RESUMEN
Ganoderma lucidum (Curtis) P. Karst.(G. lucidum) is a kind of fungi, which also a traditional Chinese medicine used for "wisdom growth" in China. Triterpenoids from G. lucidum (GLTs) are one of the main active ingredients. Based on the strategy of early intervention on Alzheimer's disease (AD) and the inextricable association between disordered gut microbiota and metabolites with AD, this study aimed to explore the mechanisms of GLTs in the protection against AD via microbiota-gut-brain axis with the aid of network pharmacology. In this study, LC-MS/MS was used to identify the main active ingredients of GLTs. Network pharmacology was used to predict the potential target and validated with Caco-2 cell model. D-galactose was used to induce the slow-onset AD on rats. Metabolomics methods basing on GC-MS combined with 16S rRNA sequencing technology was used to carry out microbiota-gut-metabolomics analysis in order to reveal the potential mechanisms of GLTs in the protection of AD. As results, GLTs showed a protection against AD effect on rats by intervening administration. The mechanisms were inextricably linked to GLTs interference with the balance of gut microbiota and metabolites. The main fecal metabolites involved were short-chain fatty acids and aromatic amino acid metabolites.
RESUMEN
In this study, an enzyme-assisted microwave extraction process was obtained by response surface method of polysaccharide from roots of Rubus crataegifolius Bunge. The optimized extraction process was as follow: enzyme dosage 2 %, enzymatic time was 3.6 h, enzymatic pH 4.9, and microwave time 4.7 min, with the extraction yield of 9.07 %. Four homogeneous polysaccharides (RCP-1, RCP-3, RCP-4 and RCP-5) were purified through column chromatography. Four polysaccharides have the relative higher molecular weights of 1.70 × 106 Da, 5.56 × 106 Da, 4.97 × 106 Da, and 9.80 × 106 Da and mainly consisted of GluN, GluA, Glu, Gal and Arab. FT-IR and NMR spectral analysis confirmed that the purified polysaccharides were polypyranose containing α- and ß-glycosidic bonds. RCP - 1 has a relative high crystallinity. Four purified polysaccharides contained triple helical conformations, and have good antioxidant activities. Among the purified polysaccharides, RCP - 1 was found to reduce the oxidative cell damage induced by H2O2 through increasing of cell viability, inhibition of AST and ALT levels, ROS production and cell apoptosis, increasing of the activities of antioxidative enzymes, as well as reduction of MDA content. Our findings would provide a foundation for purified polysaccharides efficient extraction and demonstrated that the polysaccharides from R. crataegifolius roots could be a promising hepatoprotective agent.
Asunto(s)
Antioxidantes , Peróxido de Hidrógeno , Microondas , Raíces de Plantas , Polisacáridos , Rubus , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Humanos , Raíces de Plantas/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Células Hep G2 , Rubus/química , Estrés Oxidativo/efectos de los fármacos , Peso Molecular , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
This study aims to optimize the processing of Myristica fragrans Houtt. by talcum powder simmering using single-factor and orthogonal experimental methods, and the overall desirability values of dehydrodiisoeugenol and essential oils content were selected as indicators of the process. The new process reduced the total content of the three toxic components, namely myristicin, safrole and elemicin, from 1.91% to 1.16% before and after processing, indicating that the toxic components were reduced by 39%. The IC50 of the essential oils before and after processing were 1.002 ± 0.05 and 0.233 ± 0.05 mg/mL for DPPH scavenging activity and 0.132 ± 0.04 and 0.057 ± 0.05 mg/mL for ABTS scavenging activity, respectively. And the absorbance of the antioxidant activity against Ferric reducing power ranged from 0.213 to 0.709 and from 0.225 to 0.755, respectively. The minimum inhibitory concentration for Staphylococcus aureus, Bacillus pumilus and Escherichia coli were all lower after processing than before. The antioxidant activity and antibacterial activity of the essential oils after processing were better than before. The results of the survival of zebrafish embryos at different concentrations of essential oils at 0-168 h post fertilisation were higher after processing than before. These findings suggest that processing plays the role of reducing toxicity and increasing beneficial effects. They provide a scientific basis not only for the processing of M. fragrans, but also for the processing of other foods.
