RESUMEN
Ferroptosis is a form of cell death that is induced by iron-mediated accumulation of lipid peroxidation. The involvement of ferroptosis in different pathophysiological conditions has offered new perspectives on potential therapeutic interventions. Natural products, which are widely recognized for their significance in drug discovery and repurposing, have shown great promise in regulating ferroptosis by targeting various ferroptosis players. In this review, we discuss the regulatory mechanisms of ferroptosis and its implications in different pathological conditions. We dissect the interactions between natural products and ferroptosis in cancer, ischemia/reperfusion, neurodegenerative diseases, acute kidney injury, liver injury, and cardiomyopathy, with an emphasis on the relevance of ferroptosis players to disease targetability.
Asunto(s)
Productos Biológicos , Ferroptosis , Neoplasias , Ferroptosis/efectos de los fármacos , Humanos , Productos Biológicos/uso terapéutico , Productos Biológicos/farmacología , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/fisiopatología , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/fisiopatología , Cardiomiopatías/fisiopatología , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/metabolismo , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/metabolismo , Hierro/metabolismoRESUMEN
BACKGROUND: The peroxisome is a dynamic organelle with variety in number, size, shape, and activity in different cell types and physiological states. Recent studies have implicated peroxisomal homeostasis in ferroptosis susceptibility. Here, we developed a U-2OS cell line with a fluorescent peroxisomal tag and screened a target-selective chemical library through high-content imaging analysis. METHODS: U-2OS cells stably expressing the mOrange2-Peroxisomes2 tag were generated to screen a target-selective inhibitor library. The nuclear DNA was counterstained with Hoechst 33342 for cell cycle analysis. Cellular images were recorded and quantitatively analyzed through a high-content imaging platform. The effect of selected compounds on ferroptosis induction was analyzed in combination with ferroptosis inducers (RSL3 and erastin). Flow cytometry analysis was conducted to assess the level of reactive oxygen species (ROS) and cell death events. RESULTS: Through the quantification of DNA content and peroxisomal signals in single cells, we demonstrated that peroxisomal abundance was closely linked with cell cycle progression and that peroxisomal biogenesis mainly occurred in the G1/S phase. We further identified compounds that positively and negatively regulated peroxisomal abundance without significantly affecting the cell cycle distribution. Some compounds promoted peroxisomal signals by inducing oxidative stress, while others regulated peroxisomal abundance independent of redox status. Importantly, compounds with peroxisome-enhancing activity potentiated ferroptosis induction. CONCLUSIONS: Our findings pinpoint novel cellular targets that might be involved in peroxisome homeostasis and indicate that compounds promoting peroxisomal abundance could be jointly applied with ferroptosis inducers to potentiate anticancer effect.
Asunto(s)
Ferroptosis , Peroxisomas , Peroxisomas/metabolismo , Línea Celular , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , ADN/metabolismoRESUMEN
Ferroptosis has been conceptualized as a novel cell death modality distinct from apoptosis, necroptosis, pyroptosis and autophagic cell death. The sensitivity of cellular ferroptosis is regulated at multiple layers, including polyunsaturated fatty acid metabolism, glutathione-GPX4 axis, iron homeostasis, mitochondria and other parallel pathways. In addition, microRNAs (miRNAs) have been implicated in modulating ferroptosis susceptibility through targeting different players involved in the execution or avoidance of ferroptosis. A growing body of evidence pinpoints the deregulation of miRNA-regulated ferroptosis as a critical factor in the development and progression of various pathophysiological conditions related to iron overload. The revelation of mechanisms of miRNA-dependent ferroptosis provides novel insights into the etiology of diseases and offers opportunities for therapeutic intervention. In this review, we discuss the interplay of emerging miRNA regulators and ferroptosis players under different pathological conditions, such as cancers, ischemia/reperfusion, neurodegenerative diseases, acute kidney injury and cardiomyopathy. We emphasize on the relevance of miRNA-regulated ferroptosis to disease progression and the targetability for therapeutic interventions.
