxicity, followed by real time PCR (qPCR) for verification. High performance liquid chromatography analysis was performed to determine the chemoprofile of this herb. RESULTS: The acute toxicity result showed that rPN exerted higher acute toxicity than dPN in inducing death of larval zebrafishes (P<0.01). After daily oral intake for 21 days, dPN at doses of 0.5, 1.5 and 5.0 µ g/mL decreased the body weight, body length, and vertebral number of larval zebrafishes, indicating developmental toxicity of dPN. No other adverse outcome was observed during the experimental period. RNA-seq data revealed 38 genes differentially expressed in dPN-treated zebrafishes, of which carboxypeptidase A1 (cpa1) and opioid growth factor receptor-like 2 (ogfrl2) were identified as functional genes in regulating body development of zebrafishes. qPCR data showed that dPN significantly down-regulated the mRNA expressions of cpa1 and ogfrl2 (both P<0.01), verifying cpa1 and ogfrl2 as target genes for dPN. CONCLUSION: This report uncovers the developmental toxicity of dPN, suggesting potential risk of its clinical application in children.


Assuntos
Panax notoginseng , Saponinas , Animais , Peixe-Zebra/genética , Saponinas/farmacologia , Panax notoginseng/química , Larva , Análise de Sequência de RNA
3.
Plant Divers ; 44(5): 455-467, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36187546

RESUMO

Polyploids contribute substantially to plant evolution and biodiversity; however, the mechanisms by which they succeed are still unclear. According to the polyploid adaptation hypothesis, successful polyploids spread by repeated adaptive responses to new environments. Here, we tested this hypothesis using two tetraploid yellowcresses (Rorippa), the endemic Rorippa elata and the widespread Rorippa palustris, in the temperate biodiversity hotspot of the Hengduan Mountains. Speciation modes were resolved by phylogenetic modeling using 12 low-copy nuclear loci. Phylogeographical patterns were then examined using haplotypes phased from four plastid and ITS markers, coupled with historical niche reconstruction by ecological niche modeling. We inferred the time of hybrid origins for both species as the mid-Pleistocene, with shared glacial refugia within the southern Hengduan Mountains. Phylogeographic and ecological niche reconstruction indicated recurrent northward colonization by both species after speciation, possibly tracking denuded habitats created by glacial retreat during interglacial periods. Common garden experiment involving perennial R. elata conducted over two years revealed significant changes in fitness-related traits across source latitudes or altitudes, including latitudinal increases in survival rate and compactness of plant architecture, suggesting gradual adaptation during range expansion. These findings support the polyploid adaptation hypothesis and suggest that the spread of polyploids was aided by adaptive responses to environmental changes during the Pleistocene. Our results thus provide insight into the evolutionary success of polyploids in high-altitude environments.

4.
Journal of Preventive Medicine ; (12): 1200-1203, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-875774

RESUMO

Objective@#To establish a method for the determination of furans in tea by headspace-gas chromatographic mass spectrometry. @*Methods@#The 20% sodium chloride solution and isotope internal standards were added to the crushed and weighed tea sample. Furan, 2-methylfuran, 3-methylfuran, 2,5-dimethylfuran were separated by HP-PLOT Q capillary column and then determined by gas chromatography mass spectrometry with electron impact ionization mode.@*Results@# In the range of 5-400 ng, good linear relationships were observed in the four furan compounds, with the correlation coefficients ranging from 0.999 2 to 0.999 6. The detection limits ranged from 0.2 to 1.9 μg/kg, the quantification limit ranged from 0.4 to 3.1 μg/kg. The recovery rates of furans ranged from 95.4% to 128.2% when spiked at 5.0, 20.0 and 100.0 μg/kg, and the relative standard deviations ranged from 0.8% to 11.3%. Eighty-one tea samples were determined, the concentration of four furan compounds was highest in black tea, followed by dark tea, oolong tea, green tea and scented tea. @*Conclusion@# Headspace-gas chromatography-mass spectrometry can reduce the matrix interference of tea, and meet the requirements in the linear range, recovery and precision, which is suitable for simultaneous determination of four furan compounds in tea.

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