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Three chromomycin derivatives, chromomycins A3 (1, CA3), A5 (2, CA5), and monodeacetylchromomycin A3 (3, MDA-CA3), were identified from the soil-derived Streptomyces sp. CGMCC 26516. A reinvestigation of the structure of CA5 is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA3 based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds 1-3 showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC50 values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, 1 and 2 both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.
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BACKGROUND: Acute liver injury is liver cell injury that occurs rapidly in a short period of time. Caffeine has been shown to maintain hepatoprotective effect with an unclear mechanism. Endoplasmic reticulum stress (ERS) has significant effects in acute liver injury. Induction of GRP78 is a hallmark of ERS. Whether or not caffeine's function is related to GRP78 remains to be explored. METHODS: Acute liver injury model was established by LPS-treated L02 cells and in vivo administration of LPS/D-Gal in mice. Caffeine was pre-treated in L02 cells or mice. Gene levels was determined by real-time PCR and western blot. Cell viability was tested by CCK-8 assay and cell apoptosis was tested by flow cytometry. The interaction of GRP78 and NEDD4L was determined by Pull-down and co-immunoprecipitation (Co-IP) assay. The ubiquitination by NEDD4L on GRP78 was validated by in vitro ubiquitination assay. RESULTS: Caffeine protected liver cells against acute injury induced cell apoptosis and ERS both in vitro and in vivo. Suppression of GRP78 could block the LPS-induced cell apoptosis and ERS. NEDD4L was found to interact with GRP78 and ubiquitinate its lysine of 324 site directly. Caffeine treatment induced the expression of NEDD4L, resulting in the ubiquitination and inhibition of GRP78. CONCLUSION: Caffeine mitigated the acute liver injury by stimulating NEDD4L expression, which inhibited GRP78 expression via ubiquitination at its K324 site. Low dose of caffeine could be a promising therapeutic treatment for acute liver injury.
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Cafeína , Enfermedad Hepática Inducida por Sustancias y Drogas , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Ubiquitina-Proteína Ligasas Nedd4 , Animales , Ratones , Apoptosis , Cafeína/farmacología , Cafeína/uso terapéutico , Chaperón BiP del Retículo Endoplásmico/metabolismo , Lipopolisacáridos/farmacología , Hígado/efectos de los fármacos , Ubiquitinación , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológicoRESUMEN
The forkhead box M1 (FoxM1) protein, a transcription factor, plays critical roles in regulating tumor growth and drug resistance, while cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, is involved in the ubiquitin-proteasome pathway. In this study, we investigated the effects of c-FLIP on the expression and ubiquitination levels of FoxM1 along with drug susceptibility in non-small-cell lung cancer (NSCLC) cells. We first showed that the expression levels of FoxM1 and c-FLIP were increased and positively correlated (R2 = 0.1106, P < 0.0001) in 90 NSCLC samples. The survival data from prognostic analysis demonstrated that high expression of c-FLIP and/or FoxM1 was related to poor prognosis in NSCLC patients and that the combination of FoxM1 and c-FLIP could be a more precise prognostic biomarker than either alone. Then, we explored the functions of c-FLIP/FoxM1 in drug resistance in NSCLC cell lines and a xenograft mouse model in vivo. We showed that c-FLIP stabilized FoxM1 by inhibiting its ubiquitination, thus upregulated the expression of FoxM1 at post-transcriptional level. In addition, a positive feedback loop composed of FoxM1, ß-catenin and p65 also participated in c-FLIP-FoxM1 axis. We revealed that c-FLIP promoted the resistance of NSCLC cells to thiostrepton and osimertinib by upregulating FoxM1. Taken together, these results reveal a new mechanism by which c-FLIP regulates FoxM1 and the function of this interaction in the development of thiostrepton and osimertinib resistance. This study provides experimental evidence for the potential therapeutic benefit of targeting the c-FLIP-FoxM1 axis for lung cancer treatment.
