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1.
Acta Biochim Biophys Sin (Shanghai) ; 56(5): 763-775, 2024 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-38516703

RESUMEN

Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.


Asunto(s)
Proliferación Celular , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/química , Humanos , Animales , Femenino , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Farmacología en Red , Movimiento Celular/efectos de los fármacos , Ratones Desnudos , Luteolina/farmacología , Luteolina/uso terapéutico , Ratones Endogámicos BALB C , Quercetina/farmacología , Quercetina/química , Medicina Tradicional China , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
2.
Nano Lett ; 24(9): 2894-2903, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38407042

RESUMEN

Harnessing the potential of tumor-associated macrophages (TAMs) to engulf tumor cells offers promising avenues for cancer therapy. Targeting phagocytosis checkpoints, particularly the CD47-signal regulatory protein α (SIRPα) axis, is crucial for modulating TAM activity. However, single checkpoint inhibition has shown a limited efficacy. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-mediated magnetic hyperthermia effectively suppresses the expression of CD47 protein on Hepa1-6 tumor cells and SIRPα receptor on macrophages, which disrupts CD47-SIRPα interaction. FVIO-mediated magnetic hyperthermia also induces immunogenic cell death and polarizes TAMs toward M1 phenotype. These changes collectively bolster the phagocytic ability of macrophages to eliminate tumor cells. Furthermore, FVIO-mediated magnetic hyperthermia concurrently escalates cytotoxic T lymphocyte levels and diminishes regulatory T cell levels. Our findings reveal that magnetic hyperthermia offers a novel approach for dual down-regulation of CD47 and SIRPα, reshaping the tumor microenvironment to stimulate immune responses, culminating in significant antitumor activity.


Asunto(s)
Hipertermia Inducida , Neoplasias , Humanos , Antígeno CD47 , Regulación hacia Abajo , Inmunoterapia , Fagocitosis , Fenómenos Magnéticos , Neoplasias/patología , Microambiente Tumoral
3.
Food Res Int ; 173(Pt 2): 113473, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37803796

RESUMEN

This study aimed to hydrolyze soy isolate protein (SPI) using five enzymes (alcalase, pepsin, trypsin, papain, and bromelain) in order to obtain five enzymatic hydrolysates and to elucidate the effect of enzymes on structural and biological activities of the resulting hydrolysates. The antioxidant and hypoglycemic activities of the soy protein isolate hydrolysates (SPIEHs) were evaluated through in silico analysis, revealing that the alcalase hydrolysate exhibited the highest potential, followed by the papain and bromelain hydrolysates. Subsequently, the degree of hydrolysis (DH), molecular weight distribution (MWD), amino acid composition, structure, antioxidant activities, and hypoglycemic activity in vitro of SPIEHs were analyzed. After enzymatic treatment, the particle size, polymer dispersity index (PDI), ζ-potentials, ß-sheet content and α-helix content of SPIEHs was decreased, and the maximum emission wavelength of all SPIEHs exhibited red-shifted, which all suggesting the structure of SPIEHs was unfolded. More total amino acids (TAAs), aromatic amino acids (AAAs), and hydrophobic amino acids (HAAs) were found in alcalase hydrolysate. For 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, metal ion chelating activity, α-glucosidase inhibitory activity and α-amylase inhibitory activity, alcalase hydrolysate had the lowest IC50; alcalase hydrolysate and papain hydrolysate had the lowest IC50 for hydroxyl radical scavenging activity. Physiological activity of SPIEHs was evaluated thoroughly by 5-Axe cobweb charts, and the results revealed that alcalase hydrolysate exhibited the greatest biological activities.


Asunto(s)
Antioxidantes , Bromelaínas , Antioxidantes/farmacología , Antioxidantes/química , Glycine max/metabolismo , Papaína/química , Hidrolisados de Proteína/química , Proteínas de Soja , Aminoácidos , Subtilisinas/química
4.
J Transl Med ; 21(1): 147, 2023 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-36829235

