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1.
Clin Nutr ; 40(7): 4579-4584, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34229262

RESUMO

BACKGROUND: Hyperhomocysteinemia has been repeatedly found to increase the risk of dementia. However, the effects of hypohomocysteinemia on the risk of dementia have been barely investigated. If hypohomocysteinemia, like hyperhomocysteinemia, increases the risk of dementia, misuse or overuse of homocysteine-lowing agents such as vitamin supplements may increase the risk of dementia. AIMS: To investigate whether hypohomocysteinemia, like hyperhomocysteinemia, could increase the risk of dementia and Alzheimer's disease (AD) in a large population-based cohort of older adults. METHODS: This prospective cohort study followed 2655 randomly sampled, community-dwelling, non-demented individuals aged 60 years or older from 2010 to 2018. We measured baseline serum total homocysteine (tHcy) levels and examined the effect of serum tHcy on the risks of dementia and AD using Cox proportional hazards models. RESULTS: During the follow-up period (mean = 5.4 years, SD = 0.9), dementia and AD developed in 85 and 64 participants, respectively. Not only the participants with high serum tHcy (≥10.6 µmol/L) but also those with low serum tHcy (≤8.9 µmol/L) were 4-5 times more likely to develop dementia and AD compared to those with serum tHcy levels between 9.0 and 10.5 µmol/L. With the increase in serum tHcy concentration, the use of vitamin supplements decreased, and 41.2% of the participants with low serum tHcy (≤8.9 µmol/L) were taking vitamin supplements. CONCLUSIONS: Not only hyperhomocysteinemia but also hypohomocysteinemia considerably increased the risk of dementia and AD in older adults. The risk of dementia that results from overuse or misuse of vitamin supplements should be acknowledged and homocysteine-lowering health policies should be tailored to consider dementia risks that are associated with hypohomocysteinemia.


Assuntos
Doença de Alzheimer/etiologia , Demência/etiologia , Suplementos Nutricionais/efeitos adversos , Homocisteína/sangue , Homocisteína/deficiência , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologia , Demência/sangue , Demência/epidemiologia , Feminino , Humanos , Vida Independente/psicologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos
2.
Mol Cells ; 22(1): 104-12, 2006 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-16951557

RESUMO

We previously reported that DA-9601, ethanol herbal extract of Artemisia asiatica, inhibited histamine and leukotriene releases in guinea pig lung mast cells activated with specific antigen/antibody reaction. This study aimed to evaluate the inhibitory effect of DA-9601 on the OVA-induced airway inflammation in allergic asthma mouse model. BALB/c mice were sensitized and challenged with OVA. DA-9601 was administered orally 1 h before every local OVA-challenge. OVA-specific serum IgE was measured by ELISA, recruitment of inflammatory cells in BAL fluids and lung tissues by Diff-Quik and H&E staining, respectively, the expressions of CD40, CD40L and VCAM-1 by immunohistochemistry, goblet cell hyperplasia by PAS staining, activities of MMPs by gelatin zymography, expressions of mRNA and proteins of cytokines by RT-PCR and ELISA, activities of MAP kinases by western blot, and activity of NF-KappaB by EMSA. DA-9601 reduced IgE level, recruitment of inflammatory cells into the BAL fluid and lung tissues, expressions of CD40, CD40L and VCAM-1 molecules, goblet cell hyperplasia, MMPs activity, expressions of mRNA and productions of various cytokines, activities of MAP kinases and NK-KappaB increased from OVA-challenged mice. These data suggest that DA-9601 may be developed as a clinical therapeutic agent in allergic diseases due to suppressing the airway allergic inflammation via regulation of various cellular molecules expressed by MAP kinases/NF-KappaB pathway.


Assuntos
Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Artemisia/química , Asma/tratamento farmacológico , Extratos Vegetais/farmacologia , Administração Oral , Animais , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar/citologia , Antígenos CD40/biossíntese , Ligante de CD40/biossíntese , Citocinas/biossíntese , MAP Quinases Reguladas por Sinal Extracelular/biossíntese , Feminino , Pulmão/metabolismo , Pulmão/patologia , MAP Quinase Quinase 4/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/biossíntese , Ovalbumina , Extratos Vegetais/administração & dosagem , Molécula 1 de Adesão de Célula Vascular/biossíntese
3.
Bioorg Med Chem Lett ; 14(8): 2001-3, 2004 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-15050646

RESUMO

(+)-Deoxoartemisitene and its C-11, 13 derivatives were synthesized from artemisinic acid via a short and regiospecific process and several derivatives show 10-20 times more in vitro antimalarial activities against Plasmodium falciparum than artemisinin.


Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Artemisininas/síntese química , Artemisininas/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/química , Artemisininas/química , Avaliação Pré-Clínica de Medicamentos , Estrutura Molecular
4.
Mini Rev Med Chem ; 3(2): 159-65, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12570849

RESUMO

New natural peroxides that have potent biological activities with novel diverse structures are reviewed with classification as secondary metabolites such as terpenes, polyketides, phenolics, and hydroperoxides. These compounds, isolated mainly from medicinal plants and marine sponges, are valuable sources in the drug discovery for particularly antitumor and antimalarial agents.


Assuntos
Produtos Biológicos/química , Produtos Biológicos/farmacologia , Peróxidos/química , Peróxidos/farmacologia , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Biologia Marinha , Fenóis/química , Fenóis/farmacologia , Plantas Medicinais/química , Poríferos/química , Estereoisomerismo , Terpenos/química , Terpenos/farmacologia
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