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OBJECTIVE: Personality, emotions, and olfaction exhibit partial anatomical overlap in the limbic system structure, establishing potential mechanisms between personality, affective disorders, and olfactory-related aspects. Thus, this study aims to investigate the associations among the Big Five personality traits, alexithymia, anxiety symptoms, and odor awareness. METHODS: A total of 863 college participants were recruited for this study. All participants completed the Chinese Big Five Personality Inventory-15, the Odor Awareness Scale (OAS), the Toronto Alexithymia Scale-20, and the Generalized Anxiety Disorder Screener-7. Structural equation modeling was employed to examine the hypothesized mediated model. RESULTS: The findings revealed the majority of significant intercorrelations among the dimensions of the Big Five personality traits, alexithymia, anxiety symptoms, and OAS (|r| = 0.072-0.567, p < 0.05). Alexithymia and anxiety symptoms exhibited a serial mediation effect between neuroticism and OAS (95%CI[0.001, 0.014]), conscientiousness and OAS (95%CI[-0.008, -0.001]), and extraversion and OAS (95%CI[-0.006, -0.001]). Anxiety symptoms mediated the relationship between agreeableness and OAS (95%CI[-0.023, -0.001]) and between openness and OAS (95%CI [0.004, 0.024]). CONCLUSION: The mediating roles of alexithymia and anxiety symptoms between the Big Five personality traits and odor awareness support the idea of a certain level of association among personality, emotions, and olfaction, with the underlying role of the limbic system structure. This enhances our understanding of personality, emotions, and olfaction and provides insights for future intervention measures for affective disorders and olfactory dysfunctions.
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Síntomas Afectivos , Odorantes , Humanos , Síntomas Afectivos/diagnóstico , Análisis de Mediación , Personalidad , AnsiedadRESUMEN
Objective: This study reports on a translation of the Menstrual Symptom Questionnaire (MSQ) into Chinese, a cross-cultural adaptation among Chinese women of reproductive age, and an assessment of its reliability and validity. Methods: Previously published translation guidelines were followed to translate and cross-culturally adapt the English version of MSQ to produce a Chinese version. This Chinese version was then administered to 2800 Chinese women of reproductive age recruited by convenience sampling method. The reliability of the Chinese MSQ was tested for internal consistency and test-retest reliability. The concurrent and construct validity of the questionnaire was evaluated using correlation and factor analysis. Results: The Chinese version of the MSQ showed no linguistic or semantic issues. The internal consistency of the Chinese MSQ Cronbach'α = 0.912, and the test-retest reliability r = 0.911. The exploratory factor analysis identified four factors. The confirmatory factor analysis demonstrated that the four factor structure of the Chinese version of the MSQ (Pain Experience, Emotional Changes, Pain Coping Strategies, and Other Physical Symptoms) is reasonable among Chinese women of reproductive age. There was a significant correlation found between these four factors and both the Pittsburgh Sleep Quality Index and the SF-8 Health Survey. Conclusion: The Chinese version of the MSQ achieved semantic equivalence in translation and demonstrated good reliability and validity among Chinese women of reproductive age. Thus, it can serve as an effective tool to assess the experience of menstrual symptoms among Chinese women.
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Background: The Odor Awareness Scale (OAS) is a questionnaire that assesses individual differences in awareness of odors in the surrounding environment, which has been shown to be associated with affective symptoms in recent researches. To further research, A Chinese version of the OAS needs to be introduced. Objective: To investigate the factor structure and validate the psychometric properties of the OAS. Methods: A total of 978 participants from college were randomly allocated into two groups for exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), respectively. Additionally, the study entailed item analysis and scrutinized internal consistency reliability, test-retest reliability, and concurrent validity. Test-retest reliability was assessed by having 214 participants complete the OAS twice at a one-week interval. Concurrent validity was measured using the Body Odor Sniffing Questionnaire (BOSQ), the Generalized Anxiety Disorder Scale (GAD-7), and the Toronto Alexithymia Scale (TAS-20). Results: EFA identified three factors that best fit the data: odor sensitivity, odor impact, and odor attention. CFA validated a second-order factor model, yielding good fit indices: χ2/ Df = 2.326, RMSEA = 0.052, CFI = 0.911, TLI = 0.900, SRMR = 0.053. The final version of the OAS comprised 27 items and exhibited a commendable internal consistency reliability (Cronbach's α = 0.913), and a good test-retest reliability, as evidenced by the high Pearson correlation coefficient (r = 0.940) and intraclass correlation coefficient (ICC = 0.940). The OAS was significantly correlated with BOSQ (r = 0.416), GAD-7 (r = 0.155), and TAS-20 (r = -0.081). Conclusion: The Chinese version of the OAS demonstrated robust reliability and validity, rendering it a valuable instrument for evaluating odor awareness in the Chinese population.
