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1.
J Agric Food Chem ; 68(10): 3099-3111, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32067456

RESUMO

Sesamol, a lignan in sesame, possesses several bioactivities, such as antioxidation, anti-inflammation, and neuroprotective capability. In this study, the effects of sesamol on aging-caused cognitive defects are investigated. Twelve-month-old mice were treated with sesamol (0.1%, w/w) as dietary supplementation for 12 weeks. Behavioral tests revealed that sesamol improved aging-associated cognitive impairments. Sesamol decreased aging-induced oxidative stress via suppression of malondialdehyde production and increased antioxidant enzymes. Histological staining showed that sesamol treatment improved aging-induced neuronal damage and synaptic dysfunction in the hippocampus. Furthermore, sesamol significantly reduced aging-induced neuroinflammation by inhibiting the microglial overactivation and inflammatory cytokine expressions. Meanwhile, the accumulation of Aß1-42 was reduced by sesamol treatment. Moreover, sesamol protected the gut barrier integrity and reduced LPS release, which was highly associated with its beneficial effects on behavioral and inflammatory changes. In conclusion, our findings indicated that the use of sesamol is feasible in the treatment of aging-related diseases.


Assuntos
Envelhecimento/efeitos dos fármacos , Benzodioxóis/administração & dosagem , Disfunção Cognitiva/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Fenóis/administração & dosagem , Envelhecimento/imunologia , Envelhecimento/psicologia , Peptídeos beta-Amiloides/imunologia , Animais , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/psicologia , Hipocampo/efeitos dos fármacos , Hipocampo/imunologia , Humanos , Masculino , Malondialdeído/imunologia , Camundongos , Microglia/efeitos dos fármacos , Microglia/imunologia , Estresse Oxidativo/efeitos dos fármacos
2.
Life Sci ; 248: 117452, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32088214

RESUMO

AIMS: The aim of this study was to elucidate the signaling pathway involved in the anti-aging effect of tropisetron and to clarify whether it affects mitochondrial oxidative stress, apoptosis and inflammation in the aging mouse brain by upregulating Sirtuin 1 or silent information regulator 1 (SIRT1). MATERIALS AND METHODS: Aging was induced by d-galactose (DG) at the dose of 200 mg/kg body weight/day subcutaneously injected to male mice for six weeks. Tropisetron was simultaneously administered intraperitoneally once a day at three various doses (1, 3 and 5 mg/kg body weight). Oxidative stress and mitochondrial dysfunction markers were evaluated. Nitric oxide (NO) and pro-inflammatory cytokines levels including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were studied. Besides, the expressions of apoptosis-associated genes (Bax and Bcl-2) and the aging-related gene (SIRT1) were determined by the real time polymerase chain reaction (RT-PCR). In addition, histopathological alterations were assessed. KEY FINDINGS: Tropisetron reversed the induction of oxidative damage, mitochondrial dysfunction and overproduction of inflammatory mediators induced by DG in the brain tissue. In addition, tropisetron suppressed DG-induced apoptosis and found to significantly elevate SIRT1 gene expression. Besides, tropisetron could markedly alleviate DG-induced abnormal changes in the brain morphology. SIGNIFICANCE: Tropisetron exhibited anti-aging effects in the context of DG-induced senescence in mouse brain through various pathways. Our results suggest that tropisetron may attenuate DG-induced brain aging via SIRT1 signaling activation.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia , Sirtuína 1/genética , Tropizetrona/farmacologia , Envelhecimento/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Encéfalo/metabolismo , Encéfalo/patologia , Esquema de Medicação , Galactose/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação , Injeções Intraperitoneais , Injeções Subcutâneas , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
3.
Food Chem Toxicol ; 135: 110881, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31622731

RESUMO

Dietary peptide has been of great interest because of its perspective in nutrition and health of human body. The aim of this study was to develop a dietary nutritional supplement exerting both antioxidant and anti-aging effects. Peptide, named as ERJ-CP, was prepared by mixing enzyme-treated royal jelly (ERJ) with collagen peptide (CP), showing stronger antioxidant activity in vitro. Drosophila was used as model animal to investigate anti-aging effect of ERJ-CP in vivo. ERJ-CP significantly prolonged the average life span of Drosophila treated with H2O2 and paraquat, reducing malondialdehyde (MDA) and protein carbonyl (PCO) levels in Drosophila. In addition, 3 mg/mL of ERJ-CP could prolong the lifespan of natural aging Drosophila by 11.16%. ERJ-CP could up-regulate the levels of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and down-regulate the contents of MDA and PCO. Moreover, the intake of ERJ-CP increased the food consumption, weight gain and exercise capacity of Drosophila. The results showed that ERJ-CP played a protective role in both antioxidant and anti-aging effects on Drosophila, and the anti-aging effect may be achieved by alleviating oxidative damage. It suggests that ERJ-CP could be developed as a health-promoting ingredient with antioxidant and anti-aging effects for human body.


