RESUMO
BACKGROUND: Peucedanum japonicum Thunb. (PJ) is a vegetable widely consumed in East Asia and is known to have anticancer and anti-inflammatory effects. However, the effect of PJ on muscle atrophy remains elusive. PURPOSE: This study aimed to investigate the effect of PJ and its active compound on dexamethasone (DEX)-induced muscle atrophy. METHODS: We performed qualitative and quantitative analysis of PJ using ultra-performance liquid chromatography-mass spectrometry tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC), respectively. The efficacy of PJ and its main compound 4-caffeoylquinic acid (CQA) on muscle atrophy was evaluated in DEX-induced myotube atrophy and DEX-induced muscle atrophy in mouse myoblasts (C2C12) and C57BL/6 mice, in vitro and in vivo, respectively. RESULTS: The UPLC-MS/MS and HPLC data showed that the concentration of 4-CQA in PJ was 18.845 mg/g. PJ and 4-CQA treatments significantly inhibited DEX-induced myotube atrophy by decreasing protein synthesis and glucocorticoid translocation to the nucleus in C2C12 myotubes. In addition, PJ enhanced myogenesis by upregulating myogenin and myogenic differentiation 1 in C2C12 cells. PJ supplementation effectively increased muscle function and mass, downregulated atrogenes, and decreased proteasome activity in C57BL/6 mice. Additionally, PJ effectively decreased the nuclear translocation of forkhead transcription factor 3 alpha by inhibiting glucocorticoid receptor. CONCLUSION: Overall, PJ and its active compound 4-CQA alleviated skeletal muscle atrophy by inhibiting protein degradation. Hence, our findings present PJ as a potential novel pharmaceutical candidate for the treatment of muscle atrophy.
Assuntos
Apiaceae , Dexametasona , Camundongos Endogâmicos C57BL , Atrofia Muscular , Extratos Vegetais , Ácido Quínico/análogos & derivados , Animais , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Dexametasona/farmacologia , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Apiaceae/química , Masculino , Linhagem Celular , Espectrometria de Massas em Tandem , Fibras Musculares Esqueléticas/efeitos dos fármacos , Ácido Quínico/farmacologia , Cromatografia Líquida de Alta Pressão , Miogenina/metabolismoRESUMO
Gromwell (Lithospermum erythrorhizon, LE) can mitigate obesity-induced skeletal muscle atrophy in C2C12 myotubes and high-fat diet (HFD)-induced obese mice. The purpose of this study was to investigate the anti-skeletal muscle atrophy effects of LE and the underlying molecular mechanism. C2C12 myotubes were pretreated with LE or shikonin, and active component of LE, for 24 h and then treated with 500 µM palmitic acid (PA) for an additional 24 h. Additionally, mice were fed a HFD for 8 weeks to induced obesity, and then fed either the same diet or a version containing 0.25% LE for 10 weeks. LE attenuated PA-induced myotubes atrophy in differentiated C2C12 myotubes. The supplementation of LE to obese mice significantly increased skeletal muscle weight, lean body mass, muscle strength, and exercise performance compared with those in the HFD group. LE supplementation not only suppressed obesity-induced skeletal muscle lipid accumulation, but also downregulated TNF-α and atrophic genes. LE increased protein synthesis in the skeletal muscle via the mTOR pathway. We observed LE induced increase of mitochondrial biogenesis and upregulation of oxidative phosphorylation related genes in the skeletal muscles. Furthermore, LE increased the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and the phosphorylation of adenosine monophosphate-activated protein kinase. Collectively, LE may be useful in ameliorating the detrimental effects of obesity-induced skeletal muscle atrophy through the increase of protein synthesis and mitochondrial biogenesis of skeletal muscle.
