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ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry leaf (Folium Mori) is a dried leaf of the dicotyledonous mulberry tree and is a homologous food and medicine. Treating insomnia with it is a common practice in traditional Chinese medicine. But still, its potential sleep-improving mechanism remains to be elucidated. AIM OF REVIEW: Potential bioactive components and mechanisms of the sleep-improving effect of purified flavone from mulberry leaves (MLF) were explored through in vivo experiments, network pharmacology analysis, and molecular experimental validation. MATERIALS AND METHODS: The mice model was established by pentobarbital sodium induction to evaluate the sleep-improving effect of MLF. The MLF's chemical composition was identified through a liquid chromatograph quadrupole time-of-flight mass spectrometer (Q-TOF LC/MS) to elucidate its sleep-improving active ingredient. At last, the underlying mechanism of MLF's sleep-improving effect was elucidated through neurotransmitter detection (ELISA), network pharmacology analysis, and molecular experimental validation (quantitative real-time PCR and western blotting). RESULTS: MLF could dramatically reduce sleep latency by 35%, prolong sleep duration by 123%, and increase the sleep rate of mice through increasing γ-aminobutyric acid (GABA) and serotonin (5-HT) release in serum, hypothalamus, and hippocampus. Q-TOF LC/MS identified 17 flavonoid components in MLF. Network pharmacological analysis suggested that the key sleep-improving active ingredients in MLF might be quercetin, kaempferol, morin, and delphinidin. The key path for MLF to improve sleep might be the tryptophan metabolism and neuroactive ligand-receptor interaction, and the key targets might be gamma-aminobutyric acid type A receptor subunit alpha2 Gene (GABRA2) and serotonin 1A (5-HT1A) receptors. CONCLUSIONS: MLF has shown significant sleep-improving effects in mice and may take effect through regulating the GABA and 5-HT receptors.
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Prolonged or high-dose exposure to ionizing radiation (IR) can cause damage to normal tissues of the body. Therefore, it is imperative to find effective radiation protective agents to mitigate IR-induced damage. This study evaluated the effects of sodium alginate (SA) on the radiation protection and modulatory effects of gut microorganisms using a 60Coγ-induced damage model in mice. Results showed that SA could reduce the damage of hematopoietic system; and alleviate the oxidative damage in irradiated mice by inhibiting the content of malondialdehyde (MDA) and increasing the activities of superoxide dismutase (SOD) and glutathione (GSH) in serum, spleen, jejunum and liver. Moreover, SA treatment ameliorated IR-induced small intestine lesions and alleviated liver injury. This was consistent with decreased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α), and increased levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2) after SA treatment. Furthermore, SA treatment reversed IR-induced gut dysbiosis, elevated the Firmicutes/Bacteroidetes ratio, increased the beneficial bacteria and reduced the pathogenic bacteria in the small intestine. In conclusion, the present study demonstrated that SA exerted good radioprotective effect by improving hematopoietic system, alleviating oxidative stress, attenuating liver injury and inflammatory response, and modulating the intestinal microbiota in irradiated mice.
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As insufficient sleep has become a widespread concern in modern society, potential sleep-improving effect of mulberry (Morus alba L.) leaf ethanol extract (MLE) and the related mechanism were investigated in the present study. According to the results, MLE could significantly shorten sleep latency by 33 %, extend sleep duration by 56 % and increase sleep ratio of mice through increasing 5-HT and GABA release in serum, hypothalamus and hippocampus. Metabonomic analysis showed that phenylalanine metabolism, arginine and proline metabolism might be the potential pathways of MLE to improve sleep. Network pharmacological and LC-MS analysis suggested that the key sleep-improving active ingredients in MLE might be luteolin, kaempferol, naringenin, morin, stigmasterol and ß-sitosterol. Further molecular docking and qRT-PCR results demonstrated that the key targets for MLE to improve sleep might be MAOA, GABRA1 and GABRA2. In conclusion, MLE showed outstanding sleep-improving effect and great potential for the application as novel sleep-improving functional food.