RESUMEN

BACKGROUND: Valtrate, a natural compound isolated from the root of Valeriana, exhibits antitumor activity in many cancers through different mechanisms. However, its efficacy for the treatment of glioblastoma (GBM), a tumor type with a poor prognosis, has not yet been rigorously investigated. METHODS: GBM cell lines were treated with valtrate and CCK-8, colony formation and EdU assays, flow cytometry, and transwell, 3D tumor spheroid invasion and GBM-brain organoid co-culture invasion assays were performed to assess properties of proliferation, viability, apoptosis and invasion/migration. RNA sequencing analysis on valtrate-treated cells was performed to identify putative target genes underlying the antitumor activity of the drug in GBM cells. Western blot analysis, immunofluorescence and immunohistochemistry were performed to evaluate protein levels in valtrate-treated cell lines and in samples obtained from orthotopic xenografts. A specific activator of extracellular signal-regulated kinase (ERK) was used to identify the pathways mediating the effect. RESULTS: Valtrate significantly inhibited the proliferation of GBM cells in vitro by inducing mitochondrial apoptosis and suppressed invasion and migration of GBM cells by inhibiting levels of proteins associated with epithelial mesenchymal transition (EMT). RNA sequencing analysis of valtrate-treated GBM cells revealed platelet-derived growth factor receptor A (PDGFRA) as a potential target downregulated by the drug. Analysis of PDGFRA protein and downstream mediators demonstrated that valtrate inhibited PDGFRA/MEK/ERK signaling. Finally, treatment of tumor-bearing nude mice with valtrate led to decreased tumor volume (fivefold difference at day 28) and enhanced survival (day 27 vs day 36, control vs valtrate-treated) relative to controls. CONCLUSIONS: Taken together, our study demonstrated that the natural product valtrate elicits antitumor activity in GBM cells through targeting PDGFRA and thus provides a candidate therapeutic compound for the treatment of GBM.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Valeriana , Ratones , Animales , Humanos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Valeriana/metabolismo , Ratones Desnudos , Proliferación Celular , Glioblastoma/patología , Transducción de Señal , Iridoides/farmacología , Iridoides/uso terapéutico , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/farmacología , Quinasas de Proteína Quinasa Activadas por Mitógenos/uso terapéutico , Línea Celular Tumoral , Neoplasias Encefálicas/genética , Movimiento Celular
5.
Int J Mol Sci ; 24(2)2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36675040

RESUMEN

Sacha inchi meal (SIM) is a by-product of sacha inchi (considered as a "super-food") processing. In previous studies, we found that SIM protein hydrolysates exhibited pancreatic lipase inhibition activity. In this study, 10 bioactive peptides from those hydrolysates were identified. The top five peptides (NLYYKVV (NV-7), WWYVK (WK-5), WLLMWPYK (WK-8), EGLLMWPY (EY-8), and FPFFGYVWK (FK-9)) with strong pancreatic lipase inhibition activity had IC50 values of 34.01-246.50 µM, and displayed various inhibition types (mixed, non-competitive, and competitive type) by enzyme inhibition kinetics analysis. Fluorescence quenching analysis demonstrated that the interaction between the peptides and pancreatic lipase was mainly hydrogen bond and van der Waals force. The key residues involved in the peptide-enzyme interaction were determined by molecular docking. Moreover, the top two peptides were found to significantly inhibit fat accumulation and regulate lipid metabolism by alleviating the level of reactive oxygen species in HepG2 cells. Collectively, sacha inchi meal-derived peptides displayed potent lipid-lowering activity and could be used as materials of functional food.


Asunto(s)
Metabolismo de los Lípidos , Aceites de Plantas , Aceites de Plantas/metabolismo , Simulación del Acoplamiento Molecular , Péptidos/farmacología , Péptidos/metabolismo
6.
Environ Pollut ; 308: 119582, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35671896

RESUMEN

Selenium engineered nanomaterials (Se ENMs)-enabled agriculture has developed rapidly, however, the roles of surface charge in the bioavailability and enrichment efficiency of Se ENMs are still unknown. Herein, various Se ENMs of homogenous size (40-60 nm) and different surface charges (3.2 ± 0.7, -29.0 ± 0.4, and 45.5 ± 1.3 mV) were prepared to explore the Se content and nutritional quality in Brassica chinensis L. The results demonstrated that soil application of various Se ENMs (0.05 mg kg-1) displayed different bio-availabilities via modulating the secretion of root exudates (e.g., tartaric, malic, and citric acids), microbial community composition (e.g., Flavobacterium, Pseudomonas, Paracoccus, Bacillus and Rhizobium) and root cell wall. Negatively charged Se ENMs (Se (-)) showed the highest Se content in the shoot of B. chinensis (3.7-folds). Se (-) also significantly increased yield (156.9%) and improved nutritional quality (e.g., ascorbic acid, amino acids, flavonoids, fatty acids, and tricarboxylic acid) of B. chinensis. Moreover, after harvest, the Se (-) did not lead to significant change in Se residue in soil, but the amount of Se residue in soil was increased by 5.5% after applying the traditional Se fertilizer (selenite). Therefore, this study provides useful information for producing Se-fortified agricultural products, while minimizing environmental risk.