Assuntos
Lithospermum , Camundongos , Animais , Biogênese de Organelas , Camundongos Obesos , Músculo Esquelético/metabolismo , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Ácido Palmítico , Obesidade/metabolismo , Dieta Hiperlipídica/efeitos adversosRESUMO
Fuzhuan brick tea (FBT) is a post-fermented tea fermented by the fungus Eurotium cristatum and is mainly produced in Hunan Province, China. Our previous study revealed that FBT extract prevents obesity by increasing energy expenditure and mitochondrial content in mice. Therefore, in this study, we hypothesized that FBT extract could be effective in alleviating obesity-induced muscle atrophy by addressing mitochondrial dysfunction, and aimed to explore the underlying molecular mechanism of FBT extract in high-fat diet-induced obese mice. FBT extract increased skeletal muscle weight and size, myosin heavy chain isoforms, and muscle performance in obese mice. Additionally, FBT extract reduced obesity-induced intramuscular lipids, skeletal muscle inflammation, and the expression of skeletal muscle atrophy markers, and increased the expression of fibronectin type III domain-containing protein 5 in skeletal muscles. Obesity-induced skeletal muscle mitochondrial dysfunction was improved by FBT extract as analyzed through mitochondrial morphology, fatty acid oxidation, respiratory chain complexes, and mitochondrial dynamics and biogenesis. Epigallocatechin, a major bioactive compound in FBT extract, attenuated palmitic acid-induced muscle atrophy by regulating mitochondrial functions in C2C12 cells. In conclusion, FBT extract may prevent obesity-induced muscle atrophy by alleviating mitochondrial dysfunction in mice.
Assuntos
Doenças Mitocondriais , Chá , Camundongos , Animais , Camundongos Obesos , Obesidade/metabolismo , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Atrofia Muscular/prevenção & controle , Músculo Esquelético/metabolismo , Extratos Vegetais/farmacologiaRESUMO
The plant Justicia procumbens is traditionally used in Asia to treat fever, cough, and pain. Previous studies have reported its anticancer and anti-asthmatic properties. However, its potential for preventing androgenic alopecia (AGA) has not yet been reported. AGA is a widespread hair loss condition primarily caused by male hormones. In this study, we examined the hair loss-preventing effects of an aqueous extract of J. procumbens (JPAE) using human hair follicle dermal papilla cell (HFDPC) and a mouse model of testosterone-induced AGA. JPAE treatment increased HFDPC proliferation by activating the Wnt/ß-catenin signaling pathway. Additionally, JPAE increased the expression of Wnt targets, such as cyclin D1 and VEGF, by promoting the translocation of ß-catenin to the nucleus. Administration of JPAE reduced hair loss, increased hair thickness, and enhanced hair shine in an AGA mouse model. Furthermore, it increased the expression of p-GSK-3ß and ß-catenin in the dorsal skin of the mice. These findings imply that JPAE promotes the proliferation of HFDPC and prevents hair loss in an AGA mouse model. JPAE can therefore be used as a functional food and natural treatment option for AGA to prevent hair loss.
Assuntos
Justicia , beta Catenina , Humanos , Camundongos , Animais , beta Catenina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Alopecia/induzido quimicamente , Alopecia/prevenção & controle , Alopecia/metabolismo , Cabelo/metabolismo , Via de Sinalização WntRESUMO
BACKGROUND: Geniposide (GP) is an iridoid glycoside that is present in nearly 40 species, including Gardenia jasminoides Ellis. GP has been reported to exhibit neuroprotective effects in various Alzheimer's disease (AD) models; however, the effects of GP on AD models of Caenorhabditis elegans (C. elegans) and aging-accelerated mouse predisposition-8 (SAMP8) mice have not yet been evaluated. PURPOSE: To determine whether GP improves the pathology of AD and sarcopenia. METHODS: AD models of C. elegans and SAMP8 mice were employed and subjected to behavioral analyses. Further, RT-PCR, histological analysis, and western blot analyses were performed to assess the expression of genes and proteins related to AD and muscle atrophy. RESULTS: GP treatment in the AD model of C. elegans significantly restored the observed deterioration in lifespan and motility. In SAMP8 mice, GP did not improve cognitive function deterioration by accelerated aging but ameliorated physical function deterioration. Furthermore, in differentiated C2C12 cells, GP ameliorated muscle atrophy induced by dexamethasone treatment and inhibited FoxO1 activity by activating AKT. CONCLUSION: Although GP did not improve the AD pathology in SAMP8 mice, we suggest that GP has the potential to improve muscle deterioration caused by aging. This effect of GP may be attributed to the suppression of FoxO1 activity.