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A low catalyst loading Zn(OTf)2-catalysed C3-H borylation of indoles with pinacolborane was developed. This transformation represents the use of an abundant, cheap and environmentally benign zinc catalyst in catalytic direct aromatic C-H borylation and offers a simple and prompt route towards the synthesis of C3-borylated indoles. The 1,1-diboration of terminal alkynes was also achieved using the same catalytic system to produce 1,1-diborylated alkenes.
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A benzoic acid-promoted C2-H borylation of indoles with pinacolborane to afford C2-borylated indoles is developed. Preliminary mechanistic studies indicate BH3-related borane species formed via the decomposition of pinacolborane to be the probable catalyst. This transformation provides a prompt route toward the synthesis of diverse C2-functionalized indoles.
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Cholestasis is defined as a functional impairment of bile secretion which results in the accumulation of bile acids (BAs) and other toxic molecules in the blood and liver, however, there are very few effective therapies for cholestasis. The farnesoid X receptor (FXR), as a nuclear receptor for BAs, is important in the regulation of BA levels in enterohepatic circulation. It has previously been demonstrated that activation of the FXR pathway may be a useful strategy with which to treat cholestasis. Resveratrol, one of the important ingredients from grape skins and Chinese medicine Polygonum cuspidatum, resulted in FXRactivated effects in vitro and exhibited a protective effect against αnaphthylisothiocyanate (ANIT)induced cholestasis through FXR regulation in vivo. The underlying mechanisms of resveratrol against ANITinduced cholestasis may be due to the regulation of BA homeostasis, improvement of liver injury and attenuation of the inflammatory response, which were regulated in a FXRdependent manner and in turn contributed to overall cholestasis alleviation. Overall, resveratrol as a FXR agonist may act as a potential compound for the treatment of druginduced cholestasis.
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Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Colestasis/tratamiento farmacológico , Receptores Citoplasmáticos y Nucleares/metabolismo , Estilbenos/farmacología , 1-Naftilisotiocianato , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Colestasis/inducido químicamente , Colestasis/inmunología , Colestasis/metabolismo , Células HEK293 , Células Hep G2 , Hepatocitos/inmunología , Hepatocitos/metabolismo , Humanos , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/metabolismo , Resveratrol , Transducción de Señal/efectos de los fármacos , Estilbenos/uso terapéuticoRESUMEN
Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance.
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Curcumina/farmacología , Diabetes Mellitus Tipo 2/fisiopatología , Resistencia a la Insulina/fisiología , Obesidad/fisiopatología , Proteínas de Unión a los Elementos Reguladores de Esteroles/antagonistas & inhibidores , Tejido Adiposo/efectos de los fármacos , Animales , Glucemia , Colesterol/biosíntesis , Dieta Alta en Grasa , Regulación hacia Abajo , Metabolismo Energético/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Triglicéridos/biosíntesis , Aumento de Peso/efectos de los fármacosRESUMEN
Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acids, and triglycerides. We investigated the effect of the specific SREBP suppressor andrographolide, a natural compound isolated from Andrographis paniculata, on the regulation of SREBP signaling by use of Western blot, reporter gene assay, and quantitative real-time polymerase chain reaction analysis. In addition, the antiobesity effects of andrographolide were evaluated in C57BL/6 mice with high-fat diet (HFD)-induced obesity. Our results showed that andrographolide downregulated the expressions of SREBPs target genes and decreased cellular lipid accumulation in vitro. Further, andrographolide (100 mg/kg per day) attenuated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin or glucose sensitivity in HFD-induced obese mice. Andrographolide effectively suppressed the respiratory quotient, energy expenditure, and oxygen consumption, which may have contributed to the decreased body-weight gain of the obese mice fed with a HFD. Consistently, andrographolide regulated SREBP target genes and metabolism-associated genes in liver or brown adipose tissue, which may have directly contributed to the lower lipid levels and enhanced insulin sensitivity. Taken together, our results indicated that andrographolide ameliorated lipid metabolism and improved glucose use in mice with HFD-induced obesity. Andrographolide has potential as a leading compound in the prevention or treatment of obesity and insulin resistance.