Asunto(s)
Brassica , Selenio , Contaminantes del Suelo , Brassica/metabolismo , Valor Nutritivo , Ácido Selenioso , Selenio/análisis , Suelo/química , Contaminantes del Suelo/análisis
7.
Plant Dis ; 2022 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-35581918

RESUMEN

Sanqi (Panax notoginseng (Burk.) F. H. Chen) is a precious traditional Chinese herbal medicine. During April of 2021, a root rot disease with approximate 15% incidence was observed on 2-year-old Sanqi plants in a field of Zhouning (27º12' N, 119°33' E), Fujian Province of China. The disease symptoms included severe stunting, leaf chlorosis, root rotting and necrosis, as the disease progressed, the whole plant gradually wilted and died. To recover the causal agent, symptomatic roots were excised, surface sterilized in 75% alcohol for 1.5 min, rinsed in sterilized water three times, dried, and placed on PARP selective medium (Jeffers and Martin 1986), and incubated at 20°C in dark. After 5 days, total of 26 Pythium-like isolates were obtained, and one representative isolate Py21-6 (available from the Institute of Plant Protection, Fujian Academy of Agricultural Sciences) was selected for further identification. Colonies of Py21-6 on PARP plate were white with dense, cottony, aerial, and transparent mycelia. Sporangia were terminal or intercalary, non-papillate, spherical, pyriform or ovoid, measuring 21.7 ± 2.8 × 19.3 ± 2.3 µm (n = 30). Zoospores were saucer-like, released out of sporangium after maturation, and dispersed quickly by swimming. Oogonia were spherical, terminal or occasionally intercalary. Oospores were globose, smooth and aplerotic. The dimensions of zoospores, oogonia, and oospores were 6.8 ± 0.7 µm, 21.6 ± 2.2 µm and 18.2 ± 2.7 µm (n = 30), respectively. Antheridia were bell-shaped or irregular, terminal, monoclinous, and usually one per oogonium. According to the morphological characteristics the isolate was initially identified as Pythium spp. (Van der Plaats-Niterink 1981, Yong et al. 2016). For further identification, DNA extracted from Py21-6, the cytochrome c oxidase subunit I (COI) gene and internal transcribed spacer (ITS) region were amplified and sequenced with primers FM55/FM52R (Long et al. 2012) and ITS1 /ITS4 (White et al. 1990), respectively. BLAST analysis of 680-bp COI (OM688194) and 728-bp ITS (OM663703) sequences revealed 99.86% and 99.99% similarity to Pythium vexans in GenBank (HQ708995 [COI], GU133572 [ITS]). Therefore, the pathogen was identified as P. vexans. In order to fulfill Koch's postulates, isolate Py21-6 was grown on Martin's liquid medium (Martin 1992) for 72 h to produce a spore suspensions of 106 oospores/ml, and the pathogenicity test was conducted by root-dip method. Three groups of 2-year-old Sanqi (15 plants per group) with root soaked for 20 min in oospore suspension were used for pathogenicity, and the other three groups (15 plants per group) with root dipped in sterilized water as control. All treated plants were replanted in (15-cm-diameter) pots (2 plants/pot) filled with mixture of sterilized soil: vermiculite: pearlite (2:1:1, v/v), maintained in greenhouse under 60% black shade cloth at 20 to 26°C with 80% relative humidity, and watered once every three days. After 21days, all inoculated plants showed the same symptoms observed on the original diseased plants in the field, whereas, the control plants remained symptomless. The same pathogen was successfully re-isolated from the inoculated plants, and identical to those of the originals based on morphological and sequence data. To our knowledge, this is the first report of P. vexans causing root rot on Sanqi in China (Farr and Rossman 2022). Root rot is one of the destructive diseases in Sanqi production, identification of the pathogen will be useful to develop effective field management strategies to control this disease.

8.
Mar Drugs ; 20(3)2022 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-35323471

RESUMEN

In the present study, a selenium-chondroitin sulfate (SeCS) was synthesized by the sodium selenite (Na2SeO3) and ascorbic acid (Vc) redox reaction using chondroitin sulfate derived from shark cartilage as a template, and characterized by SEM, SEM-EDS, FTIR and XRD. Meanwhile, its stability was investigated at different conditions of pH and temperatures. Besides, its antioxidant activity was further determined by the DPPH and ABTS assays. The results showed the SeCS with the smallest particle size of 131.3 ± 4.4 nm and selenium content of 33.18% was obtained under the optimal condition (CS concentration of 0.1 mg/mL, mass ratio of Na2SeO3 to Vc of 1:8, the reaction time of 3 h, and the reaction temperature of 25 °C). SEM image showed the SeCS was an individual and spherical nanostructure and its structure was evidenced by FTIR and XRD. Meanwhile, SeCS remained stable at an alkaline pH and possessed good storage stability at 4 °C for 28 days. The results on scavenging free radical levels showed that SeCS exhibited significantly higher antioxidant activity than SeNPs and CS, indicating that SeCS had a potential antioxidant effect.


