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INTRODUCTION: Passive smoking is considered a major public health issue in China. Prospective evidence regarding the link between secondhand smoke (SHS) and ischemic stroke in China is scarce. METHODS: The China Kadoorie Biobank (CKB) study in Liuzhou City recruited 50,174 participants during 2004-2008. Of these 30,456 never-smokers were included in our study. The median follow-up period was 10.7 years. The incidence of ischemic stroke was obtained through the China Disease Surveillance Points (DSP) system and the Health Insurance (HI) database. Cox proportional risk models were used to evaluate the association between SHS exposure and ischemic stroke. RESULTS: During 320,678 person-years of follow-up, there were 2059 patients with ischemic stroke observed and the incidence of ischemic stroke was 6.42 per thousand person-years. Participants exposed to SHS daily faced a 21 % higher risk of ischemic stroke (HR = 1.21, 95 %CI: 1.09-1.34) compared to those exposed to SHS less than once a week. Subgroup analyses revealed that daily SHS exposure was linked to heightened risk of ischemic stroke among women, non-employed, and non-weekly tea drinkers. CONCLUSIONS: Daily SHS exposure was associated with higher risks of ischemic stroke. Proactive tobacco control strategies are necessary to decrease the risk of ischemic stroke in never smokers.
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AVC Isquêmico , Poluição por Fumaça de Tabaco , Humanos , Feminino , Poluição por Fumaça de Tabaco/efeitos adversos , Estudos Prospectivos , Bancos de Espécimes Biológicos , China/epidemiologiaRESUMO
BACKGROUND: The potential link between environmental pollutants, including metals, and schizophrenia development remains debated. This study aimed to explore the association between plasma levels of three non-essential metals-barium (Ba), tungsten (W), and uranium (U)-and schizophrenia risk among Chinese individuals. METHOD: We recruited a total of 221 patients and 219 healthy controls. Plasma levels of three non-essential metals were measured using inductively coupled plasma mass spectrometry. We employed unconditional logistic regression and Bayesian kernel machine regression (BKMR) to explore the relationship between exposure to multiple metals and the risk of schizophrenia. RESULTS: Logistic regression analysis revealed that the highest quartile (Q4) of W had an odds ratio (OR) of 1.87 (95% CI: 1.08-3.21) compared to the lowest quartile (Q1), with a significant P-trend of 0.017. For U, the ORs (95% CI) for Q2, Q3, and Q4 were 2.06 (1.19-3.56), 1.99 (1.15-3.44), and 1.74 (1.00-3.00), respectively. BKMR analyses revealed a progressive increase in the risk of schizophrenia with increasing cumulative levels of the three metals at concentrations below 35%, with U playing a major role in this association. U showed a non-linear positive correlation with schizophrenia, particularly at the 75th percentile level. Moreover, potential interactions were observed between W and Ba, as well as between W and U. CONCLUSION: Higher plasma W and U concentrations were positively associated with the risk of schizophrenia, which was potentially related to the severity of symptoms in schizophrenic patients.
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ETHNOPHARMACOLOGICAL RELEVANCE: Ludwigia hyssopifolia (LH), an ethnopharmacological herb used in Guangxi Zhuang medicine, is known for its extensive therapeutic use in treating throat disorders. The anti-laryngeal-cancer benefits of the ethyl acetate and petroleum ether fractions of the ethanolic extracts of LH have been shown in our prior cell-based research. Nevertheless, the specific impacts and underlying processes by which LH combats throat cancer effects have not been fully understood. AIM OF THE STUDY: This study involved the extraction of a composition containing two derivatives of ursolic acid from LH (LH-CUAD). The present study aimed to assess the anti-throat-cancer effects of these derivatives and the underlying mechanisms through in vitro and in vivo experiments. MATERIALS AND METHODS: Solvent extraction, fractionation, chromatography, and semipreparative high-performance liquid chromatography were used for the extraction, purification, and analysis of LH-CUAD. The in vitro and in vivo anti-throat-cancer effects of LH-CUAD were investigated using the throat cancer cell lines Hep-2 and FaDu as well as Hep-2 tumor-bearing nude mice. RESULTS: LH-CUAD significantly inhibited the proliferation and migration of throat cancer cells without any prominent toxicity. The Hoechst 33258 staining, Annexin V-FITC/PI double-staining assays, and flow cytometry confirmed that LH-CUAD could induce throat cancer cell death from early to late apoptosis in vitro. LH-CUAD exhibited significant antitumor activity and low toxicity in a xenograft model, and induced throat cancer cells apoptosis in vivo. The apoptotic effects of LH-CUAD therapy were validated using Western blotting, which demonstrated the activation of a caspase cascade response triggered by an imbalance between the endoplasmic reticulum and mitochondria. In addition, it was observed that LH-CUAD exhibited inhibitory effects on Akt and mTOR phosphorylation, hence promoting apoptosis. CONCLUSIONS: LH-CUAD induces apoptosis in both in vivo and in vitro models of throat cancer. This effect is achieved by activating the mitochondrial pathway, inhibiting the Akt/mTOR pathway and initiating endoplasmic reticulum stress. The findings of this study suggest that LH-CUAD has the potential to offer a novel approach to the clinical management of throat cancer.