Assuntos
Envelhecimento/efeitos dos fármacos , Colágeno/farmacologia , Drosophila/fisiologia , Ácidos Graxos/química , Estresse Oxidativo/efeitos dos fármacos , Aminoácidos/análise , Animais , Peso Corporal/efeitos dos fármacos , Colágeno/química , Comportamento Alimentar/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Longevidade/efeitos dos fármacos , Peso Molecular , Paraquat/farmacologia
4.
Carbohydr Polym ; 228: 115381, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635744

RESUMO

Sargassum fusiforme polysaccharides, acidic water-soluble polysaccharides extract from Sargassum fusiforme, are mainly composed of alginic acid, fucoidan and laminaran. Alginic acid is carboxyl-containing polysaccharide formed by joining ß-D-mannuronic acid and α-L-guluronic acid through ß-(1→4)/α-(1→4) glycosidic bond. Fucoidan, a natural water-soluble sulfated heteropolysaccharide with fucose and sulfuric acid groups as the core structure, is mainly linked by L-fucose through α-(1→3) glycosidic bond and has the strongest biological activity. Laminaran is mainly composed of ß-D-glucose through ß-(1→3) glycosidic bond linkage. Sargassum fusiforme polysaccharides have a variety of pharmacological activities, including antioxidant, anti-tumor, promoting immunity, anti-aging, prompting bone growth, lowering blood glucose, anti-coagulation, anti-virus, anti-bacteria, anti-fatigue, promoting growth and development, and skin protection. These activities are closely related to the functions of fucoidan in Sargassum fusiforme polysaccharides, which fucoidan is able to strengthen immune system and antioxidation in human body. In this review, the composition, the isolation and purification, and the biological activities of Sargassum fusiforme polysaccharides are discussed and can bereference for further study.


Assuntos
Ácido Algínico , Glucanos , Polissacarídeos , Sargassum/metabolismo , Envelhecimento/efeitos dos fármacos , Ácido Algínico/química , Ácido Algínico/isolamento & purificação , Ácido Algínico/farmacologia , Animais , Bactérias/efeitos dos fármacos , Linhagem Celular , Carboidratos da Dieta/isolamento & purificação , Carboidratos da Dieta/farmacologia , Glucanos/química , Glucanos/isolamento & purificação , Glucanos/farmacologia , Humanos , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Camundongos , Neoplasias/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Ratos , Vírus/efeitos dos fármacos
5.
Ecotoxicol Environ Saf ; 188: 109898, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31711775

RESUMO

Gamma-aminobutyric acid (GABA) plays a critical role in regulation of gonadotropin-releasing hormone (GnRH) through GABAA receptor (GABAAR). Nitric oxide (NO) production has correlation with GABA and regulates GnRH secretion. This study was performed to examine the mechanisms by which manganese (Mn) accelerate puberty onset involves GABAAR/NO pathway in the preoptic area-anterior hypothalamus (POA-AH) in immature female rats. First, female rats received daily dose of MnCl2 0 (saline), 2.5, 5 and 10 mg/kg b.w by oral gavage during postnatal day (PND) 21-32. Animals administered with 10 mg/kg MnCl2 exhibited earlier puberty onset age and advanced ovary and uterus development than these in saline-treatment group. Furthermore, we found that decrease of GABAAR result in elevated production of nitric oxide synthase1 (NOS1), NO and GnRH in the POA-AH. Second, we recorded the neuronal spikes alternation after perfusion with GABAAR inhibitor bicuculline (BIC), GABAAR agonist isoguvacine (isog), and MnCl2 from the POA-AH in acute brain slices of PND21 rats. Spontaneous firing revealed a powerful GABAAR-mediated action on immature POA-AH and confirm that MnCl2 has a significant effect on GABAAR. Third, we revealed that decrease in NOS1 and NO production by treatment with isog-alone or isog+MnCl2 contribute to the decrease of GnRH in the POA-AH and a delayed puberty onset age compared to treatment with MnCl2-alone. Together, these results suggested that excessive exposure to MnCl2 stimulates NO production through decreased GABAAR in the POA-AH to advance puberty onset in immature female rats.