Assuntos
Doença de Alzheimer , Caenorhabditis elegans , Iridoides , Camundongos , Animais , Doença de Alzheimer/patologia , Envelhecimento , Atrofia Muscular/tratamento farmacológicoRESUMO
Skeletal muscle atrophy is defined as wasting or loss of muscle. Although glucocorticoids (GCs) are well-known anti-inflammatory drugs, their long-term or high-dose use induces skeletal muscle atrophy. Valeriana fauriei (VF) is used to treat restlessness, anxiety, and sleep disorders; however, its effects on skeletal muscle health have not been investigated. This study investigated whether Valeriana fauriei could ameliorate muscle atrophy. We induced muscle atrophy in vitro and in vivo, by treatment with dexamethasone (DEX), a synthetic GC. In DEX-induced myotube atrophy, Valeriana fauriei treatment increased the fusion index and decreased the expression of muscle atrophic genes such as muscle atrophy F-box (MAFbx/Atrogin-1) and muscle RING-finger protein 1 (MuRF1). In DEX-treated mice with muscle atrophy, Valeriana fauriei supplementation increased the ability to exercise, muscle weight, and cross-sectional area, whereas it inhibited myosin heavy chain isoform transition and the expression of muscle atrophy biomarkers. Valeriana fauriei treatment led to via the downregulation of muscle atrophic genes via inhibition of GC receptor translocation. Valeriana fauriei was also found to act as a reactive oxygen species (ROS) scavenger. Didrovaltrate (DI), an iridoid compound from Valeriana fauriei, was found to downregulate atrophic genes and decrease ROS in the DEX-induced myotube atrophy. Consolidated, our results indicate that Valeriana fauriei prevents DEX-induced muscle atrophy by inhibiting GC receptor translocation. Further, Valeriana fauriei acts as a ROS scavenger, and its functional compound is didrovaltrate. We suggest that Valeriana fauriei and its functional compound didrovaltrate possess therapeutic potentials against muscle atrophy.
Assuntos
Antioxidantes/uso terapêutico , Dexametasona/efeitos adversos , Glucocorticoides/efeitos adversos , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Valeriana/química , Animais , Antioxidantes/farmacologia , Humanos , Masculino , CamundongosRESUMO
BACKGROUND: 2,6-Dimethoxy-1,4-benzoquinone (DMBQ), a natural phytochemical present in fermented wheat germ, has been reported to exert anti-cancer, anti-inflammatory, and anti-adipogenic effects. However, the effect of DMBQ on muscle hypertrophy and myoblast differentiation has not been elucidated. PURPOSE: We investigated the effect of DMBQ on skeletal muscle mass and muscle function and then determined the possible mechanism of DMBQ. METHODS: To examine myogenic differentiation and hypertrophy, confluent C2C12 cells were incubated in differentiation medium with or without various concentrations of DMBQ for 4 days. In animal experiments, C57BL/6 mice were fed DMBQ-containing AIN-93 diet for 7 weeks. Grip strength, treadmill, microscopic evaluation of muscle tissue, western blotting, and quantitative real-time PCR were performed. RESULTS: DMBQ significantly increased fusion index, myotube size, and the protein expression of myosin heavy chain (MHC). DMBQ increased the phosphorylation of protein kinase B (AKT) and p70 ribosomal protein S6 kinase (S6K), whereas the phosphorylation of these proteins was abolished by the phosphoinositide 3-kinase inhibitor LY294002 in C2C12 cells. In addition, DMBQ treatment increased peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), which programs mitochondrial biogenesis, protein levels compared with control C2C12 cells. DMBQ significantly increased maximal respiration and spare respiratory capacity in C2C12 cells. In animal experiments, DMBQ increased skeletal muscle weights and skeletal muscle fiber size compared with the control group values. In addition, the DMBQ group showed increased grip strength and running distance on an accelerating treadmill. The protein expression of total MHC, MHC1, MHC2A, and MHC2B in skeletal muscle was upregulated by DMBQ supplementation. We found that DMBQ increased the phosphorylation of AKT and mammalian target of rapamycin (mTOR), as well as downstream S6K and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in skeletal muscle. DMBQ also stimulated mRNA expression of PGC1α, accompanied by an increase in mitochondrial DNA content, oxidative phosphorylation (OXPHOS) proteins, and oxidative enzyme activity. CONCLUSION: Collectively, DMBQ was shown to increase skeletal muscle mass and performance by regulating the AKT/mTOR signaling pathway and enhancing mitochondrial function, which might be useful for the treatment and prevention of skeletal muscle atrophy.