Asunto(s)
Antioxidantes/química , Cartílago/química , Sulfatos de Condroitina/química , Nanopartículas/química , Selenio/química , Tiburones , Animales , Benzotiazoles/química , Compuestos de Bifenilo/química , Sulfatos de Condroitina/aislamiento & purificación , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Picratos/química , Ácidos Sulfónicos/química , Temperatura
9.
Sci Total Environ ; 824: 153712, 2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-35149065

RESUMEN

A selenium (Se)-nanoenabled agriculture strategy was established in this work to improve crop yield and quality. The results demonstrated that Se engineering nanomaterials (Se ENMs, 10 mg·L-1) were absorbed and translocated in cherry radish (Raphanus sativus L. var. radculus pers) from shoots to taproots after foliar application. RNA-Seq and metabolomic results indicated that the glucolysis, pyruvate and tricarboxylic acid (TCA) cycle metabolism pathways were accelerated by exposure to Se ENMs, resulting in increased production of flavonoids (3.2-fold), amino acids (1.4-fold), and TCA (2.5-fold) compared with the control. Moreover, Se content was enhanced by 5.4 and 2.6 times in pericarp and pulp upon Se ENMs exposure, respectively, which was more efficient (2.2 and 1.1 times) than SeO32- treatment. Additionally, the yield of cherry radish was increased by 67.6% under Se ENMs, whereas SeO32- exposure only led to an increase of 7.4%. Therefore, the application of Se ENMs could reduce the amount of fertilizer used to minimize the environmental impact in agriculture while improve crop production and quality. These findings highlighted the significant potential of Se ENMs-enabled agriculture practices as an eco-friendly and sustainable crop strategy.


Asunto(s)
Nanoestructuras , Raphanus , Selenio , Antioxidantes/metabolismo , Raphanus/metabolismo , Selenio/metabolismo
10.
Sci Total Environ ; 806(Pt 1): 150343, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34571238

RESUMEN

Buffering capacity could provide a comprehensive view to recognize the response between external loads and water quality and help address the significant challenges associated with the reduction of lake pollution. However, quantification of the dynamic change in the holistic buffering capacity of biogenic elements in lakes and its driving mechanisms has not been fully understood. Taking Erhai Lake in China as an example, this study quantified the long-term (2000-2019) dynamic changes in buffering capacity and revealed key driving forces for the changes in buffering capacity. The results showed that nitrogen buffering capacity (NBC) and organic buffering capacity (CODBC) decreased during the past 20 years, while phosphorus buffering capacity (PBC) did not change significantly. Endogenous factors are the main controlling factors of buffering capacity. Specifically, algal biomass drove the change in NBC (interpretation rate of 62.2%); the adsorption and sedimentation effects of sediments maintained the relative stability of PBC (56.30%) while algal biomass indirectly impacted the PBC (1.69% only) by affecting the redox environment of the sediments; and algae-derived organic matter and refractory organic matter accumulation dominated the change in CODBC (61.4% and 32.8%, respectively). Water inflow is another controlling factor for NBC and CODBC due to dilution of lake water. This study indicated that the accumulation of endogenous loads and a decrease in water inflow drove the decrease in the lake's buffering capacity (mainly NBC and CODBC), which could help explain why the decrease in external loads in Erhai Lake has not yet reversed the trend of water quality decline. Our study highlights the importance of comprehensive buffering capacity improvement instead of simple external load control to optimize lake environmental management. In the future, attention should be given to controlling endogenous loads, especially preventing algal blooms, and to optimizing hydrodynamic conditions to cope with the decrease in water inflow.


Asunto(s)
Monitoreo del Ambiente , Lagos , China , Eutrofización , Nitrógeno/análisis , Fósforo/análisis , Calidad del Agua
11.
World J Clin Cases ; 9(27): 8249-8259, 2021 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-34621888

RESUMEN

BACKGROUND: Granulomatous lobular mastitis (GLM) is a type of benign chronic inflammatory disease that poses therapeutic challenges to healthcare providers. The diagnosis of GLM relies on tissue biopsy, and incorrect treatment may lead to delayed diagnosis, considerable aesthetic damage, and even mastectomy. CASE SUMMARY: We report the case of a 37-year-old Chinese woman who was lactating and had GLM in both breasts. At the time of treatment, the right breast had a mass of approximately 15 cm × 11 cm, which was hard and had poor mobility. Multiple skin ulcerations and pus spills were also observed on the surface of the breast. The left breast had a mass of about 13 cm × 9 cm, which was hard and had poor mobility. CONCLUSION: Herein, we report a case of bilateral GLM in a lactating woman that was successfully treated with traditional Chinese medicine (TCM), without the requirement for surgery or other treatments. Therefore, TCM may have advantages in the nonsurgical treatment of GLM.