Assuntos
Envelhecimento/efeitos dos fármacos , Cloretos/toxicidade , Disruptores Endócrinos/toxicidade , Óxido Nítrico/metabolismo , Área Pré-Óptica/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Maturidade Sexual/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Compostos de Manganês , Neurônios/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Área Pré-Óptica/crescimento & desenvolvimento , Área Pré-Óptica/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Útero/diagnóstico por imagem , Útero/efeitos dos fármacos , Desmame
6.
J Photochem Photobiol B ; 201: 111637, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706086

RESUMO

Plants are considered to be a leading source for possible human therapeutic agents. This holistic study has investigated the anti-quorum sensing (anti-QS), anti-infection, antioxidant and anti-photoaging properties of neglected plant Diplocyclos palmatus. The results showed that D. palmatus methanolic leaf extract (DPME) effectively inhibited the quorum sensing (QS) regulated virulence factor production as well as biofilm formation in Serratia marcescens. The transcriptomic analysis revealed that DPME significantly downed the expression of QS-regulated genes such as fimA, fimC, flhC, bsmB, pigP and shlA in S. marcescens, which supports the outcome of in vitro bioassays. Further, the docking study revealed that the presence of active compounds, namely tocopherols and phytol, DPME exhibited its anti-QS activity against S. marcescens. In addition, DPME treatment extended the lifespan of S. marcescens infected C. elegans by the action of dropping the internal accumulation. Further, qPCR analysis clearly revealed that DPME treatment significantly up-regulated the expression of the lifespan-related gene (daf-16) and immune-related genes (clec-60, clec-87, lys-7 and bec-1) in S. marcescens infected C.elegans. On the other hand, DPME extensively reduced the UV-A induced ROS stress, thereby, extended the lifespan in UV-A photoaged C. elegans. Further, the qPCR analysis also confirmed the up-regulation of daf-16, clec-60, clec-87 and col-19 genes which advocated the improvement of the lifespan, healthspan and collagen production in UV-A photoaged C. elegans. Further bioassays evidenced that that the lifespan extension of photoaged C. elegans was accomplished by the actions of antioxidants such as tocopherols and phytol in DPME.


Assuntos
Envelhecimento/efeitos dos fármacos , Caenorhabditis elegans/efeitos da radiação , Cucurbitaceae/química , Extratos Vegetais/farmacologia , Percepção de Quorum/efeitos dos fármacos , Serratia marcescens/fisiologia , Raios Ultravioleta , Envelhecimento/efeitos da radiação , Animais , Antioxidantes/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Colágeno/metabolismo , Cucurbitaceae/metabolismo , Longevidade/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Infecções por Serratia/patologia , Infecções por Serratia/veterinária , Regulação para Cima/efeitos dos fármacos
7.
BMC Complement Altern Med ; 19(1): 297, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694618

RESUMO

BACKGROUND: Radix isatidis (Isatis indigotica Fort.) is an ancient medicinal herb, which has been applied to the prevention and treatment of influenza virus since ancient times. In recent years, the antioxidant activity of Radix isatidis has been widely concerned by researchers. Our previous studies have shown that Radix isatidis protein (RIP) has good antioxidant activity in vitro. In this study, the composition of the protein was characterized and its antioxidant activity in vivo was evaluated. METHODS: The model of oxidative damage in mice was established by subcutaneous injection of D-galactose for 7 weeks. Commercially available kits were used to determine the content of protein and several oxidation indexes in different tissues of mice. The tissue samples were stained with hematoxylin and eosin (H&E) and the pathological changes were observed by optical microscope. The molecular weight of RIP was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The amino acid composition of RIP was determined by a non-derivative method developed by our research group. RESULTS: RIP significantly increased the activities of antioxidant enzymes such as SOD, CAT, GSH-Px and total antioxidant capability (TAOC) but decreased the MDA level in the serum, kidney and liver. H&E stained sections of liver and kidney revealed D-galactose could cause serious injury and RIP could substantially attenuate the injury. The analysis of SDS-PAGE showed that four bands with molecular weights of 19.2 kDa, 21.5 kDa, 24.8 kDa and 40.0 kDa were the main protein components of RIP. CONCLUSIONS: The results suggested that RIP had excellent antioxidant activity, which could be explored as a health-care product to retard aging and a good source of protein nutrition for human consumption.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/química , Medicamentos de Ervas Chinesas/química , Galactose/efeitos adversos , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/química , Envelhecimento/metabolismo , Animais , Antioxidantes/isolamento & purificação , Catalase/metabolismo , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Peso Molecular , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Plantas/isolamento & purificação , Raízes de Plantas/química , Superóxido Dismutase/metabolismo
8.
Adv Exp Med Biol ; 1182: 299-309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777025