Assuntos
Benzoquinonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Transdução de Sinais , Animais , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
SCOPE: γ-Oryzanol, a well-known antioxidant, has been used by body builders and athletes to boost strength and increase muscle gain, without major side effects. However, the effect of γ-Oryzanol on sarcopenia and the underlying molecular mechanism is poorly understood. RESULTS: Aged mice fed with the γ-Oryzanol diet do not show significant changes in muscle weight, but show increased running endurance as well as improved grip strength. The expression and activity of PPARδ and ERRγ are increased in skeletal muscle of γ-Oryzanol supplemented mice. γ-Oryzanol upregulates oxidative muscle fibers by MEF2 transcription factor, and PGC-1α and ERRα expressions. Fatty acid oxidation related genes and mitochondria biogenesis are upregulated by γ-Oryzanol. In addition, γ-Oryzanol inhibits TGF-ß-Smad-NADPH oxidase 4 pathway and inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and p65 NF-κB subunit, which cause skeletal muscle weakness. Collectively, γ-Oryzanol attenuates muscle weakness pathway and increases oxidative capacity by increasing PPARδ and ERRγ activity, which contributes to enhance strength and improve oxidative capacity in muscles, consequently enhancing exercise capacity in aged mice. Particularly, γ-Oryzanol directly binds to PPARδ. CONCLUSIONS: These are the first findings showing that γ-Oryzanol enhances skeletal muscle function in aged mice by regulating PPARδ and ERRγ activity without muscle gain.
Assuntos
Envelhecimento , PPAR delta/metabolismo , Fenilpropionatos/farmacologia , Condicionamento Físico Animal , Receptores de Estrogênio/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Musculares , Força Muscular , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Biogênese de Organelas , Resistência Física , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
Codium fragile (CF) is a type of green algae consumed as kimchi in Asia. UPLC-QTOF-MS/MS analysis showed that CF contain lysophosphatidyl choline, canthaxanthin, retinoic acid, α-tocopherol, and unsaturated fatty acids, which reportedly improve skeletal muscle health. However, the effect of CF on skeletal muscle mass and function remains to be elucidated. In mice fed with CF extracts, exercise endurance and muscle weight increased. CF extracts enhanced protein synthesis and myogenic differentiation through the mTORC1 pathway. CF extracts also promoted oxidative muscle fiber formation and mitochondrial biogenesis through the PGC-1α-related signaling pathway. Upregulation of PGC-1α by CF extracts was abolished by EX527 SIRT1 inhibitor treatment. Changed signaling molecules in the CF extracts were partially regulated by canthaxanthin, a new compound in CF extracts, suggesting that canthaxanthin contribute synergistically to the effect of CF extracts. Therefore, CF is a potential food source for sport nutrition or prevention of sarcopenia.
Assuntos
Clorófitas/química , Músculo Esquelético/efeitos dos fármacos , Resistência Física/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Cantaxantina/análise , Carbazóis/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/fisiologia , Tamanho do Órgão/efeitos dos fármacos , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Condicionamento Físico Animal/fisiologia , Resistência Física/fisiologia , Extratos Vegetais/análise , Alga Marinha/química , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas em Tandem , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: The enhancement of energy expenditure has attracted attention as a therapeutic target for the management of body weight. Withaferin A (WFA), a major constituent of Withania somnifera extract, has been reported to possess anti-obesity properties, however the underlying mechanism remains unknown. PURPOSE: To investigate whether WFA exerts anti-obesity effects via increased energy expenditure, and if so, to characterize the underlying pathway. METHODS: C57BL/6 J mice were fed a high-fat diet (HFD) for 10 weeks, and WFA was orally administered for 7 days. The oxygen consumption rate of mice was measured at 9 weeks using an OxyletPro™ system. Hematoxylin and eosin (H&E), immunohistochemistry, immunoblotting, and real-time PCR methods were used. RESULTS: Treatment with WFA ameliorated HFD-induced obesity by increasing energy expenditure by improving of mitochondrial activity in brown adipose tissue (BAT) and promotion of subcutaneous white adipose tissue (scWAT) browning via increasing uncoupling protein 1 levels. WFA administration also significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the BAT of obese mice. Additionally, WFA activated mitogen-activated protein kinase (MAPK) signaling, including p38/extracellular signal-regulated kinase MAPK, in both BAT and scWAT. CONCLUSION: WFA enhances energy expenditure and ameliorates obesity via the induction of AMPK and activating p38/extracellular signal-regulated kinase MAPK, which triggers mitochondrial biogenesis and browning-related gene expression.