12.
Environ Manage ; 68(3): 340-352, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34274979

RESUMEN

Invasive alien species (IAS) significantly impact biodiversity, human health, and economies, and considerable resources are often used to manage their spread. Few studies have focused on the human perception of IAS management, and little is known about approaches to improve stakeholder perception. This study examined perception gaps between managers and non-managers of a notorious weed Mikania micrantha and the preference for educational approaches to bridge those gaps. Household questionnaires and key informant interviews were conducted in the China-Myanmar Border Region (China), and ordinal logistic regressions and Wilcoxon rank sum tests were used in statistical analyses. We found a high level of perception of M. micrantha among stakeholders, and a significant influence of socio-demographic factors including gender, educational level, ethnic group, and geographical location. Scores of the identification, damage, control measure, and manual treatment of M. micrantha were significantly higher for managers than those for non-managers, indicating that there were certain perception gaps between two stakeholder groups. Nine educational approaches were identified as being effective in improving stakeholder perception of IAS, of which training workshops were mostly preferred, followed by brochures (or leaflets) and other promotional materials. Additionally, we propose that well-designed and well-conducted educational approaches would benefit stakeholder perception of IAS, and that integration of IAS management into a comprehensive rural development scheme would improve its long-term performance in marginalized rural communities.


Asunto(s)
Mikania , Biodiversidad , China , Humanos , Especies Introducidas , Percepción
13.
J Ethnopharmacol ; 279: 114379, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34216727

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Tiaogeng decoction (TGD), a mixture of 10 traditional Chinese herbs, has been used clinically for over 30 years in treating menopause-related symptoms such as cognitive changes, mood disorders, vasomotor symptoms, and sleep disorders. These central nervous system symptoms are closely associated with declined ovarian function, which dramatically increases the risk of neurodegenerative disease. Previous studies revealed that TGD may have anti-oxidative and anti-apoptotic properties, potentially preventing neurodegenerative conditions; however, the underlying pharmacological mechanism remains unclear. AIM OF THE STUDY: This study aimed to examine whether TGD could activate the Nrf2 and C-Jun N-terminal kinase (JNK) signaling pathways to effectively reduce oxidative injury and apoptosis in PC12 cells and elucidate the mechanism by which this medicine may prevent neurodegenerative disease. MATERIALS AND METHODS: PC12 cells were exposed to different concentrations of TGD (125, 250, 500 µg/mL) and H2O2 (150 µM). 17ß-estradiol (0.05 µg/mL) was used as the positive control. A cell counting kit-8 (CCK-8) and a lactate dehydrogenase (LDH) assay were used to detect cell viability and cytotoxicity, while Hoechst and flow cytometry were performed to evaluate apoptosis levels. Mitochondrial function was assessed by measuring mitochondrial membrane potential (MMP), and superoxide dismutase (SOD), and reactive oxygen species (ROS) levels were used to measure oxidative stress (OS). Western blot analysis was used to identify the levels of Nrf2, phospho-JNK (p-JNK), phospho-mitogen-activated protein kinase kinase 7 (p-MKK7), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), Caspase3 (Casp3), Caspase9 (Casp9), Bax, and Bcl-2 proteins. Moreover, JNK agonist anisomycin and Nrf2 inhibitor ML385 were used to validate pathways. RESULTS: TGD pretreatment significantly alleviated H2O2-induced cytotoxicity, apoptosis, MMP, and OS levels. H2O2 stimulated the activation of Nrf2 and JNK signaling pathways, but TGD increased the extent of Nrf2 antioxidant activation, decreased the activation of JNK, and eventually reversed the H2O2-induced protein expression of p-MKK7, Keap1, HO-1, Cleaved Caspase3 (CL-Casp3), Cleaved Caspase9 (CL-Casp9), Bax, and Bcl-2. CONCLUSIONS: This study's findings suggest that TGD may attenuate oxidative injury and apoptosis via the Nrf2 and JNK signaling pathways, making it a potential therapeutic candidate for neurodegenerative diseases.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Fármacos Neuroprotectores/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular , Medicamentos Herbarios Chinos/química , Factor 2 Relacionado con NF-E2/genética , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Ratas
14.
J Ethnopharmacol ; 269: 113669, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33338591

