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1.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198754

RESUMO

BACKGROUND: There is an increasing need for botanicals to be used as an alternative and complementary medicine in the management of male infertility. Male infertility has been a major health/social challenge to people all over the world. This study, therefore, investigated the ameliorative potential of hydroethanolic leaf extract of Parquetina nigrescens (HELEPN) against d-galactose-induced testicular injury. METHODS: Thirty male Wistar rats were randomly allotted into six groups (n = 5). Group I (Normal control), Group II (300 mg/kg b.w. d-galactose), Group III and IV (250 and 500 mg/kg b.w. HELEPN, respectively), Group V and VI (both received 300 mg/kg b.w. of d-galactose with 250 and 500 mg/kg b.w of HELEPN, respectively). d-galactose administration started two weeks prior to HELEPN treatment which lasted for six weeks. All assays were carried out using established protocols. RESULTS: Administration of HELEPN at 250mg/kg and 500mg/kg concomitantly with d-galactose improved paired and relative testicular weights, levels of gonadotropins (LH and FSH) and testosterone, and poor sperm quality. HELEPN treatment reduced the levels of oxidative stress biomarkers (MDA, 8-OHDG, and AGEs) and inflammatory response (TNF-alpha and NO) to normal, as well as restoring the reduced activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). In addition, HELEPN treatment mitigated testicular DNA fragmentation and down-regulated caspase 3-activities. HELEPN at 500 mg/kg was observed to have the greatest ameliorative effect. CONCLUSION: HELEPN protects against d-galactose-induced testicular injury through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.


Assuntos
Apocynaceae/química , Galactose/efeitos adversos , Infertilidade Masculina/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Testículo/lesões , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/química , Gonadotropinas/metabolismo , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Distribuição Aleatória , Ratos , Ratos Wistar , Análise do Sêmen , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo
2.
Phytother Res ; 35(8): 4411-4424, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34028092

RESUMO

Successive evidence has established that maltol, a flavor-enhancing agent, could provide resistance to oxidative stress-induced tissue injury in various animal models though its benefits for aging-induced liver and kidney injuries are still undetermined. In the present work, for demonstrating maltol's ameliorative effect and probable mechanism against aging-induced liver and kidney injuries, D-galactose (D-Gal)-induced animal in vivo and HEK293 cells in vitro models were established and results demonstrated that long-term D-Gal treatment increases the accumulation of advanced glycation end products (AGEs) in liver and kidney tissues, mitigates cell viability, and arrests the cycle. Interestingly, 4-weeks maltol treatment at 50 and 100 mg/kg activated aging-associated proteins including p53, p21, and p16 followed by inhibiting malondialdehyde (MDA)'s over-production and increasing the levels of antioxidant enzymes. Therefore, decreases in cytochrome P450 E1 (CYP2E1) and 4-hydroxydecene (4-HNE)'s immunofluorescence expression levels are confirmed. Furthermore, maltol improved oxidative stress injury by activating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. In conclusion, the purpose of the present study was to estimate the mechanistic insights into maltol's role as an antioxidant in liver and kidney cell senescence and injury, which will reflect potential of therapeutic strategy for antiaging and aging-related disease treatment.


Assuntos
Galactose , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pironas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Envelhecimento , Animais , Galactose/efeitos adversos , Células HEK293 , Humanos , Rim/metabolismo , Fígado/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
3.
Biomed Res Int ; 2021: 6654683, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997037

RESUMO

Chick (CE) or duck embryo eggs are known for nutritional supplement foods in traditional East countries for physical fitness enhancement and postpartum conditioning for many years. In this study, we evaluated the effects of different parts of the 10-day CE (embryo: CEr, yolk: CEw, and chorioallantoic membrane: CEp) on the antifatigue and antiaging activities in a D-galactose- (D-gal) induced aging mice model. The results showed CEp obviously increased the muscle weight and the liver and muscle glycogen content and enhanced exercise performance. In the antiaging assay, CEp significantly increased the activity of superoxide dismutase (SOD) and Glutathione Peroxidase (GPx). Moreover, the immunohistochemistry results of NRF-2 and HO-1 were also detected in the livers of mice in the D-gal/CEp group. The only partially potential such as CEr might improve OFT function with TG level, and CEw had strange grip strength. Therefore, we suggest that CEp has a potent antifatigue ability and could minimize the occurrence of age-associated disorders, more than other parts of the 10 days chicken embryo egg.