RESUMO

Although Ganoderma (Lingzhi in Chinese) has been used as an elixir for thousands of years, its anti-aging effects still need to be clarified. Aging is related to immunoregulation, oxidation stress, and free radical product. Till now, Ganoderma exert life span elongation activities by inhibiting ROS production, lipid peroxidation, and advanced oxidation protein products; increasing production of mitochondrial electron transport complexes, SOD, CAT, GSH and GSH-Px, DPPH, and ABTS radical scavenger activities; and having immunomodulatory and antioxidant activity by increasing radical scavenging activity and ferric reducing antioxidant power. Ganoderma's anti-aging effect on human remains a mystery, and its potential mechanisms underlying anti-aging effect for its clinical application still need to be elucidated.


Assuntos
Envelhecimento/efeitos dos fármacos , Produtos Biológicos/farmacologia , Aptidão Física , Reishi/química , Antioxidantes/farmacologia , Humanos , Peroxidação de Lipídeos , Estresse Oxidativo
9.
Int J Med Mushrooms ; 21(6): 561-570, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679228

RESUMO

The in vitro antioxidant effects of petroleum ether, ethyl acetate, and ethanol extracts isolated from Hericium coralloides were investigated. Overall, the ethyl acetate extract of H. coralloides (HcEAE) showed better antioxidant activity in vitro than the petroleum ether and ethanol extracts (HcPEE and HcETE, respectively) of H. coralloides. A comprehensive investigation of the antioxidant activity of the HcEAE in vitro indicated that it possessed superior antioxidant activity, with half maximal inhibitory concentration (IC50) values of 0.93, 1.84, 1.59, and 0.6 mg/mL against DPPH, hydroxyl, ABTS+, and superoxide (O2- ) radicals, respectively. To assess in vivo antioxidant activity, three different doses of HcEAE were orally administered in a D-galactose-induced aged mouse model. Administration of HcEAE significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and lowered the levels of malondialdehyde (MDA) in brains and sera of mice in a dose-dependent manner. A histopathology assessment indicated that the HcEAE could ameliorate the anile condition of the model mice. These results suggest that the HcEAE has potent antioxidant activity and could minimize the occurrence of age-associated disorders associated with free radicals.


Assuntos
Agaricales/química , Envelhecimento , Antioxidantes/análise , Extratos Celulares/farmacologia , Acetatos/análise , Envelhecimento/efeitos dos fármacos , Alcanos/análise , Animais , Catalase/análise , Extratos Celulares/química , Etanol , Radicais Livres/análise , Concentração Inibidora 50 , Masculino , Camundongos , Superóxido Dismutase/análise
10.
BMC Complement Altern Med ; 19(1): 313, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730453

RESUMO

BACKGROUND: Jianpi-yangwei (JPYW), a traditional Chinese medicine (TCM), helps to nourish the stomach and spleen and is primarily used to treat functional declines related to aging. This study aimed to explore the antiaging effects and mechanism of JPYW by employing a Caenorhabditis elegans model. METHODS: Wild-type C. elegans N2 worms were cultured in growth medium with or without JPYW, and lifespan analysis, oxidative and heat stress resistance assays, and other aging-related assays were performed. The effects of JPYW on the levels of superoxide dismutase (SOD) and the expression of specific genes were examined to explore the underlying mechanism of JPYW. RESULTS: Compared to control worms, JPYW-treated wild-type worms showed increased survival times under both normal and stress conditions (P < 0.05). JPYW-treated worms also exhibited enhanced reproduction, movement and growth and decreased intestinal lipofuscin accumulation compared to controls (P < 0.05). Furthermore, increased activity of SOD, downregulated expression levels of the proaging gene clk-2 and upregulated expression levels of the antiaging genes daf-16, skn-1, and sir-2.1 were observed in the JPYW group compared to the control group. CONCLUSION: Our findings suggest that JPYW extends the lifespan of C. elegans and exerts antiaging effects by increasing the activity of an antioxidant enzyme (SOD) and by regulating the expression of aging-related genes. This study not only indicates that this Chinese compound exerts antiaging effects by activating and repressing target genes but also provides a proven methodology for studying the biological mechanisms of TCMs.