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PURPOSE: Novel uses of genome sequencing (GS) present an opportunity for return of results to healthy individuals, prompting the need for scalable genetic counseling strategies. We evaluate the effectiveness of a genomic counseling model (GCM) and explore preferences for GS findings in the general population. METHODS: Participants (N = 466) completed GS and our GCM (digital genomics platform and group-based webinar) and indicated results preferences. Surveys were administered before (T0) and after (T1) GCM. Change in knowledge and decisional conflict (DC) were evaluated using paired-sample T and Wilcoxon tests. Factors influencing knowledge and results preferences were evaluated using linear and logistic regression models. RESULTS: Participants were 56% female, 58% white, and 53% ≥40 years of age. Mean knowledge scores increased (Limitations: 3.73 to 5.63; Benefits: 4.34 to 5.48, P < .0001), and DC decreased (-21.9, P < .0001) at T1 versus T0. Eighty-six percent of participants wished to learn all GS findings at T1 vs 78% at T0 (P < .0001). Older age, negative/mixed attitudes toward genetics and greater DC were associated with change in preferences after intervention. CONCLUSION: In a population-based cohort undergoing GS interested in learning GS findings, our GCM increased knowledge and reduced DC, illustrating the GCM's potential effectiveness for GS counseling in the general population.
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Isorhamnetin has recently been found to exhibit a remarkable anti-motion sickness effect, yet the underlying mechanism is still unclear. Herein, network pharmacology was employed to conduct a preliminary analysis on the possible biological processes involved. Results showed that common targets were localized in membranes, mitochondria, and glutamatergic synapses. In particular, protein phosphorylation, protein serine/threonine/tyrosinase activity and signal transduction might play a role in isorhamnetin's anti-motion sickness effect. Thus, mice phosphoproteomics analysis was further performed to explore the phosphorylated protein changes in the motion sickness process. Results showed that differentially phosphorylated proteins have an effect on postsynaptic density, glutamatergic synapses and other sites and are involved in various neurodegenerative disease pathways, endocytic pathways, cAMP signaling pathways and MAPK signaling pathways. Two key differentially phosphorylated proteins in glutamatergic synapses, namely, DLGAP and EPS8, might play key roles in isorhamnetin's anti-motion sickness process. The final molecular experimental verification results from qRT-PCR and western blot analyses indicated that isorhamnetin firstly regulates glutamatergic synapses and then reduces the excitability of the vestibular nucleus through inhibiting the NMDAR1/CaMKII/CREB signaling pathway, ultimately alleviating a series of symptoms of motion sickness in mice. The findings of this study provide valuable insights and a useful theoretical basis for the application of isorhamnetin as a new anti-motion sickness food ingredient.
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Enjoo devido ao Movimento , Proteômica , Quercetina , Animais , Quercetina/análogos & derivados , Quercetina/farmacologia , Camundongos , Enjoo devido ao Movimento/tratamento farmacológico , Masculino , Transdução de Sinais/efeitos dos fármacos , Fosforilação , Farmacologia em RedeRESUMO
Snail mucus is rich in proteins and polysaccharides, which has been proved to promote wound healing in mice in our previous research. The aim of this study was to investigate the effective component in snail mucus that can exert the wound healing potential and its structural characterization. Here, the glycoprotein from the snail mucus (SM1S) was obtained by DEAE-Sepharose Fast Flow and Sephacryl S-300 columns. The structural characteristics of SM1S were investigated via chromatographic techniques, periodic acid oxidation, FT-IR spectroscopy and NMR spectroscopy. Results showed that SM1S was a glycoprotein with a molecular weight of 3.8 kDa (83.23 %), consists of mannose, glucuronic acid, glucose, galactose, xylose, arabinose, fucose at a ratio of 13.180:4.875:1043.173:7.552:1:3.501:2.058. In addition, the periodic acid oxidation and NMR analysis showed that SM1S contained 1,6-glycosidic bonds, and might also contain 1 â 4 and 1 â 2 glycosidic or 1 â 3 glycosidic bonds. Furthermore, the migration experiment of human skin fibroblasts in vitro suggested that SM1S had a good effect to accelerate the scratch healing of cells. This study suggested that SM1S may be a prospective candidate as a natural wound dressing for the development of snail mucus products.