Assuntos
Envelhecimento/efeitos dos fármacos , Produtos Biológicos/farmacologia , Embrião de Galinha , Suplementos Nutricionais , Animais , Membrana Corioalantoide/química , Gema de Ovo/química , Galactose/efeitos adversos , Força da Mão , Fígado/química , Fígado/efeitos dos fármacos , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Força Muscular/efeitos dos fármacos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Superóxido Dismutase/metabolismo
4.
PLoS One ; 16(4): e0249487, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33857158

RESUMO

Erectile dysfunction (ED) is defined as the inability to achieve and/or maintain penile erection sufficient for satisfactory sexual relations, and aging is one of the main risk factors involved. The D-(+)-Galactose aging model is a consolidated methodology for studies of cardiovascular aging; however, its potential for use with ED remain unexplored. The present study proposed to characterize a new experimental model for ED, using the D-(+)-Galactose aging model. For the experiments, the animals were randomly divided into three groups receiving: vehicle (CTL), D-galactose 150 mg/kg (DGAL), and D-(+)-galactose 150 mg/Kg + sildenafil 1.5 mg/Kg (DGAL+SD1.5) being administered daily for a period of eight weeks. All of the experimental protocols were previously approved by the Ethics Committee on the Use of Animals at the Federal University of Paraíba n° 9706070319. During the treatment, we analyzed physical, molecular, and physiological aspects related to the aging process and implicated in the development of ED. Our findings demonstrate for the first time that D-(+)-Galactose-induced aging represents a suitable experimental model for ED assessment. This was evidenced by an observed hyper-contractility in corpora cavernosa, significant endothelial dysfunction, increased ROS levels, an increase in cavernous tissue senescence, and the loss of essential penile erectile components.


Assuntos
Envelhecimento , Disfunção Erétil/etiologia , Galactose/efeitos adversos , Envelhecimento/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Estimulação Elétrica , Disfunção Erétil/metabolismo , Galactose/farmacologia , Masculino , Ereção Peniana , Pênis/patologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Citrato de Sildenafila/efeitos adversos , Citrato de Sildenafila/farmacologia
5.
Exp Anim ; 70(3): 284-292, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-33583937

RESUMO

Long-term administration of D-galactose induces oxidative stress and accelerates normal age-related changes. Hence, the D-galactose-treated rodent model has been widely used for aging research. In this study, we examined the immunological characteristics, especially CD4+ T-cell subset composition, of D-galactose-induced aging model mice to evaluate the model's utility in immunosenescence studies. The spleens of aging model mice subjected to repeated subcutaneous injections of D-galactose exhibited significant increases in T cells with the memory phenotype (CD62Llow CD44high) and individual T-cell subsets (Th1, Th2, Th17 and Treg). Furthermore, cells with the phenotype of T follicular helper (Tfh) cells were spontaneously increased. The features of T-cell subset composition in D-galactose-treated mice were in close agreement with those observed in normal aged mice and appeared to mimic the currently known normal aging processes associated with T-cell homeostasis. Our results suggest that D-galactose-induced aging models would be useful for immunosenescence studies focusing on T-cell homeostasis and give valuable insight into age-related immune system dysregulation.


Assuntos
Envelhecimento , Galactose/efeitos adversos , Estresse Oxidativo , Subpopulações de Linfócitos T/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Animais , Camundongos , Modelos Animais
6.
Food Funct ; 12(5): 2148-2160, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33565551