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Tiao Geng (TG) decoction is a Chinese herbal medicine extract that has been utilized for the treatment of menopausal symptoms for a history of over 30 years. In our previous study, we suggest that TG decoction possibly exerts an anti-apoptotic effect on hypothalamic neurons of ovariectomized rats via the ASK1/MKK7/JNK pathway. Tributyltin chloride (TBTC) causes oxidative damage and induces apoptosis of primary hypothalamic neurons in rats. AIM OF THE STUDY: The present work aimed to explore the inhibition of TG decoction on TBTC-induced GT1-7 cell apoptosis and its possible molecular mechanism. MATERIALS AND METHODS: The GT1-7 cell line was exposed to TG decoction at diverse doses (31.25, 62.5, 125 µg/mL) for 24 h and later with TBTC (1 mg/L) for 1 h, with 17ß-E2 (100 nM) treatment being the positive control. Then, CCK8 assay was conducted to evaluate cell viability, while flow cytometric analysis was conducted to examine the apoptosis level. Related pathways and differentially expressed proteins were identified by tandem mass tag (TMT)-based quantitative phosphoproteomics. qRT-PCR was carried out to examine mRNA levels of Bax and B-cell lymphoma-2 (Bcl-2). Western blotting was performed to detect the levels of Bax, Bcl-2, c-Jun, c-Jun N-terminal kinase (JNK), Caspase-3 (Casp3), Mitogen-activated protein kinase kinase 7 (MKK7), and apoptosis signal-regulating kinase 1 (ASK1) . Finally, cells were pretreated with SP600125, an inhibitor of JNK, later the expression of JNK and Casp3 was measured. RESULTS: Application of TG decoction mitigated the GT1-7 cell apoptosis and injury caused by TBTC; besides, it inhibited the activation of the ASK1/MKK7/JNK pathway. Moreover, Bcl-2/Bax ratio became higher, and the MKK7, ASK1, Casp3 and c-Jun levels were inhibited. Besides, TG decoction combined with SP600125 (the JNK inhibitor) more significantly inhibited GT1-7 cell apoptosis caused by TBTC. CONCLUSION: As discovered from the experiment in this study, TG decoction has a neuroprotective effect, which is achieved through inhibiting the ASK1/MKK7/JNK signal transduction pathway to reduce GT1-7 cell apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , MAP Quinasa Quinasa Quinasa 5/antagonistas & inhibidores , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Compuestos de Trialquiltina/toxicidad , Animales , Apoptosis/fisiología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , MAP Quinasa Quinasa Quinasa 5/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Compuestos de Trialquiltina/antagonistas & inhibidores
15.
Chemosphere ; 263: 128334, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33297262

RESUMEN

Nutrient partition, especially for phosphorus (P), has been prominently changed that was caused by variation of river-lake relationship during the post-Three Gorges Reservoir and catchment alternations. Changes in proportion of total particulate phosphorus (TPP) and total dissolved phosphorus (TDP) might accelerate lake eutrophication, but limited attention has been paid to P partition over suspended particle (SP) levels. Data analysis showed that SP concentration presented a positive effect on TPP in wet season and soluble reactive phosphorus (SRP) in dry season, indicating seasonal physical and chemical variations. Based on this phenomenon, we proposed a hypothesis that the SP levels would affect TDP and TPP proportions by partition in aqueous-solid. It was found that using the parabola models to fit the sorption relationships of SRP and TDP (R2 > 0.6, p < 0.01), the maximum sorption capacity (Qmax) was 64.54 mg/kg and 60.52 mg/kg at 400 mg/L of SP level, respectively. In addition, the partition coefficients (KP) of TDP and SRP were logarithmically increased with SP levels, indicating that higher SP levels (>400 mg/L) would hinder the sorption process. Furthermore, enhancing turbulence lead to less sorption of SRP and TDP at high SP levels (>800 mg/L). The sorption of SRP and TDP related to the presence of Fe/Al oxy-hydroxides were enriched in the Fe/Al-P fraction (47% of TP). The findings of this study indicated that the low SP levels would increase P bioavailability for alga and is not conducive for lake eutrophication management.


Asunto(s)
Lagos , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente , Eutrofización , Fósforo/análisis , Agua , Contaminantes Químicos del Agua/análisis
16.
J Ethnopharmacol ; 261: 113061, 2020 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-32525065