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Glicoproteínas , Polissacarídeos , Caramujos , Animais , Humanos , Camundongos , Espectroscopia de Infravermelho com Transformada de Fourier , Ácido Periódico , Polissacarídeos/farmacologia , Polissacarídeos/química , CicatrizaçãoRESUMO
Foeniculum vulgare Mill. is a medicinal and food homologous plant, and it has various biological activities. Yet, no research has explored its anti-motion sickness effects. Chemical properties of fennel extracts (FvE) and flavonoids (Fvf) were analyzed based on UPLC-QTRAP-MS to elucidate its potential anti-motion sickness components in the present study. The mice models of motion sickness were stimulated by biaxial rotational acceleration. Behavioral experiments such as motion sickness index and open field test and the measurement of neurotransmitters were used to evaluate the efficacy of compounds on motion sickness. Results showed that FvE contains terpenes, alkaloids, flavonoids, etc. Eight flavonoids including quercetin-3ß-D-glucoside, rutin, hyperoside, quercetin, miquelianin, trifolin, isorhamnetin and kaempferol were identified in the purified Fvf. FvE and Fvf significantly reduced the motion sickness index of mice by 53.2% and 48.9%, respectively. Fvf also significantly alleviated the anxious behavior of mice after rotational stimulation. Among the eight flavonoids, isorhamnetin had the highest oral bioavailability and moderate drug-likeness index and thus speculated to be the bioactive compound in fennel for its anti-motion sickness effect. It reduced the release of 5-HT and Ach to alleviate the motion sickness response and improve the work completing ability of mice and nervous system dysfunction after rotational stimulation. This study provided in-depth understanding of the anti-motion sickness bioactive chemical properties of fennel and its flavonoids, which will contribute to the new development and utilization of fennel.
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Foeniculum , Enjoo devido ao Movimento , Flavonoides/farmacologia , Flavonoides/análise , Quercetina , Foeniculum/química , Espectrometria de Massa com Cromatografia Líquida , Cromatografia Líquida , Espectrometria de Massas em Tandem , Estrutura Molecular , Extratos Vegetais/química , Enjoo devido ao Movimento/tratamento farmacológicoRESUMO
Our aim was to investigate the preparation of self-assembled garlic essential oil-amylose inclusion complexes (SGAs) using garlic essential oil (GEO) and corn starch (CS), and evaluated their release properties. SGAs were fabricated by pre-gelatinization coupling with high-speed shear at different GEO-CS mass ratios. When the mass ratio of GEO to pre-gelatinized corn starch was set at 15 % (SGA-15 %), with a fixed shear rate of 9000 rpm and a shear time of 30 min, the allicin content was 0.573 ± 0.023 mg/g. X-ray diffraction (XRD) results revealed a starch V-type crystalline structure in SGAs with peaks at 13.0°, 18.0°, and 20.0° (2θ). Fourier Transform Infrared (FTIR) spectra of SGAs displayed a shift in the characteristic peak of diallyl trisulfide from 987.51 cm-1 to 991.45 cm-1. Scanning electron microscope (SEM) images revealed that SGAs exhibited lamellar structures covered with small granules. SGAs exhibited higher residual mass (approximately 12 %) than other samples. The resistant starch content of SGAs increased from 10.1 % to 18.4 % as GEO contents varied from 5 % to 15 %. In vitro digestion tests showed that about 53.21 % of allicin remained in SGA-15 % after 8 h. Therefore, this dual treatment can be a new method for fabricating controlled-release inclusion complexes of guest molecules.