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Dieta Alta en Grasa/efectos adversos , Diterpenos/farmacología , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Animales , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Glucosa/metabolismo , Células Hep G2 , Humanos , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Consumo de Oxígeno/efectos de los fármacos , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: The Danning tablets (DNts) is commonly prescribed in China as a cholagogic formula. Our previous studies showed that DNts exerted the protective effect on α-naphthylisothiocyanate (ANIT)-induced liver injury with cholestasis in a dose-dependent mannar. However, the detailed molecular mechanisms of DNts against ANIT-induced cholestasis are still not fully explored. METHODS: Danning tablet (3 g/kg body weight/day) was administered orally to experimental rats for seven days before they were treated with ANIT (60 mg/kg daily via gastrogavage) which caused cholestasis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (T-Bil), direct bilirubin (D-Bil) and total bile acid (TBA) were measured to evaluate the protective effect of Danning tablet at 12, 24 and 48h after ANIT treatment. Meanwhile, total bilirubin or total bile acid in the bile, urine and liver were also measured at 48h after ANIT treatment. Furthermore, the hepatic or renal mRNA and protein levels of metabolic enzymes and transports were investigated to elucidate the protective mechanisms of Danning tablet against ANIT-induced cholestasis. RESULTS: In this study, we found that DNts significantly attenuated translocation of multidrug resistance-associated protein 2 (Mrp2) from the canalicular membrane into an intracellular and up-regulated the hepatic mRNA and protein expressions of metabolic enzymes including cytochrome P450 2b1(Cyp2b1) and uridine diphosphate-5¢- glucuronosyltransferase (Ugt1a1)) and transporters including bile salt export pump (Bsep) and multidrug resistance protein 2 (Mdr2)) as well as renal organic solute transporter beta (Ostß), accompanied by further increase in urinary and biliary excretion of bile acid and bilirubin. CONCLUSIONS: DNts might promote bile acid and bilirubin elimination by regulating the expressions of hepatic and renal transporters as well as hepatic metabolic enzymes.
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1-Naftilisotiocianato/toxicidad , Colestasis/tratamiento farmacológico , Colestasis/metabolismo , Medicamentos Herbarios Chinos/farmacología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Ácidos y Sales Biliares/metabolismo , Bilirrubina/metabolismo , Transporte Biológico/efectos de los fármacos , Colestasis/inducido químicamente , Colestasis/enzimología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Four new compounds, impecylone (1), deacetylimpecyloside (2), seguinoside K 4-methylether (3) and impecylenolide (4), were isolated from Imperata cylindrica along with two known compounds, impecyloside (5) and seguinoside K (6). Their structures were elucidated mainly by spectroscopic analyses including 1D- and 2D-NMR techniques, and the absolute configuration of 1 was confirmed by X-ray diffraction analysis. In calcium assay, the result indicated that compounds 1, 2, 4 and 5 cannot obviously inhibit the calcium peak value compared with the negative control, and suggested that the four compounds could not have anti-inflammatory activity.
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Fitoquímicos/química , Poaceae/químicaRESUMEN
Chemical investigation of Imperata cylindrica led to the isolation of thirteen compounds using various chromatographic techniques. The structure of these compounds were identified as: three phenylpropanoids, 1-(3,4,5-trimethoxyphenyl)-1,2,3-propanetriol ( 1 ), 1-O-p-coumaroylglycerol (2), 4-methoxy-5-methyl coumarin-7-O-beta-D-glucopyranoside (3); four organic acids, 4-hydroxybenzene carboxylic acid(4), 3,4-dihydroxybenzoic acid (5), vanillic acid (6), 3, 4-dihydroxybutyric acid (7); one phenolic compound, salicin (8); and five triterpenes, namely, arundoin (9), cylindrin (10), fernenol (11), simiarenol (12), glutinone (13) by their physicochemical properties and spectral data analysis. Among them, compounds 1-8 were isolated from the genus Imperata for the first time.
