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1.
J Microbiol Biotechnol ; 34(6): 1206-1213, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38693048

RESUMO

Citrus fruits offer a range of health benefits due to their rich nutritional profile, including vitamin C, flavonoids, carotenoids, and fiber. It is known that unripe citrus has higher levels of vitamin C, dietary fiber, polyphenols, and flavonoids compared to mature fruits. In this study, we assessed the nutritional components of unripe citrus peel and pressed juices, as well as their anti-obesity potential through the modulation of adipocyte differentiation and the expression of adipogenesis-related genes, specifically PPARγ and C/EBPα, in 3T3-L1 preadipocytes. Our analysis revealed that unripe citrus peel exhibited elevated levels of fiber and protein compared to pressed juice, with markedly low levels of free sugar, particularly sucrose. The content of hesperidin, a representative flavonoid in citrus fruits, was 3,157.6 mg/kg in unripe citrus peel and 455.5 mg/kg in pressed juice, indicating that it was approximately seven times higher in unripe citrus peel compared to pressed juice. Moreover, we observed that the peel had a dose-dependently inhibitory effect on adipocyte differentiation, which was linked to a significant downregulation of adipogenesis-related gene expression. Thus, our findings suggest that unripe citrus possesses anti-obesity effects by impeding adipogenesis and adipocyte differentiation, with the peel demonstrating a more pronounced effect compared to pressed juice.


Assuntos
Células 3T3-L1 , Adipócitos , Adipogenia , Diferenciação Celular , Citrus , PPAR gama , Citrus/química , Adipogenia/efeitos dos fármacos , Animais , Camundongos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/citologia , Diferenciação Celular/efeitos dos fármacos , PPAR gama/metabolismo , PPAR gama/genética , Frutas/química , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Fibras na Dieta/análise , Flavonoides/farmacologia , Flavonoides/análise , Hesperidina/farmacologia , Fármacos Antiobesidade/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Sucos de Frutas e Vegetais/análise , Ácido Ascórbico/farmacologia
2.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732125

RESUMO

"Ganghwal" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that Ostericum koreanum extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.


Assuntos
Células 3T3-L1 , Adipócitos , Adipogenia , Fármacos Antiobesidade , Hipoglicemiantes , PPAR gama , Extratos Vegetais , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Adipogenia/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , PPAR gama/metabolismo , PPAR gama/genética , Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Transportador de Glucose Tipo 4/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , alfa-Glucosidases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Crassulaceae/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos
3.
Oncogene ; 43(24): 1852-1860, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38664499

RESUMO

The deubiquitinase OTUB1, implicated as a potential oncogene in various tumors, lacks clarity in its regulatory mechanism in tumor progression. Our study investigated the effects and underlying mechanisms of OTUB1 on the breast cancer cell cycle and proliferation in IFNγ stimulation. Loss of OTUB1 abrogated IFNγ-induced cell cycle arrest by regulating p27 protein expression, whereas OTUB1 overexpression significantly enhanced p27 expression even without IFNγ treatment. Tyr26 phosphorylation residue of OTUB1 directly bound to p27, modulating its post-translational expression. Furthermore, we identified crucial lysine residues (K134, K153, and K163) for p27 ubiquitination. Src downregulation reduced OTUB1 and p27 expression, suggesting that IFNγ-induced cell cycle arrest is mediated by the Src-OTUB1-p27 signaling pathway. Our findings highlight the pivotal role of OTUB1 in IFNγ-induced p27 expression and cell cycle arrest, offering therapeutic implications.


