RESUMO
We demonstrated the effect of Ishige okamurae extract (IOE) on the receptor activator of nuclear factor-κB ligand (RANKL)-promoted osteoclastogenesis in RAW 264.7 cells and confirmed that IOE inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation. IOE inhibited protein expression of TRAP, metallopeptidase-9 (MMP-9), the calcitonin receptor (CTR), and cathepsin K (CTK). IOE treatment suppressed the expression of activated T cell cytoplasmic 1 and activator protein-1, thus controlling the expression of osteoclast-related factors. Moreover, IOE significantly reduced RANKL-phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). It also reduced the RANKL-induced phosphorylation of NF-κB and nuclear translocation of p65. IOE inhibited Dex-induced bone loss and osteoclast-related gene expression in zebrafish larvae. HPLC analysis shows that IOE consists of 3.13% and 3.42% DPHC and IPA, respectively. Our results show that IOE has inhibitory effects on osteoclastogenesis in vitro and in vivo and is a potential therapeutic for osteoporosis.
Assuntos
Osteogênese , Peixe-Zebra , Animais , Osteoclastos , Cromatografia Líquida de Alta Pressão , MAP Quinases Reguladas por Sinal Extracelular , Ligante RANKRESUMO
Mandarin peel, a main by-product from the processing of citrus juice, has been highlighted for its various bioactivities and functional ingredients. Our previous study proved the inhibitory effects of Celluclast extract from mandarin peel (MPCE) on lipid accumulation and differentiation in 3T3-L1 adipocytes. Therefore, the current study aimed to evaluate the anti-obesity effect of MPCE in high-fat diet (HFD)-induced obese mice. The high-performance liquid chromatography (HPLC) analysis exhibited that narirutin and hesperidin are the main active components of MPCE. Our current results showed that MPCE supplementation decreased adiposity by reducing body and organ weights in HFD-induced obese mice. MPCE also reduced triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and leptin contents in the serum of HFD-fed mice. Moreover, MPCE significantly inhibited hepatic lipid accumulation by regulating the expression levels of proteins associated with lipid metabolism, including sterol regulatory element-binding protein (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Furthermore, MPCE administration significantly inhibited both adipogenesis and lipogenesis, with modulation of energy metabolism by activating 5' adenosine monophosphate-activated protein kinase (AMPK) and lipolytic enzymes such as hormone-sensitive lipase (HSL) in the white adipose tissue (WAT). Altogether, our findings indicate that MPCE improves HFD-induced obesity and can be used as a curative agent in pharmaceuticals and nutraceuticals to alleviate obesity and related disorders.
Assuntos
Adipogenia , Citrus , Dieta Hiperlipídica , Dissacarídeos , Metabolismo Energético , Flavanonas , Camundongos Endogâmicos C57BL , Obesidade , Extratos Vegetais , Animais , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Obesidade/etiologia , Citrus/química , Camundongos , Metabolismo Energético/efeitos dos fármacos , Extratos Vegetais/farmacologia , Masculino , Adipogenia/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Células 3T3-L1 , Fármacos Antiobesidade/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Triglicerídeos/metabolismo , Triglicerídeos/sangueRESUMO
Brown seaweed is a rich source of fucoidan, which exhibits a variety of biological activities. The present study discloses the protective effect of low molecular weight fucoidan (FSSQ) isolated from an edible brown alga, Sargassum siliquastrum, on lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW 264.7 macrophages. The findings of the study revealed that FSSQ increases cell viability while decreasing intracellular reactive oxygen species production in LPS-stimulated RAW 264.7 macrophages dose-dependently. FSSQ reduced the iNOS and COX-2 expression, inhibiting the NO and prostaglandin E2 production. Furthermore, mRNA expression of IL-1ß, IL-6, and TNF-α was downregulated by FSSQ via modulating MAPK and NF-κB signaling. The NLRP3 inflammasome protein complex, including NLRP3, ASC, and caspase-1, as well as the subsequent release of pro-inflammatory cytokines, such as IL-1ß and IL-18, release in LPS-stimulated RAW 264.7 macrophages was inhibited by FSSQ. The cytoprotective effect of FSSQ is indicated via Nrf2/HO-1 signaling activation, which is considerably reduced upon suppression of HO-1 activity by ZnPP. Collectively, the study revealed the therapeutic potential of FSSQ against inflammatory responses in LPS-stimulated RAW 264.7 macrophages. Moreover, the study suggests further investigations on commercially viable methods for fucoidan isolation.
