RESUMO
In the present study, andrographolide (Andro, 1) derivatives were screened to identify potent inhibitors against tumor-cell migration and invasion, and associated structure-activity relationships were studied. Compared to 1, compounds 8a-8d exhibited more potent activities against migration in SGC-7901, PC-3, A549, HT-29 and Ec109 cell lines. Improved activities against tumor-cell migration and invasion were proved to be associated with the down-regulation of MMPs.
Assuntos
Movimento Celular/efeitos dos fármacos , Diterpenos/química , Diterpenos/farmacologia , Neoplasias/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Diterpenos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Neoplasias/patologia , Relação Estrutura-AtividadeRESUMO
Uncovering an efficient and stable photocatalytic system for seawater splitting is a highly desirable but challenging goal. Herein, Cd0.2Zn0.8S@Silicalite-1 (CZS@S-1) composites, in which CZS is embedded in the hierarchical zeolite S-1, were prepared and show remarkably high activity, stability and salt resistance in seawater.
Assuntos
Zeolitas , Cádmio , Água do Mar , Hidrogênio , ZincoRESUMO
Accumulating evidence suggests a role of bisphenol A (BPA) in non-alcoholic fatty liver disease (NAFLD), and its mechanism may be related to the up-regulation of lipogenic genes, but the mechanism of BPA induced lipogenic gene expression remains unknown. The aim of this study was to investigate the effects of perinatal exposure to BPA on NAFLD and its mechanisms. Pregnant Sprague-Dawley rats had access to drinking water containing 1 or 10 µg/ml BPA from gestational day 6 to post-natal day 21. For 5 weeks after weaning, offspring drank normal water without BPA. Body weight, lipid profile and the expression of genes or proteins involved in mTOR mediated lipid metabolism and autophagy, as well as inflammatory response were investigated in the 8-wk-old offspring of different genders. The results showed that body weight was increased only in females, however, males, and females from dams treated with BPA had significantly excess visceral adipose tissue, which was consistent with adipocyte hypertrophy. Elevated TG levels and up-regulation of lipogenic genes or proteins in liver, such as sterol regulatory element binding protein 1 (SREBP1), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS) were consistent with increased liver lipid droplets in offspring exposed to BPA. Compared with controls, the protein levels of InsR, p-IRS-1, IRS-1, TSC1, and TSC2 were decreased, p-PI3K, p-Akt (S473), p-Akt (T308), p-mTOR, and mTOR were increased, and the impaired autophagic degradation was evidenced by increased protein levels of p62, although the levels of p-ULK1, Beclin1, and LC3B proteins were increased in liver of BPA-exposed offspring. The levels of TLR4 and NF-κB proteins were also significantly increased, and ERα protein was significantly decreased in BPA-exposed offspring. Our findings indicate that perinatal exposure to BPA causes the development of NAFLD in both female and male offspring, which is associated with up-regulation of lipogenic genes, dysregulated autophagy and activated inflammatory response involving the PI3K/Akt/mTOR and TLR4/NF-κB pathways.
RESUMO
Alzheimer's disease (AD) is a common neurodegenerative disorders, in which oxidative stress plays an important role. The present study investigated the effect of eicosapentaenoic acid-enriched phospholipids (EPA-enriched PL) from the sea cucumber Cucumaria frondosa on oxidative injury in PC12 cells induced by hydrogen peroxide (H2O2) and tert-butylhydroperoxide (t-BHP). We also studied the effect of EPA-enriched PL on learning and memory functions in senescence-accelerated prone mouse strain 8 (SAMP8) in vivo. Pretreatment with EPA-enriched PL resulted in an enhancement of survival in a dose-dependent manner in H2O2 or t-BHP damaged PC12 cells. EPA-enriched PL pretreatment could also reduce the leakage of lactate dehydrogenase (LDH), and increase the intracellular total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity compared with the H2O2 or t-BHP group. The down-regulated Bcl-2 mRNA level and up-regulated Bax, Caspase-9, and Caspase-3 mRNA expression induced by H2O2 or t-BHP could be restored by EPA-enriched PL pretreatment. These results demonstrated that EPA-enriched PL exhibited its neuroprotective effects by virtue of its antioxidant activity, which might be achieved by inhibiting the mitochondria-dependent apoptotic pathway. The neuroprotective effect of EPA-enriched PL was also verified in vivo test: the EPA-enriched PL administration prevented the development of learning and memory impairments in SAMP8 mice. Our results indicated that EPA-enriched PL could offer an efficient and novel strategy to explore novel drugs or functional food for neuronprotection and cognitive improvement.