Assuntos
Envelhecimento/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Envelhecimento/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Humanos , Longevidade/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
11.
EMBO J ; 38(23): e101982, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31633821

RESUMO

Cellular senescence has been shown to contribute to skin ageing. However, the role of melanocytes in the process is understudied. Our data show that melanocytes are the only epidermal cell type to express the senescence marker p16INK4A during human skin ageing. Aged melanocytes also display additional markers of senescence such as reduced HMGB1 and dysfunctional telomeres, without detectable telomere shortening. Additionally, senescent melanocyte SASP induces telomere dysfunction in paracrine manner and limits proliferation of surrounding cells via activation of CXCR3-dependent mitochondrial ROS. Finally, senescent melanocytes impair basal keratinocyte proliferation and contribute to epidermal atrophy in vitro using 3D human epidermal equivalents. Crucially, clearance of senescent melanocytes using the senolytic drug ABT737 or treatment with mitochondria-targeted antioxidant MitoQ suppressed this effect. In conclusion, our study provides proof-of-concept evidence that senescent melanocytes affect keratinocyte function and act as drivers of human skin ageing.


Assuntos
Envelhecimento/patologia , Atrofia/patologia , Senescência Celular , Melanócitos/patologia , Pele/patologia , Telômero/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/efeitos dos fármacos , Atrofia/induzido quimicamente , Células Cultivadas , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/patologia , Feminino , Humanos , Masculino , Melanócitos/metabolismo , Pessoa de Meia-Idade , Comunicação Parácrina , Espécies Reativas de Oxigênio/metabolismo , Receptores CXCR4/metabolismo , Pele/metabolismo , Telômero/metabolismo , Adulto Jovem
12.
BMC Complement Altern Med ; 19(1): 287, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660942

RESUMO

BACKGROUND: Sarcopenia, the decline of skeletal muscle tissue attributed to primary aging is a major concern in older adults. Flavonoids might have potential benefits by modulating the regulation of satellite cells, thus preventing muscle loss. Sinensetin (SIN), a citrus methylated flavone with anti-inflammatory and anti-proliferative activity, can enhance lipolysis. The objective of the present study was to investigate whether SIN might have sarcopenia-suppressing effect on satellite cells from thigh and calf muscle tissues of young and old rats. METHODS: Primary muscle cells were obtained from thigh and calf tissues of young and old group rats by dissection. Obtained satellite cells were incubated with indicated concentrations of SIN (50 and 100 µM) treated and untreated condition in differentiation medium. Morphological changes of cells were examined using a phase-contrast microscope. Protein expression levels of myoD and myogenin were analyzed by Western blot. Cells treated with or without SIN under differentiation condition were also immunocytochemically stained for myogenin and 4',6-diamidino-2-phenylindole (DAPI). RESULTS: Morphologically, the differentiation extracted satellite cells was found to be more evident in SIN treated group of aged rat's cells than that in SIN untreated group. Expression levels of myoD and myogenin proteins involved in myogenesis were increased upon treatment with SIN. CONCLUSIONS: Collectively, our results indicate that SIN can alleviate age-related sarcopenia by increasing differentiation rate and protein levels of myoD and myogenin.


Assuntos
Envelhecimento/efeitos dos fármacos , Flavonoides/farmacologia , Células Musculares/efeitos dos fármacos , Sarcopenia/tratamento farmacológico , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Células Cultivadas , Humanos , Masculino , Células Musculares/metabolismo , Desenvolvimento Muscular/efeitos dos fármacos , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Proteína MyoD/genética , Proteína MyoD/metabolismo , Miogenina/genética , Miogenina/metabolismo , Ratos , Ratos Sprague-Dawley
14.
J Food Sci ; 84(11): 3083-3090, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599975

