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1.
Environ Res ; 238(Pt 2): 117161, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37717800

RESUMO

BACKGROUND: A growing number of studies have shown that prenatal exposure to chemical and non-chemical stressors has effects on fetal growth. The co-exposure of both better reflects real-life exposure patterns. However, no studies have included air pollutants and pregnancy-related anxiety (PrA) as mixtures in the analysis. METHOD: Using the birth cohort study method, 576 mother-child pairs were included in the Ma'anshan Maternal and Child Health Hospital. Evaluate the exposure levels of six air pollutants during pregnancy using inverse distance weighting (IDW) based on the pregnant woman's residential address and air pollution data from monitoring stations. Prenatal anxiety levels were assessed using the PrA Questionnaire. Generalized linear regression (GLR), quantile g-computation (QgC) and bayesian kernel machine regression (BKMR) were used to assess the independent or combined effects of air pollutants and PrA on birth weight for gestational age z-score (BWz). RESULT: The results of GLR indicate that the correlation between the six air pollutants and PrA with BWz varies depending on the different stages of pregnancy and pollutants. The QgC shows that during trimester 1, when air pollutants and PrA are considered as a whole exposure, an increase of one quartile is significantly negatively correlated with BWz. The BKMR similarly indicates that during trimester 1, the combined exposure of air pollutants and PrA is moderately correlated with a decrease in BWz. CONCLUSION: Using the method of analyzing mixed exposures, we found that during pregnancy, the combined exposure of air pollutants and PrA, particularly during trimester 1, is associated with BWz decrease. This supports the view that prenatal exposure to chemical and non-chemical stressors has an impact on fetal growth.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Humanos , Peso ao Nascer , Estudos de Coortes , Estudos Prospectivos , Teorema de Bayes , Exposição Materna , Poluição do Ar/análise , Poluentes Atmosféricos/análise , China , Ansiedade , Material Particulado/análise
2.
Arch Gynecol Obstet ; 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773466

RESUMO

BACKGROUND: It has been suggested that gestational diabetes mellitus (GDM) alters the growth trajectory of a fetus and increases the risk of abnormal birth weight. In spite of this, there is still a significant debate regarding the mode and optimal timing of diagnosing this condition. Our aim was to determine fetal growth velocity and birth biometry in pregnant women with GDM at varying risk levels. METHODS: We conducted a cohort study involving 1023 pregnant women at a maternity hospital in Ma'anshan, China. All women completed an oral glucose tolerance test at 24-28 weeks' gestation. We measured fetal head circumference (HC), femoral length (FL), abdominal circumference (AC), biparietal diameter (BPD), and estimate fetal weight (EFW) by ultrasound at 17, 24, 31, and 35 weeks' gestation, respectively. RESULTS: Overall, 5115 ultrasound scans were performed. Among both low-risk and medium-high-risk pregnant women at 17-24 weeks' gestation, GDM exposure was associated with an increase in fetal growth velocity. Neonates born to women with GDM at medium-high risk had significantly larger birth weights than those born to women without GDM, while this was not observed in women at low risk. CONCLUSION: In medium-high-risk pregnant women, exposure to GDM has a greater effect on the fetus, leading to abnormal fetal growth velocity that lasts beyond week 24. It is evident from our results that the effects of GDM on fetal growth differ between medium-high-risk pregnant women and low-risk pregnant women, and therefore a different screening program based on the risk factor for GDM is warranted.

3.
Environ Geochem Health ; 45(11): 8187-8202, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37552412

RESUMO

We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Gengivite , Doenças Periodontais , Periodontite , Humanos , Idoso , Dióxido de Nitrogênio/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Material Particulado/análise , Conceitos Meteorológicos , Doenças Periodontais/etiologia , Doenças Periodontais/induzido quimicamente , Periodontite/induzido quimicamente , Gengivite/induzido quimicamente , Gengivite/epidemiologia , China , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise
4.
Environ Sci Technol ; 55(24): 16627-16635, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34889591