RESUMO

Phlorizin is the main active ingredient of apple peel and has potential utilization value. Some recent studies have suggested that phlorizin may have antioxidant capacity and protect the liver. The injection of a low dose of d-galactose can cause some changes that resemble accelerated aging in mice. This study explored the protective effects of phlorizin on d-galactose-induced mice and PC12 cells. In this study, ICR mice were divided into a normal group (NOR), a d-galactose model group (d-gal) and phlorizin treatment groups (100 mg kg-1, 200 mg kg-1 and 400 mg kg-1). In addition to the NOR group, four other groups were injected with d-galactose (120 mg kg-1) for 12 weeks. The results showed that phlorizin reduced the decline of strength, coordination and spatial memory caused by aging, increased the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), increased total antioxidant capacity (T-AOC), and reduced the content of malondialdehyde (MDA). On the other hand, phlorizin increased the levels of interleukin-2 (IL-2) and acetylcholine (ACh), reduced the release of interleukin-6 (IL-6), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and decreased the activity of acetylcholinesterase (AChE) in the brain, improved the expression of antioxidant genes related to the nuclear factor E2-related factor 2 (Nrf2) pathway, and reduced the occurrence of morphological lesions in the hippocampus and liver. In addition, phlorizin improved cell viability and reduced the cytotoxicity of d-galactose-induced oxidative stress in PC12 cells. Meanwhile, the protective effect of phlorizin was abolished in Nrf2 gene knockdown PC12 cells. Furthermore, molecular docking showed that phlorizin could bind Keap1 protein, which can interact with Nrf2 protein. Therefore, these results suggest that phlorizin may delay senescence and enhance antioxidant capacity through the Nrf2 pathway.


Assuntos
Envelhecimento/efeitos dos fármacos , Galactose/efeitos adversos , Florizina , Substâncias Protetoras , Animais , Encéfalo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Florizina/química , Florizina/metabolismo , Florizina/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Ratos
7.
Food Funct ; 12(6): 2531-2542, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33621295

RESUMO

The aim of this study was to investigate the effects of ethyl acetate extract from Coreopsis tinctoria (EACC) on learning and memory impairment in d-galactose-induced aging mice and the underlying molecular mechanism. The composition of EACC was analyzed by UPLC-MS, and the targets and pathways of EACC to improve learning and memory impairment were predicted and analyzed by the network pharmacology method. A mouse aging model was established by subcutaneous injection of d-galactose in mice, and EACC and piracetam were given to the model mice by gavage to observe their behavioral changes and changes in their SOD and GSH-Px activities in MDA contents in their peripheral blood serum and in the contents of Glu and GABA in their brain tissues. Then the hippocampus of the three mice selected from each of the MOD group and EACC-H group was separated for RT-qPCR assay. The results of the animal experiments showed that EACC could improve the learning and memory impairment of model mice by affecting the level of oxidative stress enzymes in serum and the content of neurotransmitters in the brain tissue. The results of network pharmacology analysis showed that the EACC components corresponded to 74 learning and memory-related targets, of which 13 were enriched in the long-term potentiation pathway. The results of RT-qPCR showed that 12 of the 13 detected targets were consistent with the predicted targets, and 9 of them were located in the NMDA receptor-related pathway of the long-term potentiation process and the pathway played an important regulatory role. It is believed that EACC could improve the learning and memory impairment of d-galactose-induced aging mice by acting on the nine targets Grin1, Grin2a, Camk2a, Camk2b, Kras, Raf1, Mapk1, Mapk3 and Creb to affect the NMDA receptor-related pathway of long-term potentiation.


Assuntos
Coreopsis/química , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acetatos , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Modelos Animais de Doenças , Galactose/efeitos adversos , Hipocampo/efeitos dos fármacos , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos
8.
Biomed Res Int ; 2021: 6623328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506023