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Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Proteína Forkhead Box M1 , Animales , Humanos , Ratones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/genética , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Línea Celular Tumoral , Proliferación Celular , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Tioestreptona/farmacología , Tioestreptona/uso terapéutico , Tioestreptona/metabolismo , Resistencia a Antineoplásicos/genéticaRESUMEN
The Jin-Gu-Lian capsule, a Chinese Miao herbal compound, is widely used to treat rheumatoid arthritis. In this study, a rapid, selective, and sensitive UHPLC-Orbitrap Exploris 240 MS method was developed to analyze the chemical composition of Jin-Gu-Lian capsules. A total of 88 compounds were identified, including 23 flavonoids, 23 organic acids, 14 phenylpropanoids, 12 phenols, eight alkaloids, four terpenes, three quinones, and one ketone. Among these, 21 compounds were clearly detected based on a comparison with reference standards and selected as quality control markers. Thereafter, these compounds were simultaneously determined in the Jin-Gu-Lian capsules. The established method was successfully validated and applied for the simultaneous determination of 21 biologically active compounds in Jin-Gu-Lian capsules of 27 sample batches. Quantitative data of the analytes were analyzed using multivariate statistical analysis to determine the quality of the Jin-Gu-Lian capsules. Four compounds (JGLC6 [salidroside], JGLC8 [chlorogenic acid], JGLC12 [liriodendrin], JGLC19 [quercetin]) were identified as chemical markers for quality control of Jin-Gu-Lian capsules. Altogether, the established method was validated as a novel and efficient tool, that can be used for rapid analysis of Jin-Gu-Lian capsules. Accordingly, this study serves as a reference for scientific research on traditional Chinese and ethnic medicine.
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Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/análisis , Flavonoides/análisis , Control de Calidad , Espectrometría de Masas en Tándem/métodosRESUMEN
The study investigated the difference of intestinal absorption characteristics of root tuber of Cynanchum auriculatum extract between normal and functional dyspepsia(FD) model rats with everted intestine sac model.The content of syringic acid, scopoletin, caudatin, baishouwu benzophenone, qingyangshengenin and deacyhmetaplexigenin in the C.auriculatum extract in different intestinal segments was detected by UPLC-MS/MS.The cumulative absorption amount(Q) and absorption rate constant(K_a) of the six chemical constituents were calculated.The results showed that the six components could be absorbed into the intestinal sac and were unsaturated, which indicated that the absorption mechanism of scopoletin was active transport in the intestine, while that of the other five components were passive diffusion.For normal group, the syringic acid and baishouwu benzophenone in ileum, qingyangshengenin and deacyhmetaplexigenin in ileum and duodenum, and caudatin in colon were well absorbed and scopoletin at low, medium and high concentrations was found excellent absorption in jejunum, ileum, and colon, respectively.Whereas the best absorption site of each component was ileum in model group.The absorption characteristics of each component between normal group and model group were complex at different concentrations, showing inconsistent tendency of absorption, which suggested that the components of root tuber of C.auriculatum extract were selectively absorbed in small intestine, and the absorption characteristics of the six components could be changed under FD status.This study provided theoretical basis for the clinical drug application and development of root tuber of C.auriculatum.
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Cynanchum , Medicamentos Herbarios Chinos , Dispepsia , Animales , Benzofenonas , Cromatografía Liquida , Cynanchum/química , Dispepsia/tratamiento farmacológico , Absorción Intestinal , Intestinos , Ratas , Escopoletina , Espectrometría de Masas en TándemRESUMEN
To study the active chemical components and mechanism of Liangfu Dropping Pills in treatment of gastrointestinal diseases. The UHPLC-Q-TOF-MS method was employed to analyze the components of Liangfu Dropping Pills in plasma. The protein targets of the absorbed compounds were predicted in the TCMSP database and the SwissTargetPrediction database. The targets associated with gastrointestinal diseases were collected from OMIM, CTD, GeneCards, and DrugBank. The common target genes between components and diseases were screened out for the building of protein-protein interaction(PPI) network in the STRING database. Metascape was used to carry out gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. Cytoscape was employed to construct the PPI network diagram and absorbed component-target network diagram. The molecular docking between the components absorbed in blood and potential key targets was performed by AutoDock vina 4.2.6 to screen and verify the main active components and targets. Twelve chemcial components were identified in Liangfu Dropping Pills, in which four components were absorbed in blood, including galangin, rhamnocitrin, galangin 3-methyl ether, and α-cyperone. These components acted on 189 common targets which were mainly involved in the cell responses to nitrogen compounds, organic cyclic compounds, and hormones, and enriched in the PI3 K-Akt signaling pathway, Foxo signaling pathway, and IL-17 signaling pathway. Molecular docking results showed that the four components had strong affinity with core targets. The material basis of Liangfu Dropping Pills treating gastrointestinal diseases may be galangin, rhamnocitrin, galangin 3-methyl ether, and α-cyperone. This study provides a theoretical basis for further development and application of Liangfu Dripping Pills.
