RESUMO
Hypoxic-ischemic encephalopathy (HIE) at high-altitudes leads to neonatal mortality and long-term neurological complications without effective treatment. Acer truncatum Bunge Seed extract (ASO) is reported to have effect on cognitive improvement, but its molecular mechanisms on HIE are unclear. In this study, ASO administration contributed to reduced neuronal cell edema and improved motor ability in HIE rats at a simulated 4500-meter altitude. Transcriptomics and WGCNA analysis showed genes associated with lipid biosynthesis, redox homeostasis, neuronal growth, and synaptic plasticity regulated in the ASO group. Targeted and untargeted-lipidomics revealed decreased free fatty acids and increased phospholipids with favorable ω-3/ω-6/ω-9 fatty acid ratios, as well as reduced oxidized glycerophospholipids (OxGPs) in the ASO group. Combining multi-omics analysis demonstrated FA to FA-CoA, phospholipids metabolism, and lipid peroxidation were regulated by ASO treatment. Our results illuminated preliminary metabolism mechanism of ASO ingesting in rats, implying ASO administration as potential intervention strategy for HIE under high-altitude.
Assuntos
Acer , Hipóxia-Isquemia Encefálica , Ratos , Animais , Neuroproteção , Altitude , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/prevenção & controle , Hipóxia-Isquemia Encefálica/complicações , Multiômica , Extratos Vegetais/farmacologia , IsquemiaRESUMO
Acer truncatum Bunge seed oil (ASO) is rich in ω-9 (53.93%) and ω-6 (30.7%) fatty acids (FAs) and characterized by 3-7% nervonic acid (NA, C24:1ω-9). Evidence suggests that ω-9 FAs such as NA participate in processes of cognitive improvement; however, their mechanism remains ambiguous. In this study, we investigated the effect of ASO on rat memory and the change in lipid profiling and underlying metabolism. After ASO was administrated to rats for one, three and seven days, their capacity for learning and memory significantly increased via the MWM test. Lipid profiling showed alterations in a wide range of metabolic features after ASO was administrated to the rats, in which sphingolipids (SP) in the serum and glycerophospholipids (GP) in the brain were regulated significantly. The changes in the fatty acids in the serum and brain showed the synergetic effects of NA, EA, OA and DHA, where NA, EA and OA exhibited similar change trends. The enrichment analysis based on KEGG indicated that ASO supplementation evoked the pathways of neurotrophin signaling, glycerophospholipid metabolism and sphingolipid metabolism, which are related to memory and cognition improvement. Among the metabolites with different molecular forms, the biomarkers with C24:1ω-9 chains exhibited a positive correlation with others both in the serum SP and brain GP. These results suggest the synergistic effects of ω-9 FAs and that their conversion into each other may result in enhanced cognition in rats ingesting Acer truncatum Bunge seed oil.
Assuntos
Acer , Ácidos Graxos Essenciais/farmacologia , Ácidos Graxos Monoinsaturados/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Óleos de Plantas/farmacologia , Animais , Cognição/efeitos dos fármacos , Dieta , Modelos Animais de Doenças , Aprendizagem em Labirinto/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
The study is aimed at investigating the effects of Ginkgo biloba extract EGB761 on renal tubular damage and endoplasmic reticulum stress (ERS) in diabetic kidney disease (DKD). A total of 50 C57BL/6 N mice were randomly divided into the normal group, DKD group, DKD+EGB761 group (36 mg/kg), and DKD+4-phenylbutyrate (4-PBA) group (1 g/kg). The DKD model was replicated by high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). Renal tubular epithelial cells (HK-2) were divided into the control group, high-glucose group (30 mmol/L), EGB761 group (40 mg/L, 20 mg/L, 10 mg/L), TM group, and TM+4-PBA group. After 8 weeks of administration, expressions of serum creatinine (Scr), blood urea nitrogen (BUN), 24 h urinary protein (24 h Pro), fasting blood glucose (FBG), ß 2-microglobulin (ß 2-MG), and retinol binding protein 4 (RBP4) of mice were tested. The pathological changes of renal tissue were observed. The expressions of extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) markers α-smooth muscle actin (α-SMA), E-cadherin, fibronectin, and collagen IV, as well as the ERS markers GRP78 and ATF6, were tested by Western blot, qPCR, immunohistochemistry, or immunofluorescence. EGB761 could decrease the Scr, BUN, 24 h Pro, and FBG levels in the DKD group, alleviate renal pathological injury, decrease urine ß 2-MG, RBP4 levels, and decrease the expression of α-SMA, collagen IV, fibronectin, and GRP78, as well as ATF6, while increase the expression of E-cadherin. These findings demonstrate that EGB761 can improve renal function, reduce tubular injury, and ameliorate ECM accumulation and EMT in DKD kidney tubules, and the mechanism may be related to the inhibition of ERS.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Estresse do Retículo Endoplasmático , Matriz Extracelular/metabolismo , Mesoderma/patologia , Extratos Vegetais/uso terapêutico , Animais , Linhagem Celular , Linhagem Celular Transformada , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/ultraestrutura , Ginkgo biloba , Humanos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/lesões , Túbulos Renais/fisiopatologia , Túbulos Renais/ultraestrutura , Masculino , Mesoderma/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Extratos Vegetais/farmacologia , Proteínas Plasmáticas de Ligação ao Retinol/urina , Microglobulina beta-2/urinaRESUMO