Asunto(s)
Lesión Renal Aguda , Ferroptosis , Sobrecarga de Hierro , MicroARNs , Humanos , Apoptosis , Ferroptosis/genética , Sobrecarga de Hierro/genética , MicroARNs/genéticaRESUMEN
In this study, the complete mitochondrial genome sequence of a Xenocypris davidi from Cao'e River was sequenced. The complete mitogenome of X. davidi was 16,630 bp in length, it contains the structure of 22 transfer RNA genes, 13 protein coding genes, 2 ribosomal RNA genes, and 1 non-coding region. The gene arrangement and organization in the mitogenome of X. davidi were in accordance with other Cyprinidae fishes. The results of phylogenetic analysis revealed that the mitochondrial genome sequence could provide useful information for the conservation genetics and evolution study of X. davidi.
RESUMEN
Anthocyanins have attracted attention over the past several decades because of their beneficial health effects. In this research, a strategy combining column chromatography and high-speed countercurrent chromatography was developed for the separation of high-purity anthocyanin monomers from mulberry fruits. After purification using Amberlite XAD-7HP column with 80% ethanol (0.1% HCl), a fraction of anthocyanins mixtures with a purity of 68.6% was obtained. High-speed countercurrent chromatography with a biphasic solvent system of n-butanol/methyl tert-butyl ether/acetonitrile/water/trifluoroacetic acid (30:10:10:50:0.05, v/v) was used to separate the anthocyanin monomers. Three monomers of delphinidin-3-O-rutinoside, cyanidin-3-O-rutinoside, and cyanidin-3-O-glucoside were obtained, and identified by 1 H and 13 C NMR spectroscopy and high-performance liquid chromatography with electrospray ionization-mass spectrometry. The method developed in this work can be used to conduct large-scale separations of anthocyanin monomers from mulberry fruits and other plants.
Asunto(s)
Antocianinas/aislamiento & purificación , Frutas/química , Morus/química , Cromatografía Líquida de Alta Presión , Distribución en Contracorriente , Espectroscopía de Resonancia MagnéticaRESUMEN
BACKGROUND: Hibiscus sabdariffa L. is not only used traditionally as a component of herbal drinks, beverages and flavoring agents but also as a herbal medicine in the drug industry. Bioactive polysaccharides are important constituents of H. sabdariffa that may contribute to the plant's beneficial effects. This study was designed to investigate the structural characteristics of a water-soluble polysaccharide from H. sabdariffa, HSP41, and its immunoregulatory activity on RAW264.7 cells. RESULTS: HSP41 was mainly composed of arabinose, xylose and mannose at a molar ratio of 1:1.34:15.6, with an average molecular weight of 3.3 × 105 Da. Fourier transform infrared (FTIR) spectra exhibited absorption peaks characteristic of HSP41. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) revealed the amorphous form and aggregation conformation of HSP41 respectively. HSP41 significantly induced interleukin 1ß (IL-1ß) and inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells in vitro, promoting an increase in nuclear factor kB p65 (NF-kB p65) levels in the nucleus. CONCLUSION: The results indicated that HSP41 up-regulated the immune response by stimulating RAW264.7 cell activity. HSP41, a promising immunoregulator, possibly contributes to the health benefits of H. sabdariffa and might have potential applications in health food or medicine. © 2016 Society of Chemical Industry.
Asunto(s)
Hibiscus/química , Interleucina-1beta/efectos de los fármacos , FN-kappa B/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Animales , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células RAW 264.7RESUMEN
An efficient ultrasonic-cellulase-assisted extraction (UCE) of Cistanche tubulosa polysaccharide (CTP) was established. The response surface methodology based on Box-Behnken Design was employed to further optimize extraction conditions. After quaternary ammonium salt precipitation, the polysaccharide of C. tubulosa was characterized by different techniques. The results showed that a maximum polysaccharide yield of 22.31±0.45% was achieved at a pH of 5.2 for 31.5min at 54.1°C. Compared to hot water extraction, the yield of CTP in UCE and polysaccharide content increased to 44.96% and 70.13±2.19%, respectively. There was no marked difference among polysaccharides extracted using different methods from the infrared spectrum. Ultrasonic-cellulase-assisted extraction polysaccharide showed a fibrous structure from scanning electron microscopy and was composed of rhamnose, mannose, glucose, and galactose in a molar ratio of 2.18:1:28.29:1.43 by gas chromatography. The circular dichroism results indicated that polysaccharides had a maximum positive peak around 210nm with different peak values. The thermogravimetric analysis and differential scanning calorimetry were used to test the thermostability of CTP. Besides, CTP demonstrated appreciable antioxidant potential on antioxidant experiments in vitro. The results suggested that UCE is an effective method for CTP extraction and its polysaccharide showed appreciable antioxidant activity.
