RESUMEN
Parkin (PARK2) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1 transcription is activated by Parkin-induced endogenous TGF-ß production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1 promotor. TGF-ß inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1ß and p53, which accounts for the suppression of TGF-ß production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-ß/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.
Asunto(s)
Movimiento Celular , Neoplasias Hepáticas , Proteína Smad2 , Proteína smad3 , Factor de Crecimiento Transformador beta , Ubiquitina-Proteína Ligasas , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular Tumoral , Transducción de Señal , Activación Transcripcional , Animales , Transición Epitelial-Mesenquimal , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Metástasis de la Neoplasia , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Ratones Desnudos , RatonesRESUMEN
Forty-three quinolizidine alkaloids (1-43), including twelve new matrine-type ones, sophalodes A-L (1-7, 17, 19 and 28-30), were isolated from the seeds of Sophora alopecuroides. Structurally, compounds 1-4 were the first examples of C-11 oxidized matrine-type alkaloids from Sophora plants. The structures and absolute configurations of new compounds were elucidated by extensive spectroscopic techniques, X-ray diffraction analysis, and quantum chemical calculation. In addition, the NMR data and absolute configuration of compound 18 was reported for the first time. All the isolates were evaluated for their inhibition on nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophages, among them, compounds 29, 38 and 42 exhibited the most significant activity with IC50 values of 29.19, 25.86 and 33.30⯵M, respectively. Further research about new compound 29 showed that it also suppressed the protein levels of iNOS and COX-2, which revealed its anti-inflammatory potential. Moreover, additional research showed that compound 16 exhibited marginal cytotoxicity against HeLa cell lines, with an IC50 value of 24.27⯵M.
Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Simulación del Acoplamiento Molecular , Quinolizidinas/farmacología , Sophora/química , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Quinolizidinas/química , Quinolizidinas/aislamiento & purificación , Células RAW 264.7 , Relación Estructura-ActividadRESUMEN
Four undescribed ent-kaurane diterpenoids, wilkaunoids A - D (1-4), and three undescribed abietane diterpenoids, wilabinoids A - C (13-15), along with thirteen known ones (5-12 and 16-20), were isolated from Tripterygium wilfordii. Their structures were elucidated by extensive spectroscopic methods, electroniccirculardichroism calculation, and X-ray diffraction analysis. Compounds 1 and 2 were a pair of C-19 epimers of ent-kaurane diterpenoids, featuring a rare 19,20-epoxy-19,20-dimethoxy-kaurane fragment. Compound 3 possessed a rare naturally occurring 1,3-dioxacyclohexane moiety. Compounds 13 and 15 represented the first example of abietane diterpenoids with an isovalerate substitution from the genus of Tripterygium. The possible biosynthetic pathways of 1-3 were postulated. The effect of 1-20 on nitric oxide production was examined in lipopolysaccharide-stimulated RAW 264.7 cells. Abietane diterpenoid quinones 7-13 (IC50: 1.9-10.2 µM) exhibited the significant activity to inhibit nitric oxide production versus positive control (NG-monomethyl-l-arginine acetate salt, IC50 = 24.9 µM). The structure activity relationship of 7-13 in inhibiting nitric oxide production was then discussed. The most potent 7 and 8 were found to significantly suppress the expression of cyclooxygenase-2 and inducible nitric oxide synthase proteins, showing a good anti-inflammatory potential. The findings provided some valuable insights for the discovery and structural modification of abietane diterpenoids towards anti-inflammatory lead compounds.
Asunto(s)
Abietanos/farmacología , Antiinflamatorios/farmacología , Diterpenos de Tipo Kaurano/farmacología , Tripterygium/química , Abietanos/química , Animales , Antiinflamatorios/química , Diterpenos de Tipo Kaurano/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Óxido Nítrico/metabolismo , Células RAW 264.7RESUMEN
Three new matrine-type alkaloids, 8ß-hydroxyoxysophoridine (1), 9ß-hydroxysophoridine (2), 9ß-hydroxyisosophocarpine (3), together with one known analog, 11,12-dehydromatrine (4), were isolated from the seeds of Sophora alopecuroides L. The structures of new compounds were elucidated using extensive spectroscopic techniques including the experimental and calculated ECD data. The anti-inflammatory activities of all the isolates on NO production in RAW 264.7 cells stimulated by lipopolysaccharide were evaluated. Among them, 8ß-hydroxyoxysophoridine (1) showed a significant inhibitory effect with an IC50 value of 18.26â µM.
