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Metal-organic frameworks (MOFs) are porous materials composed of metal ions and organic ligands. Due to their large surface area, easy modification, and good biocompatibility, MOFs are often used in bio-related fields. Fe-based metal-organic frameworks (Fe-MOFs), as important types of MOF, are favored by biomedical researchers for their advantages, such as low toxicity, good stability, high drug-loading capacity, and flexible structure. Fe-MOFs are diverse and widely used. Many new Fe-MOFs have appeared in recent years, with new modification methods and innovative design ideas, leading to the transformation of Fe-MOFs from single-mode therapy to multi-mode therapy. In this paper, the therapeutic principles, classification, characteristics, preparation methods, surface modification, and applications of Fe-MOFs in recent years are reviewed to understand the development trends and existing problems in Fe-MOFs, with the view to provide new ideas and directions for future research.
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As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.
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Arsênio , Arsenicais , Produtos Biológicos , Medicamentos de Ervas Chinesas , Arsênio/toxicidade , Arsênio/análise , Arsenicais/análise , Sulfetos , Trióxido de Arsênio , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/toxicidade , Medicamentos de Ervas Chinesas/análiseRESUMO
At present, several experiments have been carried out to study the changes in total arsenic content of realgar and its prescription, but few researches on its form and valence. We evaluated the change in arsenic species concentration in realgar from the perspective of absorption by using an in vitro dissolution study, an in vivo unidirectional intestinal perfusion study, transmembrane transport in Caco-2 cells, and a pharmacokinetic study in rats. In the gastrointestinal tract, arsenic species are mainly present inorganic forms of AsIII and AsV. The cumulative dissolution rates of soluble arsenic in 4 h artificial gastric fluid and 8 h artificial intestinal fluid were 21.99% and 59.20%, respectively. The P app values of soluble arsenic in realgar in the duodenum, jejunum, and ileum of rats were 5.4 × 10-3, 6.1 × 10-3 and 5.8 × 10-3 cm/min, respectively. In the process of small intestine perfusion, the AsIII of realgar was partially converted into AsV in the duodenum and jejunum. As the transport time increased, the transmembrane transport rate and P app value of soluble arsenic in realgar were increased in Caco-2 cells, and it also suggested that arsenic species may be passively transported across the Caco-2 cell monolayer. The C max and AUC (0-24) of AsIII, AsV, and DMA in plasma of realgar were 41.26 ng L-1/343.977 ng h mL-1, 21.626 ng L-1/47.310 ng h mL-1, and 2.372 ng L-1/30.429 ng h mL-1, respectively. T max and MRT (0-∞) of AsIII, AsV, and DMA were 2.571 h/9.649 h, 0.393 h/2.790 h, and 3.143 h/23.145 h, respectively. It is hoped to provide a basis for clarifying the arsenic species in realgar.