Asunto(s)
Myristica , Aceites Volátiles , Animales , Antioxidantes/farmacología , Cromatografía de Gases y Espectrometría de Masas/métodos , Pez Cebra , Semillas , Aceites Volátiles/farmacologíaRESUMEN
Ganoderic acid A (GAA) is a kind of lanostane-type triterpenoid isolated from Ganoderma lucidum. Imbalance of the Th17/Tregs axis exists in the progress of neuroinflammation of Alzheimer's disease (AD). In this study, the alleviating neuroinflammatory effect of GAA on d-galactose mice was studied from the aspect of regulating the imbalance of the Th17/Tregs axis. The Morris water maze test was used to evaluate the cognitive ability of AD mice. Flow cytometry was used to detect the percentages of IL-17A, IL-17F, IL-21, IL-22, and CD4+CD25+Foxp3+ in peripheral blood. Transmission electron microscopy was used to assess the cerebral mitochondrial ultrastructure. Metabolomic analysis based on gas chromatography-mass spectrometry was used to evaluate the mitochondrial dysfunction metabolism. Western blot analysis was used to detect the protein expressions of cytokines secreted by Th17 cells and Treg cells in the brain. As the results show, GAA has an alleviating neuroinflammatory effect on AD mice via regulating the imbalance of the Th17/Tregs axis. The potential mechanism was related to inhibition of the JAK/STAT signaling pathway induced by Th17 cells and enhancement of the mitochondrial oxidative phosphorylation by regulating Treg cells, thereby improving mitochondrial dysfunction of AD mice.
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Enfermedad de Alzheimer , Células Th17 , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Animales , Ácidos Heptanoicos , Lanosterol/análogos & derivados , RatonesRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicinal, Bidens bipinnata L. has been used to treat many diseases with a long history in China. The anti-diabetic effects of extract from B. bipinnata have been demonstrated in the previous reports. AIM OF THE STUDY: The protective effects of flavonoids-rich extract from B. bipinnata (BBTF) on cell damage induced by H2O2 in pancreatic ß cell and its potential mechanisms were evaluated. MATERIALS AND METHODS: MTT, ROS production, nuclear staining and flow cytometry assays were adopted to determine the effects of BBTF on cell viability, production of ROS and cell apoptosis in H2O2-treated INS-1 cell. Cell apoptosis-related proteins expressions were detected by Western blot assay. RESULTS: Pre-treatment of BBTF could significantly increase INS-1 cell viability, inhibit the production of intracellular ROS and reduced the characteristic features of cell apoptosis induced by H2O2 in INS-1 cells. The studies of the underlying mechanism showed that BBTF could regulate Bax and Bcl-2 proteins expressions, suppress the phosphorylation of JNK, ERK and p38, as well as down-regulate Fas and FasL proteins expressions induced by H2O2. The expressions of caspase-8, caspase-9 and caspase-3 were therefore decreased. CONCLUSION: The results indicated that flavonoids-rich extract from B. bipinnata could be a natural agent in diabetic prevention and therapy.
Asunto(s)
Apoptosis/efectos de los fármacos , Bidens/química , Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , Células Secretoras de Insulina/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Caspasas/metabolismo , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/aislamiento & purificación , Proteína Ligando Fas/metabolismo , Flavonoides/aislamiento & purificación , Peróxido de Hidrógeno/toxicidad , Células Secretoras de Insulina/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Receptor fas/metabolismoRESUMEN
Gentianae Radix et Rhizoma is a medical plant that is widely cultivated in China, North Korea, Japan, and Russia, and gentiopicroside is one of its major active compounds. In this study, the hepatoprotective activity of gentiopicroside on rats with alcoholic liver damage (ALD) was evaluated using the transaminase and blood lipid levels and antioxidant capacity. The potential mechanism of hepatoprotective effect of gentiopicroside was evaluated by mitochondrial function detection, gas chromatography-mass spectrometry (GC-MS) metabolomic analysis, and anti-apoptosis analysis. Results showed that the gentiopicroside exhibited good hepatoprotective activity on rats with ALD by decreasing the transaminase levels, regulating the blood lipid levels, and increasing the antioxidant capacity. The potential mechanisms were related to regulating mitochondrial dysfunction by recovering mitochondrial membrane potential level, adenosine triphosphate concentration, activities of key enzymes in tricarboxylic acid cycle, and activities of complex I-V, regulating micromolecular metabolism and anti-apoptosis. These findings supported the further exploration of Gentianae Radix et Rhizoma as effective phytotherapy to prevent and treat ALD.