Asunto(s)
Cistanche/química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/aislamiento & purificación , Polisacáridos/química , Polisacáridos/aislamiento & purificaciónRESUMEN
The complete mitogenome sequence of Sarcocheilichthys parvus was identified using polymerase chain reaction and sequenced with primer walking method. The complete mitogenome was 16,674 bp in length, containing 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding regions. The gene arrangement and composition of S. parvus was similar to most other fishes.
Asunto(s)
Cyprinidae/genética , Genoma Mitocondrial , Animales , ADN Mitocondrial/química , ADN Mitocondrial/aislamiento & purificación , ADN Mitocondrial/metabolismo , Proteínas de Peces/química , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Reacción en Cadena de la Polimerasa , ARN Ribosómico/química , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , ARN de Transferencia/química , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Análisis de Secuencia de ADNRESUMEN
Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the effect of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism in type 2 diabetic rats. Our results showed that fasting blood glucose, serum insulin level, insulin resistance index and C-peptide level in the high dose group had a significant downward trend when compared with the model group, chromium picolinate group and chromium trichloride group. The hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, Glut4, phosphor-AMPKß1 and Akt levels in the high dose group were significantly higher than those of the model, chromium picolinate and chromium trichloride groups. Chromium malate in a high dose group can significantly increase high density lipoprotein cholesterol level while decreasing the total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared with chromium picolinate and chromium trichloride. The serum chromium content in chromium malate and chromium picolinate group is significantly higher than that of the chromium trichloride group. The results indicated that the curative effects of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism changes are better than those of chromium picolinate and chromium trichloride. Chromium malate contributes to glucose uptake and transport in order to improved glycometabolism and glycometabolism-related enzymes.
Asunto(s)
Cromo , Diabetes Mellitus Tipo 2/metabolismo , Suplementos Dietéticos , Glucosa/metabolismo , Metabolismo de los Lípidos , Malatos , Animales , Transporte Biológico , Glucemia , Peso Corporal , Cromo/farmacología , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/enzimología , Modelos Animales de Enfermedad , Ayuno , Microbioma Gastrointestinal/efectos de los fármacos , Glucógeno/metabolismo , Insulina/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/microbiología , Malatos/farmacología , Masculino , Aprendizaje por Laberinto , RatasRESUMEN
A water-soluble polysaccharide (OFPS11) was obtained from okra (Abelmoschus esculentus) flowers using aqueous extraction and purification with DEAE-52 cellulose and Sephacryl™ S-500 column. Its preliminary characterization and immunomodulating activity were investigated. Results showed that OFPS11 is mainly composed of galactose and rhamnose in a molar ratio of 2.23:1 with molecular mass of 1,700 kDa. RAW264.7 cells pretreated with OFPS11 significantly inhibited the proliferation of HepG-2 cells. Additionally, OFPS11 enhanced the phagocytic ability and induced the elevation of NO production, TNF-α and IL-1ß secretion of RAW264.7 cells. Furthermore, OFPS11 promoted both the expression of iNOS protein and of iNOS and TNF-α mRNA. OFPS11 can strongly increase NF-κB levels in nucleuses, which is an important transcription factor that can modulate expressions of iNOS, NO and TNF-α. These outcomes support that OFPS11 exerts its antitumor activity by probably stimulating macrophage activities through nuclear NF-κB pathway.