Assuntos
Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Metabolismo Energético/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Obesidade/tratamento farmacológico , Termogênese/efeitos dos fármacos , Vitanolídeos/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Mitocôndrias/metabolismo , Termogênese/genética , Proteína Desacopladora 1/metabolismo , Withania/química , Vitanolídeos/farmacologiaRESUMO
Chrysanthemum zawadskii Herbich (CZH) is used in traditional medicine to treat inflammatory diseases and diabetes. However, the effects of CZH on muscle wasting remains to be studied. Here, we investigated the effect of CZH on dexamethasone (DEX), a synthetic glucocorticoid, induced muscle atrophy. To examine the effect of CZH on muscle atrophy, C2C12 myotubes were co-treated with DEX and CZH for 24 h. The treatment with CZH prevented DEX-induced myotube atrophy in a dose-dependent manner. CZH inhibited the DEX-induced decrease of the MHC isoforms and the upregulation of atrogin-1 and MuRF1 in C2C12 differentiated cells. C57BL/6 mice were supplemented with 0.1 % CZH for 8 weeks, with DEX-induced muscle atrophy stimulated in the last 3 weeks. In the mice, CZH supplementation effectively reversed DEX-induced skeletal muscle atrophy and increased the exercise capacity of the mice through the inhibition of glucocorticoid receptor translocation. Additionally, we observed that DEX-evoked impaired proteostasis was ameliorated via the Akt/mTOR pathway. CZH also prevented the DEX-induced decrease in the mitochondrial respiration. HPLC analysis demonstrated the highest concentration of acacetin-7-O-ß-d-rutinoside (AR) among 4 compounds. Moreover, AR, a functional compound of CZH, prevented DEX-evoked muscle atrophy. Thus, we suggest that CZH could be a potential therapeutic candidate against muscle atrophy and AR is the main functional compound of CZH.
Assuntos
Chrysanthemum , Flavonoides/farmacologia , Glicosídeos/farmacologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Chrysanthemum/química , Dexametasona , Modelos Animais de Doenças , Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/patologia , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Extratos Vegetais/isolamento & purificação , ProteostaseRESUMO
BACKGROUND: Atopic dermatitis (AD) is an inflammatory chronic skin disease that is characterized by the dysfunction or lack of skin barrier proteins. Recent studies have proposed that the pharmacological upregulation of skin barrier proteins is an effective treatment for AD. Aryl hydrocarbon receptor (AhR) is a transcription factor that positively regulates the expression of skin barrier proteins upon its activation. PURPOSE: This study aimed to identify AhR agonists from phytochemicals and investigate its effect on skin barrier restoration as well as its mechanisms of action in AD. STUDY DESIGN: A publicly available assay database and HaCaT cells stably transduced with a luciferase gene driven by an AhR-target gene promoter (CYP1A1) were used to screen for the activity of AhR agonists from phytochemicals. Normal human epidermal keratinocytes (NHEKs) and a human skin equivalent (HSE) model were used to investigate the effect of AhR agonists on skin restoration and its underlying mechanisms. METHODS: A Gaussia luciferase assaywas performed to screen for AhR agonist activity. Western blotting, qRT-PCR analysis, immunofluorescence, drug affinity responsive target stability assay, and siRNA-mediated AhR knockdown were performed in NHEKs. Hematoxylin and eosin staining was performed to measure epidermal thickness in the HSE model. RESULTS: Diosmin, a potential AhR agonist derived from natural products, upregulated the expression of skin barrier proteins (filaggrin and loricrin) and their upstream regulator (OVOL1) in NHEKs. Diosmin treatment also increased epidermal thickness in the HSE model. In addition, incubating NHEKs with diosmin restored the expression of skin barrier proteins and mRNAs that were suppressed by Th2 cytokines and inhibited STAT3 phosphorylation that was induced by Th2 cytokines. Diosmin also upregulated the expression of NQO1, a negative regulator of STAT3. Immunofluorescence results showed that diosmin stimulated AhR nuclear translocation, and the drug affinity responsive target stability assay revealed that this phytochemical directly bound to AhR. Furthermore, AhR knockdown abolished diosmin-induced filaggrin and loricrin expression. CONCLUSION: These results suggest that diosmin is a potential treatment for AD that targets AhR.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/farmacologia , Diosmina/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismo , Pele/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/agonistas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Linhagem Celular , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Proteínas de Ligação a DNA/metabolismo , Dermatite Atópica/patologia , Avaliação Pré-Clínica de Medicamentos/métodos , Proteínas Filagrinas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Compostos Fitoquímicos/farmacologia , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/genética , Pele/metabolismo , Pele/patologia , Células Th2/metabolismo , Fatores de Transcrição/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Although drug therapies are available for postmenopausal osteoporosis, these drugs are not free of side effects and long-term adherence to them are low. A safe and effective nutritional approach to counter postmenopausal osteoporosis is an important research goal. We fed ovariectomized (OVX) Sprague-Dawley rats a diet supplemented with 1% or 2% green tomato extract (GTE). After 12 weeks, micro-computed tomography scans revealed that GTE supplementation effectively prevented distal femur bone loss. This prevention was due to improved bone formation and suppressed bone resorption as observed by the regulation of osteoblast and osteoclast activities. GTE supplementation also improved bone formation through Bmp2-Smad 1/5/8-Runx2 signaling, while bone resorption was regulated by the receptor activator of nuclear factor kappa-B (RANKL)/osteoprogeterin (OPG) pathway. These results suggest that GTE supplementation prevents severe postmenopausal bone loss by maintaining the regulation of bone homeostasis in OVX rats. GTE as a diet supplement might be a potential novel alternative for the prevention of postmenopausal osteoporosis.