RESUMO

Studies on the discovery and function of antioxidants are consistently being performed because oxidative stress can cause various diseases. Many compounds and natural products have antioxidant activity in vitro; however, it is often difficult to reproduce their effects in vivo. Additionally, methods to measure antioxidant activities in cells are also scarce. Here, we investigated the antioxidant activity of milk proteins by observing the formation of arsenite-induced stress granules as a tool to evaluate antioxidant activity in cells. Milk proteins not only decreased the formation of stress granules in several cell types but also scavenged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cations in vitro. In addition, milk proteins inhibited cellular senescence based on an SA-ß-galactosidase assay, and increased differentiation to myotubes from myoblasts isolated from the skeletal muscles of mouse pups. Taken together, our results demonstrate that milk proteins have an antiaging effect, especially prevention of skeletal muscle loss, through their antioxidant activities. PRACTICAL APPLICATION: Our results provide that antioxidant effects of milk proteins containing α-caseins, ß-caseins, and ß-lactoglobulin can mitigate aging-related damage induced by oxidative stress through showing inhibition of cellular senescence and increase of differentiation and maturation of myoblast. Therefore, we suggest that milk proteins could be potent health supplements to prevent aging-associated diseases, especially sarcopenia.


Assuntos
Antioxidantes/farmacologia , Caseínas/farmacologia , Bovinos , Lactoglobulinas/farmacologia , Leite/química , Envelhecimento/efeitos dos fármacos , Animais , Antioxidantes/análise , Arsenitos/farmacologia , Senescência Celular/efeitos dos fármacos , Feminino , Camundongos , Proteínas do Leite/farmacologia , Estresse Oxidativo/efeitos dos fármacos
15.
Nat Commun ; 10(1): 4905, 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659167

RESUMO

Therapeutic activation of mitochondrial function has been suggested as an effective strategy to combat aging. Hydralazine is an FDA-approved drug used in the treatment of hypertension, heart failure and cancer. Hydralazine has been recently shown to promote lifespan in C. elegans, rotifer and yeast through a mechanism which has remained elusive. Here we report cAMP-dependent protein kinase (PKA) as the direct target of hydralazine. Using in vitro and in vivo models, we demonstrate a mechanism in which binding and stabilization of a catalytic subunit of PKA by hydralazine lead to improved mitochondrial function and metabolic homeostasis via the SIRT1/SIRT5 axis, which underlies hydralazine's prolongevity and stress resistance benefits. Hydralazine also protects mitochondrial metabolism and function resulting in restoration of health and lifespan in C. elegans under high glucose and other stress conditions. Our data also provide new insights into the mechanism(s) that explain various other known beneficial effects of hydralazine.


Assuntos
Envelhecimento/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Hidralazina/administração & dosagem , Sirtuína 1/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Feminino , Humanos , Longevidade/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Sirtuína 1/genética
16.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502578

RESUMO

Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed after treatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterally ovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX+OA control, OVX+OA + diclofenac (5 mg/kg) (positive control), OVX+OA + LP leaf extract (150 and 300 mg/kg) and healthy sham control. After 8 weeks' treatment, their conditions were evaluated via serum biomarkers, knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilage erosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenac and the non-treated OA. The cartilage catabolic markers' (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa, CASP3 and HIF-2 alpha) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased by LP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilage protective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondral bone restoration. The cartilage ER alpha over-expression showed a strong positive correlation with MMP-13, COL10 alpha1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.


Assuntos
Envelhecimento/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Osteoartrite/tratamento farmacológico , Extratos Vegetais/farmacologia , Primulaceae/química , Envelhecimento/genética , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Diclofenaco/farmacologia , Modelos Animais de Doenças , Flavonoides/farmacologia , Ácido Gálico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Iodoacetatos/farmacologia , Metaloproteinase 13 da Matriz/genética , Metabolismo/efeitos dos fármacos , Osteoartrite/genética , Osteoartrite/patologia , Ovariectomia , Extratos Vegetais/química , Ratos
17.
Drug Discov Ther ; 13(4): 198-206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534071