Assuntos
NF-kappa B , Sargassum , Animais , Camundongos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Sargassum/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peso Molecular , Macrófagos , Transdução de Sinais , Citocinas/metabolismo , Anti-Inflamatórios/uso terapêutico , Células RAW 264.7 , Inflamação/tratamento farmacológicoRESUMO
The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is essential for the bone remodeling process. This study aimed to investigate the effect of Ishophloroglucin A (IPA) isolated from Ishige okamurae on the function of osteoclasts and osteoblasts in vitro. First, we demonstrated the effect of IPA on osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW 264.7 cells. IPA inhibited the tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation in RANKL-induced RAW 264.7 cells. Moreover, it inhibited the RANKL-induced osteoclast-related factors, such as TRAP, matrix metalloproteinase-9 (MMP-9), and calcitonin receptor (CTR), and transcription factors, such as nuclear factor of activated T cells 1 (NFATc1) and c-Fos. IPA significantly suppressed RANKL-activated extracellular signal-regulated kinase (ERK), and NF-κB in RAW 264.7 cells. Our data indicated that the ERK and NF-κB pathways were associated with the osteoclastogenesis inhibitory activity of IPA. Next, we demonstrated the effect of IPA on osteoblastogenesis in MG-63 cells. IPA significantly promoted alkaline phosphatase (ALP) activity in MG-63 cells, along with the osteoblast differentiation-related markers bone morphogenetic protein 2 (BMP2), type 1 collage (COL1), p-Smad1/5/8, and Runx2, by activating the MAPK signaling pathways. Taken together, the study indicated that IPA could be effective in treating bone diseases, such as osteoporosis.
Assuntos
NF-kappa B , Osteogênese , Animais , Camundongos , NF-kappa B/metabolismo , Transdução de Sinais , Fatores de Transcrição NFATC/metabolismo , Fatores de Transcrição NFATC/farmacologia , Osteoclastos , Ligante RANK/farmacologia , Ligante RANK/metabolismo , Diferenciação Celular , Células RAW 264.7RESUMO
In this study, we investigated the anti-allergic effects of 3,4-dihydroxybenzaldehyde (DHB) isolated from the marine red alga, Polysiphonia morrowii, in mouse bone-marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in anti-dinitrophenyl (DNP) immunoglobulin E (IgE)-sensitized mice. DHB inhibited IgE/bovine serum albumin (BSA)-induced BMCMCs degranulation by reducing the release of ß-hexosaminidase without inducing cytotoxicity. Further, DHB dose-dependently decreased the IgE binding and high-affinity IgE receptor (FcεRI) expression and FcεRI-IgE binding on the surface of BMCMCs. Moreover, DHB suppressed the secretion and/or the expression of the allergic cytokines, interleukin (IL)-4, IL-5, IL-6, IL-13, and tumor necrosis factor (TNF)-α, and the chemokine, thymus activation-regulated chemokine (TARC), by regulating the phosphorylation of IκBα and the translocation of cytoplasmic NF-κB into the nucleus. Furthermore, DHB attenuated the passive cutaneous anaphylactic (PCA) reaction reducing the exuded Evans blue amount in the mouse ear stimulated by IgE/BSA. These results suggest that DHB is a potential therapeutic candidate for the prevention and treatment of type I allergic disorders.