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Medicamentos Herbarios Chinos , Enfermedades Gastrointestinales , Humanos , Simulación del Acoplamiento Molecular , Transducción de SeñalRESUMEN
BACKGROUND: Sheath blight (SB), caused by Rhizoctonia solani, is a common rice disease worldwide. Currently, rice cultivars with robust resistance to R. solani are still lacking. To provide theoretic basis for molecular breeding of R. solani-resistant rice cultivars, the changes of transcriptome profiles in response to R. solani infection were compared between a moderate resistant cultivar (Yanhui-888, YH) and a susceptible cultivar (Jingang-30, JG). RESULTS: In the present study, 3085 differentially express genes (DEGs) were detected between the infected leaves and the control in JG, with 2853 DEGs in YH. A total of 4091 unigenes were significantly upregulated in YH than in JG before infection, while 3192 were significantly upregulated after infection. Further analysis revealed that YH and JG showed similar molecular responses to R. solani infection, but the responses were earlier in JG than in YH. Expression levels of trans-cinnamate 4-monooxygenase (C4H), ethylene-insensitive protein 2 (EIN2), transcriptome factor WRKY33 and the KEGG pathway plant-pathogen interaction were significantly affected by R. solani infection. More importantly, these components were all over-represented in YH cultivar than in JG cultivar before and/or after infection. CONCLUSIONS: These genes possibly contribute to the higher resistance of YH to R. solani than JG and were potential target genes to molecularly breed R. solani-resistant rice cultivar.
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Oryza/genética , Oryza/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Hojas de la Planta/genética , Hojas de la Planta/microbiología , Rhizoctonia , Transcriptoma/genética , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
This project is to study the metabolites of Laportea bulbifera extract in rat feces. After the SD rats were gavaged with the extract(136 g·kg~(-1), according to the crude drug dose), the metabolites in their feces were detected by UHPLC-Q-TOF-MS~E technique, and the obtained mass spectrometry data was combined with UNIFI software for prediction. The prototype components and metabolites in rat feces were identified with reference materials and related literature. A total of 43 metabolites were identified(including 8 prototype components and 35 metabolites). The metabolic pathways mainly include monocaffeoylquinic acid(hydrogenation reduction, ring-opening cracking, sulfation, hydroxylation, glucuronidation), quercetin(O-C2 bond ring-opening cleavage, C2-C3 double bond reduction, rutin carbonylation) and so on. The metabolites and metabolic process of L. bulbifera extract in rat feces were clarified, which provided a basis for the study of the active substances and its mechanism of action.