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Medicamentos Herbarios Chinos/química , Poaceae/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Hidroxibenzoatos/química , Hidroxibenzoatos/aislamiento & purificación , Estructura Molecular , Triterpenos/química , Triterpenos/aislamiento & purificación , Ácido Vanílico/química , Ácido Vanílico/aislamiento & purificaciónRESUMEN
The ß-carboline alkaloids, harmaline and harmine, are present in hallucinogenic plants Ayahuasca and Peganum harmala, and in a variety of foods. In order to establish the metabolic pathway and bioactivities of endogenous and xenobiotic bioactive ß-carbolines, high-performance liquid chromatography, coupled with mass spectrometry, was used to identify these metabolites in human liver microsomes (HLMs) in vitro and in rat urine and bile samples after oral administration of the alkaloids. Three metabolites of harmaline and two of harmine were found in the HLMs. Nine metabolites for harmaline and seven metabolites for harmine, from the rat urine and bile samples, were identified. Among them, four in vivo metabolites were isolated and fully characterised by NMR analysis. For the first time, harmaline is shown transforming to harmine by oxidative dehydrogenation in rat. Five metabolic pathways were therefore proposed, namely, oxidative dehydrogenation, 7-O-demethylation, hydroxylation, O-glucuronide conjugation and O-sulphate conjugation.
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Banisteriopsis/metabolismo , Carbolinas/metabolismo , Medicamentos Herbarios Chinos/metabolismo , Harmalina/metabolismo , Harmina/metabolismo , Peganum/metabolismo , Animales , Banisteriopsis/química , Carbolinas/química , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Harmalina/química , Harmina/química , Humanos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Estructura Molecular , Peganum/química , Ratas , Ratas Sprague-Dawley , Espectrometría de Masa por Ionización de Electrospray/métodos , Orina/químicaRESUMEN
Lysimachia christinae Hance (Primulaceae) is a medicinal plant. The present study was undertaken to investigate protection of L. christinae against acute alcohol-induced liver injury in mice, the related mechanism of oxidative stress and its hepatoprotective chemical compound for the first time. Mice were orally administered alcohol at 6 g/kg 2 h after a 75% ethanol extract of L. christinae (ET) (100, 200, 400 mg/kg), quercetin (2, 4, 8 mg/kg) isolated from L. christinae, or bifendate (150 mg/kg) for seven consecutive days by intragastric administration (i.g.) except the normal group. Serum and liver tissue samples were collected 6 h after alcohol administration and the amount of quercetin in ET was analyzed by high-performance liquid chromatography (HPLC) with a diode array detector (DAD). The results showed that alcohol-induced elevated serum alanine transferase (ALT) and aspartate transaminase (AST) activities were significantly reduced by ET (200, 400 mg/kg), quercetin (4, 8 mg/kg) and bifendate (150 mg/kg), respectively. Further analysis demonstrated that lipid peroxidation (LPO) levels significantly decreased, while glutathione amounts, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities all increased in livers of ET-, quercetin-, and bifendate-treated mice. Besides, amount of quercetin in ET was 1.03%. Taken together, our results indicate that L. christinae can protect against acute alcohol-induced liver injury in mice, the potential mechanism can be related to inhibiting liver oxidative stress injury, and its main hepatoprotective compound is quercetin, for the first time.