Asunto(s)
Alcaloides/farmacología , Antiinflamatorios/farmacología , Óxido Nítrico/antagonistas & inhibidores , Extractos Vegetales/farmacología , Semillas/química , Sophora/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Ratones , Óxido Nítrico/biosíntesis , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Células RAW 264.7RESUMEN
(±)-Petchilactones A-C (1-3), three pairs of enantiomeric meroterpenoids respectively with a 6/6/5/5 or a 5/5/5/7/6 ring system were isolated from Ganoderma petchii. Their structures including absolute configurations were assigned by using spectroscopic, computational, and X-ray diffraction methods. Compounds 1 and 2 represent a new skeletal meroterpenoid. Biological evaluation found that (-)-1 and (-)-3 could induce umbilical cord mesenchymal stem cells into keratinocyte-like cells.
Asunto(s)
Ganoderma/química , Queratinocitos/citología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Terpenos/química , Terpenos/farmacología , Línea Celular , Transdiferenciación Celular/efectos de los fármacos , Técnicas de Reprogramación Celular/métodos , Cristalografía por Rayos X , Humanos , Queratinocitos/efectos de los fármacos , Modelos Moleculares , Estereoisomerismo , Terpenos/aislamiento & purificación , Cordón Umbilical/citologíaRESUMEN
Volatiles have been regarded as active substances in many foods, whose chemicals can be analyzed by GC-MS qualitatively and quantitatively. However, the activities of volatiles are often studied as a whole, and it has no an effective method to determine that which molecule is active in volatiles by far. In order to identify the antioxidant molecules in volatiles, a rapid determination method was developed by GC-FID/MS combined with DPPH radical reaction in this study. Three antioxidant molecules were identified and validated among 20 components in rose tea infusion. Their activity validation and the methodological evaluation indicated this method could be used for distinguishing antioxidant molecules in volatiles rapidly and effectively.
RESUMEN
Three new compounds (1â-â3), including a sesterterpenoid, aspterpenacid C (1), with an unusual 5/3/7/6/5 pentacyclic skeleton, together with seven known ones (4â-â10), were isolated from the ethanol extract of the traditional Chinese medicinal plant Swertia bimaculata. Their structures were elucidated on the basis of the methods of spectroscopic NMR, MS, and computational chemistry. The structure of 1 was further confirmed by single-crystal X-ray diffraction analysis. Compounds 1â-â10 were tested for activities on the inhibition of nitric oxide production and HIV-1 replication in vitro. Compound 1 exhibited moderate activity in inhibiting nitric oxide production (IC50 = 16.1 µM) and HIV-1 replication (EC50 = 1.35 µM).
Asunto(s)
Fármacos Anti-VIH/aislamiento & purificación , Fármacos Anti-VIH/farmacología , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , VIH-1/efectos de los fármacos , Swertia/química , Animales , Fármacos Anti-VIH/química , Antiinflamatorios/química , China , Medicamentos Herbarios Chinos/química , Ratones , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Células RAW 264.7 , Replicación Viral/efectos de los fármacosRESUMEN
Two new [neougonins A (1) and B (2)] and nine known prenylated flavonoids were isolated from the whole plants of Helminthostachys zeylanica. The structures of the new isolates were elucidated by extensive NMR techniques, including one and two dimensional (1D)- and (2D)-NMR experiments, as well as comparison with spectroscopic data of known analogous compounds. Moreover, compound 1 inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells with an IC50 value of 3.32 µM.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Helechos/química , Flavonoides/farmacología , Macrófagos/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Flavonoides/química , Flavonoides/aislamiento & purificación , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Ratones , Estructura Molecular , Óxido Nítrico/biosíntesis , Prenilación , Relación Estructura-ActividadRESUMEN
BACKGROUND: A series of novel oligomers with various types and complex skeletons are isolated from Annonaceae plants, which displayed anti-inflammatory, antimalarial, antibacterial and other biological activities. Thus, their structures and functions have received more and more attention. AIM AND OBJECTIVE: The purpose of this review is to provide a systematic reference for chemical structures and biological activities of oligomers and some clues for finding more analogues from Annonaceae. METHODS: Publications relevant to Annonaceae were retrieved from the Web of Science and SciFinder and surveyed for a literature review. RESULTS: This article summarized the chemical structures, the base source plants and the biofunctions of oligomers from Annonaceae. CONCLUSION: The oligomers from Annonaceae have the characteristics of various connection modes and rich functional groups, which provides more possibilities for the discovery of lead compounds with new or higher biological activities.
Asunto(s)
Annonaceae , Antimaláricos , Annonaceae/química , Antibacterianos/farmacología , Antimaláricos/farmacologíaRESUMEN
Ganoderpetchoids A-E and (-)-dayaolingzhiol H, six undescribed meroterpenoids, were isolated from Ganoderma petchii. Their structures including the relative configurations were identified by means of spectroscopic methods and 13C NMR calculations. Chiral separation of the new racemics was performed to afford their respective enantiomers. The absolute configurations of the new isolates were clarified by computational approaches, CD comparisons and X-ray diffraction analysis. Biological studies toward triple negative breast cancer indicated that (+)-6 and (-)-6 significantly inhibit the migration of MDA-MB-231 cell line.