Assuntos
Antialérgicos/farmacologia , Benzaldeídos/farmacologia , Catecóis/farmacologia , Mastócitos/efeitos dos fármacos , Rodófitas/metabolismo , Animais , Antialérgicos/administração & dosagem , Antialérgicos/isolamento & purificação , Benzaldeídos/administração & dosagem , Benzaldeídos/isolamento & purificação , Catecóis/administração & dosagem , Catecóis/isolamento & purificação , Células Cultivadas , Citocinas/imunologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Imunoglobulina E/imunologia , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Anafilaxia Cutânea Passiva/imunologia , Soroalbumina Bovina/imunologiaRESUMO
Polysiphonia morrowii is a well-known red alga that has promising pharmacological characteristics. The current study evaluates the protective effect of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) isolated from P. morrowii on tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated inflammation and skin barrier deterioration in HaCaT keratinocytes. The anti-inflammatory effect of BDB in TNF-α/IFN-γ-stimulated HaCaT keratinocytes is evaluated by investigating nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, inflammatory cytokines, and chemokines. Further, the interaction between BDB and the skin barrier functions in stimulated HaCaT keratinocytes is investigated. The findings of the study reveal that BDB dose-dependently increases cell viability while decreasing intracellular reactive oxygen species (ROS) production. BDB downregulates the expression of inflammatory cytokines, interleukin (IL)-6, -8, -13, IFN-γ, TNF-α, and chemokines, Eotaxin, macrophage-derived chemokine (MDC), regulated on activation, normal T cells expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC) by modulating the MAPK and NF-κB signaling pathways in TNF-α/IFN-γ-stimulated HaCaT keratinocytes. Furthermore, BDB increases the production of skin hydration proteins and tight junction proteins in stimulated HaCaT keratinocytes by preserving skin moisturization and tight junction stability. These findings imply that BDB exhibits a protective ability against inflammation and deterioration of skin barrier via suppressing the expression of inflammatory signaling in TNF-α/IFN-γ-stimulated HaCaT keratinocytes.
Assuntos
Benzaldeídos , Queratinócitos , Rodófitas , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Benzaldeídos/farmacologia , Quimiocina CCL17/metabolismo , Quimiocina CCL22/metabolismo , Quimiocina CCL5/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interferon gama/metabolismo , Interleucinas/metabolismo , Queratinócitos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rodófitas/química , Fator de Transcrição STAT1/metabolismo , Proteínas de Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Growth and maintenance of skeletal muscle is essential for athletic performance and a healthy life. Stimulating the proliferation and differentiation of muscle cells may help prevent loss of muscle mass. To discover effective natural substances enabling to mitigate muscle loss without side effects, we evaluated muscle growth with several compounds extracted from Catalpa bignonioides Walt. Among these compounds, pinoresinol and vanillic acid increased C2C12, a mouse myoblast cell line, proliferation being the most without cytotoxicity. These substances activated the Akt/mammalian target of the rapamycin (mTOR) pathway, which positively regulates the proliferation of muscle cells. In addition, the results of in silico molecular docking study showed that they may bind to the active site of insulin-like growth factor 1 receptor (IGF-1R), which is an upstream of the Akt/mTOR pathway, indicating that both pinoresinol and vanillic acid stimulate myoblast proliferation through direct interaction with IGF-1R. These results suggest that pinoresinol and vanillic acid may be a natural supplement to improve the proliferation of skeletal muscle via IGF-1R/Akt/mTOR signaling and thus strengthen muscles.
Assuntos
Proteínas Proto-Oncogênicas c-akt , Ácido Vanílico , Animais , Proliferação de Células , Furanos , Fator de Crescimento Insulin-Like I/metabolismo , Lignanas , Mamíferos/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Ácido Vanílico/metabolismo , Ácido Vanílico/farmacologiaRESUMO
Skeletal muscle is an important tissue in energy metabolism and athletic performance. The use of effective synthetic supplements and drugs to promote muscle growth is limited by various side effects. Moreover, their use is prohibited by anti-doping agencies; hence, natural alternatives are needed. Therefore, we evaluated the muscle growth effect of substances that can act like synthetic supplements from edible marine algae. First, we isolated six marine algal polyphenols belonging to the phlorotannin class, namely dieckol (DK), 2,7â³-phloroglucinol-6,6'-bieckol (PHB), phlorofucofuroeckol A (PFFA), 6,6'-bieckol (6,6-BK), pyrogallol-phloroglucinol-6,6'-bieckol (PPB), and phloroglucinol (PG) from an edible brown alga, Ecklonia cava and evaluated their effects on C2C12 myoblasts proliferation and differentiation. Of the six phlorotannin isolates evaluated, DK and PHB induced the highest degree of C2C12 myoblast proliferation. In addition, DK and PHB regulates myogenesis by down-regulating the Smad signaling, a negative regulator, and up-regulating the insulin-like growth factor-1 (IGF-1) signaling, a positive regulator. Interestingly, DK and PHB bind strongly to myostatin, which is an inhibitor of myoblast proliferation, while also binding to IGF-1 receptors. Moreover, they bind to IGF-1 receptor. These results suggest that DK and PHB are potential natural muscle building supplements and could be a safer alternative to synthetic drugs.