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: TG-decoction (Tiao Geng decoction) is the extract of a Chinese herb mixture that has been used for treating menopausal symptoms for over 30 years. We have previously reported anti-aging and anti-oxidative effects of the TG-decoction on hypothalamic neurons in ovariectomized (OVX) rats. AIM OF THE STUDY: The present study further investigates the effects of TG-decoction on the prevention of aging-related ultrastructural changes in menopausal hypothalamic neurons and the likely molecular mechanism. MATERIALS AND METHODS: A total of 120 four-month-old female SPF Sprague Dawley rats were divided into six groups. Five groups were ovariectomized (OVX) and one group served as a sham control. Three OVX groups received TG-decoction at three different doses. The remaining two OVX groups served as positive and negative controls by receiving estradiol valerate and saline solution. The sham group received saline. After one month, aging-related ultrastructural alterations in hypothalamic neurons were evaluated using transmission electron microscopy. Nissl staining was used to assess the pathomorphological changes of the hypothalamic neurons. Cell apoptosis was evaluated by TUNEL. Expression of Bcl-2 family genes was studied using qRT-PCR. Expression of the apoptosis-related proteins ASK1, MKK7, JNK, c-Jun, Bax, Casp3 and Bcl-2 was studied using western blotting. RESULTS: Ovariectomy of female rats led to visible damage and aging-like alterations in the mitochondria and endoplasmic reticulum as well as large deposits of lipofuscin in hypothalamic tissue. TG-decoction treatment prevented this visible damage and lipofuscin deposition, increased the number of nerve cells and normally-shaped Nissl bodies, and reduced the number of TUNEL-positive cells. Expression of Bcl-2 gene was increased, while Bax gene reduced. Expression of the proteins ASK1, MKK7, JNK, c-Jun, Bax and Casp3 was reduced, while that of Bcl-2 was increased. CONCLUSION: TG-decoction reduces aging-related ultrastructural changes in hypothalamic neurons, likely by suppressing ASK1/MKK7/JNK-mediated apoptosis in neuronal mitochondria or nuclei.


Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Hipotálamo/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , MAP Quinasa Quinasa Quinasa 5/metabolismo , Menopausia/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neuronas/efectos de los fármacos , Factores de Edad , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/enzimología , Retículo Endoplásmico/ultraestructura , Femenino , Hipotálamo/enzimología , Hipotálamo/patología , Menopausia/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Mitocondrias/ultraestructura , Neuronas/enzimología , Neuronas/ultraestructura , Ovariectomía , Ratas Sprague-Dawley , Transducción de Señal , Síndrome
17.
Environ Sci Pollut Res Int ; 27(9): 9490-9502, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31919821

RESUMEN

Selenium (Se) is beneficial for plant growth under different stressful conditions. In this study, we investigated the protective effects of Se supply from Cd-induced damages in tall fescue under Cd stress. Tall fescue seedlings (40 days old) were treated with Cd (30 mg/L, as CdSO4·8/3 H2O) and Se (0.1 mg/L, as Na2SeO3) individually and in combination using 1/2 Hoagland's solution system for 7 days. Various physiological parameters, photosynthetic behaviors, and gene expressions were measured. The results showed that Cd-stressed plants displayed obvious toxicity symptoms such as leaf yellowing, decreasing plant height, and root length. Cd stress significantly increased the malondialdehyde (MDA) content and electrolyte leakage (EL), and remarkably reduced the chlorophyll and soluble protein content, antioxidant enzyme activities, and photosynthetic efficiency. Cd stress significantly inhibited the expression of two photosynthesis-related genes (psbB and psbC), but not psbA. In addition, it significantly inhibited the expression of antioxidant system-related genes such as ChlCu/ZnSOD, CytCu/ZnSOD, GPX, and pAPX, but significantly increased the expression of GR. However, Se improved the overall physiological and photosynthetic behaviors of Cd-stressed plants. Se significantly enhanced the chlorophyll and soluble protein content and CAT and SOD activities, but decreased MDA contents, EL, and Cd content and translocation in tall fescue under Cd stress. Furthermore, under Cd stress, Se increased the expression of psbA, psbB psbC, ChlCu/ZnSOD, CytCu/ZnSOD, GPx, and PAPx. The result suggests that Se alleviated the deleterious effects of Cd and improved Cd resistance in tall fescue through upregulating the antioxidant system, photosynthesis activities, and gene expressions.


Asunto(s)
Antioxidantes , Selenio , Cadmio , Clorofila , Suplementos Dietéticos , Estrés Oxidativo , Fotosíntesis , Hojas de la Planta
18.
Ying Yong Sheng Tai Xue Bao ; 30(11): 3662-3670, 2019 Nov.
Artículo en Chino | MEDLINE | ID: mdl-31833678