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Urticaceae , Administración Oral , Animales , Cromatografía Líquida de Alta Presión , Heces , Extractos Vegetales , Ratas , Ratas Sprague-DawleyRESUMEN
This study is to study the absorption properties of different particle size of Gastrodiae Rhizoma powder in rats. In vivo circulation pass perfusion model combined with ultra high performance liquid chromatography-mass spectrometry(UPLC-MS/MS) method was used to determine the cumulative absorption of each component in different particle size of Gastrodiae Rhizoma powder, and the effect of different particle size, different concentrations, different intestine segments and bile on the intestine absorption of gastrodin and other compositions in Gastrodiae Rhizoma powder was investigated to illuminate the absorption properties and compare the absorption difference of gastrodin and other compositions in Gastrodiae Rhizoma powder in different particle size. The results showed that the absorption of gastrodin in each intestinal segment has no significant difference, pointing out that gastrodin may be passive absorption and the absorption of barrison glycosides may be active absorption; the absorption of gastrodin in ultrafine powder was better than that of common powder and superfine powder of Gastrodiae Rhizoma; the absorption of these barrison glycosides was good in ultrafine powder of Gastrodiae Rhizoma under the high concentration. However, an appropriate degree of superfine grinding can promote the absorption of active ingredients of Gastrodiae Rhizoma. This test can provide information for the deep development of Gastrodiae Rhizoma.
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Medicamentos Herbarios Chinos/farmacocinética , Gastrodia , Absorción Intestinal , Animales , Cromatografía Líquida de Alta Presión , Tamaño de la Partícula , Polvos , Ratas , Espectrometría de Masas en TándemRESUMEN
This study aims to reveal the pharmacokinetics of Shuganning Injection in normal rats. In this experiment,ultra-high performance liquid chromatography-electrospray-tandem mass spectrometry( UPLC-ESI-MS/MS) was used to establish an analytical method for simultaneous determination of chlorogenic acid,gardenioside,oroxylin A and baicalin in rat plasma. Then,the non-compartmental model( NCA) in Phoenix WinN onL in 6. 4 software was used to fit pharmacokinetic parameters. The methodological validation showed that the linear relationship of the components in rat plasma samples were good( r>0. 995). The recovery rate and matrix effect of plasma samples with low,middle and high concentration were 79. 14%-101. 4%. The intra-day and inter-day precision,accuracy and stability meet the requirements of biological sample analysis. The half-life( t1/2) of chlorogenic acid,gardenioside,oroxylin A did not change significantly and the area under blood concentration-time curve( AUC0-t) is proportional to the dose,which suggested that three components showed a linear kinetic characteristics,but baicalin showed nonlinear kinetic characteristics. Moreover,the retention time of each component in rats was short. The established UPLC-MS/MS quantitative analysis method is rapid,sensitive and accurate,which can be used for the determination of chlorogenic acid,gardenioside,oroxylin A and baicalin in rat plasma and pharmacokinetic study of Shuganning Injection.
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Plasma , Espectrometría de Masas en Tándem , Animales , Ácido Clorogénico , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los ResultadosRESUMEN
Small bowel obstruction is common in emergency departments. However, the exact cause of intestinal pseudo-obstruction (IPO) is often misdiagnosed. IPO is considered a severe manifestation of systemic lupus erythematosus (SLE). However, IPO is rare as the initial manifestation of SLE. This paper reports a female patient who presented with IPO as the initial manifestation and was ultimately diagnosed with SLE. The 31-year-old female was definitively diagnosed with SLE after IPO symptoms for 1â¯month. She then presented multiple organ dysfunction syndrome (MODS) leading to a poor prognosis. Patients with unexplained SBO symptoms should be aware of systemic diseases. Early diagnosis and prompt medical treatment are crucial to avoid unnecessary surgery and obtain satisfactory outcomes.