Assuntos
Pontos de Checagem do Ciclo Celular , Inibidor de Quinase Dependente de Ciclina p27 , Enzimas Desubiquitinantes , Interferon gama , Ubiquitinação , Humanos , Interferon gama/farmacologia , Interferon gama/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Pontos de Checagem do Ciclo Celular/genética , Enzimas Desubiquitinantes/metabolismo , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/genética , Linhagem Celular Tumoral , Feminino , Proliferação de Células , Fosforilação , Transdução de Sinais , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Estabilidade Proteica
4.
Biomed Pharmacother ; 172: 116249, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340399

RESUMO

Maca (Lepidium meyenii) is a plant that grows in the central Andes region of Peru, and it has been reported to have various bioactive functions, such as improving or preventing osteoporosis, sexual dysfunction, and memory impairment. In this study, maca roots of various colors (yellow, red, or black) were extracted using different polar solvents (PE, HEX, or BuOH) to compare their effects on muscle differentiation. Among them, the red maca lipophilic extract, which showed the most effectiveness, was chosen for further investigation. Our results show that RMLE enhances muscle differentiation by inducing MyoD-E2A heterodimerization through the activation of the AKT/p38 pathway. Additionally, RMLE attenuated dexamethasone-induced muscle atrophy by inhibiting nuclear translocation of FoxO3a and expression of E3-ligase (MAFbx and MURF1) in vitro and in vivo. Therefore, based on these results suggest that lipophilic extract of maca, which can abundantly contain nonpolar compounds, macamides, can enhance the functional properties of maca in alleviating muscle homeostasis.


Assuntos
Lepidium , Proteínas Proto-Oncogênicas c-akt , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/tratamento farmacológico , Dexametasona/farmacologia , Extratos Vegetais/farmacologia
5.
Exp Mol Med ; 56(2): 383-394, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297161

RESUMO

M2-like tumor-associated macrophages (TAMs) are risk factors for cancer progression and metastasis. However, the mechanisms underlying their polarization are still not fully understood. Although cathepsin D (Cat D) has been reported as a procarcinogenic factor, little is known about the functional role of Cat D in the tumor microenvironment (TME). This study aimed to explore the effect and molecular mechanisms of Cat D in the TME. Cat D knockout (KO) altered the cytokine secretion pattern and induced TAM reprogramming from the M2 to M1 subtype, thereby preventing epithelial-mesenchymal transition and tumor metastasis. Mechanistically, we identified transforming growth factor beta-induced protein (TGFBI) as a Cat D target protein that is specifically associated with TAM polarization. Elevated TGFBI expression in Cat D KO cancer cells resulted in a decline in M2-like TAM polarization. Our RNA-sequencing results indicated that the cancer cell-secreted chemokine CCL20 is a major secretory chemokine for Cat D-TGFBI-mediated TAM polarization. In contrast, Cat D overexpression accelerated TAM polarization into M2-like cells by suppressing TGFBI expression. In addition, the double Cat D and TGFBI KO rescued the inhibitory effects of Cat D KO on tumor metastasis by controlling TAM and T-cell activation. These findings indicated that Cat D contributes to cancer metastasis through TGFBI-mediated TAM reprogramming. Cat D deletion inhibits M2-like TAM polarization through TGFBI-mediated CCL20 expression, reprogramming the immunosuppressive TME. Our results open a potential new avenue for therapy focused on eliminating tumor metastasis.


Assuntos
Catepsina D , Polaridade Celular , Quimiocina CCL20 , Metástase Neoplásica , Fator de Crescimento Transformador beta , Macrófagos Associados a Tumor , Transporte Biológico , Catepsina D/genética , Catepsina D/metabolismo , Transdução de Sinais , Feminino , Animais , Camundongos , Camundongos SCID , Fator de Crescimento Transformador beta/metabolismo
6.
Nutrients ; 15(14)2023 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-37513496

RESUMO

During the worldwide COVID-19 outbreak, there was an increase in the prevalence of obesity, including childhood obesity, due to which the awareness of obesity and interest in treatment increased. Accordingly, we describe EJF (Euscaphis japonica Kanitz fruit) extract as a candidate for naturally derived antiobesity agents. In this study, we found that EJF is involved in the early stage of adipogenic differentiation in vitro and finally inhibits adipogenesis. We propose two mechanisms for the antiobesity effect of EJF. First, EJF inhibits MDI-induced mitotic clonal expansion (MCE) by inducing cell cycle arrest at the initiation of adipogenic differentiation. The second aims to regulate stability and activation at the protein level of IRS1, which initiates differentiation in the early stage of differentiation. As a result, it was found that the activation of Akt decreased, leading to the inhibition of the expression of adipogenesis-related transcription factors (PPARγ, C/EBPα) and the subsequent suppression of adipogenic differentiation. In summary, we suggest that EJF can inhibit adipogenesis and lipid accumulation by suppressing the early stage of adipogenic differentiation in 3T3-L1 adipocytes. These findings indicate that EJF's functionality could be beneficial in the treatment of obesity, particularly childhood obesity associated with adipocyte hyperplasia.