RESUMO

Aging is an independent risk factor for the development of age-related progressive kidney injury. As a part of the aging process, kidney aging has been indicated to be associated with oxidative stress-induced damage. Ameliorating oxidative damage is therefore considered a promising strategy for delaying kidney aging. Alginate oligosaccharide (AOS) has been reported to have a wide range of biological and pharmacological activities. However, no studies have focused on the role of AOS in delaying the kidney aging process. In this study, we aimed to evaluate the potential effects of AOS on kidney aging and its possible mechanisms. Subcutaneous injection of D-galactose (D-gal) (200 mg·kg-1·d-1) in C57BL/6J mice for 8 weeks was used to establish the aging model. AOS (200 mg·kg-1·d-1) was administered via oral gavage for the last four weeks. As a result, AOS inhibited the D-gal-induced upregulation of aging markers and significantly improved the kidney index and kidney function of D-gal-induced mice. In addition, AOS ameliorated the degree of tissue damage and fibrosis in the aging kidney. To further explore the potential mechanisms by which AOS attenuates the kidney aging process, the associated oxidative stress-induced damage was analyzed in depth. The data showed that AOS upregulated the expression of Klotho and decreased malondialdehyde levels by increasing the expression of antioxidant enzymes. Furthermore, our results suggested that AOS activated the nuclear factor erythrogen-2 associated factor 2 (Nrf2) pathway by promoting Nrf2 nuclear translocation in aging mice and upregulated the downstream expression of heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). In conclusion, the present study demonstrated that AOS is a promising agent for attenuating kidney aging, and the underlying molecular mechanisms are related to the activation of the Nrf2 signaling pathway.


Assuntos
Alginatos/farmacologia , Galactose/efeitos adversos , Nefropatias , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Envelhecimento , Animais , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia
9.
J Appl Microbiol ; 130(4): 1307-1322, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32638482

RESUMO

AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system. METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P < 0·05). Strain L. fermentum DR9 demonstrated improved expression of SOD in bone and muscle compared to the aged rats (P < 0·05). In the evaluation of myogenesis-related genes, L. paracasei OFS 0291 and L. fermentum DR9 increased the mRNA expression of IGF-1; L. helveticus OFS 1515 and L. fermentum DR9 reduced the expression of MyoD, in contrast to the aged controls (P < 0·05). Protective effects of L. fermentum DR9 on ageing muscle were believed to be contributed by increased AMPK-α2 expression. Among the osteoclastogenesis genes studied, TNF-α expression was highly elevated in tibia of aged rats, while all three probiotics strains ameliorated the expression. Lactobacillus fermentum DR9 also reduced the expression of IL-6 and TRAP in tibia when compared to the aged rats (P < 0·05). All probiotics treatment resulted in declined proinflammatory cytokines IL-1ß in muscle and bone. CONCLUSIONS: Lactobacillus fermentum DR9 appeared to be the strongest strain in modulation of musculoskeletal health during ageing. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated the protective effects of the bacteria on muscle and bone through antioxidative and anti-inflammatory actions. Therefore, L. fermentum DR9 may serve as a promising targeted anti-ageing therapy.


Assuntos
Envelhecimento/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Galactose/efeitos adversos , Lactobacillus fermentum/fisiologia , Lactobacillus helveticus/fisiologia , Lactobacillus paracasei/fisiologia , Sistema Musculoesquelético/efeitos dos fármacos , Probióticos/administração & dosagem , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Desenvolvimento Musculoesquelético/efeitos dos fármacos , Sistema Musculoesquelético/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Phytother Res ; 35(4): 2252-2266, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33325602

RESUMO

D-galactose (d-gal) induces aging and memory impairment via oxidative stress and neuroinflammation pathways. This study evaluated the neuroprotective activity of thymoquinone (TQ) against d-gal. d-gal (400 mg/kg, SC), d-gal plus TQ (2.5, 5, 10 mg/kg, i.p.), and TQ alone (2.5 and 10 mg/kg) for 8 weeks were administered to rats. The effect of TQ on learning and memory were studied using the Morris water maze test. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the hippocampus. The levels of MAPKs (p-ERK/ERK, p-P38/P38), cAMP response elements binding (p-CREB/CREB), advanced glycation end products (AGEs), inflammatory markers (TNFα, IL-1ß), glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF) were analyzed by western blotting. Telomere length was evaluated using real-time PCR. Memory and learning impairment, MDA enhancement, GSH reduction, and neuroinflammation via increasing the TNFα, IL-1ß, and GFAP contents were observed in d-gal group. TQ with d-gal, improved memory impairment, reduced oxidative stress, and alleviated neuroinflammation. The elevated level of AGEs decreased by TQ compared to d-gal. No changes were observed in the levels of p-ERK/ERK, p-CREB/CREB, p-P38/P38, BDNF, and telomere length following administration of d-gal or TQ plus d-gal. TQ improved memory deficits of d-gal through anti-oxidative and anti-inflammatory mechanisms.