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Seudoobstrucción Intestinal/diagnóstico por imagen , Seudoobstrucción Intestinal/etiología , Intestino Delgado/diagnóstico por imagen , Lupus Eritematoso Sistémico/complicaciones , Adulto , Combinación Cilastatina e Imipenem/uso terapéutico , Diagnóstico Tardío , Servicio de Urgencia en Hospital , Femenino , Humanos , Inmunoglobulinas/uso terapéutico , Inmunosupresores/uso terapéutico , Seudoobstrucción Intestinal/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Insuficiencia Multiorgánica/complicaciones , Pronóstico , Radiografía Abdominal , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To study the clinical characteristics, drug sensitivity of isolated strains, and risk factors of drug resistance in children with invasive pneumococcal disease (IPD). METHODS: The clinical characteristics and drug sensitivity of the isolated strains of 246 hospitalized children with IPD in nine grade A tertiary children's hospitals from January 2016 to June 2018 were analyzed. RESULTS: Of the 246 children with IPD, there were 122 males and 124 females. Their ages ranged from 1 day to 14 years, and among them, 68 (27.6%) patients were less than 1 year old, 54 (22.0%) patients were 1 to 2 years old, 97 (39.4%) patients were 2 to 5 years old, and 27 (11.0%) patients were 5 to 14 years old. Pneumonia with sepsis was the most common infection type (58.5%, 144/246), followed by bloodstream infection without focus (19.9%, 49/246) and meningitis (15.0%, 37/246). Forty-nine (19.9%) patients had underlying diseases, and 160 (65.0%) had various risk factors for drug resistance. The isolated Streptococcus pneumoniae strains were 100% sensitive to vancomycin, linezolid, moxifloxacin, and levofloxacin, 90% sensitive to ertapenem, ofloxacin, and ceftriaxone, but had a low sensitivity to erythromycin (4.2%), clindamycin (7.9%), and tetracycline (6.3%). CONCLUSIONS: IPD is more common in children under 5 years old, especially in those under 2 years old. Some children with IPD have underlying diseases, and most of the patients have various risk factors for drug resistance. Pneumonia with sepsis is the most common infection type. The isolated Streptococcus pneumoniae strains are highly sensitive to vancomycin, linezolid, moxifloxacin, levofloxacin, ertapenem, and ceftriaxone in children with IPD.
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Infecciones Neumocócicas , Antibacterianos , Ceftriaxona , Niño , Preescolar , Resistencia a Medicamentos , Femenino , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Streptococcus pneumoniaeRESUMEN
The cerebral ischemia-reperfusion model was established to investigate the anti-oxidation and anti-apoptosis mechanism of Xinshao formula on the cerebral ischemia reperfusion injury in rats. SD rats were randomly divided into five groups: sham operation group, model group, and low, middle and high-dose Xinshao formula groups (0.31, 0.62, 1.25 g·kg⻹). After administration with Xinshao formula for 7 days, the rats were used to establish the cerebral ischemia-reperfusion model. The neurological behavior was evaluated. TTC staining was implemented to determine the volume of cerebral infarction. The levels of ROS, SOD, GSH-PX, NO and iNOS in serum were examined, and the mRNA and protein levels of Bcl-2, Bax and caspase 3 in hippocampal CA1 were detected by qRT-PCR, immunohistochemical assay and Western blot. It is found that Xinshao formula could significantly reduce the symptoms of nervous function and the volume of cerebral infarction in MACO rats. Compared with model group, the rats in Xinshao formula group showed increases in the activities of SOD and GSH-PX (P<0.01), and decreases in the activities of iNOS and the contents of NO, ROS and MDA (P<0.01). In addition, Xinshao formula could down-regulate the mRNA and protein levels of Bax and caspase 3 (P<0.01), and up-regulated those of Bcl-2 (P<0.01) in MACO rats. In conclusion, Xinshao formula showed aprotective effect on cerebral ischemia reperfusion injuryin rats, which may be associated with the promotion of anti-oxidation and anti-apoptosis.
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Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Infarto Cerebral/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Daño por Reperfusión/tratamiento farmacológico , Animales , Ratas , Ratas Sprague-DawleyRESUMEN
To investigate the absorptive characteristics of Inula cappa extract based on the rat everted intestinal sac method in vitro. Nine representative ingredients in I. cappa extract were selected as the study objects. An UPLC-MS/MS method was established to determine and detect their cumulative absorption amount for expounding the absorptive characteristics of ingredients in different intestinal sections. According to the resultsï¼ the transport mechanism of 8 compounds showed passive diffusion by the reverted gut sac method. And scopolin was actively transported in the intestine. The best absorption site of chlorogenic acid was duodenum. The best absorption site of cryptochlorogenic acidï¼ 1ï¼3-O-dicaffeoylquinic acidï¼ luteolin-7-glucoside and 3ï¼4-O-dicaffeoylquinic acid were jejunum. The best absorption site of neochlorogenic acidï¼ scopolinï¼ 4ï¼5-O-dicaffeoylquinic acid and 3ï¼5-O-dicaffeoylquinic acid was ileum. The absorption of all the compounds was affected by pH and bile. All of the nine ingredients in I. cappa extract could be absorbed in intestinesï¼ but with differences in the absorption rateï¼ the best absorptive site and mechanismï¼ indicating that the intestinal absorption of I. cappa extract was selective.