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Medicamentos Herbarios Chinos/química , Glucósidos Iridoides/química , Hepatopatías Alcohólicas/tratamiento farmacológico , Hígado/patología , Mitocondrias/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The aim of this study was to investigate the performance of ethanolic extract from Morus alba L. leaves (MLEE) in preserving chilled pork under retail conditions. The four treatments were 5 mg/mL sodium benzoate solution (SB), 1 mg/mL MLEE solution (high-concentration MLEE; HM), 0.5 mg/mL MLEE solution (low-concentration MLEE; LM), and 0 mg/mL MLEE solution (C). The quality characteristics, pH, thiobarbituric acid reactive substances values, metmyoglobin, total volatile basic nitrogen, and number of microbes of MLEE-treated chilled pork stored at 4 °C for 9 days were consistent with those obtained by the SB treatment and lower than those obtained by the C treatment. Sensory analyses showed that treatment of pork with MLEE did not have a negative impact on its sensory characteristics. MLEE can extend the shelf life of chilled pork from 3 days to 6 days (9 days) in first-class (second-class) fresh meat. Results suggest that MLEE could be a candidate resource in the preservation of chilled pork.
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Conservantes de Alimentos/farmacología , Morus/química , Extractos Vegetales/farmacología , Carne de Cerdo/análisis , Animales , Humanos , Metamioglobina/análisis , Odorantes , Hojas de la Planta/química , Carne de Cerdo/microbiología , Benzoato de Sodio/farmacología , Porcinos , Gusto , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
The extract of Bidens bipinnata L. exhibited wide spectrum of bioactivities owing to the presence of flavonoids. In this study, a purification process was developed to enrich the flavonoid-rich extract from B. bipinnata L. (BBTF). AB-8 resin was selected for the purification of total flavonoids. Response surface methodology coupled with Box-Behnken design was employed to optimize the purification condition; it was optimized as pH 5.1, volume of ethanol 80 ml, flow rate of ethanol 1.8 bed volume per hour (BV/h) and concentration of ethanol 76.0%. The total flavonoid content of BBTF was 56.48% under the optimal conditions. The identification of flavonoids in BBTF was conducted using UHPLC-ESI-Q-TOF MS. A total of 14 compounds, including 12 flavonoids, were identified in BBTF. Finally, the in vitro antioxidant activities, α-glucosidase and α-amylase inhibitory activities of BBTF were comprehensively analyzed by an analytical hierarchy process. The results indicated that it exhibited higher bioactivities than the crude extract. These findings suggested that the optimized process could significantly enhance the purity of flavonoids and their bioactivities. This study showed a comprehensive analysis of a total flavonoid extract of B. bipinnata L. for the first time, which could provide a useful approach for its purification process and quality control as well as bioactivities.
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Bidens/química , Cromatografía Líquida de Alta Presión/métodos , Flavonoides , Espectrometría de Masas en Tándem/métodos , Flavonoides/análisis , Flavonoides/química , Flavonoides/aislamiento & purificación , Modelos Estadísticos , Extractos Vegetales/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
To explore the flavonoids from Morus alba L. leaves (MLF), the process of extracting was optimized by a response surface methodology and the antimicrobial and antioxidant activities were evaluated in vitro. The yield of flavonoids reached 50.52 mg g-1 under the optimized extraction conditions (i.e., extraction temperature, 70.85 °C; solvent concentration, 39.30%; extraction time, 120.18 min; and liquid/solid ratio, 34.60:1). The total flavonoids were extracted in organic solvents with various polarities, including petroleum ether (MLFp), ethyl acetate (MLFe), and n-butanol (MLFb). In vitro, the four MLF samples exhibited good antioxidant activities for scavenging of 2, 2'-azinobis-(3-ethylbenz-thiazoline-6-sulphonate) radical, 1, 1-diphenyl-2-picrylhydrazyl radical, and total reducing power. Regarding antimicrobial efficacy, the MLF samples suppressed the development of Staphylococcus aureus, Bacillus subtilis, and Bacillus pumilus. The MLF samples inhibited α-amylase activity to a certain extent. The analytical hierarchy process (AHP) was used to evaluate comprehensively the bioactivities of the MLF samples. The AHP results revealed that the bioactivity comprehensive score (78.83 µg mL-1) of MLFe was optimal among the four MLF samples. Morus alba L. leaves also exhibited non-hemolytic properties. All bioactivities suggested the potential of MLFe as a candidate resource in the food and drug industries.