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In this study, the critical quality attributes of Wuzhuyu Decoction reference sample were explored by using characteristic chromatogram, index component content and dry extract rate as indexes.The dissemination relationship of quantity value between medicinal materials-decoction pieces-reference sample was investigated to preliminarily formulate the quality standard of the reference sample.The characteristic chromatogram of 15 batches of Wuzhuyu Decoction was established by high performance liquid chromatography(HPLC) and the similarity analysis was conducted.Common peaks were demarcated and assigned to medicinal materials.Moreover, quantitative determination of limonin, evodiamine, rutaecarpine and ginsenoside Rb_1 of Wuzhuyu Decoction were performed.The dissemination of quantity value was explored combined with dry extract rate, similarity of characteristic chromatogram and transfer rate of index component content.A total of 18 common peaks were identified in the corresponding materials of Wuzhuyu Decoction reference sample, with the similarity of characteristic chromatogram greater than 0.9, and Fructus Evodiae, Radix Ginseng, Rhizoma Zingiberis Recens and Fructus Jujubae contributed 9, 5, 8 and 2 chromatographic peaks, respectively.The index component content of corresponding materials and the transfer rates of medicinal materials-decoction pieces and decoction pieces-reference sample of different batches of Wuzhuyu Decoction reference sample were as follows: the content of limonin was 0.16%-0.51%, and the transfer rates were 83.66%-115.60% and 38.54%-54.58%, respectively; the content of evodiamine was 0.01%-0.11%, the transfer rated were 80.80%-116.15% and 3.23%-12.93%, respectively; the content of rutaecarpine was 0.01%-0.05%, the transfer rates were 84.33%-134.53% and 5.72%-21.24%, respectively; the content of ginsenoside Rb_1 was 0.06%-0.11%, and the transfer rates were 90.00%-96.92% and 32.45%-67.24%, respectively.The dry extract rate of the whole prescription was 22.58%-29.89%.In this experiment, the dissemination of quantity value of Wuzhuyu Decoction reference sample was analyzed by the combination of characteristic chromatogram, index component content and dry extract rate.A scientific and stable quality evaluation method of the reference sample was preliminarily established, which provided basis for the subsequent development of Wuzhuyu Decoction and the quality control of related preparations.
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Medicamentos de Ervas Chinesas , Ginsenosídeos , Limoninas , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Ginsenosídeos/análise , Limoninas/análise , Controle de QualidadeRESUMO
Xiaoer Huanglong Granule is the only Chinese Patent Medicine widely used for treating attention deficit hyperactivity disorder. However, not much is known about the bioactive components and pharmacokinetics of Xiaoer Huanglong Granule even after it was successfully introduced into clinical use. This study analyzed the components in the medication and rat plasma after oral administration with the help of the UNIFI platform and Masslynx. A total of 119 and 37 components were detected in the medication and plasma, respectively, using an ultra-performance liquid chromatography-tandem mass spectrometer. We established a rapid and sensitive simultaneous determination of one triterpene saponin, three monoterpene glycosides, and three lignans in rat plasma by solid-phase extraction. The determination was accomplished within 7.50 min via gradient elution. The values of the lower limit of quantitation were validated at 0.08 ng/ml for tenuifolin, 0.8 ng/ml for lactiflorin, 1.828 ng/ml for albiflorin, 2 ng/ml for paeoniflorin, gomisin B, and gomisin D, 10 ng/ml for schisandrin. The results from validations of other methods were all acceptable (relative standard deviation ≤ 14.94%). This is the first report on the identification and pharmacokinetics studies of components in Xiaoer Huanglong Granule. Moreover, the pharmacokinetic behavior of lactiflorin was studied for the first time.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Compostos Fitoquímicos , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodosRESUMO
Curcumin (CUR) has a bright future in the treatment of cancer as a natural active ingredient with great potential. However, curcumin has a low solubility, which limits its clinical application. In this study, IRMOF-10 was created by the direct addition of triethylamine, CUR was loaded into IRMOF-10 using the solvent adsorption method, and the two were characterized using a scanning electron microscope (SEM), X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG) methods, and Brunauer-Emmett-Teller (BET) analysis. We also used the MTT method, 4',6-diamidino-2-phenylindole (DAPI) staining, the annexin V/PI method, cellular uptake, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) to perform a safety analysis and anticancer activity study of IRMOF-10 and CUR@IRMOF-10 on HepG2 cells. Our results showed that CUR@IRMOF-10 had a CUR load of 63.96%, with an obvious slow-release phenomenon. The CUR levels released under different conditions at 60 h were 33.58% (pH 7.4) and 31.86% (pH 5.5). Cell experiments proved that IRMOF-10 was biologically safe and could promote curcumin entering the nucleus, causing a series of reactions, such as an increase in reactive oxygen species and a decrease in the mitochondrial membrane potential, thereby leading to cell apoptosis. In summary, IRMOF-10 is an excellent drug carrier and CUR@IRMOF-10 is an effective anti-liver cancer sustained-release preparation.