Asunto(s)
Ganoderma , Neoplasias de la Mama Triple Negativas , Humanos , Terpenos/farmacología , Terpenos/química , Estructura Molecular , Ganoderma/química , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Línea CelularRESUMEN
In the current times, achieving specific targeted and controllable drug delivery remains one of the major challenges in the treatment of hepatocellular carcinoma (HCC). The present study reported the development of a multiple functional indocyanine green (ICG)-cyclodextrin (CD) system, wherein loaded etoposide (EPS) was used as the model chemotherapeutic drug. In the developed system, ICG segment served as a photosensitizer for photothermal therapy (PTT) and the targeting moiety, which was primarily attributed to the specific retention properties in HCC tissues. The Ex vivo evaluation showed that ICG-CD@EPS exhibited a laser-triggered release profile with the photothermal efficiency and cytotoxicity towards HepG2 cells. In vivo evaluation suggested that ICG could navigate the systems to HCC tissues and retained at the site for 48 h, producing a drug accumulation in HCC. Further, laser irradiation boosted EPS release and local hyperthermia effects in HCC. Thus, the present study explored a novel and specific HCC targeting mechanism, and provided a feasible and controllable strategy for synergistic PTT and chemotherapy treatments for HCC.
Asunto(s)
Carcinoma Hepatocelular , Hipertermia Inducida , Neoplasias Hepáticas , Nanopartículas , Fotoquimioterapia , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Humanos , Verde de Indocianina , Neoplasias Hepáticas/tratamiento farmacológico , FototerapiaRESUMEN
Thrombosis and its related events have become a major concern during the development and optimization of ventricular assist devices (VADs, also called blood pumps), and limit their clinical use and economic benefits. Attempts have been made to model the thrombosis formation, considering hemodynamic and biochemical processes. However, the complexities and computational expenses are prohibitive. Blood stasis is one of the key factors which may lead to the formation of thrombosis and excessive thromboembolic risks for patients. This study proposed a novel approach for modeling blood stasis, based on a two-phase flow principle. The locations of blood residual can be tracked over time, so that regions of blood stasis can be identified. The blood stasis in an axial blood pump is simulated under various working conditions, the results agree well with the experimental results. In contrast, conventional hemodynamic metrics such as velocity, time-averaged wall shear stress (TAWSS), and relative residence time (RRT), were contradictory in judging risk of blood stasis and thrombosis, and inconsistent with experimental results. We also found that the pump operating at the designed rotational speed is less prone to blood stasis. The model provides an efficient and fast alternative for evaluating blood stasis and thrombosis potential in blood pumps, and will be a valuable addition to the tools to support the design and improvement of VADs.
Asunto(s)
Corazón Auxiliar , Trombosis , Velocidad del Flujo Sanguíneo , Simulación por Computador , Corazón Auxiliar/efectos adversos , Hemodinámica , Humanos , Modelos Cardiovasculares , Estrés Mecánico , Trombosis/diagnóstico , Trombosis/etiologíaRESUMEN
Montan resin (MR) is an industrial by-product or solid waste generated during the production of refined montan wax and is not typically reused. In this paper, a bio-modification method using three strains of microorganisms, Acinetobacter venetianus (AV), Pseudomonas aeruginosa (PA), and Phanerochaete chrysosporium (PC), was studied to promote the performance and bio-function of MR so that MR could be recycled. MR can be degraded by these three microorganisms, and their weight loss rates were similar over the treatment period of 15 days. Compared with the original MR, the hydrophilicity of modified MRs was improved, which was related to the increase in apparent oil-water partition coefficients (Kows) and oxygen-containing and hydrophilic groups in modified MRs based on IR and GC-MS analysis. The bio-function of modified MRs by the three strains in terms of promoting maize seed germination and seedling growth was greater compared with untreated MR. Overall, these findings indicate that biomodified MRs might have useful agriculture applications.Implications: An environmentally-friendly method using microorganisms to achieve recycle of solid waste, montan resin (MR) was established in this study. Through this bio-treatment, the performance and bio-function of MR were both improved, that is the appearance and hydrophilicity of modified MRs were better than thoes in before, and the modified MRs treated by three strains showed the better promoting effects on maize seed germination and seedling growth than untreated MR, indicating the modified MRs have the certain potential of agricultural utilization in the future.