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Absorción Intestinal , Intestinos/efectos de los fármacos , Inula/química , Extractos Vegetales/farmacología , Animales , Cromatografía Líquida de Alta Presión , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en TándemRESUMEN
Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, exhibits beneficial effects on metabolic syndrome. Sustained inflammation plays a crucial role in the pathogenesis of metabolic syndrome. Here we explored the effects of PSPC on high-fat diet (HFD)-induced hepatic inflammation and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + PSPC group, and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. Nicotinamide riboside (NR) was used to increase NAD⺠levels. Our results showed that PSPC effectively ameliorated obesity and liver injuries in HFD-fed mice. Moreover, PSPC notably blocked hepatic oxidative stress in HFD-treated mice. Furthermore, PSPC dramatically restored NAD⺠level to abate endoplasmic reticulum stress (ER stress) in HFD-treated mouse livers, which was confirmed by NR treatment. Consequently, PSPC remarkably suppressed the nuclear factor-κB (NF-κB) p65 nuclear translocation and nucleotide oligomerization domain protein1/2 (NOD1/2) signaling in HFD-treated mouse livers. Thereby, PSPC markedly diminished the NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation, ultimately lowering the expressions of inflammation-related genes in HFD-treated mouse livers. In summary, PSPC protected against HFD-induced hepatic inflammation by boosting NAD⺠level to inhibit NLRP3 inflammasome activation.
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Antiinflamatorios/farmacología , Hepatitis Animal/tratamiento farmacológico , Hepatitis Animal/metabolismo , Inflamasomas/metabolismo , Ipomoea batatas/química , NAD/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pigmentos Biológicos/farmacología , Extractos Vegetales/farmacología , Animales , Antocianinas/química , Antocianinas/farmacología , Antiinflamatorios/química , Dieta Alta en Grasa , Estrés del Retículo Endoplásmico , Regulación de la Expresión Génica/efectos de los fármacos , Hepatitis Animal/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Ratones , FN-kappa B/metabolismo , Proteínas Adaptadoras de Señalización NOD/genética , Proteínas Adaptadoras de Señalización NOD/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/patología , Estrés Oxidativo/efectos de los fármacos , Pigmentos Biológicos/química , Extractos Vegetales/química , Transporte de ProteínasRESUMEN
The principal active constituents of Polygonum capitatum are phenolic acids and flavonoids, such as gallic acid, quercitrin, and quercetin. The aim of this study was to develop and validate a method to determine the three constituents and the corresponding conjugated metabolites of Polygonum capitatum in vivo and to conduct pharmacokinetic studies on the herb, a well-known Miao medicinal plant in China. Gallic acid, quercitrin, and quercetin were analysed by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Protein precipitation in plasma samples was performed using methanol. For the determination of total forms of analytes, an additional process of hydrolysis was conducted using ß-glucuronidase and sulphatase. The analytes were separated on a BEH C18 column (50 mm × 2.1 mm; i.d., 1.7 µm) and quantified by multiple reaction monitoring (MRM) mode. The linear regression showed high linearity over a 729-fold dynamic range for the three analytes. The relative standard deviations of intra- and inter-day measurements were less than 9.5%, and the method was accurate to within -11.1% to 12.5%. The extraction recoveries for gallic acid, quercitrin, and quercetin were 94.3%-98.8%, 88.9%-98.8%, and 95.7%-98.5%, respectively. All samples were stable under short- and long-term storage conditions. The validated method was successfully applied to a comparative pharmacokinetic study of gallic acid, quercitrin, and quercetin in their free and total forms in rat plasma. The study revealed significantly higher exposure of the constituents in total forms for gallic acid and quercetin, while quercitrin was detected mainly in its corresponding free form in vivo. The established method was rapid and sensitive for the simultaneous quantification of free and total forms of multiple constituents of Polygonum capitatum extract in plasma.