Assuntos
Organismos Aquáticos/química , Cianobactérias/química , Fator de Crescimento Insulin-Like I/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Polifenóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Creatina Quinase Forma MM/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Células Musculares/efeitos dos fármacos , Desenvolvimento Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Miostatina/química , Miostatina/metabolismo , Proibitinas , Receptor IGF Tipo 1/química , Receptor IGF Tipo 1/metabolismoRESUMO
Chinese chive (Allium tuberosum) is a medicinal food that is cultivated and consumed mainly in Asian countries. Its various phytochemicals and physiological effects have been reported, but only a few phytochemicals are available for skeletal muscle cell proliferation. Herein, we isolated a new compound, kaempferol-3-O-(6â³-feruloyl)-sophoroside (1), along with one known flavonoid glycoside (2) and six amino acid (3-8) compounds from the water-soluble fraction of the shoot of the Chinese chive. The isolated compounds were identified using extensive spectroscopic methods, including 1D and 2D NMR, and evaluated for their proliferation activity on skeletal muscle cells. Among the tested compounds, newly isolated flavonoid (1) and 5-aminouridine (7) up-regulated PI3K/Akt/mTOR pathways, which implies a positive effect on skeletal muscle growth and differentiation. In particular, compound 1 down-regulated the Smad pathways, which are negative regulators of skeletal muscle growth. Collectively, we suggest that major constituents of Chinese chive, flavonoids and amino acids, might be used in dietary supplements that aid skeletal muscle growth.
Assuntos
Proliferação de Células/efeitos dos fármacos , Cebolinha-Francesa/química , Músculo Esquelético/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Compostos Fitoquímicos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Aminoácidos/análise , Aminoácidos/química , Aminoácidos/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Cromatografia Líquida , Suplementos Nutricionais/análise , Flavonoides/análise , Flavonoides/química , Flavonoides/farmacologia , Quempferóis/análise , Quempferóis/química , Quempferóis/farmacologia , Espectrometria de Massas , Camundongos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Análise EspectralRESUMO
Inflammation affects various organs of the human body, including skeletal muscle. Phlorotannins are natural biologically active substances found in marine brown algae and exhibit anti-inflammatory activities. In this study, we focused on the effects of phlorotannins on anti-inflammatory activity and skeletal muscle cell proliferation activity to identify the protective effects on the inflammatory myopathy. First, the five species of marine brown algal extracts dramatically inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells without toxicity at all the concentrations tested. Moreover, the extracts collected from Ishige okamurae (I. okamurae) significantly increased cell proliferation of C2C12 myoblasts compared to the non-treated cells with non-toxicity. In addition, as a result of finding a potential tumor necrosis factor (TNF)-α inhibitor that regulates the signaling pathway of muscle degradation in I. okamurae-derived natural bioactive compounds, Diphlorethohydroxycarmalol (DPHC) is favorably docked to the TNF-α with the lowest binding energy and docking interaction energy value. Moreover, DPHC down-regulated the mRNA expression level of pro-inflammatory cytokines and suppressed the muscle RING-finger protein (MuRF)-1 and Muscle Atrophy F-box (MAFbx)/Atrgoin-1, which are the key protein muscle atrophy via nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPKs) signaling pathways in TNF-α-stimulated C2C12 myotubes. Therefore, it is expected that DPHC isolated from IO would be developed as a TNF-α inhibitor against inflammatory myopathy.