RESUMO

Antibiotics are widely found in nitrogen-containing wastewater, which may affect the operation stability of anaerobic ammonium oxidation (anammox)-based biological treatment systems. Extracellular polymeric substances (EPSs) of anammox sludge play a pivotal role in combining with antibiotics; however, the exact role and how the structure of the leading component of EPSs (i.e., extracellular proteins) changes under antibiotic stress remain to be elucidated. Here, the interaction between sulfamethoxazole and the extracellular proteins of anammox sludge was investigated via multiple spectra and molecular simulation. Results showed that sulfamethoxazole statically quenched the fluorescent components of EPSs, and the quenching constant of the aromatic proteins was the largest, with a value of 1.73 × 104 M-1. The overall binding was an enthalpy-driven process, with ΔH = -75.15 kJ mol-1, ΔS = -0.175 kJ mol-1 K-1, and ΔG = -21.10 kJ mol-1 at 35 °C. The O-P-O and C═O groups responded first under the disturbance of sulfamethoxazole. Excessive sulfamethoxazole (20 mg L-1) would decrease the ratio of α-helix/(ß-sheet + random coil) of extracellular proteins, resulting in a loose structure. Molecular docking and dynamic simulation revealed that extracellular proteins would provide abundant sites to bind with sulfamethoxazole, through hydrogen bond and Pi-Akyl hydrophobic interaction forces. Once sulfamethoxazole penetrates into the cell surface and combines with the transmembrane ammonium transport domain, it may inhibit the NH4+ transport. Our findings enhance the understanding on the interaction of extracellular proteins and sulfamethoxazole, which may be valuable for deciphering the response property of anammox sludge under the antibiotic stress.


Assuntos
Compostos de Amônio , Esgotos , Oxidação Anaeróbia da Amônia , Anaerobiose , Reatores Biológicos , Simulação de Acoplamento Molecular , Nitrogênio , Oxirredução , Sulfametoxazol
5.
J Asian Nat Prod Res ; 22(8): 738-745, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31131622

RESUMO

Two new isopimarane diterpenoids, named 1α-hydroxy-7-oxoisopimara-8, 15-diene (1), 11ß-hydroxy-7-oxoisopimara-8(14), 15-diene (2), together with six known compounds (3-8), were isolated from the medicinal plant Salacia cochinchinensis. All isolates were assayed for their cytotoxicity and α-glucosidase inhibitory activity. Results suggested compounds 1, 3 possessed significant cytotoxic activity against HepG2, HL60, and Hela cell lines with IC50 values ranging from 0.23 to 0.35 µM, and compounds 7, 8 exhibited noticeable α-glucosidase inhibitory ability with IC50 values of 0.25 and 0.31 µM, respectively.


Assuntos
Diterpenos , Salacia , Células HeLa , Humanos , Estrutura Molecular , alfa-Glucosidases
6.
Zhongguo Zhong Yao Za Zhi ; 43(13): 2705-2712, 2018 Jul.
Artigo em Zh | MEDLINE | ID: mdl-30111020

RESUMO

In order to establish a more perfect evaluation system for dryness effect of Atractylodis Rhizoma, determine the main dry parts of Atractylodis Rhizoma,and further define the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness. The healthy rats were given with different doses of water extract and volatile oil of raw Atractylodis Rhizoma and stir-baked Atractylodis Rhizoma for 21 days. Based on the theory of the dry-dry and dryness-induced Yin deficiency, the amount of drinking water, tissue morphology of submandibular glands, urine volume and the expression of aquaporin 2 (AQP2) in the kidneys, as well as blood rheology, ratio of cAMP/cGMP in serum and the content of Na⁺-K⁺-ATP enzyme were selected as the evaluation indexes. The results indicated that the rats with high dose volatile oil from raw Atractylodis Rhizoma had a significant increase in the amount of drinking water, urine volume, blood viscosity, ratio of cAMP/cGMP and content of Na⁺-K⁺-ATP enzyme in the serum(P<0.05)as compared with the soybean oil group; meanwhile, atrophy of submandibular acinar gland was obvious,and the expression of aquaporin 2 was reduced significantly(P<0.05). There were significant differences between volatile oil high dose group of raw Atractylodis Rhizoma and volatile oil high dose group of stir-baked Atractylodis Rhizoma. There was no significant difference between the water extract groups of raw and stir-baked Atractylodis Rhizoma and the saline group. A comprehensive evaluation system for the dryness effect of Atractylodis Rhizoma was established. It was confirmed that the volatile oil part was the main dry part of Atractylodis Rhizoma. It revealed that the mechanism of dryness effect of Atractylodis Rhizoma was not only related to the decrease of the total content of the volatile oil, but also may be related to the transformation of dryness components in the volatile oil. It provides references for the study of material basis of Atractylodis Rhizoma dryness, provides an experimental basis for the clinical application of Atractylodis Rhizoma, further clarifies the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness, and provides thoughts for the evaluation of other dry traditional Chinese medicines.