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Amilose , Alho , Amilose/química , Amido/química , Dissulfetos , Difração de Raios XRESUMO
Resveratrol (RES) is a common active factor in the functional food field, but poor water solubility and low bioavailability have limited its application. In the present study, the novel nanoparticles (RES-CBFMP NPs) using floral mushroom polysaccharide as the wall material have been developed for delivering RES, aiming to overcome its application shortcomings. After ratio optimization, RES-CBFMP NPs (RES-CBFMP,1:8 w/w), which combined through the hydrogen bonds between RES and CBFMP, showed the best overall performance, with the encapsulation efficiency (EE) of 49.74 ± 0.16%, loading efficiency (LE) of 5.53 ± 0.02%, particle size of 158.56 ± 1.97 nm and zeta-potential of -17.56 ± 0.24 mV. In addition, RES-CBFMP NPs exhibited good physicochemical stabilities, sustained gastrointestinal digestive release property, as well as improved in vitro antioxidant and anticancer activities. This study may contribute to the development of RES oral delivery systems and the application of hydrophobic active molecules in the functional food field.
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Agaricales , Nanopartículas , Resveratrol/química , Antioxidantes/química , Nanopartículas/química , Digestão , Tamanho da Partícula , Portadores de Fármacos/químicaRESUMO
Caffeic acid phenethyl ester (CAPE) is an efficient bioactive polyphenol ester derived from propolis. However, its poor water solubility, bioavailability, and stability significantly limit its application. Based on the assembly properties of some natural small molecules (NSMs), asiatic acid-caffeic acid phenethyl ester nanoparticles (ASA-CAPE NPs) were prepared to overcome the above defects. After proportion optimization, the encapsulation and loading efficiencies of ASA-CAPE NPs reached 47.72 ± 0.17 % and 11.62 ± 0.42 %, respectively. Characterization results showed that ASA-CAPE NPs, mainly assembled by hydrogen bonds and hydrophobic forces, possessed regular spherical morphology with a diameter size of less than 300 nm. Additionally, ASA-CAPE NPs presented improved water solubility, stability, and bioactivities than free CAPE. Besides, ASA-CAPE NPs also exhibited good sustained release of CAPE during the gastrointestinal digestion in vitro. Above all, ASA-CAPE NPs provide a new idea for efficiently utilizing hydrophobic active compounds in the functional food field.
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Nanopartículas , Álcool Feniletílico , Álcool Feniletílico/química , Ácidos Cafeicos/química , Nanopartículas/química , ÁguaRESUMO
With the accelerated pace of modern life, people are facing more and more health pressure. The study of polysaccharides seemed a good choice as a potential treasure trove. Polysaccharides, one of the four basic substances (proteins, nucleic acids, lipids and carbohydrates) that constitute life activities, are obviously an underrated macromolecular substance with great potential. Compared with protein and nucleic acid, the research of polysaccharides is still in the primary stage. The relationship between structure and function of polysaccharides is not clear. In this review, we highlighted the main methods of extraction, purification and structure identification of polysaccharides; summarized their biological activities including immunoregulation, hypoglycemic, anti-tumor, anti-virus, anti-coagulation, and so on. Particularly, the relationship between their structures and activities was described. In addition, the applications of polysaccharides in health food, medicine and cosmetics were also reviewed. This review can help polysaccharide researchers quickly understand the whole process of polysaccharides research, and also provide a reference for the comprehensive utilization of polysaccharides. We need to standardize the research of polysaccharides to make the experimental data more universal, and take it as important references in the review process. Glycomic may appear as the next "omic" after genomic and proteomic in the future. This review provides support for the advancement of glycomics.
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Polissacarídeos , Proteômica , Humanos , Polissacarídeos/química , Carboidratos , Antioxidantes , CogniçãoRESUMO
Rapid advancements of genome sequencing (GS) technologies have enhanced our understanding of the relationship between genes and human disease. To incorporate genomic information into the practice of medicine, new processes for the analysis, reporting, and communication of GS data are needed. Blood samples were collected from adults with a PCR-confirmed SARS-CoV-2 (COVID-19) diagnosis (target N = 1500). GS was performed. Data were filtered and analyzed using custom pipelines and gene panels. We developed unique patient-facing materials, including an online intake survey, group counseling presentation, and consultation letters in addition to a comprehensive GS report. The final report includes results generated from GS data: (1) monogenic disease risks; (2) carrier status; (3) pharmacogenomic variants; (4) polygenic risk scores for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group; and, (8) COVID-19 viral lineage. Participants complete pre-test genetic counseling and confirm preferences for secondary findings before receiving results. Counseling and referrals are initiated for clinically significant findings. We developed a genetic counseling, reporting, and return of results framework that integrates GS information across multiple areas of human health, presenting possibilities for the clinical application of comprehensive GS data in healthy individuals.