Assuntos
COVID-19 , Obesidade Infantil , Criança , Humanos , Camundongos , Animais , Adipogenia , Frutas/metabolismo , Diferenciação Celular , PPAR gama/metabolismo , Células 3T3-L1
7.
Biomed Pharmacother ; 163: 114810, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37163777

RESUMO

Garlic (Allium sativum L.) is a primary dietary component worldwide because of its health benefits and use as a traditional medicine. Elephant garlic (Allium ampeloprasum L.), a related species in the same genus, is less intense and sweeter than A. sativum. The object of this study was to investigate the alleviative effects of aged black garlic (ABG) and aged black elephant garlic (ABEG) on obesity and muscle atrophy induced by obesity in high fat diet-induced obese mice. We demonstrated that ABG and ABEG alleviated obesity and muscle atrophy and enhanced myogenic differentiation and myotube hypertrophy, and this effect was mediated by the upregulation of Akt/mTOR/p70S6K signaling. Furthermore, a candidate bioactive compound of ABG and ABEG was suggested in this study through analysis using gas chromatography-mass spectroscopy and ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectroscopy. In conclusion, ABG and ABEG may alleviate obesity and treat obesity-induced muscle atrophy.


Assuntos
Allium , Alho , Animais , Camundongos , Alho/química , Camundongos Endogâmicos C57BL , Allium/química , Cebolas , Antioxidantes/farmacologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Atrofia Muscular/prevenção & controle , Obesidade/complicações , Obesidade/tratamento farmacológico , Dieta
8.
Exp Mol Med ; 55(3): 520-531, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36854775

RESUMO

Extracellular matrix proteins are associated with metabolically healthy adipose tissue and regulate inflammation, fibrosis, angiogenesis, and subsequent metabolic deterioration. In this study, we demonstrated that transforming growth factor-beta (TGFBI), an extracellular matrix (ECM) component, plays an important role in adipose metabolism and browning during high-fat diet-induced obesity. TGFBI KO mice were resistant to adipose tissue hypertrophy, liver steatosis, and insulin resistance. Furthermore, adipose tissue from TGFBI KO mice contained a large population of CD11b+ and CD206+ M2 macrophages, which possibly control adipokine secretion through paracrine mechanisms. Mechanistically, we showed that inhibiting TGFBI-stimulated release of adipsin by Notch-1-dependent signaling resulted in adipocyte browning. TGFBI was physiologically bound to Notch-1 and stimulated its activation in adipocytes. Our findings revealed a novel protective effect of TGFBI deficiency in obesity that is realized via the activation of the Notch-1 signaling pathway.


Assuntos
Resistência à Insulina , Fator de Crescimento Transformador beta , Camundongos , Animais , Fator de Crescimento Transformador beta/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Adipócitos/metabolismo , Transdução de Sinais , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Tecido Adiposo Branco/metabolismo
9.
Nutrients ; 14(21)2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36364945