RESUMO

Curcumin, a compound found in Indian yellow curry, is known to possess various biological activities, including anti-oxidant, anti-inflammatory, and anti-cancer activities. Cur2004-8 is a synthetic curcumin derivative having symmetrical bis-alkynyl pyridines that shows a strong anti-angiogenic activity. In the present study, we examined the effect of dietary supplementation with Cur2004-8 on response to environmental stresses and aging using Caenorhabditis elegans as a model system. Dietary intervention with Cur2004-8 significantly increased resistance of C. elegans to oxidative stress. Its anti-oxidative-stress effect was greater than curcumin. However, response of C. elegans to heat stress or ultraviolet irradiation was not significantly affected by Cur2004-8. Next, we examined the effect of Cur2004-8 on aging. Cur2004-8 significantly extended both mean and maximum lifespan, accompanying a shift in time-course distribution of progeny production. Age-related decline in motility was also delayed by supplementation with Cur2004-8. In addition, Cur2004-8 prevented amyloid-beta-induced toxicity in Alzheimer's disease model animals which required a forkhead box (FOXO) transcription factor DAF-16. Dietary supplementation with Cur2004-8 also reversed the increase of mortality observed in worms treated with high-glucose-diet. These results suggest that Cur2004-8 has higher anti-oxidant and anti-aging activities than curcumin. It can be used for the development of novel anti-aging product.


Assuntos
Envelhecimento/efeitos dos fármacos , Catecóis/administração & dosagem , Curcumina/análogos & derivados , Longevidade/efeitos dos fármacos , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/toxicidade , Animais , Caenorhabditis elegans , Catecóis/química , Catecóis/farmacologia , Curcumina/administração & dosagem , Curcumina/farmacologia , Suplementos Nutricionais , Modelos Animais de Doenças , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos
18.
Adv Gerontol ; 32(3): 331-337, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512418

RESUMO

Aging of extracellular proteins colloidal systems is one of major synchronizing mechanism in mammal`s «biological clock¼. We hypothesized that induced controllable modification of connective tissue composition could reverse aging. In murine experimental models collagenase was used for selective destruction of old collagen. Oxygen consumption, urine hydroxyproline excretion, density and distribution of mature and old collagen and elastine fibers in dermal biopsies were determined. Collagenase injections significantly increased hydroxyproline excretion. We observed reduced density of mature and old collagen fibers and increased oxygen consumption in dermal biopsies after course of collagenase injections. Collagenase treatment intensified the destruction of mature and old collagen matrix and enhanced synthesis of new collagen and elastine fibers. Furthermore oxygen consumption increased. Our findings can be considered as indicator of collagenase systemic anti-aging (rejuvenation) activity.


Assuntos
Envelhecimento , Colágeno , Envelhecimento/efeitos dos fármacos , Animais , Colágeno/metabolismo , Colagenases/farmacologia , Hidroxiprolina/metabolismo , Camundongos , Modelos Animais , Consumo de Oxigênio/efeitos dos fármacos , Pele/efeitos dos fármacos
20.
Molecules ; 24(18)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527444

RESUMO

The purpose of this study was to characterize the polysaccharides from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and explore the protective mechanism against d-galactose-induced oxidative stress in aging mice. METHODS: A series of experiments, including molecular weight, monosaccharide composition, Fourier transform infrared (FT-IR) spectroscopy, and 1H nuclear magnetic resonance (1H NMR) spectroscopy were carried out to characterize AMC polysaccharides. The mechanism was investigated exploring d-galactose-induced aging mouse model. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting assays were performed to assess the gene and protein expression in liver. KEY FINDINGS: Our results showed that AMC polysaccharides were mainly composed of mannose (Man), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galactose (Gal), arabinose (Ara), and fucose (Fuc) in a molar ratio of 0.077:0.088:0.09:1:0.375:0.354:0.04 with a molecular weight of 33203 Da (Mw). AMC polysaccharides strikingly reversed d-galactose-induced changes in mice, including upregulated phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor-erythroid 2-related factor 2 (Nrf2), forkhead box O3a (FOXO3a), and hemeoxygenase-1 (HO-1) mRNA expression, raised Bcl-2/Bax ratio, downregulated caspase-3 mRNA expression, enhanced Akt, phosphorylation of Akt (p-Akt), Nrf2 and HO-1 protein expression, decreased caspase-3, and Bax protein expression. CONCLUSION: AMC polysaccharides attenuated d-galactose-induced oxidative stress and cell apoptosis by activating the PI3K/AKT pathway, which might in part contributed to their anti-aging activity.


Assuntos
Antioxidantes/farmacologia , Gleiquênias/química , Fosfatidilinositol 3-Quinase/metabolismo , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Galactose/administração & dosagem , Espectroscopia de Ressonância Magnética , Camundongos , Monossacarídeos/química , Extratos Vegetais/química , Polissacarídeos/química
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