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COVID-19 , Aconselhamento Genético , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/genética , SARS-CoV-2/genética , Genômica/métodos , GenótipoRESUMO
Genome sequencing holds the promise for great public health benefits. It is currently being used in the context of rare disease diagnosis and novel gene identification, but also has the potential to identify genetic disease risk factors in healthy individuals. Genome sequencing technologies are currently being used to identify genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. The GENCOV study aims to look at the relationship between genetic, serological, and biochemical factors and variability of SARS-CoV-2 symptom severity, and to evaluate the utility of returning genome screening results to study participants. Study participants select which results they wish to receive with a decision aid. Medically actionable information for diagnosis, disease risk estimation, disease prevention, and patient management are provided in a comprehensive genome report. Using a combination of bioinformatics software and custom tools, this article describes a pipeline for the analysis and reporting of genetic results to individuals with COVID-19, including HLA genotyping, large-scale continental ancestry estimation, and pharmacogenomic analysis to determine metabolizer status and drug response. In addition, this pipeline includes reporting of medically actionable conditions from comprehensive gene panels for Cardiology, Neurology, Metabolism, Hereditary Cancer, and Hereditary Kidney, and carrier screening for reproductive planning. Incorporated into the genome report are polygenic risk scores for six diseases-coronary artery disease; atrial fibrillation; type-2 diabetes; and breast, prostate, and colon cancer-as well as blood group genotyping analysis for ABO and Rh blood types and genotyping for other antigens of clinical relevance. The genome report summarizes the findings of these analyses in a way that extensively communicates clinically relevant results to patients and their physicians. © 2022 Wiley Periodicals LLC. Basic Protocol 1: HLA genotyping and disease association Basic Protocol 2: Large-scale continental ancestry estimation Basic Protocol 3: Dosage recommendations for pharmacogenomic gene variants associated with drug response Support Protocol: System setup.
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Antígenos de Grupos Sanguíneos , COVID-19 , COVID-19/genética , Biologia Computacional/métodos , Genômica , Humanos , Masculino , SARS-CoV-2/genéticaRESUMO
BACKGROUND & AIMS: Hypoxia inducible factor (HIF) is a hypoxia-associated transcription factor that has a protective role against hypoxia-induced damage. Prolyl hydroxylase-2 (PHD2) is a dioxygenase enzyme that specifically hydroxylates HIF targeting it for degradation, therefore, inhibition of the PHD2 enzyme activity acts to upregulate HIF function. This study was to identify novel PHD2 inhibitors. METHODS: An established fluorescence-based PHD2 activity assay was used for inhibitors screening. Western blot and quantitative real-time PCR was used to detect the protein and mRNA levels respectively. Further animal experiment was carried out. RESULTS: Caffeic acid was screened and identified as a novel PHD2 inhibitor. Caffeic acid treated PC12 and SH-SY5Y neuronal cell lines stabilized endogenous HIF-1α protein levels and consequently increased mRNA levels of its downstream regulated genes VEGF and EPO. Caffeic acid treatment reduced hypoxia-induced cell apoptosis and promoted HIF/BNIP3-mediated mitophagy. Moreover, animal studies indicated that caffeic acid increased the level of HIF-1α protein and mRNA levels of VEGF and EPO in the brain of mice exposed to hypoxia. Conventional brain injury markers including malondialdehyde, lactic acid and lactate dehydrogenase in the caffeic acid treated mice were shown to be reduced to the levels of the control group. CONCLUSIONS: This study suggests that caffeic acid inhibits PHD2 enzyme activity which then activates the hypoxia-associated transcription factor HIF leading to a neuroprotective effect against hypoxia.