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Neoplasias , Faringe , Animais , Camundongos , Humanos , Proteínas Proto-Oncogênicas c-akt , Camundongos Nus , China , Transdução de Sinais , Serina-Treonina Quinases TOR , Apoptose , Ácido UrsólicoRESUMO
Guided by MS/MS-based molecular networking strategy, four new cyathane diterpenoids japonin A-D (1-4), together with the known analogues (5 and 6), have been isolated from aerial parts of Onychium japonicum. The structures of the new compounds were elucidated through a combination of NMR and MS experiments. Through single-crystal X-ray diffraction analysis, and comparison of experimental and calculated computational electronic circular dichroism (ECD) spectra, the absolute configurations of compounds 1-4 were determined. The new compound 1 showed promoting effects on the differentiation of PC12 at a concentration of 40 µM.
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Diterpenos , Espectrometria de Massas em Tandem , Estrutura Molecular , Crescimento NeuronalRESUMO
BACKGROUND: Abrus cantoniensis Hance. (Ac) and Abrus mollis (Am), two edible and medicinal plants with economic value in southern China, belong to the Abrus genus. Due to its growth characteristics, Am often replaces Ac in folk medicine. However, the latest National Pharmacopeia of China only recommends Ac. The differences in the metabolite composition of the plants are directly related to the differences in their clinical efficacy. RESULTS: The difference in metabolites were analyzed using an untargeted metabolomic approach based on ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLCâESIâMS/MS). The roots (R), stems (S) and leaves (L) of the two varieties were examined, and 635 metabolites belonging to 8 classes were detected. A comparative study revealed clear variations in the metabolic profiles of the two plants, and the AmR group had more active ingredients (flavonoids and terpenoids) than the AcR group. The metabolites classified as flavonoids and triterpene saponins showed considerable variations among the various samples. Both Ac and Am had unique metabolites. Two metabolites (isovitexin-2''-xyloside and soyasaponin V) specifically belong to Ac, and nine metabolites (vitexin-2"-O-galactoside, ethyl salicylate, 6-acetamidohexanoic acid, rhein-8-O-glucoside, hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)-glucoside, methyl dioxindole-3-acetate, veratric acid, isorhamnetin-3-O-sophoroside-7-O-rhamnoside, and isorhamnetin-3-O-sophoroside) specifically belong to Am. CONCLUSIONS: The metabolite differences between Ac and Am cause the differences in their clinical efficacy. Our findings serve as a foundation for further investigation of biosynthesis pathways and associated bioactivities and provide guidance for the clinical application of traditional Chinese medicine.
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Abrus , Abrus/química , Espectrometria de Massas em Tandem , Flavonoides/química , Glucosídeos , MetabolômicaRESUMO
Four new triterpenoid saponins, tigensides A-D (1-4), and one new C21 steroid, tipregnane A(9), together with six known compounds were isolated from the EtOAc fraction of the roots and stems of Gymnema tingens. The chemical structures of the new compounds were determined based on their spectroscopic data, including IR, UV, NMR, and mass spectrometric analysis. All compounds were isolated for the first time. Compounds 1-11 promoted glucose uptake in the range of 1.12 to 2.52 fold, respectively. Compound 2 showed the most potent glucose uptake, with 2.52 fold enhancement. Additionally, compound 2 showed a medium effect on the GLUT4 translocation activity in L6 cells in further study.
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We report herein the design and synthesis of a series of novel acridine-triazole and acridine-thiadiazole derivatives. The newly synthesized compounds and the key intermediates were all evaluated for their antitumor activities against human foreskin fibroblasts (HFF), human gastric cancer cells-803 (MGC-803), hepatocellular carcinoma bel-7404 (BEL-7404), large cell lung cancer cells (NCI-H460), and bladder cancer cells (T24). Most of the compounds exhibited high levels of antitumor activity against MGC-803 and T24 but low toxicity against human normal liver cells (LO2), and their effect was even better than the commercial anticancer drugs, 5-fluorouracil (5-FU) and cis-platinum. Further, pharmacological mechanisms such as topo I, cell cycle, cell apoptosis, and neovascularization were all evaluated. Only a few compounds exhibited potent topo I inhibitory activity at 100 µM. In addition, the most active compounds with an IC50 value of 5.52-8.93 µM were chosen, and they could induce cell apoptosis in the G2 stage of MGC-803 or mainly arrest T24 cells in the S stage. To our delight, most of the compounds exhibited lower zebrafish cytotoxicity but could strongly inhibit the formation of zebrafish sub-intestinal veins, indicating a potential for clinical application.