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Antibacterianos/farmacología , Antioxidantes/farmacología , Flavonoides/farmacología , Morus/química , alfa-Amilasas/antagonistas & inhibidores , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Bacillus/efectos de los fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Flavonoides/química , Flavonoides/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Hojas de la Planta/química , Staphylococcus aureus/efectos de los fármacosRESUMEN
This study was performed to evaluate the cognitive-enhancing effect Flammulina velutipes polysaccharides (FVP) by compatibilizing with ginsenosides on D-galactose-induced Alzheimer's disease (AD) rats. Results of the Morris water maze test suggested that the cognitive ability of AD rats was significantly elevated after combined treatment with FVP and ginsenosides. Moreover, the anti-oxidant effect was also elevated as reflected by the increased levels of superoxide dismutase, catalase, and glutathione peroxidase and decreased levels of malondialdehyde in the combination group. Terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labeling (TUNEL), immunohistochemistry, and Western blot analysis showed that the TUNEL apoptosis cell rate, Bax, cytochrome C, caspase-3, caspase-9, and apoptosis-inducing factor expression levels were obviously decreased, and the Bcl-2 expression levels were obviously increased in the hippocampi of rats treated with FVP and ginsenosides. The results suggested that the beneficial effect of FVP against AD can be significantly elevated by compatibilizing with ginsenosides. These findings provide scientific evidence supporting the use of FVP as a safe and effective drug to prevent and treat AD.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/fisiopatología , Cognición , Flammulina/química , Ginsenósidos/uso terapéutico , Polisacáridos/uso terapéutico , Enfermedad de Alzheimer/patología , Animales , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Catalasa/metabolismo , Cognición/efectos de los fármacos , Ginsenósidos/farmacología , Glutatión Peroxidasa/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Etiquetado Corte-Fin in Situ , Masculino , Malondialdehído/sangre , Aprendizaje por Laberinto/efectos de los fármacos , Polisacáridos/farmacología , Ratas Wistar , Superóxido Dismutasa/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Oviductus ranae (OR) is a traditional Chinese medicine, which was first recorded in the Compendium of Materia Medica in the Ming Dynasty. OR contains high amounts of proteins and elicits therapeutic effects on neurasthenia, insomnia, and respiratory symptoms, which are related to oxidative stress and immunodeficiency. This study aimed to obtain the potential of OR for the development of functional food possessing antioxidant and immune-enhancement functions in the same dose. In antioxidant evaluation, OR can significantly decrease malondialdehyde and protein carbonyls (P < 0.05, P < 0.01) and significantly increase total superoxide dismutase and glutathione in a dose-dependent manner (P< 0.05, P < 0.01) against ethanol-induced oxidative stress in mice at 0.1, 1.0, and 3.0 g/kg BW. In immunomodulatory evaluation, OR could significantly enhance the phagocytosis of liver macrophages (P < 0.05, P < 0.01), delayed-type hypersensitivity response (P < 0.05, P < 0.01), hemolytic activity (P < 0.05), antibody-producing cells (P < 0.05), and natural killer cell activity (P < 0.05) in the same dose range described in antioxidant evaluation compared with those in the normal control. OR slightly influenced lymphocyte proliferation, peritoneal macrophage phagocytosis, and immune organ indices in mice. Thus, 3.0 g/kg BW OR showed potential for the development of functional food with antioxidant and immune-enhancement activities
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Animales , Masculino , Ratones , Medicina Tradicional China/instrumentación , Antioxidantes/análisis , Alimentos Funcionales/análisis , InmunomodulaciónRESUMEN
In the present study, 16 marine-derived fungi were isolated from four types of marine materials including float, algae, animals and drift woods along with the coast of Jeju Island, Korea and evaluated for anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 24.7 cells. The broth and mycelium extracts from the 16 fungi were prepared and the broth extract (BE) of Eurotium amstelodami (015-2) inhibited nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells without cytotoxicity. By further bioassay-guided isolation, three compounds including asperflavin, neoechinulin A and preechinulin were successfully isolated from the BE of E. amstelodami. It was revealed that asperflavin showed no cytotoxicity up to 200 µM and significantly inhibited LPS-induced NO and PGE2 production in a dose-dependent manner. In the western blot results, asperflavin suppressed only inducible NOS (iNOS), but COX-2 were slightly down-regulated. Asperflavin was also observed to inhibit the production of pro-inflammatory cytokines including TNF-α, IL-1ß, and IL-6. In conclusion, this study reports a potential use of asperflavin isolated from a marine fungus, E. amstelodami as an anti-inflammatory agent via suppression of iNOS and pro-inflammatory cytokines as well as no cytotoxicity.