RESUMO

Akebia quinata, commonly called chocolate vine, has various bioactivities, including antioxidant and anti-obesity properties. However, the anti-obesity effects of bioconverted extracts of A. quinate have not been examined. In this study, A. quinata fruit extracts was bioconverted using the enzyme isolated from the soybean paste fungi Aspergillus kawachii. To determine whether the bioconversion process could influence the anti-obesity effects of A. quinata fruit extracts, we employed 3T3-L1 adipocytes and HFD-induced obese rats. We observed that the bioconverted fruit extract of A. quinata (BFE) afforded anti-obesity effects, which were stronger than that for the non-bioconverted fruit extract (FE) of A. quinata. In 3T3-L1 adipocytes, treatment with BFE at concentrations of 20 and 40 µg reduced intracellular lipids by 74.8 (p < 0.05) and 54.9% (p < 0.01), respectively, without inducing cytotoxicity in preadipocytes. Moreover, the oral administration of BFE at the concentration of 300 mg/kg/day significantly reduced body and adipose tissue weights (p < 0.01) in HFD-induced obese rats. Plasma cholesterol values were reduced, whereas HDL was increased in BFE receiving rats. Although FE could exert anti-obesity effects, BFE supplementation induced more robust effects than FE. These results could be attributed to the bioconversion-induced alteration of bioactive compound content within the extract.


Assuntos
Fármacos Antiobesidade , Dieta Hiperlipídica , Camundongos , Ratos , Animais , Dieta Hiperlipídica/efeitos adversos , Fármacos Antiobesidade/farmacologia , Adipogenia , Frutas , Células 3T3-L1 , Obesidade/tratamento farmacológico , Obesidade/etiologia , Extratos Vegetais/farmacologia , Camundongos Endogâmicos C57BL
10.
Biology (Basel) ; 11(7)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-36101393

RESUMO

Nidus vespae, commonly known as the wasp nest, has antioxidative, anti-inflammatory, antimicrobial, and antitumor properties. However, the anti-obesity effects of Nidus vespae extract (NV) have not yet been reported. This study aimed to elucidate the potential anti-obesity effects of NV in vivo and in vitro, using a high-fat diet (HFD)-induced obese mouse model and 3T3-L1 adipocytes, respectively. NV administration to HFD-induced obese mice significantly decreased the mass and plasma lipid content of adipose tissues. Uncoupling protein-1 expression was significantly higher in the inguinal white adipose tissues of NV-treated mice than in those of HFD-fed mice. Furthermore, we found that NV inhibited the differentiation and intracellular lipid accumulation of 3T3-L1 adipocytes by regulating the insulin signaling cascade, including protein kinase B, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, and adiponectin. These findings suggest that NV may exhibit therapeutic effects against obesity by suppressing adipose tissue expansion and preadipocyte differentiation, thereby providing critical information for the development of new drugs for disease prevention and treatment. To our knowledge, this study provides the first evidence of the anti-obesity effects of NV.

11.
Cell Death Dis ; 13(2): 115, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-35121737

RESUMO

Cathepsin D (Cat D) is well known for its roles in metastasis, angiogenesis, proliferation, and carcinogenesis in cancer. Despite Cat D being a promising target in cancer cells, effects and underlying mechanism of its inhibition remain unclear. Here, we investigated the plausibility of using Cat D inhibition as an adjuvant or sensitizer for enhancing anticancer drug-induced apoptosis. Inhibition of Cat D markedly enhanced anticancer drug-induced apoptosis in human carcinoma cell lines and xenograft models. The inhibition destabilized Bcl-xL through upregulation of the expression of RNF183, an E3 ligase of Bcl-xL, via NF-κB activation. Furthermore, Cat D inhibition increased the proteasome activity, which is another important factor in the degradation of proteins. Cat D inhibition resulted in p62-dependent activation of Nrf2, which increased the expression of proteasome subunits (PSMA5 and PSMB5), and thereby, the proteasome activity. Overall, Cat D inhibition sensitized cancer cells to anticancer drugs through the destabilization of Bcl-xL. Furthermore, human renal clear carcinoma (RCC) tissues revealed a positive correlation between Cat D and Bcl-xL expression, whereas RNF183 and Bcl-xL expression indicated inverse correlation. Our results suggest that inhibition of Cat D is promising as an adjuvant or sensitizer for enhancing anticancer drug-induced apoptosis in cancer cells.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Catepsina D , Neoplasias Renais , Ubiquitina-Proteína Ligases , Antineoplásicos/farmacologia , Apoptose , Carcinoma de Células Renais/tratamento farmacológico , Catepsina D/antagonistas & inibidores , Linhagem Celular Tumoral , Humanos , Neoplasias Renais/tratamento farmacológico , Complexo de Endopeptidases do Proteassoma , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteína bcl-X/metabolismo
12.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502316