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Ácido Gálico/sangre , Polygonum/química , Quercetina/análogos & derivados , Quercetina/sangre , Animales , Cromatografía Líquida de Alta Presión , Ácido Gálico/química , Ácido Gálico/farmacocinética , Masculino , Extractos Vegetales/química , Plantas Medicinales/química , Plasma/química , Quercetina/química , Quercetina/farmacocinética , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en TándemRESUMEN
The Mycoplasma hominis infection is a rare postoperative complication after joint replacement. Based on our knowledge, there were only two cases reported by Korea all over the world currently. A case of postoperative Mycoplasma hominis infection after total knee replacement in our hospital was reported in this article. It was confirmed through mass spectrometer and Mycoplasma cultivation and treated by the first stage debridement, polyethylene insert replacement, and then drainage and irrigation combined with sensitive antibiotics after the operation. We observed that the C reactive protein (CRP) level correlates with the development of disease, while the erythrocyte sedimentation rate (ESR) remains at a high level, indicating the relevance between the Mycoplasma hominis infection caused by knee joint replacement and CRP. This study aims to report the case and review relevant literature.
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Artroplastia de Reemplazo de Rodilla/efectos adversos , Infecciones por Mycoplasma/etiología , Mycoplasma hominis , Complicaciones Posoperatorias/etiología , Infecciones Relacionadas con Prótesis/etiología , Proteína C-Reactiva/análisis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
To investigate the metabolism of major components in Inula cappa by rat intestinal bacteria in vitro. I. cappa extract was incubated for 24 h with rat intestinal bacteria under anaerobic environment. After the samples were precipitated by n-butanol, UPLC-Q-TOF-MS/MS was applied for the qualitative analysis of the metabolites, combined with data software such as Metabolite Tools, Data Analysis and so on. The potential metabolites in rat intestinal bacteria were analyzed by comparing the total ion current of the test samples and blank samples and analyzing the quasi-molecular ion and fragment ion of all chromatograms. The results injected that fourteen metabolites were detected in rat intestinal flora. Various types of metabolic reactions happen to caffeoylquinic acid in intestinal flora, including isomerization, hydrolyzation, there were also methylation, hydrogenation and acetylation of caffeic acid. At the same time, a methylate of dicaffeoylquinic acid was also detected. Presumably, caffeoylquinic acids were gradually transformed into more hydrophobic metabolites with smaller molecular mass, which were better absorbed by the intestinal tract.
Asunto(s)
Bacterias/metabolismo , Intestinos/microbiología , Inula/química , Extractos Vegetales/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Ratas , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health problem and gives arise to severe chronic morbidity and mortality in the world. Inflammatory response and oxidative stress play dominant roles in the pathological mechanism of COPD, and have been regarded to be two important targets for the COPD therapy. Traditional Chinese medicines (TCMs) possess satisfying curative effects on COPD under guidance of the TCM theory in China, and merit in-depth investigations as a resource of lead compounds. METHODS: One hundred ninety-six of TCMs were collected, and extracted to establish a TCM extract library, and then further evaluated for their potency on inhibitions of oxidative stress and inflammatory response using NADP(H):quinone oxidoreductase (QR) assay and nitric oxide (NO) production assay, respectively. RESULTS: Our investigation observed that 38 of the tested TCM extracts induced QR activity in hepa 1c1c7 murine hepatoma cells, and 55 of them inhibited NO production in RAW 264.7 murine macrophages at the tested concentrations. Noteworthily, 20 of TCM extracts simultaneously inhibited oxidative stress and inflammatory responses. CONCLUSION: The observed bioactive TCMs, particularly these 20 TCMs with dual inhibitory effects, might be useful for the treatment of COPD. More importantly, the results of the present research afford us an opportunity to discover new lead molecules as COPD therapeutic agents from these active TCMs.