Asunto(s)
Abelmoschus/química , Factores Inmunológicos/aislamiento & purificación , Polisacáridos/aislamiento & purificación , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular , Núcleo Celular/metabolismo , Citotoxicidad Inmunológica/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Flores/química , Células Hep G2 , Humanos , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Peso Molecular , FN-kappa B/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Óxido Nítrico Sintasa de Tipo II/genética , Fagocitosis/efectos de los fármacos , Polisacáridos/química , Polisacáridos/farmacología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Solubilidad , Transcripción Genética/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genética , Regulación hacia Arriba/efectos de los fármacos , AguaRESUMEN
Schisandra chinensis (Turcz.) Baill has been used in traditional Chinese medicine for centuries. Previous studies have shown that Schisandra polysaccharide (SCPP11) has robust antitumor activity in vivo. In this study, the immunomodulatory activity and mechanisms of action of SCPP11 were investigated further to reveal its mechanism of action against tumors. Results showed that SCPP11 increased the thymus and spleen indices, pinocytic activity of peritoneal macrophages, and hemolysin formation in CTX-induced immunosuppressed mice. Moreover, SCPP11 significantly increased immunoglobulin levels, cytokines levels in vivo and induced RAW264.7 cells to secrete cytokines in vitro. RAW264.7 cells pretreated with SCPP11 significantly inhibited the proliferation of HepG-2 cells. In addition, SCPP11 promoted both the expression of iNOS protein and of iNOS and TNF-α mRNA. TLR-4 is a possible receptor for SCPP11-mediated macrophage activation. Therefore, the data suggest that SCPP11 exerted its antitumor activity by improving immune system functions through TLR-4-mediated up-regulation of NO and TNF-α.
Asunto(s)
Factores Inmunológicos/farmacología , Activación de Macrófagos/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Polisacáridos/farmacología , Schisandra/química , Receptor Toll-Like 4/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Proliferación Celular , Ciclofosfamida/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Proteínas Hemolisinas/sangre , Inmunoglobulinas/sangre , Interleucina-2/sangre , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/metabolismo , Ratones , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Bazo/efectos de los fármacos , Bazo/inmunología , Timo/efectos de los fármacos , Timo/inmunología , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
In this study, the total mitochondrial genome sequence of Pseudorasbora elongata (Cypriniformes: Cyprinidae) was firstly determined. The genome is 16,587 bases in length. It consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding regions. These results will contribute to the natural resources conservation and species identification of P. elongata.
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Cyprinidae/genética , Especies en Peligro de Extinción , Genes Mitocondriales/genética , Genoma Mitocondrial/genética , Animales , Composición de Base , Secuencia de Bases , China , Orden Génico , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Selenium (Se) is an essential dietary mineral and Radix puerariae (RP) (the dried root of Pueraria lobata Willd.) is a botanical supplement widely used as a nutraceutical. Food enriched with Se provides a feasible and economic approach for production of organic Se compounds. However, little is known about Se-enriched RP and the structure of Se-containing polysaccharides and proteins derived from Se-enriched RP. RESULTS: The organic form of Se accounted for 82.42% of total content. Purification by DEAE-52 and Sephadex G-100 column chromatography yielded three single fractions--RP-SeP-11, RP-SeP-22 and RP-SeP-33--with Se contents of 0.9562 × 10⻳, 0.6113 × 10⻳ and 0.3827 × 10⻳ g kg⻹, respectively. RP-SeP-11 (3.5 kDa) was made of glucose, RP-SeP-22 (19.6 kDa) was composed of xylose and glucose, and RP-SeP-33 (97.9 kDa) was made up galactose, mannose and glucose. Two Se-containing proteins were obtained with Se content of 3.175 × 10⻳ and 4.328 × 10⻳ g kg⻹, respectively. One appeared as three subunits with molecular masses of 43.0, 29.0 and 17.8 kDa while the other appeared as two subunits with molecular masses of 43.0 and 26.3 kDa. CONCLUSION: The results provide a basis for promoting the utilisation of RP resources enriched with Se as a promising tool for the food industry and are significant for its contribution to Se biochemistry in plants.