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Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Etanol/efectos adversos , Extractos Vegetales/uso terapéutico , Primulaceae/química , Animales , Compuestos de Bifenilo/uso terapéutico , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Quercetina/uso terapéuticoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Danning tablet, as a composite prescription of traditional Chinese medicine, has been used clinically to relieve liver and gallbladder diseases in China. However, the mechanisms involved are still unclear. AIM OF THE STUDY: The present investigation was designed to assess the effects and possible mechanisms of Danning tablet on α-naphthylisothiocyanate (ANIT)-induced liver injury with cholestasis. MATERIALS AND METHODS: Danning tablet (3, 1.5 or 0.75g/kg body weight/day) was intragastrically (i.g.) given to experimental rats for seven days before they were treated with ANIT (60mg/kg daily via i.g.) which caused liver injury. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GTP), total bilirubin (T-Bil), direct bilirubin (D-Bil), total bile acid (TBA) and bile flow were measured to evaluate the protective effect of Danning tablet at 48h after ANIT treatment. Furthermore, protective mechanisms of Danning tablet against ANIT-induced liver injury were elucidated by assays of liver enzyme activities and component contents including myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase (CAT) and glutathione S-transferase (GST), as well as liver lipid peroxide (LPO) and glutathione (GSH). The biochemical observations were supplemented by histopathological examination. Phytochemical analysis of Danning tablet was performed by UPLC-MASS. RESULTS: Obtained results demonstrated that high dose (3g/kg) of Danning tablet significantly prevented ANIT-induced changes in bile flow (P<0.01), and serum levels of ALT, AST, ALP, γ-GTP, T-Bil, D-Bil (P<0.01) and TBA (P<0.05). In addition, ANIT-induced increases in hepatic MPO, GST activities and GSH, LPO contents were significantly (P<0.01) reduced, while SOD, Gpx, CAT activities in the liver tissue which were suppressed by ANIT were significantly (P<0.01) elevated in the groups pretreated with Danning tablet at the dose of 3g/kg B.W. Histopathology of the liver tissue showed that pathological injuries were relieved after Danning tablet (3g/kg) pretreatment. The results also showed that medium dose (1.5g/kg) of Danning tablet exhibited partially protective effect on ANIT-induced liver injury with cholestasis by reversing part of biochemical parameters and histopathological changes. Low dose (0.75g/kg) of Danning tablet did not show any protective effect on ANIT-induced liver injury with cholestasis. Phytochemical analyses revealed the presence of anthraquinones, flavonoids and stilbene in the Danning tablet. CONCLUSION: These findings indicate that Danning tablet exerts a dose-dependently protective effect on ANIT-induced liver injury with cholestasis in rats, and the possible mechanism of this activity is likely due to its attenuation of oxidative stress in the liver tissue and neutrophil infiltration.
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Antioxidantes/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Colestasis/prevención & control , Medicamentos Herbarios Chinos/uso terapéutico , Hígado/efectos de los fármacos , Magnoliopsida/química , Fitoterapia , 1-Naftilisotiocianato , Enfermedad Aguda , Animales , Antraquinonas/análisis , Antraquinonas/farmacología , Antraquinonas/uso terapéutico , Antioxidantes/farmacología , Bilis/metabolismo , Bilirrubina/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colestasis/inducido químicamente , Colestasis/metabolismo , Colestasis/patología , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Flavonoides/análisis , Flavonoides/farmacología , Flavonoides/uso terapéutico , Hígado/metabolismo , Hígado/patología , Masculino , Infiltración Neutrófila/efectos de los fármacos , Ratas Wistar , Estilbenos/análisis , Estilbenos/farmacología , Estilbenos/uso terapéutico , Transaminasas/sangreRESUMEN
OBJECTIVE: To study the chemical constituents from the aerial parts of Gelsemium elegans. METHOD: Compounds were isolated and purified by repeated column chromatography, as well as semiprep arative HPLC, and their structures were identified by physicochemical properties and spectroscopic methods, such as NMR and MS. RESULT: Sixteen compounds were obtained and identified from G. elegans, including nine alkaloids: koumine (1), gelsenicine (2), 19-(Z)-akuammidine (3), gelsemoxonine(4), gelsemin (5), gelsevirine (6), humantenine (7), 11-methoxygelsemamide (8) and gelegamine D (9). Three megastigmane glycosides: (3R, 5S, 6S, 7E, 9R)-megastigman-7-ene-3, 5, 6, 9-tetrol-9-O-beta-D-glucopyranoside (10), (6R, 7E, 9R)-9-hydroxy-4, 7-megastigmadien-3-one-9-O-[alpha-L-arabinopyranosyl-(1 --> 6)-beta-D-glucopyranoside] (11) and (6S, 7E, 9R) -6, 9-dihydroxy-4, 7-megastigmadien-3-one-9-O-[alpha-L-arabinopyranosyl-(1 --> 6) -beta-D-glucopyranoside] (12). Two flavone C-glycosides: orientin (13) and isorientin (14); one iridoid glycoside, sweroside (15) and one fructoside, n-butyl-alpha-D-fructofuranoside (16). CONCLUSION: Compounds 10-16 were isolated from the genus Gelsemium for the first time.
