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1.
Environ Toxicol ; 36(9): 1932-1943, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34165232

RESUMO

Obesity is closely linked with metabolic diseases, while life and prenatal exposure to endocrine-disrupting chemicals has been implicated in the development of obesity. Magnesium lithospermate B (MLB), an active compound of Salvia miltiorrhiza (Danshen), has beneficial effects on insulin resistance and metabolic abnormalities in diet-induced obese rodents. Since exposure to endocrine-disrupting chemical Bisphenol A (BPA) during pregnancy mimics the effects of high fat diet-induced alterations of glucose and lipid metabolism in adult male offspring, the effects of daily MLB supplementation for 4 weeks on metabolic abnormalities in rats weaning from prenatal BPA-exposed dams were investigated. BPA-exposed rats developed obesity and adiposity concurrent with hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and elevation of circulating glucagon and free fatty acids. Increased hepatic fatty acid synthesis and decreased fatty acid ß-oxidation, activation of adipocytic adipogenesis, maturation, and lipogenesis, as well as reduction of muscular glucose uptake were demonstrated in BPA-exposed rats. The aforementioned alterations were improved by MLB supplementation. Additionally, MLB displayed negative effects on glucocorticoid receptor action and inflammation, and promoted lipolysis and thermogenesis in the adipose tissues. In conclusion, our findings suggest that MLB may be a potential therapeutic compound against metabolic diseases, including maternal exposure-induced metabolic abnormalities.


Assuntos
Compostos Benzidrílicos , Efeitos Tardios da Exposição Pré-Natal , Animais , Compostos Benzidrílicos/toxicidade , Suplementos Nutricionais , Medicamentos de Ervas Chinesas , Feminino , Masculino , Fenóis/toxicidade , Gravidez , Ratos
2.
Nutrients ; 14(1)2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-35010979

RESUMO

Magnesium lithospermate B (MLB) is a primary hydrophilic component of Danshen, the dried root of Salvia miltiorrhiza used in traditional medicine, and its beneficial effects on obesity-associated metabolic abnormalities were reported in our previous study. The present study investigated the anti-muscle atrophy potential of MLB in mice with high-fat diet (HFD)-induced obesity. In addition to metabolic abnormalities, the HFD mice had a net loss of skeletal muscle weight and muscle fibers and high levels of muscle-specific ubiquitin E3 ligases, namely the muscle atrophy F-box (MAFbx) and muscle RING finger protein 1 (MuRF-1). MLB supplementation alleviated those health concerns. Parallel changes were revealed in high circulating tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), skeletal TNF receptor I (TNFRI), nuclear factor-kappa light chain enhancer of activated B cells (NF-κB), p65 phosphorylation, and Forkhead box protein O1 (FoxO1) as well as low skeletal phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) phosphorylation. The study revealed that MLB prevented obesity-associated skeletal muscle atrophy, likely through the inhibition of MAFbx/MuRF-1-mediated muscular degradation. The activation of the PI3K-Akt-FoxO1 pathway and inhibition of the TNF-α/TNFRI/NF-κB pathway were assumed to be beneficial effects of MLB.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Atrofia Muscular/induzido quimicamente , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Citocinas/genética , Citocinas/metabolismo , Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Sequestradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
3.
Chem Biol Interact ; 315: 108893, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31706954

RESUMO

This study aimed to investigate the effects of teaghrelin, an active ingredient of Chin-shin oolong tea, on murine C2C12 myoblast cells. Under high serum conditions, teaghrelin inhibited C2C12 cell proliferation, indicating a cell cycle arrest and cessation of proliferative progression. Teaghrelin promoted pro-differentiation of C2C12 cells as evidenced by a progressively elongated morphology, as well as the induction of muscle specific myogenin, myosin heavy chain (MHC), and MyoD. The formation of multinucleated myotubes, and the increase of MHC-positive immunoreactivity within the myotubes, further reflected a complete differentiation and maturation of the contractile skeletal muscle cells induced by teaghrelin. Like ghrelin, teaghrelin attenuated dexamethasone-decreased myotube diameter, indicating its protective effects against skeletal muscle atrophy. Additionally, the expressions of Atrogin-1 and MuRF-1 ubiquitin E3 ligase were reduced. In conclusion, the results highlight a possibility of developing teaghrelin as a functional food for the prevention or therapeutic treatment of disease-associated skeletal muscle atrophy.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Grelina/farmacologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Mioblastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Chá/química , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Proteína MyoD/metabolismo , Mioblastos/metabolismo , Miogenina/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo
4.
Int J Mol Sci ; 20(3)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717287

RESUMO

Atypical antipsychotics, such as olanzapine, are commonly prescribed to patients with schizophrenic symptoms and other psychiatric disorders. However, weight gain and metabolic disturbance cause adverse effects, impair patient compliance and limit clinical utility. Thus, a better understanding of treatment-acquired adverse effects and identification of targets for therapeutic intervention are believed to offer more clinical benefits for patients with schizophrenia. Beyond its nutritional effects, studies have indicated that supplementation of chromium brings about beneficial outcomes against numerous metabolic disorders. In this study, we investigated whether olanzapine-induced weight gain and metabolic disturbance involved chromium dynamic mobilization in a female Sprague-Dawley rat model, and whether a dietary supplement of chromium improved olanzapine-acquired adverse effects. Olanzapine medicated rats experienced weight gain and adiposity, as well as the development of hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, and inflammation. The olanzapine-induced metabolic disturbance was accompanied by a decrease in hepatic Akt and AMP-activated Protein Kinase (AMPK) actions, as well as an increase in serum interleukin-6 (IL-6), along with tissue chromium depletion. A daily intake of chromium supplements increased tissue chromium levels and thermogenic uncoupling protein-1 (UCP-1) expression in white adipose tissues, as well as improved both post-olanzapine weight gain and metabolic disturbance. Our findings suggest that olanzapine medicated rats showed a disturbance of tissue chromium homeostasis by inducing tissue depletion and urinary excretion. This loss may be an alternative mechanism responsible for olanzapine-induced weight gain and metabolic disturbance.


Assuntos
Adiposidade/efeitos dos fármacos , Antipsicóticos/efeitos adversos , Cloretos/farmacologia , Compostos de Cromo/farmacologia , Hiperglicemia/metabolismo , Hiperinsulinismo/metabolismo , Hiperlipidemias/metabolismo , Olanzapina/efeitos adversos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adiposidade/genética , Administração Oral , Animais , Cloretos/metabolismo , Compostos de Cromo/metabolismo , Feminino , Regulação da Expressão Gênica , Hiperglicemia/induzido quimicamente , Hiperglicemia/genética , Hiperglicemia/prevenção & controle , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/genética , Hiperinsulinismo/prevenção & controle , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/genética , Hiperlipidemias/prevenção & controle , Inflamação , Resistência à Insulina/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Aumento de Peso/efeitos dos fármacos
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