Assuntos
Atractylodes , Medicamentos de Ervas Chinesas , Animais , Aquaporina 2 , Ratos , Rizoma , Deficiência da Energia Yin
7.
Chem Biodivers ; 14(7)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28419767

RESUMO

Four new diterpene glucosides, namely perovskiaditerpenosides A - D (1 - 4), were isolated from the BuOH extract of Perovskia atriplicifolia. Their structures were well elucidated by chemical methods and comprehensive spectroscopic analyses including MS, IR, and NMR (1D and 2D). The newly isolated compounds were screened for their cytotoxic activity against HepG2, NB4, HeLa, K562, MCF7, PC3, and HL60. The obtained results indicated that the new compounds possessed considerable cytotoxic activity.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Diterpenos/isolamento & purificação , Glucosídeos/isolamento & purificação , Lamiaceae/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Butanóis , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Extratos Vegetais , Análise Espectral
8.
Environ Sci Pollut Res Int ; 30(12): 34229-34242, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36504301

RESUMO

Some previous studies had linked air pollutants and greenness to the risk of death from tuberculosis (TB). Only a few studies had examined the effect of particulate matter (PM2.5) on the mortality of TB, and few studies had assessed the impact and interaction of multiple air pollutants and greenness on the mortality of newly treated TB patients. The study included 29,519 newly treated TB patients from three cities in Anhui province. We collected meteorological data and five pollutants data from The National Meteorological Science Center and air quality monitoring stations. Greenness data were generated by remote sensing inversion of medium-resolution satellite images. We geocoded each patient based on the residential address to calculate the average exposure to air pollutants and the average greenness exposure for each patient during treatment. The Cox proportional risk regression model was used to evaluate the effects of air pollutants and greenness on mortality in newly treated tuberculosis patients. Our results found that the higher the concentration of air pollutants in the living environment of newly treated TB patients, the greater the risk of death: HR 1.135 (95% CI: 1.123-1.147) and HR 1.333 (95% CI: 1.296-1.370) per 10 µg/m3 of PM2.5 and SO2, respectively. Greenness reduced the mortality among newly treated TB patients: HR for NDVI exposure 0.936 (95% CI: 0.925-0.947), HR for NDVI_250m exposure 0.927 (95% CI: 0.916-0.938), and HR for NDVI_500m exposure 0.919 (95% CI: 0.908-0.931). Stratifying the cohort by median greenness exposure, HRs for air pollutants were lower in the high greenness exposure group. Mortality in newly treated TB patients is influenced by air pollutants and greenness. Higher green exposure can mitigate the effects of air pollution. Improving air quality may help reduce mortality among newly treated TB patients.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Cidades , Exposição Ambiental/análise
9.
Environ Sci Pollut Res Int ; 30(43): 98195-98210, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37608175