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Antineoplásicos , Fármacos Dermatológicos , Neoplasias , Tiadiazóis , Animais , Humanos , Peixe-Zebra , Triazóis/farmacologia , Tiadiazóis/farmacologia , Acridinas/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Fluoruracila/farmacologia , Apoptose , Fármacos Dermatológicos/farmacologia , Proliferação de Células , Relação Estrutura-Atividade , Estrutura Molecular , Neoplasias/tratamento farmacológicoRESUMO
A pair of new isocoumarin derivative enantiomers, (S)-(-)-3-(3,3-dichloro-2-hydroxy-propyl)-4-chlorine-6,8-dihydroxy-isochromen-1- one (1a) and (R)-(+)-3-(3,3-dichloro-2-hydroxy-propyl)-4-chlorine-6,8-dihydroxy-isochromen-1- one (1 b), as well as seven known compounds (2-8) were isolated from Ludwigia hyssopifolia. Compounds 1a and 1 b were confirmed to be a pair of enantiomers by chiral HPLC-CD analysis, and the structure of compound 1 was determined by spectroscopic analyses including extensive 1 D (1H NMR, 13C NMR) and 2 D NMR spectra (COSY, HSQC and HMBC) and MS data. And the absolute configurations of compounds 1a and 1 b were determined by the quantum chemical ECD calculations. Compounds 2-8 are firstly reported from this plant. In the in vitro assays, compounds 5 and 8 can inhibit human laryngeal cancer Hep-2 cell line growth in a dose- and time-dependent manner. In addition, compounds 2 and 4 have effects on increasing glucose uptake in vitro. Compound 2 showed a strong glucose uptake in L6 cells, with enhancements by 1.8 folds.
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Isocumarinas , Onagraceae , Humanos , Isocumarinas/química , Isocumarinas/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , EstereoisomerismoRESUMO
Gymnema sylvestre (Retz.) Schult is a multi-purpose traditional medicine that has long been used for the treatment of various diseases. To discover the potential bioactive composition of G. sylvestre, a chemical investigation was thus performed. In this research, four new C21 steroidal glycosides sylvepregosides A-D (1-4) were isolated along with four known compounds, gymnepregoside H (5), deacetylkidjoladinin (6), gymnepregoside G (7) and gymnepregoside I (8), from the ethyl acetate fraction of G. sylvestre. The structures of the new compounds were established by extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectroscopy data. Compounds 1-6 promoted glucose uptake by the range of 1.10- to 2.37-fold, respectively. Compound 1 showed the most potent glucose uptake, with 1.37-fold enhancement. Further study showed that compounds 1 and 5 could promote GLUT-4 fusion with the plasma membrane in L6 cells. The result attained in this study indicated that the separation and characterization of these compounds play an important role in the research and development of new anti-diabetic drugs and pharmaceutical industry.
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Glucose/antagonistas & inibidores , Glicosídeos/farmacologia , Gymnema sylvestre/química , Hipoglicemiantes/farmacologia , Esteroides/farmacologia , Animais , Linhagem Celular , Indústria Farmacêutica , Glucose/metabolismo , Glicosídeos/química , Glicosídeos/isolamento & purificação , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Conformação Molecular , Ratos , Estereoisomerismo , Esteroides/química , Esteroides/isolamento & purificaçãoRESUMO
Four new aromatic meroterpenoids, ganocapenoids A-D (1-4), together with twelve known analogues (5-16) were isolated from the fruiting bodies of Ganoderma capense. The structures of new compounds were determined through spectroscopic methods including 1D and 2D NMR and MS analyses. Their absolute configurations were assigned by ECD calculations and specific rotation comparison. The biological activities of these substances toward regulation of lipid metabolism, neurite outgrowth-promoting activity, and AchE inhibition were assessed. Compound 15 was found to be able to block lipid accumulation at a concentration of 20⯵M, and compounds 4a, 4b, and 11 show moderate neurite outgrowth-promoting activity at 10⯵M, while compounds 3, 6, 11, and 13 exhibit potent AchE inhibition with the IC50 values of 28.6⯱â¯1.9, 18.7⯱â¯1.6, 8.2⯱â¯0.2, 26.0⯱â¯2.9⯵M, respectively.
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Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Ganoderma/química , Terpenos/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
OBJECTIVE: To study the chemical constituents of Phyllanthus emblica. METHODS: The chemical constituents were isolated and purified by silica gel, polyamide and Sephadex LH-20 chromatography. Their structures were elucidated by physicochemical proper- ties and spectral analysis. RESULTS: 13 compounds were isolated and identified as Triacontanol (1), Triacontanoic acid (2), ß-Amyrin ke- tone (3), Betulonic acid (4), Daucosterol (5), Lupeol acetate (6), ß-Amyrin-3-palmitate (7), Gallic acid (8), Betulinic acid (9), Ursolic acid (10), Oleanolic acid (11), Quercetin (12) and Rutin (13). CONCLUSION: Compounds 1,2,4,6,7,9,10 and 11 are obtained from Phyllanthus emblica for the first time.