Assuntos
Anti-Inflamatórios/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Inflamação/tratamento farmacológico , Doenças Musculares/tratamento farmacológico , Phaeophyceae/química , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anti-Inflamatórios/química , Citocinas/genética , Citocinas/metabolismo , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/química , Camundongos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Mioblastos/efeitos dos fármacos , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genéticaRESUMO
Acute myeloid leukemia (AML) is an aggressive type of human leukemia with a low survival rate, and its complete remission remains challenging. Although chemotherapy is the first-line treatment of AML, it exerts toxicity in noncancerous cells when used in high doses, thus necessitating the development of novel compounds with a high therapeutic window. This study aimed to investigate the anticancer effects of several compounds derived from the fruits of Melia azedarach (a tree with medicinal properties). Among them, 1-cinnamoyltrichilinin (CT) was found to strongly suppress the viability of HL-60 human leukemia cells. CT treatment induced apoptosis and increased nuclear fragmentation and fractional DNA content in HL-60 cells in a dose-dependent manner. CT induced phosphorylation of p38 mitogen-activated protein kinases (p38), though not of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), and activated Bcl-2 family proteins towards the proapoptosis and cleavage of caspase-3 and poly (ADP-ribose) polymerase. Both CT-mediated apoptosis and apoptotic protein expression were reversed by treatment with the p38 inhibitor, thereby indicating the p38 pathway to be critical in CT-stimulated apoptosis. The results collectively indicated CT to suppress HL-60 survival by activating the p38 pathway and inducing apoptosis, hence being a novel potential therapeutic agent for AML.
Assuntos
Apoptose/efeitos dos fármacos , Limoninas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melia azedarach/química , Extratos Vegetais/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células HL-60 , Humanos , Limoninas/química , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
Here, we investigated the hepatoprotective effect of a hot water extract from Loliolus beka gray meat (LBMH) containing plentiful taurine in H2O2-induced oxidative stress in hepatocytes. LBMH potently scavenged the 2,2-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and exhibited the good reducing power and the oxygen radical absorbance capacity (ORAC) value. Also, LBMH improved the cell viability against H2O2-induced hepatic damage in cultured hepatocytes by reducing intracellular reactive oxygen species (ROS) production. In addition, LBMH inhibited apoptosis via a reduction in sub-G1 cell population, as well as inhibition of apoptotic body formation from H2O2-induced oxidative damage in hepatocytes. Moreover, LBMH regulated the expression levels of Bax, a pro-apoptotic molecule and Bcl-2, an anti-apoptotic molecule in H2O2-treated hepatocytes. Additionally, pre-treatment with LBMH increased the expression of heme oxygenase 1 (HO-1), which is a hepatoprotective enzyme, by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) in H2O2-treated hepatocytes. Taken together, LBMH may be useful as a food ingredient for treatment of liver disease by regulating the Nrf2/HO-1 signal pathway.
Assuntos
Antioxidantes , Extratos Celulares/farmacologia , Decapodiformes/química , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo , Taurina/farmacologia , Animais , Células Cultivadas , Heme Oxigenase-1/metabolismo , Hepatócitos/citologia , Humanos , Peróxido de Hidrogênio , Carne , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Octopus ocellatus meat (OM) is well known as a plentiful protein source. In this study, we evaluated the hepatoprotective effect of an aqueous extract of OM (OMA) against H2O2-triggered oxidative stress in human hepatocytes. First of all, taurine rich OMA showed a good ORAC value and reducing power and it was similar with that of ascorbic acid, which is known as a strong antioxidant. Also, OMA significantly improved H2O2-decreased cell viability by reducing the generation of intracellular reactive oxygen species (ROS) in hepatocytes. Interestingly, the stimulation of H2O2-induced the formations of apoptotic bodies and sub-G1 DNA content, whereas they were inhibited by the treatment with OMA. Furthermore, OMA regulated the protein expression levels of apoptotic molecules, such as Bax and Bcl-2. Taken together, this study suggests that OMA, which contains an abundant amount of taurine, protects hepatocytes from H2O2-triggered oxidative stress and might be a functional food material with hepatoprotective effects.