RESUMO

BACKGROUND: Previous studies addressing the impact of environmental factors on TB prognosis are scarce, with only some studies examining the effect of particulate pollutants on TB mortality. Moreover, few studies have evaluated the effects of multiple gaseous pollutants and greenness exposures on newly treated TB patients on a large population scale. METHODS: Through the Centers for Disease Control and Prevention, data were collected from January 1, 2015 to December 31, 2020 for newly treated TB patients in Anhui Province, China. Data on gaseous pollutants sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone were collected through the National Earth System Science Data Center of China. Normalized vegetation index data were obtained through NASA. The Cox proportional risk model was also applied to calculate the hazard ratios of SO2, NO2, CO, O3, and NDVI with 95% confidence intervals for mortality among newly treated TB patients. RESULTS: Multifactorial Cox regression analysis showed that for every 0.10 µg/m3 increase in SO2, the risk of death among newly treated TB patients increased by 13.2% (HR = 1.132, 95% CI: 1.045-1.1.225), for every 10 µg/m3 increase in NO2, the risk of death among newly treated TB patients increased by 11.4%, and for each 0.1 mg/m3 increase in CO, the risk of death among newly treated TB patients increased by 5.8%. For each 0.1 increase in NDVI 250m-buffer and 500m-buffer, the risk of death among newly treated TB patients decreased by 8.5% and 6.4%, respectively. The effect of gaseous pollutants on mortality decreased progressively with elevated greenness exposure when greenness exposure was grouped from low to high. CONCLUSION: Gaseous pollutants are a risk factor during the treatment of newly treated TB patients and greenness exposure is a protective factor. Higher greenness exposure reduces the risk of death due to exposure to gaseous pollutants.


Assuntos
Poluentes Ambientais , Tuberculose , Estados Unidos , Humanos , Dióxido de Nitrogênio , Estudos de Coortes , Dióxido de Enxofre
10.
Environ Sci Pollut Res Int ; 30(49): 107887-107898, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37740806

RESUMO

Some heavy metals are associated with periodontitis; whereas most of these associations have focused on individual metal, there are no specific studies on the effects of combined heavy metal exposure on periodontitis. We conducted an analysis on the association between urinary heavy metal exposure and periodontitis in participants aged 30 years and older using multiple logistic regression and Bayesian kernel machine regression (BKMR). This analysis was performed on data from the National Health and Nutrition Examination Survey from 2011 to 2014. The study found that using logistic regression, the 4th quartile of urinary lead and molybdenum and the 3rd quartile of urinary strontium were positively associated with periodontitis compared to the reference quartile after adjusting for covariates. Odds ratio (OR) with 95% confidence interval (CI) was 1.738 (1.069-2.826), 1.515 (1.025-2.239), and 1.498 (1.010-2.222), respectively. The 3rd and 4th quartiles of urinary cobalt were negatively associated with periodontitis, and their ORs and 95% CIs were 0.639 (0.438-0.934) and 0.571 (0.377-0.964), respectively. The BKMR model showed that urinary barium, lead, and molybdenum were positively associated with periodontitis in a range of concentrations and urinary cobalt, manganese, tin, and strontium were negatively correlated with periodontitis. Furthermore, the overall association between urinary heavy metals and periodontitis was positive. Our study provides evidence for an association between exposure to multiple urinary heavy metals and periodontitis. However, further longitudinal studies are needed to explore the specific mechanisms involved.


Assuntos
Metais Pesados , Periodontite , Adulto , Humanos , Inquéritos Nutricionais , Molibdênio , Teorema de Bayes , Cobalto , Periodontite/epidemiologia , Estrôncio , Cádmio
11.
Environ Sci Pollut Res Int ; 29(33): 50304-50316, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35224697