RESUMEN

Forest harvesting changes the quantity and quality of organic matter inputs into soil, and thus would alter soil nutrient content and availability. Phosphorus (P) is a key element affecting plant growth. The effects of harvest residue treatments on soil P fractions and availability had not yet been evaluated. In this study, harvest residue retainment (RR), residue removal (R) and residue burning (RB) treatments were manipulated after clear-cutting in a mature Chinese fir (Cunninghamia lanceolata) plantation at the Sanming Forest Ecosystem and Global Change Research Station in Fujian, China. This study focused on the dynamics of soil P fractions and their driving factors in the 0-10 cm and 10-20 cm soil layers after 4-year residue treatments. The results showed that, in RR treatment, the contents of easily-available P, moderately-available P and non-available P at the 0-10 cm soil layer were all significantly higher than those in R treatment, while the contents of moderately-available P and non-available P at the 10-20 cm soil layer was significantly higher than those in RB treatments. The ratios of soil organic carbon (C) to organic P (C:Po) in both layers were over 200 for all the three treatments, with ratios in RR treatment being significantly lower than those in RB and R treatments, indicating that RR could alleviate P limitation in this ecosystem. Moreover, results of the redundancy analysis showed that changes in P fractions were mainly affected by dissolved organic C, free Fe and noncrystalline amorphous Fe. The results suggested that soil organic P and available P were mainly from the decomposition of plant residues, which supported continuous P supply for plant growth. RR could enhance soil P content, thereby improve soil P availability and mitigate P limitation in Chinese fir plantation.


Asunto(s)
Cunninghamia , Carbono , China , Ecosistema , Nitrógeno , Fósforo , Suelo
19.
Am J Chin Med ; 47(6): 1345-1363, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31495181

RESUMEN

Panax ginseng exerts good neuroprotective activity at the cell and animal level, but the specific bioactive compounds and action mechanism are needed to be investigated, verified, and confirmed. In this work, affinity ultrafiltration (AUF), UPLC-QTOF-MS, and molecular docking were integrated into one strategy to screen, identify, and evaluate the bioactive compounds in ginseng at the molecular level. Three biological macromolecules (AChE, MAO-B, and NMDA receptor) were selected as the target protein for AUF-MS screening for the first time, and 16 potential neuroactive compounds were found with suitable binding degree. Then, the bioactivity of ginseng and its components were evaluated by AChE-inhibitory test and DPPH assay, and the data indicate that ginseng extract and the screened compounds have good neuroactivity. The interaction between the three targets and the screened compounds was further analyzed by molecular docking, and the results were consistent with a few discrepancies in comparison with the AUF results. Finally, according to the corresponding relation between component-target-pathway, the action mechanism of ginseng elucidated that ginseng exerts a therapeutic effect on AD through multiple relations of components, targets, and pathways, which is in good accordance with the TCM theory.


Asunto(s)
Cromatografía Líquida de Alta Presión , Evaluación Preclínica de Medicamentos/métodos , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores , Panax/química , Extractos Vegetales/farmacología , Espectrometría de Masas en Tándem , Ultrafiltración , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Antioxidantes , Inhibidores de la Colinesterasa , Humanos , Terapia Molecular Dirigida , Monoaminooxidasa , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Receptores de N-Metil-D-Aspartato
20.
J Ethnopharmacol ; 237: 1-8, 2019 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-30878547

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin (PF) exerts a significant protective effect against neurotoxicity and mitochondrial damage in neurons. However, the mechanisms underlying PF-mediated rescue remain elusive. Therefore, we endeavored to further research the molecular mechanisms underlying PF-mediated inhibition of tributyltin chloride (TBTC)-induced apoptosis of neurons. AIM OF THE STUDY: To investigate the influence and possible mechanism of action of PF in TBTC-induced neurodegenerative disease. MATERIALS AND METHODS: First, primary hypothalamic neurons were treated with tributyltin chloride (150 µg/L) and PF (25, 50, and 100 µM). 17ß-estradiol (1 nM) was used as a positive control. Subsequently, CCK-8 assay was performed. The level of apoptosis was examined by flow cytometry and the function of mitochondria was reflected by MMP levels. The mRNA expression levels of B-cell lymphoma-2 (Bcl-2), together with Bax, were examined using qRT-PCR. The protein levels of mitogen-activated protein kinase kinase 4 (MKK4), c-Jun N-terminal kinase (JNK), Bcl-2, Bax, and Caspase-3 were examined using western blotting. Finally, pretreatment with JNK agonist, anisomycin, was done to observe the change in expressions of MKK4 and JNK. RESULTS: Paeoniflorin treatment reduced TBTC-induced damage and neuron loss in a dose-dependent manner. Decrease in mitogen-activated protein kinase (MAPK) as well as JNK levels were reversed by treatment with paeoniflorin via inhibition of JNK activation. Furthermore, ratio of levels of Bcl-2/Bax increased while the activation of caspase-3 was suppressed. In addition, pretreatment with JNK agonist, anisomycin effectively suppressed TBTC-induced cytotoxicity in hypothalamic neuron. CONCLUSIONS: PF can potentially be used to prevent and/or treat neurodegenerative diseases and neural injury by inhibiting MKK4-JNK signaling pathway.


Asunto(s)
Glucósidos/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Monoterpenos/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Compuestos de Trialquiltina/toxicidad , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Hipotálamo/citología , Neuronas/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos
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