Assuntos
Benzoquinonas/química , Galactose/efeitos adversos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Wistar , Homeostase do Telômero
11.
Mol Med Rep ; 23(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33179093

RESUMO

The aim of the present study was to investigate the effects of the ginsenoside Rg1 on D­galactose (D­gal)­induced mouse models of premature ovarian insufficiency (POI) and the related mechanisms. C57BL/6 female mice were randomly grouped into the following: i) D­gal [subcutaneously (s.c.) 200 mg/kg/d D­gal for 42 days]; ii) Rg1 [intraperitoneally (i.p.) 20 mg/kg/d Rg1 for 28 days]; iii) D­gal + Rg1 (s.c. 200 mg/kg/d D­gal for 42 days followed by i.p. 20 mg/kg/d Rg1 for 28 days); and iv) saline groups (equivalent volume of saline s.c. and i.p.). Hematoxylin and eosin staining and electron microscopy were used to analyze uterine and ovarian morphology. Expression levels of senescence factors (p21, p53 and serine/threonine kinase), secretion of pro­inflammatory cytokines [interleukin (IL)­6, tumor necrosis factor (TNF)­α and IL­1ß] and the activities of oxidation biomarkers [superoxide dismutase (T­SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH­px)] were analyzed. The results showed that mice in the Rg1 + D­gal group had significantly higher uterine and ovarian weight compared with those in the D­gal group. Uterus morphology was also improved, based on the comparison between the D­gal group and the Rg1 + D­gal group. In addition, the Rg1 treatment after D­gal administration significantly decreased the expression of senescence­associated factors, enhanced the activities of anti­oxidant enzymes total T­SOD and GSH­px in addition to reducing TNF­α, IL­1ß, MDA and IL­6 (based on the comparison between the D­gal group and the Rg1 + D­gal group). In conclusion, the present study suggested that the ginsenoside Rg1 improved pathological damages in the ovary and uterus by increasing anti­oxidant and anti­inflammatory abilities whilst reducing the expression of senescence signaling pathways in POI mouse models.


Assuntos
Galactose/análogos & derivados , Ginsenosídeos/administração & dosagem , Ovário/metabolismo , Insuficiência Ovariana Primária/tratamento farmacológico , Útero/metabolismo , Animais , Aurora Quinase B/metabolismo , Senescência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Modelos Animais de Doenças , Feminino , Galactose/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Ovário/efeitos dos fármacos , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Útero/efeitos dos fármacos
12.
Sci Rep ; 10(1): 19244, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159105

RESUMO

Aging is an irreversible process. This research aims to study the anti-aging effects of GRCP, a compound preparation made by Ganoderma lucidum and Rhodiola rosen, in aging rats. Rats were subcutaneously injected with 400 mg/kg of D-galactose daily, and aging could be induced after 8 weeks. The aging rats were treated with GRCP. This experiment was divided into 6 groups. Rats were randomly divided into the model group, positive control group, low-dose GRCP group (25 mg/kg body weight), medium-dose GRCP group (50 mg/kg body weight), and high-dose GRCP group (100 mg/kg body weight), healthy and normal rats were used as blank controls. After the end, the results show that the use of GRCP at a dose of 100 mg/kg is the best treatment for improving aging rats. Rats gained weight, spleen and thymus indexes, and splenocyte proliferation improved, and inflammatory cytokine levels decreased. Besides, biochemical indicators show that GRCP can improve the antioxidant enzyme activity and reduce the content of lipofuscin and TGF-ß in aging rats (P < 0.05). GRCP can also inhibit the activation of the MyD88/NF-κB pathway in rat hippocampus. These results seem to suggest that GRCP can be used as a potential natural supplement or functional food to prevent aging.