RESUMO

A growing number of biological studies suggest that exogenous sulfur dioxide (SO2) at a certain concentration may promote human resistance to Mycobacterium tuberculosis. However, the results of most relevant studies are inconsistent, and few studies have explored the relationship between SO2 exposure and tuberculosis risk at provincial level. In addition, occupational exposure has long been considered to have a certain impact on the human body, so for the first time, we discussed the differences between different occupations in the study on the relationship between air pollutant exposure and tuberculosis risk, and evaluated the impact of occupational exposure. This study aimed to explore the association between short-term SO2 exposure and the risk of outpatient visits to tuberculosis in Anhui province and 16 prefecture-level cities from 2015 to 2020. We used several models for multi-stage analysis, including distributed lag nonlinear model (DLNM), Poisson generalized linear regression model, and random-effects model. The association was assessed using the 28-day cumulative lag effect RR and 95%CI for each 10-unit increase in SO2 concentration. We divided all patients into the following six occupations: Worker, Farmer, Retired people, Children and Students, Cadre and Office clerk, and Service staff (catering, business, etc.). Sex, age, and season were analyzed by subgroup. Finally, the robustness of the multi-pollutant model was tested. At provincial level, the overall effect value of SO2 was RR=0.8191 (95%CI: 07702~0.8712); after grouping all patients by occupation, the association found only among Farmers (RR = 0.7150, 95%CI: 0.6699-0.7632, lag 0-28 days) and Workers (RR = 0.8566, 95%CI: 0.7930-0.9930, lag 0-4 days) was still statistically significant. Estimates for individual cities and using random-effects models to estimate average associations showed that SO2 exposure was associated with a reduced risk of outpatient TB visits in 14 municipalities, which remained significant when aggregated (RR = 0.9030, 95%CI: 0.8730-0.9340). Analysis of patients grouped by occupation in each municipality showed that statistical significance was again observed only in the Farmer (RR = 0.8880, 95%CI: 0.8610-0.9160) and Worker (RR = 0.8250, 95%CI: 0.7290-0.9340) groups. Stratified analysis of age, sex, and season showed that the effect of SO2 exposure was greater for middle-aged people (18-64 years old) and males, and less for seasonal changes. In summary, we found that exposure to SO2 reduces the risk of outpatient visits to tuberculosis, with farmers and workers more susceptible to SO2. Gender and age had a greater impact on the risk of TB outpatient visits than seasonal variations.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Tuberculose , Adolescente , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Criança , China/epidemiologia , Cidades , Humanos , Masculino , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Pacientes Ambulatoriais , Material Particulado/análise , Dióxido de Enxofre/análise , Tuberculose/epidemiologia , Adulto Jovem
12.
Carbohydr Res ; 484: 107777, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31446303

RESUMO

Four new triterpene glycosides, named salaciacochinosides A-D (1-4) were isolated from the 90% ethanol extract of Salacia cochinchinensis, together with five known compounds 2α,3ß,23-trihydroxyurs-12,18-dien-28-oic acid 28-O-ß-d-glucopyranoside (5), racemiside (6), alangiplatanoside (7), acantrifoside E (8), and syringin (9). The structures of the four new triterpenoids were characterized by chemical methods and MS, IR, 1D and 2D NMR spectral analyses. The α-glucosidase inhibitory activities of the nine compounds were assessed, compounds 6 and 7 showed remarkable α-glucosidase inhibitory activities, with IC50 values of 0.44 and 0.75 µM, respectively. Compounds 1-5 exhibited moderate α-glucosidase inhibitory activities, and compounds 8 and 9 showed none α-glucosidase inhibitory activity in our current experiments.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Glicosídeos/química , Salacia/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Concentração Inibidora 50 , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triterpenos/química , Triterpenos/farmacologia
13.
Fitoterapia ; 130: 152-155, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30172827

RESUMO

Two new terpenoids, named biperovskatone B (1) and 1α- hydroxyl demethylsalvicanol quinine (2), were isolated from the cultured Perovskia atriplicifolia. Their structures were elucidated by comprehensive analyses of the MS, IR, 1D and 2D NMR spectra. Compound 1 was a novel diterpenoid dimer, containing two different rearranged 9(10 → 20)-abeoabietane type diterpenoid fragments. Compound 2 was a new icetexane diterpenoid with characteristic ortho-quinone carbonyl groups. Both compounds were assayed for their anti-HBV activity in vitro. Results suggested compounds 1 and 2 showed noticeable anti- anti-HBV activity, inhibiting the replication of HBV DNA with IC50 values of 10.78 and 8.61 µM, respectively.


Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Salvia/química , Terpenos/farmacologia , Antivirais/isolamento & purificação , China , Células Hep G2 , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Terpenos/isolamento & purificação
14.
Nat Prod Commun ; 11(6): 747-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27534107

RESUMO

Two new 13, 14/14, 15-disecopregnane-type skeleton C21 steroidal aglycones, neocynapanogenin G (1) and neocynapanogenin H (2), were isolated from the hydrolyzed extract of the CHCl3 soluble extract of the roots of Cynanchun paniculatum. Their structures were determined on the basis of chemical evidence and extensive spectroscopic methods, including 1D and 2D NMR spectroscopy. Compound 1 displayed signifidant inhibition of the Hedgehog signaling pathway in vitro.


Assuntos
Cynanchum/química , Medicamentos de Ervas Chinesas/química , Iridoides/química , Raízes de Plantas/química , Esteroides/química , Animais , Linhagem Celular , Ouriços/genética , Ouriços/metabolismo , Humanos , Estrutura Molecular , Transdução de Sinais/efeitos dos fármacos
15.
Nat Prod Commun ; 11(12): 1797-1800, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30508336

RESUMO

Two new 8, 14-seco skeleton C(21) steroidal aglycones, cynanbungeigenin A (1) and cynanbungeigenin B (2), were isolated from the hydrolyzed extract of the EtOAc soluble extract of the roots of Cynanchum bungei. Their structures were determined on the basis of chemical evidence and extensive spectroscopic methods, including 1D and 2D NMR spectroscopy.


Assuntos
Cynanchum/química , Pregnanos/isolamento & purificação , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Proteínas Hedgehog/antagonistas & inibidores , Camundongos , Células NIH 3T3 , Extratos Vegetais/química , Raízes de Plantas/química , Pregnanos/química , Pregnanos/farmacologia , Espectroscopia de Prótons por Ressonância Magnética
16.
Eur J Pharmacol ; 789: 370-384, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27448502

RESUMO

Stephanthraniline A (STA), a C21 steroid isolated from Stephanotis mucronata (Blanco) Merr., was previously shown to inhibit T cells activation and proliferation in vitro and in vivo. The purpose of this study was to further evaluate the in vivo immunosuppressive activity of STA and to elucidate its potential mechanisms. The results showed that pretreatment with STA significantly attenuated concanavalin A (Con A)-induced hepatitis and reduced CD4(+) T cells activation and aggregation in hepatic tissue in mice. STA directly suppressed the activation and proliferation of Con A-induced CD4(+) T cells, and inhibited NFAT, NFκB and MAPK signaling cascades in activated CD4(+) T cells in vitro. Moreover, it was proved that STA inhibited T cells activation and proliferation through proximal T cell-receptor (TCR) signaling- and Ca(2+) signaling-independent way. The molecular docking studies predicted that STA could tight bind to PKCθ via five hydrogen. The further findings indicated STA directly inhibited PKCθ kinase activity, and its phosphorylation in activated CD4(+) T cells in vitro. Collectively, the present study indicated that STA could protect against CD4(+) T cell-mediated immunological hepatitis in mice through PKCθ and its downstream NFAT, NFκB and MAPK signaling cascades. These results highlight the potential of STA as an effective leading compound for use in the treatment of CD4(+) T cell-mediated inflammatory and autoimmune diseases.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Diterpenos/farmacologia , Hepatite/tratamento farmacológico , Hepatite/imunologia , Isoenzimas/antagonistas & inibidores , Ativação Linfocitária/efeitos dos fármacos , Proteína Quinase C/antagonistas & inibidores , Animais , Sinalização do Cálcio/efeitos dos fármacos , Domínio Catalítico , Agregação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diterpenos/metabolismo , Diterpenos/uso terapêutico , Feminino , Hepatite/metabolismo , Hepatite/patologia , Isoenzimas/química , Isoenzimas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Fosforilação/efeitos dos fármacos , Proteína Quinase C/química , Proteína Quinase C/metabolismo , Proteína Quinase C-theta , Proteínas Quinases/metabolismo
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