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Antracenos/farmacología , Antiinflamatorios/farmacología , Eurotium/química , Animales , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
The aim of this study was to evaluate the safety and potential of PCS as the anti-fatigue functional food. PCS was prepared by water extracting-alcohol precipitating method, and its chemical compositions of monosaccharide were analyzed. Then, acute toxicity and anti-fatigue activity of PCS were evaluated. PCS is composed of Rha, Arab, Xyl, Man, Glu, and Gal, its molar ratio is 0.17: 0.30: 0.26: 0.35: 1.00: 0.57. No mortality and general symptoms of toxicity were observed in the PCS treated mice (7.5, 15, and 20g/kg body weight), the body weight and food consumption were not significantly changed compared with the normal control group. The relative weights of main organ, and biochemical indicators also did not markedly change. PCS can significantly prolong the duration of the swimming time to exhaustion in mice, decrease BUN, LA levels, increase LDH activities, and the contents of HG in the PCS treated mice. The dose of 400mg/kg body weight is the optimal dose for anti-fatigue activity both in male and female mice. In conclusion, PCS is a promising traditional natural-based therapeutic remedy for relieving fatigue with high safety.
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Fatiga/tratamiento farmacológico , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Seda/farmacología , Zea mays/química , Animales , Peso Corporal/efectos de los fármacos , Femenino , Alimentos Funcionales , Masculino , Ratones , Natación/fisiologíaRESUMEN
This study was conducted to evaluate the regulating dyslipidemia effect of polysaccharides from Pleurotus ostreatus (POP) on fat-emulsion-induced hyperlipidemia rats. A plasma metabonomics method based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied to analyze the holistic mechanism of POP in a hyperlipidemia rat model. Multivariate statistical approaches such as principal component analysis and orthogonal projection to latent structure square-discriminant analysis revealed distinctions among the control, hyperlipidemia model, and POP groups.The results demonstrated that POP had an effect on regulating dyslipidemia. The mechanism of POP on regulating dyslipidemia was partially relevant with correcting the abnormal levels of fifteen potential biomarkers towards their normal levels. These biomarkers were belong to glycerophospholipids, fatty acids, prenol lipids, sphingolipids metabolism.