Asunto(s)
Acinetobacter , Carbón Mineral , Germinación , Plantones , SemillasRESUMEN
Twelve ent-isopimarane diterpenoids, including six undescribed ones, eupnerias J-O, were isolated from the stem barks of Euphorbia neriifolia L. Structurally, eupnerias J-M were the first examples of 18 (or 19)-norditerpenoid with ent-isopimarane skeleton from E. neriifolia. The absolute configuration of eupneria J was established based on the X-ray diffraction analysis and the experimental and calculated electronic circular dichroism (ECD), while the absolute configuration of eupnerias K-N were determined by the experimental and calculated ECD. In addition, the absolute configuration of the known compound, 3ß-hydroxysandaracopimaric acid, was determined by comparing its ECD spectrum with eupneria J, and renamed as eupneria P. Furthermore, eupneria J and eurifoloid H showed significant anti-HIV-1 activities with IC50 values of 0.31 and 6.70 µg/mL, respectively, and ent-isopimara-8(14),15-dien-3ß,12ß-diol possessed obvious anti-influenza virus activity against A/Puerto Rico/8/1934, with an IC50 at 3.86 µg/mL.
Asunto(s)
Diterpenos , Euphorbia , VIH-1 , Abietanos , Dicroismo Circular , Estructura MolecularRESUMEN
A new protostane-type triterpenoid bearing an oxetane ring in the side-chain, named alisol W (1), has been obtained from the dried rhizome of Alisma plantago-aquatica subsp. orientale. The structure and absolute configuration of compound 1 was determined from extensive spectroscopic analysis. In addition, the vasorelaxant activity and the inhibition on 11ß-HSD1 of compound 1 were also evaluated, however, it didn't show remarkable effects.
Asunto(s)
Alisma/química , Triterpenos/aislamiento & purificación , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Humanos , Estructura Molecular , Rizoma/química , Análisis Espectral , Triterpenos/química , Vasodilatadores/análisisRESUMEN
Onosmanones A (1) and B (2), two novel quinonoid xanthenes with two geranyl groups, have been isolated from the whole plants of Onosma paniculatum. Their structures were elucidated on the basis of one- and two-dimensional NMR techniques.
Asunto(s)
Boraginaceae/química , Xantenos/química , China , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Xantenos/aislamiento & purificaciónRESUMEN
Eight new sesquiterpenes, including four guaianolides (1-4), one guaian sesquiterpene (5), one norguaianolide (6), one 1, 10-secoguaianolides (7), and one eudesmane sesquiterpene (8), along with fourteen known sesquiterpenes (9-22) were isolated from the whole plants of Artemisia austro-yunnanensis. Their structures were elucidated on the basis of spectroscopic date and HRESIMS analysis. All isolated sesquiterpenes (1-22) were evaluated their activities by the assay of LPS-induced NO production on RAW264.7, of which compounds 2-4, 9, 10 and 17 produced significant inhibition of NO production with IC50 values ranging from 2.38 to 10.67µM.
Asunto(s)
Artemisia/química , Sesquiterpenos/química , Animales , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Extractos Vegetales/química , Células RAW 264.7 , Sesquiterpenos/aislamiento & purificaciónRESUMEN
The fungal species of the genus Ganoderma attracted great interest in the last decades. Our recent investigation on Ganoderma petchii afforded five new compounds, (-)-petchioics A and B (1 and 2), petchiates A and B (3 and 4), petchine (5), and a known compound. The structures of the new compounds were elucidated on the basis of spectroscopic data. The absolute configurations of 1 and 2 were assigned by computational methods. Biological activities of these isolates towards human cancer cells, COX-1/2, and influenza virus were evaluated.
Asunto(s)
Acetatos/química , Ácidos Carboxílicos/química , Ganoderma/química , Acetatos/aislamiento & purificación , Animales , Ácidos Carboxílicos/aislamiento & purificación , Línea Celular Tumoral , Ácidos Ciclohexanocarboxílicos/química , Ácidos Ciclohexanocarboxílicos/aislamiento & purificación , Inhibidores de la Ciclooxigenasa , Perros , Furanos/química , Furanos/aislamiento & purificación , Humanos , Células de Riñón Canino Madin Darby , Estructura Molecular , Orthomyxoviridae/efectos de los fármacos , Piridinas/química , Piridinas/aislamiento & purificación , Pironas/química , Pironas/aislamiento & purificaciónRESUMEN
Applanatumin A (1), a novel meroterpenoid dimer, was isolated from the fungus Ganoderma applanatum. Its structure and absolute configuration were assigned on the basis of spectroscopic and computational data. Notably, 1 possesses a new hexacyclic skeleton containing a spiro[benzofuran-2,1'-cyclopentane] motif. A plausible pathway, involving a key Diels-Alder reaction, is proposed for the biosynthesis of 1. Applanatumin A exhibits potent antifibrotic activity in TGF-ß1-induced human renal proximal tubular cells.