Assuntos
Osteoporose Pós-Menopausa/prevenção & controle , Extratos Vegetais/uso terapêutico , Solanum lycopersicum , Animais , Densidade Óssea/efeitos dos fármacos , Proteína Morfogenética Óssea 2/metabolismo , Reabsorção Óssea/prevenção & controle , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Solanum lycopersicum/química , Osteogênese/efeitos dos fármacos , Osteoprotegerina/metabolismo , Ovariectomia , Fitoterapia , Ligante RANK/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteínas Smad Reguladas por Receptor/metabolismo , Tomatina/análogos & derivados , Tomatina/análise , Aumento de PesoRESUMO
As obesity promotes ectopic fat accumulation in skeletal muscle, resulting in impaired skeletal muscle and mitochondria function, it is associated with skeletal muscle loss and dysfunction. This study investigated whether Chrysanthemi zawadskii var. latilobum (CZH) protected mice against obesity-induced skeletal muscle atrophy and the underlying molecular mechanisms. High-fat diet (HFD)-induced obese mice were orally administered either distilled water, low-dose CZH (125 mg/kg), or high-dose CZH (250 mg/kg) for 8 w. CZH reduced obesity-induced increases in inflammatory cytokines levels and skeletal muscle atrophy, which is induced by expression of atrophic genes such as muscle RING-finger protein 1 and muscle atrophy F-box. CZH also improved muscle function according to treadmill running results and increased the muscle fiber size in skeletal muscle. Furthermore, CZH upregulated mRNA and protein levels of protein arginine methyltransferases (PRMT)1 and PRMT7, which subsequently attenuated mitochondrial dysfunction in the skeletal muscle of obese mice. We also observed that CZH significantly decreased PRMT6 mRNA and protein expression, which resulted in decreased muscle atrophy. These results suggest that CZH ameliorated obesity-induced skeletal muscle atrophy in mice via regulation of PRMTs in skeletal muscle.
Assuntos
Chrysanthemum/química , Dieta Hiperlipídica/efeitos adversos , Músculo Esquelético/patologia , Atrofia Muscular/tratamento farmacológico , Obesidade/complicações , Extratos Vegetais/administração & dosagem , Proteína-Arginina N-Metiltransferases/metabolismo , Administração Oral , Animais , Citocinas/metabolismo , Masculino , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Obesidade/induzido quimicamente , Obesidade/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteína-Arginina N-Metiltransferases/genética , Regulação para Cima/efeitos dos fármacosRESUMO
Shikonin, a natural plant pigment, is known to have anti-obesity activity and to improve insulin sensitivity. This study aimed to examine the effect of shikonin on hepatic steatosis, focusing on the AMP-activated protein kinase (AMPK) and energy expenditure in Hepa 1-6 cells and in high-fat fed mice. Shikonin increased AMPK phosphorylation in a dose- and time-dependent manner, and inhibition of AMPK with compound C inhibited this activation. In an oleic acid-induced steatosis model in hepatocytes, shikonin suppressed oleic acid-induced lipid accumulation, increased AMPK phosphorylation, suppressed the expression of lipogenic genes, and stimulated fatty acid oxidation-related genes. Shikonin administration for four weeks decreased body weight gain and the accumulation of lipid droplets in the liver of high-fat fed mice. Furthermore, shikonin promoted energy expenditure by activating fatty acid oxidation. In addition, shikonin increased the expression of PPARγ coactivator-1α (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) and other mitochondrial function-related genes. These results suggest that shikonin attenuated a high fat diet-induced nonalcoholic fatty liver disease by stimulating fatty acid oxidation and energy expenditure via AMPK activation.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Metabolismo Energético/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Naftoquinonas/farmacologia , Fitoterapia , Animais , Anti-Inflamatórios não Esteroides , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fígado Gorduroso/etiologia , Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Camundongos , Naftoquinonas/uso terapêutico , Oxirredução/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