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Grasas de la Dieta/efectos adversos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/etiología , Pleurotus/química , Polisacáridos/farmacología , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Emulsiones , Hiperlipidemias/metabolismo , Hiperlipidemias/patología , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Metabolómica , Polisacáridos/uso terapéutico , Ratas , Ratas WistarRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Oviductus ranae (OR) is a traditional animal-based Chinese medicine, which has been listed in the Chinese Pharmacopoeia since 1985 edition. Although its medicinal application has been widely acknowledged, there is little available information on its potential toxicity. AIM OF THE STUDY: The aim of this study was to investigate the acute, sub-acute, and genetic toxicities of OR. MATERIALS AND METHODS: In acute toxicity evaluation, OR was administered orally to mice at doses of 2.5, 5.0, 10.0, and 20.0g/kg BW for one time. Mortality, clinical signs, and body weight were observed for 14 days after treatment. In sub-acute toxicity evaluation, OR was administered orally to rats once a day for 28 consecutive days at doses of 1.75, 3.50, and 7.00g/kg BW. Animals were observed for general behaviors, mortality, food intake, and body weight changes. At the end of treatment, relative organ weight, pathology, hematological and biochemical parameters were monitored. In genotoxicity evaluation, bacterial reverse mutation assay (Ames test) was performed by treating OR with four different Salmonella typhimurium strains at doses of 8, 40, 200, 1000, and 5000µg/plate without or with S-9 mix, respectively. The genotoxicity of OR was also evaluated by micronucleus and sperm malformation assays in mice at doses of 2.5, 5.0, and 10.0g/kg BW, respectively. RESULTS: The results of acute toxicity study showed that the LD50 value of OR is higher than 20.0g/kg BW in mice. Death and abnormal clinical symptoms were not found during the period of experiment. In sub-acute toxicity, we found that the no-observed-adverse-effect levels (NOAEL) of OR in rats is up to 7.00g/kg BW. No statistically significant or toxicologically relevant defferences in body weight, food intake, relative organ weight, pathology, hematological and biochemical parameters were observed, when compared with control group. Results of Ames test, micronucleus and sperm malformation assays indicated that OR has no mutagenicity in vitro at a limited dose of 5000µg/plate, and dose not induce micronuclei and sperm malformation in mice at the dose of up to 10.0g/kg BW in mice. CONCLUSIONS: In conclusion, OR is a tranditional Chinese medicine with high safety.
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Materia Medica/toxicidad , Medicina Tradicional China/efectos adversos , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Femenino , Dosificación Letal Mediana , Masculino , Materia Medica/administración & dosificación , Ratones , Ratones Endogámicos ICR , Pruebas de Mutagenicidad , Nivel sin Efectos Adversos Observados , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad SubcrónicaRESUMEN
Pseudoconvex optimization problem, as an important nonconvex optimization problem, plays an important role in scientific and engineering applications. In this paper, a recurrent one-layer neural network is proposed for solving the pseudoconvex optimization problem with equality and inequality constraints. It is proved that from any initial state, the state of the proposed neural network reaches the feasible region in finite time and stays there thereafter. It is also proved that the state of the proposed neural network is convergent to an optimal solution of the related problem. Compared with the related existing recurrent neural networks for the pseudoconvex optimization problems, the proposed neural network in this paper does not need the penalty parameters and has a better convergence. Meanwhile, the proposed neural network is used to solve three nonsmooth optimization problems, and we make some detailed comparisons with the known related conclusions. In the end, some numerical examples are provided to illustrate the effectiveness of the performance of the proposed neural network.
Asunto(s)
Redes Neurales de la Computación , Algoritmos , Dinámicas no LinealesRESUMEN
This study was conducted to evaluate the effects of polysaccharides extracted from Pleurotus ostreatus (POP) on d-galactose and AlCl3-induced cognitive impairments. A behavioral test suggested that POP significantly decreased escape latency and increased crossing parameters of platform quadrant in a Morris water maze test. Furthermore, POP decreased error numbers and increased passive avoidance latency in a step-down test. Biochemical examinations revealed that POP significantly elevated superoxide dismutase, glutathione peroxidase, and catalase activities; and reduced malondialdehyde levels and acetylcholinesterase activity. Moreover, POP could decrease amyloid ß peptide formation and tau phosphorylation by elevating the expression of protein phosphatase 2A as well as by reducing the expression of amyloid precursor protein (APP), ß-site APP clearing enzyme1, and glycogen synthase kinase 3beta. These findings provide scientific evidence to support the exploitation of POP as a safe and effective drug to prevent and treat Alzheimer's disease.
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Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/tratamiento farmacológico , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/tratamiento farmacológico , Pleurotus/química , Polisacáridos/uso terapéutico , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/sangre , Animales , Conducta Animal/efectos de los fármacos , Catalasa/metabolismo , Trastornos del Conocimiento/sangre , Modelos Animales de Enfermedad , Glutatión Peroxidasa/metabolismo , Hipocampo/enzimología , Hipocampo/patología , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Malondialdehído/sangre , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Proteínas del Tejido Nervioso/metabolismo , Polisacáridos/farmacología , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). There is no in vivo evidence that validates this finding, and it is unclear whether FAM20C is the only kinase for SIBLINGs. We extracted bone noncollagenous proteins (NCPs) from Fam20C-knockout (KO) mice and analyzed the phosphorylation levels. The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. The NCP phosphorylation level in the KO mice was lower than that in the wild-type (WT). On the native gel, the SIBLINGs from KO mice showed a lower migration rate (Mr) than those from the WT. Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. Phospho-Tyrs and phospho-Thrs in the SIBLINGs did not appear to be associated with FAM20C. Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone.