OBJECTIVE: To investigate the effects of Tongluo Digui decoction on renal injury and streptozotocin-induced podocyte autophagy in diabetic rats. METHODS: Male Sprague-Dawley rats were randomly divided into six groups: normal, model, Tongluo Digui decoction (high, medium, and low dose) and valsartan. Streptozotocin was injected intraperitoneally to replicate the diabetic animal model. After 8 weeks, proteinuria was evaluated to establish the diabetic nephropathy model. Treatments were administered daily via the intragastric route. At 16 weeks after gavage, we determined 24 h urine protein concentration, and blood glucose, serum creatinine, and urea nitrogen concentrations. Then, rats were sacrificed, and kidneys were harvested and stained with periodic acid-Schiff to evaluate the pathological changes in glomeruli, including glomerular podocytes by transmission electron microscopy. Western blot analysis was used to determine the expression of nephrin, podocin, p62, beclin-1, LC3â ¡/â , and p-mTOR/mTOR protein in kidney tissues. RESULTS: Compared with the model group, Tongluo Digui decoction was associated with decreases in 24 h urine protein concentration, and blood glucose, hemoglobin A1c, serum creatinine, urea nitrogen concentrations, total serum protein and albumin. Concurrently, mesangial mesenteric broadening and fusion of foot processes were reduced, the glomerular basement membrane was not significantly thickened, and the number of podocytes and the number of autophagosomes in the podocytes was increased. Further, expression of nephrin, podocin, LC3â ¡, and beclin-1 protein in kidney tissue was up-regulated, while expression of p62 protein was down-regulated and mTOR phosphorylation was inhibited. CONCLUSION: Tongluo Digui decoction may inhibit the progression of diabetic nephropathy by inhibiting mTOR phosphorylation, thereby increasing autophagy to protect podocytes and reducing proteinuria.
Assuntos
Autofagia/efeitos dos fármacos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/fisiopatologia , Medicamentos de Ervas Chinesas/administração & dosagem , Podócitos/efeitos dos fármacos , Animais , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/citologia , Rim/efeitos dos fármacos , Rim/lesões , Rim/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Podócitos/citologia , Ratos , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Mercury (Hg) exposure poses serious health risks to humans, resulting in extensive investigations examining Hg accumulation, biotransformation and uptake in crops. In this investigation, Hg accumulation in potato tubers due to bioaccumulation processes was determined and bioconcentration factors affecting bioaccumulation were identified using a greenhouse experiment. Our results showed that the percentage of available Hg concentrations from total Hg in soil samples were less than 1.2%, indicating that soils used in our experiment exhibited a high binding strength for Hg, with alkaline soil recording the lowest available Hg/total Hg ratio. Results indicated that soil type and Hg treatment, as well as their interactions, significantly affected Hg accumulation in potato tubers (P < 0.01). Importantly, our results also indicated that potatoes grown in soil with a Hg concentration two times higher than the Chinese Environmental Quality Standard exhibited no obvious toxic effects on humans; Bioconcentration factors (BCF) values (<0.04) suggested that potatoes can be considered as a low Hg accumulating species and suitable for human consumption. Potato yields in acidic soil were lower than those in neutral or alkaline soils, making this medium unsuitable for growth.
Assuntos
Bioacumulação , Poluição Ambiental/efeitos adversos , Mercúrio/análise , Poluentes do Solo/análise , Solanum tuberosum/química , China , Produção Agrícola/normas , Produtos Agrícolas/química , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Produtos Agrícolas/normas , Doenças Transmitidas por Alimentos/etiologia , Doenças Transmitidas por Alimentos/prevenção & controle , Humanos , Mercúrio/metabolismo , Mercúrio/normas , Mercúrio/toxicidade , Tubérculos/química , Tubérculos/crescimento & desenvolvimento , Tubérculos/metabolismo , Tubérculos/toxicidade , Solo/química , Poluentes do Solo/metabolismo , Poluentes do Solo/normas , Poluentes do Solo/toxicidade , Solanum tuberosum/crescimento & desenvolvimento , Solanum tuberosum/metabolismo , Solanum tuberosum/normasAssuntos
Angina Pectoris/tratamento farmacológico , Angiotensina II/sangue , Medicamentos de Ervas Chinesas/uso terapêutico , Endotelinas/sangue , Fitoterapia , Adulto , Idoso , Angina Pectoris/sangue , Cápsulas , Diagnóstico Diferencial , Método Duplo-Cego , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To observe the effect of Sappan wood (SW) on the expression of perforin mRNA in myocardium of rats after allogeneic cardiac transplantation. METHODS: The animal model of allogeneic (abdominal) cardiac transplantation was established by taking Wistar rat as provider and SD rat as receptor, perforin mRNA expression in the model's myocardium was detected by RT-PCR. RESULTS: SW could obviously reduce the perforin mRNA expression, it also could alleviate the pathological morphology and ultrastructural damage of myocardial cells. CONCLUSION: SW has obvious effect in antagonizing immune rejection after transplantation, the mechanism of its immunosuppression could be through lowering the perforin mRNA expression.