Patrinia scabiosaefolia (PS) and Hippophae rhamnoides (HR) are traditionally used functional foods. Extracts from the root of PS are known for their anti-inflammatory effects, whereas those from the leaf of HR are effective at both preventing and treating obesity. This study investigated whether the extract combination of PS and HR (PHE) affected weight loss in obese mice. In vitro experiments demonstrated that PHE showed a synergistic effect on inhibiting adipocyte differentiation as compared with treatment with the single extracts. Additionally, PHE suppressed adipogenic-related genes in a concentration-dependent manner. In vivo PHE supplementation suppressed body weight gain, inhibited hepatic lipid accumulation, decreased adipose size, serum triglycerides, and improved insulin resistance in obese mice. These results suggest that a treatment strategy using a combination of plant-derived extracts might be effective at ameliorating obesity. PRACTICAL APPLICATIONS: Currently, common methods for reducing obesity are diet and exercise. These can stimulate oxidative phosphorylation and metabolic activation so have significantly effects. However, these are largely due to individual compliance; there is no significant effect of reducing the worldwide obesity rate. Recently, herbal extracts has been reported as alternative medicine about inflammatory and obesity because diet with the herbal extracts can improve obesity with minimal side effects. Of particular, a mixture of herbal products was investigated for the treatment of obesity. Our reports demonstrated the synergistic effects of natural products and emphasizes the need for studies investigating other combinations of herbal extracts in the treatment of obesity. The results of our studies highlight the synergistic effects of combination phytochemical extracts and their role in ameliorating obesity.
Assuntos
Hippophae , Patrinia , Animais , Fígado , Camundongos , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologiaRESUMO
Dietary habits can alter the skeletal muscle performance and mass, and Undaria pinnatifida extracts are considered a potent candidate for improving the muscle mass and function. Therefore, in this study, we aimed to assess the effect of U pinnatifida extracts on exercise endurance and skeletal muscle mass. C57BL/6 mice were fed a 0.25% U pinnatifida extract-containing diet for 8 weeks. U pinnatifida extract-fed mice showed increased running distance, total running time, and extensor digitorum longus and gastrocnemius muscle weights. U pinnatifida extract supplementation upregulated the expression of myocyte enhancer factor 2C, oxidative muscle fiber markers such as myosin heavy chain 1 (MHC1), and oxidative biomarkers in the gastrocnemius muscles. Compared to the controls, U pinnatifida extract-fed mice showed larger mitochondria and increased gene and protein expression of molecules involved in mitochondrial biogenesis and oxidative phosphorylation, including nuclear respiratory factor 2 and mitochondrial transcription factor A. U pinnatifida extract supplementation also increased the mRNA expression of angiogenesis markers, including VEGFa, VEGFb, FGF1, angiopoietin 1, and angiopoietin 2, in the gastrocnemius muscles. Importantly, U pinnatifida extracts upregulated the estrogen-related receptor γ and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α)/AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) networks, which are partially increased by fucoxanthin, hesperetin, and caffeic acid treatments. Collectively, U pinnatifida extracts enhance mitochondrial biogenesis, increase oxidative muscle fiber, and promote angiogenesis in skeletal muscles, resulting in improved exercise capacity and skeletal muscle mass. These effects are attributable to fucoxanthin, hesperetin, and caffeic acid, bioactive components of U pinnatifida extracts.