Asunto(s)
Huesos/metabolismo , Calcificación Fisiológica/fisiología , Proteínas de Unión al Calcio/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Integrinas/metabolismo , Osteopontina/metabolismo , Animales , Bovinos , Electroforesis en Gel de Poliacrilamida/métodos , Ratones Noqueados , Endopeptidasa Neutra Reguladora de Fosfato PHEX/metabolismoRESUMEN
This study aimed to assess the acute toxicity and safety of flavonoid-rich extract from Maydis stigma (FMS) in mice. The in vitro antioxidant activity of FMS was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethyl-benzthiazoline-6-sulphonate) (ABTS) scavenging assays. Furthermore, the in vivo antioxidant of FMS against ethanol-induced oxidative damage in mice was determined by analysis of the serum total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, liver tissue glutathione (GSH) content, and protein carbonyl (PC) content in liver tissue. The oral administration of FMS at doses of 30 g/kg did not cause death in mice, and there were no significant biologically adverse effects in mice. These results indicated that the median lethal dose (LD50) is higher than this dose. The IC50 values of FMS for the DPPH and ABTS scavenging activity were 50.73 and 0.23 mg/mL, respectively. Meanwhile, FMS could significantly enhance T-SOD activity, reduce MDA content in the serum, increase GSH content, and decrease PC content in the liver tissue at the tested doses (25, 50, 100, 200 mg/kg·day). These results indicate that FMS can be generally regarded as safe and used potentially as a bioactive source of natural antioxidants.
Asunto(s)
Antioxidantes/farmacología , Flavonoides/farmacología , Hígado/efectos de los fármacos , Zea mays/química , Animales , Antioxidantes/aislamiento & purificación , Benzotiazoles/antagonistas & inhibidores , Compuestos de Bifenilo/antagonistas & inhibidores , Femenino , Flavonoides/aislamiento & purificación , Glutatión/metabolismo , Dosificación Letal Mediana , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Picratos/antagonistas & inhibidores , Extractos Vegetales/química , Carbonilación Proteica/efectos de los fármacos , Ácidos Sulfónicos/antagonistas & inhibidores , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: To evaluate the estrogenic efficacy of Renshen (Radix Ginseng) (GS) on reproductive target tissues in immature mice. METHODS: One hundred and ten female immature Kunming (KM) mice, 21-day-old, were randomly assigned to eleven groups, 10 for each; one served as control group treated with 0.154 mg/kg estradiol valerate (EV, n = 10), the rest were treated respectively with GS intragastrically at a daily dose of 0.5, 1.0, 1.5, 3.0, 6.0, 12.0, 18.0, 24.0 and 30.0 g/kg (n = 10 in per group) for 7 days. The estrous cycle, uterine weight, hormone levels in circulation and histomorphology changes of uterus and vagina were scrupulously examined. The estrogen receptor (ER) α and ERß expressions in the uterus and vagina were detected by immunohistochemistry and western blotting. RESULTS: Treatment with GS at the dose of 12.0, 18.0 and 24.0 g/kg resulted significant estrogenic activity in the mice, as indicated by advanced and prolonged estrous stage and increased uterine weight (all P < 0.05). GS treatment substantially promoted development of reproductive tisue by thickening the uterine endometrium and increasing vaginal epithelial layers. In addition, treatment with GS induced significant up-regulation of ERα and ERß expressions in reproductive tissues, and ERα up-regulation was stronger than that of ERß. GS could raise levels of circulating estrogen, simultaneously decrease levels of luteinizing hormone and follicle-stimulating hormone (all P < 0.001) compared with the control group. CONCLUSION: Our findings suggest that GS had estrogenic effect on reproductive tissues in immature mice by stimulating biosynthesis of estrogen in circulation and up-regulating ERs.