RESUMO

Farrerol (FA) is a flavanone isolated from the Chinese herbal medicine "Man-shan-hong" (Rhododendron dauricum L.). In the present study, FA decreased the viability of SKOV3 cells in a dose- and time-dependent manner, and it induced G2/M cell cycle arrest and cell apoptosis. Cell cycle distribution analysis via flow cytometry showed that FA decreased G1 populations and increased G2/M populations in SKOV3 cells. Additionally, Western blotting confirmed an increase in the expression level of proteins involved in the cell cycle, e.g., CDK and cyclins. FA-induced apoptosis in SKOV3 cells was also investigated using a TUNEL assay, and increased expression levels of proapoptotic factors, including Caspase-3 and poly ADP ribose polymerase (PARP), through the Extracellular signal-regulated kinase (ERK)/MAPK pathway were investigated. Proinflammatory cytokines (e.g., IL-6, TNF-α, and IL-1) have been identified as a driver of the pathological mechanisms underlying involuntary weight loss and impaired physical function, i.e., cachexia, during cancer; in the present study, we showed that farrerol attenuates TNF-α-induced lipolysis and increases adipogenic differentiation in 3T3-L1 cells. Thus, farrerol could potentially be used as an anticancer agent or anticachetic drug.


Assuntos
Cromonas/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Fator de Necrose Tumoral alfa/farmacologia , Apoptose , Ciclo Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Células Tumorais Cultivadas
13.
Antioxidants (Basel) ; 10(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34073118

RESUMO

The browning of white adipocytes, which transforms energy-storing white adipocytes to heat-producing beige adipocytes, is considered a strategy against metabolic diseases. Several dietary compounds, such as anthocyanins, flavonoids, and phenolic acids, induce a brown adipocyte-like phenotype in white adipocytes. In this study, we demonstrated that purple sweet potato (Ipomoea batatas) extract (PSP) exhibited potent radical scavenging activity. In addition, PSP was found to contain large amounts of phenolic, flavonoid, and anthocyanin compounds; the amount of these compounds was affected by fermentation. Functionally, PSP-induced adipose browning in high-fat-diet (HFD)-induced obese mice. The administration of PSP significantly suppressed the body weight gain and abnormal expansion of white adipose tissues in the obese mice. The expression of adipose browning-related genes was higher in the inguinal white adipose tissues from the PSP-treated mice than those in the HFD-fed mice. Moreover, PSP-treated 3T3-L1 adipocytes formed multilocular lipid droplets, similar to those formed in the 3T3-L1 adipocytes treated with a browning induction cocktail. The PSP-treated cells had an increased expression level of mitochondria and lipolysis-related genes. The browning effects of PSP were enhanced by fermentation with Lactobacillus. This study, to our knowledge, is the first to identify a new mechanism to increase the antiobesity effects of PSP by inducing adipocyte browning of adipocytes.

14.
Sci Rep ; 11(1): 9644, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958649

RESUMO

Several studies have suggested that extracellular matrix (ECM) remodeling and the microenvironment are tightly associated with adipogenesis and adipose angiogenesis. In the present study, we demonstrated that transforming growth factor-beta induced (TGFBI) suppresses angiogenesis stimulated by adipocyte-conditioned medium (Ad-CM), both in vitro and in vivo. TGFBI knockout (KO) mice exhibited increased numbers of blood vessels in adipose tissue, and blood vessels from these mice showed enhanced infiltration into Matrigel containing Ad-CM. The treatment of Ad-CM-stimulated SVEC-10 endothelial cells with TGFBI protein reduced migration and tube-forming activity. TGFBI protein suppressed the activation of the Src and extracellular signaling-related kinase signaling pathways of these SVEC-10 endothelial cells. Our findings indicated that TGFBI inhibited adipose angiogenesis by suppressing the activation of Src and ERK signaling pathways, possibly because of the stimulation of the angiogenic activity of endothelial cells.