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Neuroblastoma , Fármacos Neuroprotetores , Inibidores de Prolil-Hidrolase , Humanos , Camundongos , Animais , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Inibidores de Prolil-Hidrolase/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Hipóxia/metabolismo , RNA Mensageiro/genética , Ácido Láctico , Malondialdeído , Lactato Desidrogenases , Fatores de Transcrição , Subunidade alfa do Fator 1 Induzível por Hipóxia/genéticaRESUMO
There are numerous factors restricting wide application of lactic acid bacteria (LAB) in dairy industry, causing urgent demands for novel bioprotectants. Protective effects and metabolites of Lactococcus lactis subsp. lactis (L. lactis) from ultraviolet (UV)-induced supernatant were investigated and the protective mechanism was explored. The strain viability of the group treated with the supernatant of continuous UV irradiation (V1) and the group with intermittent UV irradiation (V2) was 8.45 and 14.13 times of the control group, respectively. Further exploration on the protective of L. lactis supernatant, under different dose of UV treatment, showed it was dose-dependent. The condition for the supernatant with best protective effect was vertical distance 50.00 cm, horizontal distance 25.00 cm, intermittent UV irradiation (30 s interval 30 s) for 4.5 min (V2), which was chose for untargeted metabolite analysis. And that in V1 was for comparative study. There were 181 up-regulated metabolites in V1 and 161 up-regulated metabolites in V2, respectively. Most of the up-regulated metabolites were related to secondary metabolite synthesis, environmental microbial metabolism, antibiotic synthesis and amino acid biosynthesis. Notably, production of dithiothreitol (DTT) in V2 was 65.2-fold higher than that in the control group. Trehalose in ABC transporter pathway was also up-regulated in the metabolites induced by UV. Results indicated that L. lactis could adapt to the UV stress by adjusting metabolic pathways and producing special metabolites to protect itself. This research offers the basis for robust strain development and contributes to initial study on potential bioprotectant.
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Lactococcus lactis , Adaptação Fisiológica , Lactococcus lactis/metabolismoRESUMO
Implementation of polygenic risk scores (PRS) may improve disease prevention and management but poses several challenges: the construction of clinically valid assays, interpretation for individual patients, and the development of clinical workflows and resources to support their use in patient care. For the ongoing Veterans Affairs Genomic Medicine at Veterans Affairs (GenoVA) Study we developed a clinical genotype array-based assay for six published PRS. We used data from 36,423 Mass General Brigham Biobank participants and adjustment for population structure to replicate known PRS-disease associations and published PRS thresholds for a disease odds ratio (OR) of 2 (ranging from 1.75 (95% CI: 1.57-1.95) for type 2 diabetes to 2.38 (95% CI: 2.07-2.73) for breast cancer). After confirming the high performance and robustness of the pipeline for use as a clinical assay for individual patients, we analyzed the first 227 prospective samples from the GenoVA Study and found that the frequency of PRS corresponding to published OR > 2 ranged from 13/227 (5.7%) for colorectal cancer to 23/150 (15.3%) for prostate cancer. In addition to the PRS laboratory report, we developed physician- and patient-oriented informational materials to support decision-making about PRS results. Our work illustrates the generalizable development of a clinical PRS assay for multiple conditions and the technical, reporting and clinical workflow challenges for implementing PRS information in the clinic.
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Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Fluxo de TrabalhoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: As a common medicinal and edible plant, Zingiber officinale Roscoe (ginger) is often used for the prevention of motion sickness. However, the mechanism of its anti-motion sickness remains to be elucidated. AIM OF THE STUDY: To explore novel treatment for motion sickness with less side effects, anti-motion sickness effect of ginger (Zingiber officinale) extract (GE) and the possible molecular mechanisms were investigated. MATERIALS AND METHODS: The anti-motion sickness effect of ginger was evaluated through mice animal experimental models. Components of ginger that might contribute to the anti-motion sickness effect were analyzed by LC-MS/MS. Subsequently, biochemical analysis integrated with serum metabolomic profiling were performed to reveal the systematic response of motion sickness mice to ginger extract's amelioration effect. RESULTS: Exhaustive swimming time of mice in the GE group reached 8.9 min, which was 52.2% longer than that in the model group. Motion sickness index scores and time taken traversing balance beam of mice in the GE group were decreased by 53.2% and 38.5%, respectively. LC-MS/MS analysis suggested that various active ingredients in GE, such as gingerol, ginger oil and terpenoids, might contribute to its appealing anti-motion sickness activity. Biochemical analysis revealed that GE can relieve motion sickness through reducing histamine and acetylcholine release in vestibular system, regulating fatty acid oxidation, sugar metabolism and bile acid metabolism in mice. CONCLUSION: Gavage of mice with GE can effectively relieve the symptoms of autonomic nervous system dysfunction, improve the balance and coordination ability and ameliorate the ability to complete complex work after rotation stimulation. GE has attractive potential for development and utilization as novel anti-motion sickness food or drugs.
