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1.
Pharmacol Res ; 185: 106489, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36228869

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and currently there are no available treatments. Alongside the conventional Aß and tau hypotheses, neuroinflammation and metabolism disruption have also been regarded as crucial hallmarks of AD. In this study, a novel Chinese formula Nao Tan Qing (NTQ) was developed and shown to improve AD. In vivo experiments showed that NTQ significantly mitigated cognitive impairment, Aß burden and neuroinflammation in a transgenic AD mouse model (5×FAD). Network pharmacology results revealed that the active components of NTQ could target inflammatory and metabolic pathways. In addition, hippocampal transcriptomics suggested that NTQ regulated signaling pathways related to inflammation and lipid metabolism. Consistently, serum metabolomics further indicated that NTQ could modulate glycolipid metabolism. In summary, a combination of systems pharmacology analysis and biological validation study demonstrates that NTQ could alleviate behavioral abnormality and pathological alterations of AD by targeting glycolipid metabolism and neuroinflammation, and is accordingly a potential therapeutic agent for AD.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/metabolismo , Doenças Neuroinflamatórias , Farmacologia em Rede , Camundongos Transgênicos , Modelos Animais de Doenças , Metabolismo dos Lipídeos , Glicolipídeos/uso terapêutico , Peptídeos beta-Amiloides/metabolismo
2.
PLoS One ; 11(1): e0147648, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26809065

RESUMO

OBJECTIVES: This study compared cardio-metabolic disease risk factors and their associations with serum vitamin D and omega-3 status in South Asian (SAC) and White Canadians (WC) living in Canada's capital region. METHODS: Fasting blood samples were taken from 235 SAC and 279 WC aged 20 to 79 years in Ottawa, and 22 risk factors were measured. RESULTS: SAC men and women had significantly higher fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), apolipoprotein B (ApoB), ratios of total (TC) to HDL cholesterol (HDLC) and ApoB to ApoA1, leptin, E-selectin, P-selectin, ICAM-1 and omega-3 (p < 0.05), but lower HDLC, ApoA1, vitamin D levels than WC (p < 0.05). SAC women had higher CRP and VEGF than WC women. Adequate (50-74.9 nmol/L) or optimal (≥ 75 nmol/L) levels of 25(OH)D were associated with lower BMI, glucose, insulin, HOMA-IR, TG, TC, low density lipoprotein cholesterol (LDLC), ApoB/ApoA1 ratio, CRP, leptin, and higher HDLC, ApoA1, omega-3 index, L-selectin levels in WC, but not in SAC. Intermediate (>4%-<8%) or high (≥ 8%) levels of omega-3 indices were related to lower E-selectin, P-selectin, ICAM-1 and higher HDLC, 25(OH)D levels in WC, but not in SAC. The BMIs of ≤ 25 kg/m2 were related to lower LDLC, ApoB, VEGF, creatinine and higher 25(OH)D in WC, but not in SAC. CONCLUSIONS: The associations of vitamin D, omega-3 status, BMI and risk factors were more profound in the WC than SAC. Compared to WC, vitamin D status and omega-3 index may not be good predictive risk factors for the prevalence of CVD and diabetes in SAC.


Assuntos
Ácidos Graxos Ômega-3/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Apolipoproteínas B/sangue , Povo Asiático , Glicemia , Índice de Massa Corporal , Canadá , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Selectina E/sangue , Feminino , Humanos , Insulina/sangue , Selectina L/sangue , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Fatores de Risco , Vitamina D/sangue , População Branca , Adulto Jovem
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