Assuntos
Envelhecimento/imunologia , Galactose/efeitos adversos , Estresse Oxidativo , Extratos Vegetais/farmacologia , Reishi/química , Rhodiola/química , Animais , Galactose/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley
13.
Mol Med Rep ; 22(5): 3833-3839, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000191

RESUMO

Icariin (ICA) has been used as a promising anti­aging drug; however, its underlying molecular mechanism is yet to be elucidated. The present study aimed to determine the anti­aging molecular mechanisms of ICA. D­galactose (D­gal) was used to generate a cell aging model. IMR­90 human lung fibroblasts were pretreated with different concentrations of ICA (1, 2, 4, 8 and 16 µmol/l) for 6 h and subsequently incubated with D­gal (200 mmol/l) at 37˚C for 72 h. Senescence of IMR­90 cells was assessed by senescence­associated­ß­galactosidase (SA­ß­Gal) staining assay. Cell viability, and the expression levels of p53/p21, sirtuin (SIRT) 1/6 and p50/p65 were determined via the MTT assay and western blotting respectively. The results demonstrated that D­gal notably increased the proportion of SA­ß­Gal­positive cells and decreased the viability of IMR­90 cells; however, pretreatment with ICA reversed the effects of D­gal on IMR­90 cells in a concentration­dependent manner. Furthermore, it was also demonstrated that the activation of p53/p21 and nuclear factor­κB (NF­κB) signaling, and downregulation of SIRT1/6 may be involved in IMR­90 cells, in D­gal­induced aging and ICA may effectively prevent IMR­90 cells from these changes induced by D­gal. Taken together, the results of the present study suggest that the anti­aging molecular mechanisms of ICA may be associated with the regulation of the SIRT1/NF­κB pathway.


Assuntos
Senescência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Flavonoides/farmacologia , Pulmão/citologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Envelhecimento/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Galactose/efeitos adversos , Humanos
14.
J Agric Food Chem ; 68(44): 12271-12283, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-32942847

RESUMO

This study investigated the effects of a physiologically active peptide derived from rice bran (KF-8) on oxidative stress in d-galactose (d-gal)-induced aging mice and the underlying molecular mechanisms. The aging model was developed by subcutaneously injecting Institute of Cancer Research mice with 250 mg/kg d-gal daily for 12 weeks and simultaneously treating them with 30 mg/kg KF-8. The relative expression levels of Nrf2 and NF-κB in the liver were determined by the western blot. The regulation of Nrf2 and NF-κBp65 by KF-8 was further validated in NIH/3T3 cells. Compared with the control mice, the aging mice had significantly decreased body weights as well as superoxide dismutase and GSH-Px levels (p < 0.05); however, they had increased serum reactive oxygen species and malondialdehyde and 8-hydroxydeoxyguanosine levels accompanied by aortic and brain injuries. They also had elevated RAGE, TLR4, IκB, Bax, and caspase-8 expressions and NF-κB/p65 phosphorylation but reduced BcL-2 expression in the liver. Moreover, in vitro experiments demonstrated that the pretreatment of H2O2-treated NIH/3T3 cells with KF-8 significantly mitigated the NF-κB signaling and attenuated the Nrf2 nuclear transport (both p < 0.05). In conclusion, KF-8 treatment inhibited aging-induced oxidative stress-related organ injury in mice by attenuating NF-κB/p38 signaling and preserving Nrf2 activity.


Assuntos
Envelhecimento/efeitos dos fármacos , Galactose/efeitos adversos , Oryza/química , Peptídeos/administração & dosagem , Envelhecimento/metabolismo , Animais , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Humanos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sementes/química , Superóxido Dismutase/metabolismo
15.
Int J Mol Sci ; 21(19)2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32992845

RESUMO

Age-related hearing loss (ARHL) is the most common sensory disorder among the elderly, associated with aging and auditory hair cell death due to oxidative-stress-induced mitochondrial dysfunction. Although transgenic mice and long-term aging induction cultures have been used to study ARHL, there are currently no ARHL animal models that can be stimulated by intermittent environmental changes. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined on the basis of expression of hearing-loss-induced phenotypes and aging-related factors. The incidence of hearing loss was significantly higher in dual- and triple-exposure conditions than in intermittent hypoxic conditions, high-fat diet (HFD), or d-galactose injection alone. Continuous oxidative stress and HFD accelerated cellular aging. An increase in Ucp2, usually expressed during mitochondrial dysfunction, was observed. Expression of Cdh23, Slc26a4, Kcnq4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in the cells of the hearing organ. We found that intermittent hypoxia, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects the effects of intermittent environmental changes, will benefit future research on ARHL.