Assuntos
Tecido Adiposo/irrigação sanguínea , Endotélio Vascular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Neovascularização Fisiológica , Fator de Crescimento Transformador beta/metabolismo , Tecido Adiposo/metabolismo , Animais , Capilares/crescimento & desenvolvimento , Capilares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
15.
Nat Prod Res ; 35(24): 6049-6053, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32924593

RESUMO

Jaceosidin a flavone abundant in Artemisia species has been used for its beneficial effects. This study investigated the apoptotic effect of jaceosidin treatment on MCF-7 human breast cancer cells at varying concentrations of (0, 10, 20 and 40 µM) for 24 and 48 h treatment times. Jaceosidin treatment induced a significant (p < 0.05) dose-dependent increase in apoptosis of MCF-7 cells. Jaceosidin similarly modulated the expressions of apoptosis-associated proteins, and revealing a coaction between Bax and Bcl-2, striking a balance between cell survival/cell deaths. Besides, a significant increase in pro-apoptotic expression of cleaved PARP which is a key executioner in apoptosis was observed. Apoptosis was confirmed in the cells by flow cytometry which indicated an early apoptosis (7%, 17%), as well as late apoptosis (36%, 40%) of the cells in varying percentages as treatment concentration increased. Thus, this study demonstrates that jaceosidin could be used as a potential treatment for breast cancer.


Assuntos
Neoplasias da Mama , Proteínas Quinases p38 Ativadas por Mitógeno , Apoptose , Neoplasias da Mama/tratamento farmacológico , Feminino , Flavonoides , Humanos , Células MCF-7
16.
Medicina (Kaunas) ; 56(12)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255313

RESUMO

Background and objectives: Sargassum miyabei Yendo, belonging to the family Sargassaceae, has been reported to have various biological effects such as anti-tyrosinase activity and anti-inflammation. However, the anti-obesity effect of Sargassum miyabei Yendo has not yet been reported. Materials and Methods: The effects of Sargassum miyabei Yendo extract (SME) on 3T3-L1 adipocytes were screened by3-(4,5)-dimethylthiazo-2-yl-2,5-diphenyltetrazolium bromide (MTT), Oil red O staining, western blot, and Real-time reverse transcription polymerase chain reaction analyses. Results: Here, we show that SME had potent 2,2'-azinobis-3-ehtlbezothiazoline-6-sulfonic acid radical decolorization (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant activity with half maximal inhibitory concentration (IC50) value of 0.2868 ± 0.011 mg/mL and 0.2941 ± 0.014 mg/mL, respectively. In addition, SME significantly suppressed lipid accumulation and differentiation of 3T3-L1 preadipocytes, as shown by Oil Red O staining results. SME attenuated the expression of adipogenic- and lipogenic-related genes such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding protein alpha (C/EBPα), CCAAT-enhancer-binding protein delta (C/EBPδ), adiponectin, adipose triglyceride lipase (ATGL), fatty acid synthase (FAS), hormone-sensitive lipase (HSL), and lipoprotein lipase (LPL). Conclusions: These findings suggest that SME may have therapeutic implications for developing a new anti-obesity agent.


Assuntos
Adipócitos/efeitos dos fármacos , PPAR gama , Phaeophyceae , Sargassum , Células 3T3-L1 , Animais , Antioxidantes , Diferenciação Celular , Camundongos , PPAR gama/genética
17.
Cancers (Basel) ; 12(10)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050333