Assuntos
Extratos Celulares/farmacologia , Hepatócitos/efeitos dos fármacos , Octopodiformes/química , Estresse Oxidativo , Animais , Apoptose , Células Cultivadas , Hepatócitos/citologia , Humanos , Peróxido de Hidrogênio/efeitos adversos , Carne , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Batillus cornutus (B. cornutus) is one of the gastropoda, which are distributed along the coast of China, Japan and South Korea and northeast area. In this study, we first identified the antioxidant effects of a B. cornutus meat (BM) enzymatic hydrolysate in H2O2-treated Vero cells. First of all, we prepared an Alcalase hydrolysate from BM (BMA) and revealed a high taurine content. Also, taurine rich BMA dose-dependently increased 2,2-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radical scavenging activity, reducing power and the higher oxygen radical absorbance capacity (ORAC) value. In addition, BMA significantly increased the cell viability via the down-regulation of intracellular reactive oxygen species (ROS) production, as well as the decreased formation of apoptotic bodies and sub-G1 DNA population in H2O2-treated Vero cells. Furthermore, BMA increased the expression of the anti-apoptotic molecule, Bcl-2, and decreased the expressions of Bax, p53 and cleaved PARP, all of which are pro-apoptotic molecules, in H2O2-treated Vero cells. Based on these results, this study suggests that BMA may be used as a potential protector on damage caused by oxidative stress.
Assuntos
Antioxidantes/farmacologia , Gastrópodes/química , Estresse Oxidativo , Hidrolisados de Proteína/farmacologia , Animais , Chlorocebus aethiops , Peróxido de Hidrogênio , Carne , Espécies Reativas de Oxigênio/metabolismo , Subtilisinas , Células VeroRESUMO
In the present study, we investigated the antioxidant activity of an aqueous extract from Atrina pectinate meat (APW) against H2O2-induced oxidative stress in a human hepatocyte. The extraction yield of APW was 30.01 ± 0.83% and which contained the highest taurine content among free amino acid contents. APW led to the high antioxidant activity showing 2,2-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radical scavenging activity, good reducing power and oxygen radical absorbance capacity (ORAC) value. Also, the results showed that APW improved the cell viability decreased by H2O2 stimulation as well as the reduction of intracellular reactive oxygen species (ROS) generation in hepatocytes. Additionally, APW up-regulated the production of antioxidant mechanisms related enzymes such as catalase and superoxide dismutase (SOD), compared to the only H2O2-treated hepatocytes. Moreover, APW increased the expressions of nuclear Nrf2 and cytosolic HO-1 in H2O2-treated hepatocytes. Interestingly, the treatment of ZnPP, a HO-1 inhibitor abolished the cell viability and intracellular ROS generation induced by APW treatment. In conclusion, this study suggests that APW protects H2O2 induced oxidative stress via up-regulating of Nrf2/HO-1 signal pathway in hepatocytes.
Assuntos
Antioxidantes/farmacologia , Bivalves/química , Extratos Celulares/farmacologia , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo , Animais , Heme Oxigenase-1/metabolismo , Humanos , Peróxido de Hidrogênio , Carne , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
In this study, we investigated the hepatoprotective activity of the water extract derived from Octopus vulgaris meat (OM). First of all, a water extract prepared from OM (OMW) showed the high extraction yield (48.22%) and the highest taurine content (39.84%) in free amino acids. OMW exhibited the high value of reducing power, ABTS and hydrogen peroxide radical scavenging activities in dose-dependent manner. The taurine-rich OMW also led to the reduced intracellular reactive oxygen species (ROS) generation with the increased cell survival in H2O2-treated Chang liver cells. In addition, OMW decreased the apoptotic phenomenon, including the formations of apoptotic bodies and sub-G1 DNA contents by regulating the protein expressions of apoptosis-related molecules such as Bcl-2 and Bax. From these results, this study indicated the taurine-rich OMW protected hepatocytes against oxidative stress. These findings suggest that OWM may be a novel potential antioxidant resource.
Assuntos
Extratos Celulares/farmacologia , Hepatócitos/citologia , Octopodiformes/química , Estresse Oxidativo , Taurina/farmacologia , Animais , Antioxidantes/farmacologia , Linhagem Celular , Humanos , Peróxido de Hidrogênio , Carne , Espécies Reativas de Oxigênio , ÁguaRESUMO
Gamma ray irradiation causes immune suppression, in which oxidative stress reduces cell viability and damages immune cells. In the present study, we investigated whether Loliolus beka gray meat (LBM), which contains large amounts of taurine, protects against damage of murine splenocytes by oxidative stress. An aqueous extract of LBM (LBMW) was prepared, which contained plentiful levels of taurine. LBMW improved cell viability of gamma ray-irradiated murine splenocytes, an effect that was associated with significant reduction in the production of reactive oxygen species (ROS). We also showed that the production of nitric oxide (NO) and ROS in gamma ray-irradiated zebrafish embryos, as well as the death of the embryos, were diminished by LBMW. These data suggest that the consumption of taurine-rich foods, such as LBM, may be used in the protection of cells against oxidative stress.