Assuntos
Envelhecimento , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Galactose/efeitos adversos , Perda Auditiva , Hipóxia , Animais , Senescência Celular , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Estresse Oxidativo
16.
Cancer Sci ; 111(10): 3862-3872, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32741012

RESUMO

Although intake of highly sugary foods is considered to be a potential risk factor for colorectal cancer through hyperinsulinemia, the association of sugar intake and colorectal adenoma, a precursor lesion to most colorectal cancer, is poorly understood, particularly in Asian populations. We undertook a cross-sectional study in a Japanese population to investigate the association between dietary sugar intake and the prevalence of colorectal adenoma. Study subjects were selected from participants who underwent magnifying colonoscopy with dye spraying as part of a cancer screening program and who responded to a self-administered questionnaire before the colonoscopy. A total of 738 cases with colorectal adenoma and 697 controls were enrolled. Dietary intakes of glucose, fructose, galactose, sucrose, maltose, lactose, and total sugars (sum of these six mono- or disaccharides) were calculated from a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Odds ratios and 95% confidence intervals of colorectal adenoma were estimated using unconditional logistic regression models, with adjustment for potential confounding factors. Total sugar intake was not significantly associated with the prevalence of colorectal adenoma (odds ratio for the highest intake group compared to reference group = 1.18; 95% confidence interval, 0.81-1.73; P for trend = .34). Furthermore, no statistically significant positive associations were observed for any of the six mono- or disaccharides. Findings were similar on additional analyses by site, size, and number of adenomas. Our findings do not support an association between high sugar intake and increased odds ratios of colorectal adenoma.


Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Açúcares da Dieta/efeitos adversos , Detecção Precoce de Câncer , Adenoma/induzido quimicamente , Adulto , Idoso , Colonoscopia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Estudos Transversais , Dieta/efeitos adversos , Feminino , Frutose/efeitos adversos , Galactose/efeitos adversos , Glucose/efeitos adversos , Humanos , Japão/epidemiologia , Lactose/efeitos adversos , Masculino , Maltose/efeitos adversos , Pessoa de Meia-Idade , Estado Nutricional , Fatores de Risco , Sacarose/efeitos adversos , Inquéritos e Questionários
17.
Microbiol Immunol ; 64(9): 620-629, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32691886

RESUMO

The thymic microenvironment plays an important role in the development of T cells. A decrease of thymic epithelial cells is the main cause of age-related thymic atrophy or degeneration. Resveratrol (RSV), a phytoalexin produced from plants, has been shown to inhibit the adverse effects of dietary obesity on the structure and function of the thymus. D-Galactose (D-gal) can induce accelerated aging in mice. In the present study, young mice (2 months old) were injected with D-gal (120 mg/kg/day) for 8 consecutive weeks to construct an accelerated aging model. Compared with normal control mice, the thymus epithelium of the D-gal treated mice had structural changes, the number of senescent cells increased, the number of CD4+ T cells decreased, and CD8+ T cells increased. After RSV administration by gavage for 6 weeks, it was found that RSV improved the surface phenotypes of D-gal treated mice, and recovered thymus function by maintaining the ratio of CD4+ to CD8+ cells. It also indicated that RSV enhanced the cell proliferation and inhibited cell senescence. Increased autoimmune regulator (Aire) expression was present in the RSV treated mice. The lymphotoxin-beta receptor (LTßR) expression also increased. These findings suggested that RSV intake could restore the alterations caused by D-gal treatment in the thymus via stimulation of Aire expression.