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Enjoo devido ao Movimento/patologia , Extratos Vegetais/farmacologia , Zingiber officinale/química , Acetilcolina/metabolismo , Animais , Animais não Endogâmicos , Comportamento Animal/efeitos dos fármacos , Ácidos e Sais Biliares/metabolismo , Catecóis/farmacologia , Cromatografia Líquida , Relação Dose-Resposta a Droga , Ácidos Graxos/metabolismo , Álcoois Graxos/farmacologia , Histamina/metabolismo , Masculino , Camundongos , Óleos de Plantas/farmacologia , Açúcares/metabolismo , Espectrometria de Massas em Tandem , Terpenos/farmacologiaRESUMO
Prolyl hydroxylase-2 (PHD2) is a dioxygenase enzyme that specifically hydroxylates the hypoxia inducible factor (HIF) which then targets it for degradation in oxygenated cells. Inhibition of the activity of the PHD2 enzyme under hypoxic environmental conditions acts to upregulate HIF. Thus, PHD2 inhibitors may serve as a promising treatment for HIF-dependent diseases. In this study, recombinant PHD2 protein was successfully expressed using a baculovirus-insect cell expression secretory system. PHD2 was purified and in combination with bacterially expressed functional von Hippel Lindau protein-elongin B-elongin C (VBC) protein complex was used to successfully develop a fluorescence-based PHD2 activity assay. Myricetin was identified as a novel potent PHD2 inhibitor by high-throughput screening of a natural compound library. Further studies showed that treatment of human neuroblastoma SH-SY5Y cells with Myricetin increased HIF-1α protein levels. These results indicate that the insect cell expression system is capable of producing highly active recombinant PHD2 protein from which a fluorescence-based activity assay can be developed for high-throughput screening applications.
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Dioxigenases , Prolina Dioxigenases do Fator Induzível por Hipóxia , Animais , Humanos , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Insetos/metabolismo , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Prolil Hidroxilases/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologiaRESUMO
Exposure to ionizing radiation (IR) can cause oxidative damage to human body, leading to various diseases and even death. In this study, the potential radioprotective effect of coix seed seedling extract (CSS-E) was studied through a model of 60 Co-γ radiation-induced oxidative stress in mice. Overall radioprotective effect of CSS-E against radiation-induced damage was evaluated by biochemical analysis and histopathological analysis. The results showed that CSS-E could significantly reduce the IR-induced damage to the hematopoietic system. CSS-E-M (200 mg/kg BW) pretreatment could increase the activities of superoxide dismutase in serum, liver, and spleen increased by 31.68%, 45.10%, and 56.67%, respectively, and the glutathione peroxidase levels in serum, liver, and spleen of mice were improved by 19.17%, 41.97%, and 130.56%, respectively. Meanwhile, the glutathione levels of serum, liver, and spleen in CSS-E-M group were increased by 17.10%, 35.06%, and 40.71%, respectively. The contents of MDA in different tissues and serum could be reduced by CSS-E-M treatment to the normal level. Moreover, CSS-E could markedly reduce the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in radiation mice, among which CSS-E-M group showed maximum restoration with decreased AST and ALT levels by 20.13% and 32.76% as compared against IR group. In conclusion, these results indicated that CSS-E could be used as a potential natural radioprotectant against IR-induced damage.