Assuntos
Músculo Esquelético/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal/fisiologia , Resistência Física/efeitos dos fármacos , Extratos Vegetais/farmacologia , Undaria/química , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Biomarcadores/metabolismo , Linhagem Celular , Proteínas de Ligação a DNA/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/metabolismo , Doenças Musculares/tratamento farmacológico , Doenças Musculares/metabolismo , Biogênese de Organelas , Fosforilação Oxidativa/efeitos dos fármacos , Sirtuína 1/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Withania somnifera (WS), commonly known as ashwagandha, possesses diverse biological functions. WS root has mainly been used as an herbal medicine to treat anxiety and was recently reported to have an anti-obesity effect, however, the mechanisms underlying its action remain to be explored. We hypothesized that WS exerts its anti-obesity effect by enhancing energy expenditure through improving the mitochondrial function of brown/beige adipocytes and skeletal muscle. Male C57BL/6J mice were fed a high-fat diet (HFD) containing 0.25% or 0.5% WS 70% ethanol extract (WSE) for 10 weeks. WSE (0.5%) supplementation significantly suppressed the increases in body weight and serum lipids, and lipid accumulation in the liver and adipose tissue induced by HFD. WSE supplementation increased oxygen consumption and enhanced mitochondrial activity in brown fat and skeletal muscle in the HFD-fed mice. In addition, it promoted browning of subcutaneous fat by increasing mitochondrial uncoupling protein 1 (UCP1) expression. Withaferin A (WFA), a major compound of WS, enhanced the differentiation of pre-adipocytes into beige adipocytes and oxygen consumption in C2C12 murine myoblasts. These results suggest that WSE ameliorates diet-induced obesity by enhancing energy expenditure via promoting mitochondrial function in adipose tissue and skeletal muscle, and WFA is a key regulator in this function.
Assuntos
Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Fármacos Antiobesidade , Suplementos Nutricionais , Metabolismo Energético/efeitos dos fármacos , Mitocôndrias/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Obesidade/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Withania/química , Vitanolídeos/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Consumo de Oxigênio/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Vitanolídeos/administração & dosagem , Vitanolídeos/isolamento & purificaçãoRESUMO
Nonalcoholic fatty liver disease (NAFLD) is a common risk factor for metabolic syndrome that increases the risk of future cardiovascular disease, stroke, and diabetes. Recently, autophagy has been proposed as a means to prevent NAFLD. We investigated whether substances with autophagy-inducing activity alleviate NAFLD. The Valeriana fauriei (V. fauriei) was selected as a potential autophagy inducer among various natural materials using a Cyto-ID autophagy detection kit. V. fauriei 70 % ethanol extract (VFE) increased LC3II levels in the presence of the lysosomal inhibitor and reduced the GFP/mCherry puncta ratio, suggesting that VFE enhanced autophagy. VFE reduced oleic acid (OA)-induced lipid accumulation and increased the number of autophagosome in hepatocytes. Autophagy induction by VFE is due to inhibition of mTORC1 activity. VFE supplementation reduced fatty liver by downregulating lipogenesis-related genes and increased the autophagy, as revealed by TEM and IHC analysis in the fatty liver. We identified iridoids as main compounds of VFE; didrovaltrate (DI), valeriotriate B (VAL B), valeriotetrate C (VAL C), valtrate (VAL), and valechlorine (VC) were shown to enhance autophagy. These compounds also reduced OA-induced lipid accumulation in an Atg5-dependent manner. Taken together, VFE and its iridoids might be effective in alleviating fatty liver by acting as autophagy enhancers to break down LDs.
Assuntos
Autofagia/efeitos dos fármacos , Iridoides/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Valeriana/química , Animais , Linhagem Celular Tumoral , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Iridoides/isolamento & purificação , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Extratos Vegetais/farmacologiaRESUMO
Senile osteoporosis increases the risk of skeletal fractures with age. Cheonggukjang (CGJ), a traditional Korean dry fermented soybean product, has numerous therapeutic effects; however, its effects on bone mineral density (BMD) and bone metabolism in senile osteoporosis are unclear. In this study, we treated the senescence-accelerated mouse prone 6 (SAMP6) model of senile osteoporosis with CGJ to determine its potential for ameliorating and preventing osteoporosis progression. High-performance liquid chromatography analysis for isoflavone profiles revealed that short-term fermentation significantly increased the isoflavone aglycone content in soybeans. Thereafter, we fed 6-week-old SAMP6 mice with experimental diets containing 5% or 10% CGJ for 15 weeks. Microcomputed tomography revealed that CGJ supplementation effectively increased the BMD and relative bone length. In vitro, CGJ increased the osteopontin reactivity and upregulated the expression of Alp, Col1a1, Fak, Bmp2/4, Smad1/5/8, and Runx2 in osteoblasts, and decreased Cathepsin K reactivity and downregulated Rankl and Nfatc1 expression in osteoclasts. In addition, CGJ increased the osteoprotegerin/Rankl ratio. Collectively, these results demonstrate that CGJ can ameliorate the detrimental effects of senile osteoporosis by improving osteogenesis and decreasing osteoclast activity.