Asunto(s)
Dieta , Alimentos Fortificados , Proteínas de Plantas/química , Polisacáridos/química , Pueraria/química , Compuestos de Selenio/química , Selenio/análisis , Humanos , Peso Molecular , Monosacáridos/análisis , Proteínas de Plantas/aislamiento & purificación , Raíces de Plantas/química , Polisacáridos/aislamiento & purificación , Subunidades de Proteína , Compuestos de Selenio/aislamiento & purificaciónRESUMEN
The enzyme-assisted extraction (EAE) of polysaccharides from the fruits of Hericium erinaceus was studied. In this study, response surface methodology and the Box-Behnken design based on single-factor and orthogonal experiments were applied to optimize the EAE conditions. The optimal extraction conditions were as follows: a pH of 5.71, a temperature of 52.03°C and a time of 33.79 min. The optimal extraction conditions resulted in the highest H. erinaceus polysaccharides (HEP) yield, with a value 13.46 ± 0.37%, which represented an increase of 67.72% compared to hot water extraction (HWE). The polysaccharides were characterized by FT-IR, SEM, CD, AFM, and GC. The results showed that HEP was composed of mannose, glucose, xylose, and galactose in a molar ratio of 15.16:5.55:4.21:1. The functional groups of the H. erinaceus polysaccharides extracted by HWE and EAE were fundamentally identical but had apparent conformational changes.
Asunto(s)
Basidiomycota/química , Fraccionamiento Químico/métodos , Glicósido Hidrolasas/metabolismo , Polisacáridos/aislamiento & purificación , Concentración de Iones de Hidrógeno , Modelos Estadísticos , Polisacáridos/química , TemperaturaRESUMEN
The industrial solid wastes generated during the production of silymarin from the fruits of milk thistle Silybum marianum was used as the substrate. Preparation and evaluation of the feeds produced by solid-state fermentation (SSF) of the industrial solid wastes was carried out. The protein content of the fermented feed (FF) from a combination of Aspergillus niger and Candida tropicalis was the highest among the examined strains. The optimal process parameters for protein enrichment with SSF using A. niger and C. tropicalis included incubation temperature of 30.8 °C, fermentation time of 87.0 h, and initial moisture content of 59.7 %. Under these conditions, the value additions of FF occurred. The fiber of FF was decreased by 25.07 %, while the digestibility of protein, protein content, and the ratio of total essential amino acids to total amino acids were increased by 79.85, 16.22, and 8.21 %, respectively. The analysis indicated that FF contained 1.44 mg/kg flavonoids and 0.5 mg/kg silybin, which significantly increased by 2.42 and 1.63 times, respectively than those in unfermented substrates. FF recorded reduced molecular weight of proteins from 20.1 to 44.3 kDa to below 14.3 kDa. The results of feeding trial of FF replacement with soybean meal in broilers diets for 8 weeks showed that FF significantly improved carcass characteristics including abdominal fat rate, serum biochemical parameters including aspartate transaminase, blood urea nitrogen and high density lipoprotein cholesterol, and immune responses of broilers. A potential feed quality improvement was achieved through mixed strains SSF of industrial solid wastes of S. marianum fruits.
Asunto(s)
Fermentación , Residuos Industriales , Control de Calidad , Eliminación de Residuos , Silybum marianum/metabolismo , Electroforesis en Gel de Poliacrilamida , Silybum marianum/crecimiento & desarrolloRESUMEN
A water-soluble low molecular weight polysaccharide (SCPP11) was extracted and purified using DEAE-cellulose and Sephadex G-100 column from Schisandra chinensis (Turcz.) Baill. Its in vivo and in vitro antitumor and immunomodulatory activity were investigated. The results showed that SCPP11 with a molecular weight of 3.4×10(3)Da exhibited indirect cyctotoxic activity against tumor cells in vitro, but could significantly inhibit the growth of Heps cells in vivo at dose of 50mg/kg, and its inhibition rate is higher than that in the positive group. Moreover, SCPP11 could ameliorate the hematological and biochemical parameters to almost normal and no significant changes in organ weight, and could increase the body weight. In addition, SCPP11 (at 50mg/kg) could also increased in thymus indexes as well as IL-2 and TNF-α levels in serum in vivo and significantly enhance the phagocytosis activity and the productions of NO of RAW264.7 in vitro. The results indicated that antitumor properties of SCPP11 might be achieved by improving immune response. It could be explored as a potential adjuvant against cancer used in the health food and pharmaceutical therapy.