Assuntos
Cucumaria/química , Ácido Eicosapentaenoico/farmacologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeos/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Cucumaria/metabolismo , Peróxido de Hidrogênio/toxicidade , Aprendizagem/fisiologia , Memória/fisiologia , Camundongos , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/metabolismo , Células PC12/efeitos dos fármacos , Células PC12/metabolismo , Ratos , terc-Butil Hidroperóxido/metabolismo , terc-Butil Hidroperóxido/toxicidadeRESUMO
Three polysaccharides, AAP, AVAP I, and AVAP II, were isolated from abalone Haliotis discus hannai Ino. The polysaccharides' compositions were analysed, and their effects on HepG2 cell proliferation were assessed. AVAP I had a greater growth-stimulatory effect than AAP or AVAP II. The oligosaccharide of AVAP I (Oli-AVAP I) exhibited the same growth effects, but rhamnose, the primary monosaccharide of AVAP I and Oli-AVAP I, did not exhibit this activity. Moreover, AVAP I dramatically reduced the mRNA levels of CDK6 and Cyclin E1 but significantly increased Cyclin B1, CDK1 and Cyclin F. Interestingly, AVAP I remained able to induce cell proliferation in a low serum concentration medium. AVAP I could therefore promote HepG2 cell proliferation by regulating gene expression and accelerating the cell cycle process. AVAP I may be useful as a serum supplement for stimulating the proliferation of mammalian cells. Our results offer a comprehensive method for utilising the abalone viscera, which is usually discarded as waste.
Assuntos
Proliferação de Células/efeitos dos fármacos , Gastrópodes/química , Polissacarídeos/farmacologia , Animais , Proteína Quinase CDC2/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quinase 6 Dependente de Ciclina/metabolismo , Ciclinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Células Hep G2 , HumanosRESUMO
Neurodegenerative disorders are a class of diseases that have been linked to apoptosis induced by elevated levels of reactive oxygen species (ROS). The present study was undertaken to explore the effect of sea cucumber cerebrosides (SCC) and starfish cerebrosides (SFC) on the hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in PC12 cells. Cell viability, the leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were determined for their effect on oxidative damage. Quantitative real-time PCR was investigated to analyze the mitochondrial genes expression. These results showed that both SCC and SFC decreased the leakage of LDH and intracellular ROS in a dose-dependent manner. SCC and SFC could also increase the SOD activity compared with the model groups. In H2O2 damage model, 400 µg/mL SCC increased the SOD activity by 79%, which was stronger than SFC. The results demonstrated that SCC and SFC exhibited the protective effects, which may be related to their antioxidant action. In addition, SCC and SFC dramatically increased the gene expression of B-cell lymphoma 2 (Bcl-2) but significantly decreased the gene expression of Cytochrome c, caspase9 and caspase3 compared with H2O2 or t-BHP treatment. These results suggested that SCC and SFC might exert a protective function against oxidative damage by inhibiting mitochondria-mediated apoptosis pathway. In conclusion, SCC and SFC played an important protective role in H2O2 and t-BHP-induced damage of PC12 cells, suggesting that the SCC and SFC may be a potential therapeutic agent against nervous system oxidative damage.