RESUMO

Dexamethasone (DEX), a synthetic glucocorticoid, is commonly used as immunosuppressive and chemotherapeutic agent. This study was undertaken to investigate the effects of DEX on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in cancer cells. We found that upregulation of c-FLIP(L) and downregulation of death receptor 5 (DR5; receptor for TRAIL ligand) contribute to the anti-apoptotic effect of DEX on TRAIL-induced apoptosis. DEX increased c-FLIP(L) expression at the transcriptional levels through the GSK-3ß signaling pathway. The pharmacological inhibitor and catalytic mutant of GSK-3ß suppressed DEX-induced upregulation of c-FLIP(L) expression. Furthermore, GSK-3ß specific inhibitor markedly abolished DEX-mediated reduction of TRAIL-induced apoptosis in human renal cancer cells (Caki-1 and A498), human lung cancer cells (A549), and human breast cancer cells (MDA-MB361). In addition, DEX decreased protein stability of DR5 via GSK-3ß-mediated upregulation of Cbl, an E3 ligase of DR5. Knockdown of Cbl by siRNA markedly inhibited DEX-induced DR5 downregulation. Taken together, these results suggest that DEX inhibits TRAIL-mediated apoptosis via GSK-3ß-mediated DR5 downregulation and c-FLIP(L) upregulation in cancer cells.

18.
PLoS One ; 15(7): e0236294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716960

RESUMO

Xylose, the second most abundant sugar in lignocellulosic biomass hydrolysates, can be fermented by Saccharomyces cerevisiae expressing one of two heterologous xylose pathways: a xylose oxidoreductase pathway and a xylose isomerase pathway. Depending on the type of the pathway, its optimization strategies and the fermentation efficiencies vary significantly. In the present study, we constructed two isogenic strains expressing either the oxidoreductase pathway (XYL123) or the isomerase pathway (XI-XYL3), and delved into simple and reproducible ways to improve the resulting strains. First, the strains were subjected to the deletion of PHO13, overexpression of TAL1, and adaptive evolution, but those individual approaches were only effective in the XYL123 strain but not in the XI-XYL3 strain. Among other optimization strategies of the XI-XYL3 strain, we found that increasing the copy number of the xylose isomerase gene (xylA) is the most promising but yet preliminary strategy for the improvement. These results suggest that the oxidoreductase pathway might provide a simpler metabolic engineering strategy than the isomerase pathway for the development of efficient xylose-fermenting strains under the conditions tested in the present study.


Assuntos
Engenharia Metabólica , Redes e Vias Metabólicas , Saccharomyces cerevisiae/metabolismo , Xilose/metabolismo , Aldose-Cetose Isomerases/metabolismo , Evolução Biológica , Fermentação , Deleção de Genes , Transcrição Gênica
19.
Foods ; 9(7)2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32640612

RESUMO

The systematic investigations on the value of social wasps as a food resource are deficient, in spite of the long history of the utilization of social wasps as food and pharmaceutical bioresources. Vespa velutina nigrithorax is an invasive alien wasp species that is currently dominating in East Asia and Europe, bringing huge economic damages. As a control over alien species is made when the valuable utilization of the invasive species as a potential resource are discovered, investigations on the potential of V. v. nigrithorax as a useful bioresource are also in demand. Nutritional and heavy metal analyses of the larvae revealed their balanced and rich nutritional value and safety as a food resource. The larval saliva amino acid composition was investigated for further study on amino acid supplementation and exercise enhancement.

20.
Int J Mol Sci ; 21(7)2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260306

RESUMO

Present-day lifestyles associated with high calorie-fat intake and accumulation, as well as energy imbalance, have led to the development of obesity and its comorbidities, which have emerged as some of the major health issues globally. To combat the disease, many studies have reported the anti-obesity effects of natural compounds in foods, with some advantages over chemical treatments. Carotenoids, such as xanthophyll derived from seaweeds, have attracted the attention of researchers due to their notable biological activities, which are associated mainly with their antioxidant properties. Their involvement in oxidative stress modulation, the regulation of major transcription factors and enzymes, and their antagonistic effects on various obesity parameters have been examined in both in vitro and in vivo studies. The present review is a collation of published research over the last decade on the antioxidant properties of seaweed xanthophyll carotenoids, with a focus on fucoxanthin and astaxanthin and their mechanisms of action in obesity prevention and treatment.


Assuntos
Obesidade/tratamento farmacológico , Alga Marinha/química , Xantofilas/uso terapêutico , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Obesidade/metabolismo , Manejo da Obesidade , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Xantofilas/química , Xantofilas/farmacologia
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