Assuntos
Extratos Celulares/farmacologia , Decapodiformes/química , Estresse Oxidativo , Protetores contra Radiação/farmacologia , Taurina/farmacologia , Animais , Células Cultivadas , Raios gama/efeitos adversos , Carne , Camundongos , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Baço/citologiaRESUMO
With a growing number of intracellular drug targets and the high efficacy of protein therapeutics, the targeted delivery of active proteins with negligible toxicity is a challenging issue in the field of precision medicine. Herein, a programed assembly of nucleoprotein nanoparticles (NNPs) using DNA and zinc fingers (ZnFs) for targeted protein delivery is presented. Two types of ZnFs with different sequence specificities are genetically fused to a targeting moiety and a protein cargo, respectively. Double-stranded DNA with multiple ZnF-binding sequences is grafted onto inorganic nanoparticles, followed by conjugation with the ZnF-fused proteins, generating the assembly of NNPs with a uniform size distribution and high stability. The approach enables controlled loading of a protein cargo on the NNPs, offering a high cytosolic delivery efficiency and target specificity. The utility and potential of the assembly as a versatile protein delivery vehicle is demonstrated based on their remarkable antitumor activity and target specificity with negligible toxicity in a xenograft mice model.
Assuntos
DNA/química , Nanopartículas/química , Nucleoproteínas/química , Proteínas/química , Animais , Sistemas de Liberação de Medicamentos , Humanos , Camundongos , Ligação Proteica , Dedos de ZincoRESUMO
The cosmetics industry is one of the most profitable in the world today. This multi-billion-dollar industry has a profound sociological impact worldwide. Its influence is global, with most individuals being concerned with conserving their physical appearance, beauty, and youth. The consumers' desire for novel, better, and safer products has stimulated the utilization of natural-product-based cosmeceutical formulations over synthetic chemicals. With remarkable advancements in marine bioresource technology, algal polysaccharides have gained much attention as bioactive ingredients in cosmeceuticals. Algae biosynthesize a variety of polysaccharides including fucoidans, alginates, carrageenans, galactans, agar, porphyran, glucans, and ulvans, all of which exhibit distinctive structural and functional properties. Many of these materials have been proven to possess skin-protective effects, including anti-wrinkle, lightening, moisturizing, UV protective, antioxidative, and anti-inflammatory activity. Moreover, they have a wide spectrum of physicochemical properties, such as the ability to form hydrogels, which extend their utilization as emulsifiers, stabilizers, and viscosity controlling ingredients in cosmeceuticals. Accordingly, algal hydrocolloids and their synthetic derivatives can also be applied in tissue engineering and cosmetic surgery. The challenge is to increase awareness about these polysaccharides and consequently generate value-added products. This review discusses the beneficial biological and physicochemical properties of algal polysaccharides, highlighting their potential in cosmeceutical applications.
RESUMO
Inflammation markers in zebrafish embryos reflect a toxic response that is common to other animal models and humans. Free fatty acids (FFAs) are known to cause damage in various tissues by inducing inflammation. In this study, we investigated whether a FFA (palmitate) induces inflammation in zebrafish embryos. Nitrous oxide (NO) production and cyclooxygenase-2 (COX-2) mRNA expression were increased in palmitate-treated zebrafish embryos in a dose-dependent manner. mRNA expression of pro-inflammatory cytokines, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF- α), were also increased. Additionally, the mRNA expression of p65 nuclear factor-kB and I-kB-α were significantly increased after palmitate-treatment. Increased reactive oxygen species (ROS) expression was observed in palmitate-treated zebrafish embryos as well as pericardial edema. Additionally, mRNA expression of pro-inflammatory cytokines were increased in zebrafish liver and pancreas fed with palmitate-contained diet. Taken together, these results indicated that palmitate increases pro-inflammatory mediators in zebrafish embryos, suggesting that zebrafish could be an alternative animal model for inflammatory disease including diabetes.