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Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Nanopartículas , Compostos de Bifenilo , Carcinoma Hepatocelular/tratamento farmacológico , Curcumina/química , Ácidos Dicarboxílicos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Espécies Reativas de OxigênioRESUMO
Oxidative damage to retinal pigment epithelial (RPE) has been identified as one of the major regulatory factors in the pathogenesis of age-related macular degeneration (AMD). Catalpol is an iridoid glucoside compound that has been found to possess potential antioxidant activity. In the present study, we aimed to investigate the protective effect of catalpol on RPE cells under oxidative stress and to elucidate the potential molecular mechanism involved. We found that catalpol significantly attenuated hydrogen peroxide (H2O2)-induced cytotoxicity, G0/G1 phase cell cycle arrest, and apoptosis in RPE cells. The overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA) stimulated by oxidative stress and the corresponding reductions in antioxidant glutathione (GSH) and superoxide dismutase (SOD) levels were largely reversed by catalpol pretreatment. Moreover, catalpol pretreatment markedly activated the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its downstream antioxidant enzymes, catalase (CAT), heme oxygenase-1 (HO-1), and NADPH dehydrogenase (NQO1). It also increased the expression levels of cyclin E, Bcl-2, cyclin A, and cyclin-dependent kinase 2 (CDK2) and decreased the expression levels of Bax, Fas, cleaved PARP, p-p53, and p21 cleaved caspase-3, 8, and 9. The oxidative stress-induced formation of the Keap1/Nrf2 complex in the cytoplasm was significantly blocked by catalpol pretreatment. These results indicate that catalpol protected RPE cells from oxidative stress through a mechanism involving the activation of the Keap1/Nrf2/ARE pathways and the inactivation of oxidative stress-mediated pathways of apoptosis.
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Elementos de Resposta Antioxidante/genética , Glucosídeos Iridoides/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neuroproteção , Estresse Oxidativo , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Peróxido de Hidrogênio/toxicidade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neuroproteção/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genéticaRESUMO
Triptolide (TP) is the major bioactive compound extracted from Tripterygium wilfordii Hook F. It exerts anti-inflammatory, antirheumatic, antineoplastic, and neuroprotective effects. However, the severe hepatotoxicity induced by TP limits its clinical application. Ginsenoside Rb1 has been reported to possess potential hepatoprotective effects, but its mechanism has not been fully investigated. This study was aimed at investigating the effect of ginsenoside Rb1 against TP-induced cytotoxicity in HL-7702 cells, as well as the underlying mechanism. The results revealed that ginsenoside Rb1 effectively reversed TP-induced cytotoxicity in HL-7702 cells. Apoptosis induced by TP was suppressed by ginsenoside Rb1 via inhibition of death receptor-mediated apoptotic pathway and mitochondrial-dependent apoptotic pathway. Pretreatment with ginsenoside Rb1 significantly reduced Bax/Bcl-2 ratio and down-regulated the expression of Fas, cleaved poly ADP-ribose polymerase (PARP), cleaved caspase-3, and -9. Furthermore, ginsenoside Rb1 reversed TP-induced cell cycle arrest in HL-7702 cells at S and G2/M phase, via upregulation of the expressions of cyclin-dependent kinase 2 (CDK2), cyclin E, cyclin A, and downregulation of the expressions of p53, p21, and p-p53. Ginsenoside Rb1 increased glutathione (GSH) and superoxide dismutase (SOD) levels, but decreased the reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Pretreatment with ginsenoside Rb1 enhanced the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), total Nrf2, NAD(P)H: quinone oxidoreductases-1 (NQO-1), heme oxygenase-1 (HO-1), and Kelch-like ECH-associated protein 1 (Keap1)/Nrf2 complex. Therefore, ginsenoside Rb1 effectively alleviates TP-induced cytotoxicity in HL-7702 cells through activation of the Keap1/Nrf2/ARE antioxidant pathway.