Assuntos
Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Resveratrol/farmacologia , Linfócitos T/efeitos dos fármacos , Timo/efeitos dos fármacos , Timo/metabolismo , Animais , Relação CD4-CD8 , Modelos Animais de Doenças , Galactose/efeitos adversos , Regulação da Expressão Gênica , Receptor beta de Linfotoxina/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Timócitos/efeitos dos fármacos , Timo/patologia , Fatores de Transcrição/metabolismo
18.
Am J Chin Med ; 48(5): 1141-1157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32668974

RESUMO

Oxidative stress is considered as a major factor in aging and exacerbates aging process through a variety of molecular mechanisms. D-galactose, a normal reducing sugar with high dose can cause the accumulation of reactive oxygen species (ROS) or stimulate free radical production indirectly by the formation of advanced glycation end products in tissues, finally resulting in oxidative stress. 20(R)-ginsenoside Rg3 (20(R)-Rg3), a major and representative component isolated from red ginseng (Panax ginseng C.A Meyer), has been shown to observably have an anti-oxidative effect. We thereby investigated the beneficial effects of 20(R)-Rg3 on D-galactose-induced oxidative stress injury and its underlying mechanisms. Our results showed that continuous injection of D-galactose with 800[Formula: see text]mg/kg/day for 8 weeks increased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). However, such increases were attenuated by the treatment of 20(R)-Rg3 for 4 weeks. Meanwhile, 20(R)-Rg3 markedly inhibited D-galactose-caused oxidative stress in liver and kidney. The anti-oxidants, including catalase (CAT) and superoxide dismutase (SOD), were elevated in the mice from 20(R)-Rg3-treated group compared with that from D-galactose group. In contrast, a significant decrease in levels of cytochrome P450 E1 (CYP2E1) and the lipid peroxidation product malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were observed in the 20(R)-Rg3-treated group. These effects were associated with a significant increase of AGEs. More importantly, 20(R)-Rg3 effectively attenuated D-galactose induced apoptosis in liver and kidney via restoring the upstream PI3K/AKT signaling pathway. Taken together, our study suggests that 20(R)-Rg3 may be a novel and promising anti-oxidative therapeutic agent to prevent aging-related injuries in liver and kidney.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Galactose/efeitos adversos , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Fitoterapia , Animais , Antioxidantes , Modelos Animais de Doenças , Ginsenosídeos/isolamento & purificação , Produtos Finais de Glicação Avançada/metabolismo , Camundongos Endogâmicos ICR , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Int J Mol Sci ; 21(12)2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32570962

RESUMO

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1ß, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.


Assuntos
Envelhecimento/genética , Galactose/administração & dosagem , Rim/química , Pâncreas/química , Quercetina/administração & dosagem , Envelhecimento/metabolismo , Animais , Relação Dose-Resposta a Droga , Galactose/efeitos adversos , Redes Reguladoras de Genes/efeitos dos fármacos , Rim/efeitos dos fármacos , Masculino , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Quercetina/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar
20.
J Agric Food Chem ; 68(24): 6604-6614, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32476418

RESUMO

Oxidative stress and neuroinflammation are considered as crucial culprits in Alzheimer's disease (AD). Torularhodin, a carotenoid pigment, possesses powerful antioxidant activity. This study aimed to elucidate the protective effects of torularhodin in the AD-like mouse model and investigated the underlying mechanisms. Behavioral and histopathological results suggested that torularhodin relieved cognitive impairments, attenuated Aß accumulation, and inhibited glial overactivation in d-gal/AlCl3-induced ICR mice. Simultaneously, torularhodin also markedly increased antioxidant enzyme capacities, lowered the contents of RAGE, and reduced levels of inflammatory cytokines. Western blot results showed that torularhodin ameliorated neuronal oxidative damage via activation of Nrf2 translocation, upregulation of HO-1, and inactivation of NF-κB in vivo and in vitro. Thus, torularhodin effectively ameliorated cognitive impairment, oxidative stress, and neuroinflammation, possibly through the Nrf2/NF-κB signaling pathways, suggesting torularhodin might offer a promising prevention strategy for neurodegenerative diseases.


Assuntos
Cloreto de Alumínio/efeitos adversos , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/administração & dosagem , Basidiomycota/química , Carotenoides/administração & dosagem , Disfunção Cognitiva/tratamento farmacológico , Galactose/efeitos adversos , Fármacos Neuroprotetores/administração & dosagem , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/psicologia , Hipocampo/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Estresse Oxidativo/efeitos dos fármacos
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