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Medicamentos Herbarios Chinos/química , Gelsemium/química , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/aislamiento & purificación , Espectrometría de Masas , Componentes Aéreos de las Plantas/químicaRESUMEN
Six iridoids, geleganoids, designated A-F, and five iridoid glycosides, geleganosides A and B together with three previously reported compounds, were isolated from leaves of Gelsemium elegans. Their structures were elucidated by spectroscopic and chemical analyses. The relative configuration of geleganoid A was confirmed by X-ray crystallographic diffraction analysis, and the absolute configuration of geleganoid B was determined by a modified Mosher's method. Selected compounds were evaluated for PC12 cell neurite outgrowth activity, but they were inactive.
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Gelsemium/química , Glicósidos Iridoides/química , Animales , Glicósidos/química , Glicósidos/aislamiento & purificación , Glicósidos Iridoides/aislamiento & purificación , Estructura Molecular , Células PC12 , Hojas de la Planta/química , RatasRESUMEN
Senecionine (SEN) is a representative of the hepatotoxic pyrrolizidine alkaloids. Although phase I metabolism for cytochrome P450-mediated metabolic activation of SEN was investigated extensively, phase II metabolism for glucuronidation of this compound has not been investigated until now. In our present study, one unique glucuronidation product of SEN in human liver microsomes (HLMs) was identified as SEN N-glucuronide using an authentically synthesized product for which the structure was identified via (1)H and (13)C NMR analysis. Subsequently, kinetics indicated that SEN N-glucuronidation followed the typical Michaelis-Menten model and only one major isozyme participated in it. Finally, this isozyme was demonstrated to be UDP-glucuronosyltransferase (UGT) 1A4, with the direct evidence that recombinant UGT1A4 exhibited predominant and exclusive activity on SEN N-glucuronidation. This result was confirmed by other experiments including chemical inhibition by selective inhibitors and a correlation study between activities of SEN N-glucuronidation and various UGT isozymes. The exclusive role of UGT1A4 on SEN N-glucuronidation was strengthened additionally by its inhibitory kinetic study in which the selective inhibitor of UGT1A4 showed a similar inhibition pattern and K(i) values in both HLM and recombinant UGT1A4 systems. Because UGT2B10 activity failed to correlate with SEN N-glucuronidation in HLMs from 10 individuals, it was impossible for UGT2B10 to play an important role in this metabolism.
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Antineoplásicos Fitogénicos/metabolismo , Glucuronosiltransferasa/metabolismo , Microsomas Hepáticos/metabolismo , Alcaloides de Pirrolicidina/metabolismo , Cromatografía Líquida de Alta Presión , Glucurónidos/metabolismo , Humanos , Técnicas In Vitro , Indicadores y Reactivos , Isoenzimas/metabolismo , Espectroscopía de Resonancia Magnética , Proteínas Recombinantes/metabolismo , Sapogeninas/metabolismo , Espectrometría de Masas en TándemRESUMEN
OBJECTIVE: To study the non-alkaloid chemical constituents of Gelsemium elegans. METHOD: Compounds were isolated and purified by repeated column chromatography, and their structures were elucidated by spectroscopic methods. RESULT: Ten compounds were isolated and their structures were identified as tamarixin (1), tamarixetin 3-O-beta-D-galactopyranoside (2), scopolin (3), scopoletin (4), uradine (5), caffeic acid (6), caffeic acid ethyl ester (7), ferulic acid ethyl ester (8), ethyl-alpha-D-fructofuranoside (9), and ethyl-beta-D-fructopyranoside (10). CONCLUSION: Compounds 1-3,5-10 are firstly isolated from this plant and compounds 1, 2, and 5-10 are isolated from the genus Gelsemium for the first time.