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Phyllanthus emblica/química , Compostos Fitoquímicos/química , Plantas Medicinais/química , Ácido Gálico , Ácido Oleanólico/análogos & derivados , Triterpenos Pentacíclicos , Compostos Fitoquímicos/isolamento & purificação , Quercetina , Rutina , Triterpenos , Ácido Betulínico , Ácido UrsólicoRESUMO
OBJECTIVE: To study the chemical constituents of Viscum ovalifolium. METHODS: The chemical constituents from Viscum ovalifolium were isolated and purified by silica gel column chromatography, polyamide column chromatography and recrystallization methods. Their structures were elucidated by physicochemical properties and spectral analysis. RESULTS: Twelve compounds were isolated and their structures were identified as 1-octadecene (1), ethyl palmitate (2), 28-hydrxy-amyrone (3), betulinic acid (4), rutin (5), quercetin (6), beta-amyrinpalmitate (7), lupeol acetate (8), beta-amyrin (9), beta-sitosterol (10), lupeol (11) and oleanolic acid (12). CONCLUSION: Compounds 1 - 6 are obtained from this plant for the first time.
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Alcenos/isolamento & purificação , Ácidos Palmíticos/isolamento & purificação , Triterpenos/isolamento & purificação , Viscum/química , Alcenos/química , Estrutura Molecular , Ácidos Palmíticos/química , Triterpenos Pentacíclicos , Folhas de Planta/química , Caules de Planta/química , Quercetina/química , Quercetina/isolamento & purificação , Triterpenos/química , Ácido BetulínicoRESUMO
OBJECTIVE: To study the chemical constituents of Uvaria microcarpa. METHODS: The constituents were repeatedly separated and purified with silica gel column and Sephadex LH-20 column, and identified by physico-chemical properties and spectral methods. RESULTS: Nine compounds were separated and identified as beta-sitosterol palmitate (I), euphorginol (II), beta-sitosterol (III), benzoic acid(IV), stigmasterol-3-O-beta-D-glucopyranoside (V), taraxerol (VI), emodin (VII), aristololactam A II (VI), beta-daucosterol (IX) . CONCLUSION: Compounds I, II, V, V are isolated from this plant for the first time.
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Emodina/isolamento & purificação , Glucosídeos/isolamento & purificação , Plantas Medicinais/química , Sitosteroides/isolamento & purificação , Estigmasterol/análogos & derivados , Uvaria/química , Emodina/química , Glucosídeos/química , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Caules de Planta/química , Sitosteroides/química , Espectrofotometria Ultravioleta , Estigmasterol/química , Estigmasterol/isolamento & purificaçãoRESUMO
OBJECTIVE: To study on the chemical constituents from the stem of Gymnema sylvestre. METHODS: The constituents were extracted by percolation with ethanol. Then the extract was separated by systemic solvent separation methods. The part of n-butanol extract was isolated and purified by macroporous adsorptive resins, silica gel column chromatography, sephadex gel column chromatography and recrystallization. The isolated compounds were identified by spectrum methods. RESULTS: Eight compounds were isolated and identified as fallows: Conduritol A(I), 1-Heptadecanol(II), Stigmasterol glucoside(III), 1-Quercitol(IV), 1-Octadecanol(V), Potassium nitrate(VI), Lupeol cinnamate(VII), Stigmasterol(VIII). CONCLUSION: Chemical compounds II, III, V, VII are firstly obtained from this plant.
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Álcoois Graxos/isolamento & purificação , Glucosídeos/isolamento & purificação , Gymnema sylvestre/química , Plantas Medicinais/química , Estigmasterol/análogos & derivados , Álcoois Graxos/química , Glucosídeos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Nitratos/química , Nitratos/isolamento & purificação , Caules de Planta/química , Compostos de Potássio/química , Compostos de Potássio/isolamento & purificação , Estigmasterol/química , Estigmasterol/isolamento & purificaçãoRESUMO
OBJECTIVE: To find out the optimum extraction technology of soyasaponins from residual of bean ware. METHODS: The optimum extraction conditions were investigated by the orthogonal design, and the content of soyasaponins was determined by UV-spectro-pho-tometry. RESULTS: The optimum extraction technology was A3B1C1, that is adding 7 times and 6 times amount of 70% alcohol and refluxing for two times and each time for 1.0 h. CONCLUSION: The selected technology showed higher yield of soyasaponins, good stability and high efficient.