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1.
Mikrochim Acta ; 191(2): 90, 2024 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-38214747

RESUMEN

A novel mosaic structure Silica@C/Co@ZIF-67 composite was synthesized by successfully embedding Co nanoparticles on the surface of silica spheres with the help of thermoplastic polyethyleneimine by carbon-reduction. The ZIF-67 half-shell layer structure was synthesized by the in-situ growth of ZIF-67 on the surface of silica spheres through the coordination of 2-methylimidazole with Co metal nodes. The composite was used as a magnetic solid-phase extraction adsorbent combined with high performance liquid chromatography-ultraviolet detector (HPLC-UV) for the extraction and determination of benzoylurea insecticides (BUs) in vegetables and tea. Based on the presence of π-π, hydrophobic and hydrogen bonding interactions between Silica@C/Co@ZIF-67 and BUs, the BUs were rapidly captured by the composites resulting in high adsorption performance. Under the optimal extraction parameters, the linear ranges were 0.3-200 µg L-1 for diflubenzuron, 0.6-200 µg L-1 for chlorbenzuron, and 1.0-200 µg L-1 for triflumuron, teflubenzuron, and flufenoxuron, with correlation coefficients (R2) greater than 0.9991. The limits of detection (LODs) of the method were 0.1-0.3 µg L-1, and the relative standard deviations (RSDs) were 1.2-3.0% for intra-day and 2.6-4.6% for inter-day. In the spiked recovery experiments of vegetables and tea, the recoveries of the five kinds of BUs ranged from 75.8 to 112.9%. In addition, after 10 repetitions using Silica@C/Co@ZIF-67, the recoveries of the five kinds of BUs were still as high as 78.4 to 83.9%.


Asunto(s)
Diflubenzurón , Insecticidas , Insecticidas/análisis , Cromatografía Líquida de Alta Presión/métodos , Té/química , Dióxido de Silicio
2.
Int Immunopharmacol ; 126: 111321, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38041955

RESUMEN

Vitamin C (VitC) presents excellent anti-tumor effect for long time. Recently, high dose VitC achieved by intravenous administration manifests superior anti-tumor effect. However, the functions and detailed mechanisms of high dose VitC's role in cancer immunity are not fully understood. This study investigates the effect of high dose VitC on PD-L1 expression in triple negative breast cancer (TNBC) and the potential mechanism. Results showed VitC inhibited PD-L1 expression in breast cancer cell lines and enhanced anti-tumor effects of T cells. Furthermore, we found VitC inhibited PD-L1 transcription through ROS-pSTAT3 signal pathways. Consistent with in vitro results, in vivo study showed VitC suppressed tumor growth in immunocompetent mice and enhanced CD8+ T cells infiltration and function in tumor microenvironment. Our findings identify the effects of high dose VitC on PD-L1 expression and provide a rationale for the use of high dose VitC as immunomodulator for cancer therapy.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Antígeno B7-H1/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Antineoplásicos/uso terapéutico , Transducción de Señal , Ácido Ascórbico/uso terapéutico , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Microambiente Tumoral
3.
Chin Med ; 18(1): 65, 2023 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-37264387

RESUMEN

BACKGROUND: Baphicacanthis Cusiae Rhizoma et Radix, commonly known as Nan-Ban-Lan-Gen (NBLG), is an essential traditional Chinese medicine that possesses diverse bioactivities, particularly noteworthy for its antiviral properties. Although NBLG has been listed in the Chinese Pharmacopoeia as an independent Chinese medicine, the establishment of a comprehensive quality standard for NBLG remains elusive. The absence of assay for marker compound in its quality standards has led to the lack of corresponding quality control measures for NBLG-containing preparations, and its discrimination from adulterant species in the market which thereby can significantly impact the efficacy and safety of NBLG-containing products. METHODS: Ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole-time-of-flight mass spectrometry (Q-TOF-MS) was employed for comprehensive profiling of the chemical constituents of NBLG, the stem of Baphicacanthus cusia (Nees) Bremek (NBLJ), and the roots of Isatis indigotica Fort. (Bei-Ban-Lan-Gen, BBLG). Additionally, multivariate analysis was conducted to compare the chemical components of NBLG with those of NBLJ and BBLG. Furthermore, we established an optimized and validated HPLC method to obtain the fingerprint of NBLG and quantify the content of 2-benzoxazolinone and acteoside in the samples. RESULTS: A total of 73 compounds belonging to six classes were assigned in NBLG, with alkaloids being the most abundant and diverse species. High compositional similarities with significant differences in content were observed between NBLG and NBLJ. Moreover, the chemical profile of BBLG markedly differed from that of NBLG. An informative high performance liquid chromatography (HPLC) fingerprint of NBLG comprising seven characteristic peaks that can be used for quality assessment was established. Notably, we propose a quality control standard for NBLG, stipulating that the limit of content in dry weight for both 2-benzoxazolinone and acteoside should not be less than 0.010%. CONCLUSION: This study provides the most comprehensive chemical information to date on NBLG, offering valuable insights into its authentication and quality control. Our findings highlight the importance of comprehensive chemical profiling to differentiate potential substitutions and adulterations of herbal medicines, particularly when the original source is scarce or unavailable. These results can aid in the development of quality control measures for NBLG-containing preparations, ensuring their safety and efficacy.

4.
Artículo en Inglés | MEDLINE | ID: mdl-36673842

RESUMEN

To reduce the burden caused by an increased elderly population and to provide efficient service resources, scholars worldwide have proposed and applied smart elderly care. This paper summarizes the hotspots of the existing literature and explores the research frontiers to ignite future research. CiteSpace software was used to conduct a scientometric analysis of high-quality literature collected from both the China National Knowledge Infrastructure (CNKI) and the Web of Science (WOS). Based on the results of the basic situation description, this article highlights six research hotspots in CNKI and 11 research themes in WOS. In addition, it offers three major evolution stages and three future research directions for smart elderly care research. This paper provides a holistic overview of the smart elderly care literature from two major global databases. The results will contribute to healthcare policy designers, practitioners, and developers by giving them comprehensive knowledge and generating strategies to enhance elderly people's quality of life.


Asunto(s)
Conocimiento , Calidad de Vida , Humanos , Anciano , China , Bases de Datos Factuales , Predicción
5.
Nat Prod Res ; 37(11): 1797-1805, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36083622

RESUMEN

A novel pectic polysaccharide, named GTPS3-1, was isolated and purified from Laoshan green tea polysaccharide (GTPS) through DEAE Sepharose Fast Flow and Sephacryl S-300 columns, its structure was characterized and its anti-inflammatory activity was explored. GTPS3-1, with a molecular weight of 26.05 kDa, was mainly composed of galacturonic acid, galactose, rhamnose and arabinose in a molar ratio of 4.72:2.5:1.68:1 on the basis of monosaccharide composition. Structural analysis results revealed that GTPS3-1 was a highly branched pectin consisting of →3)-Galp-(1→, →2)-Rhap-(1→, →3,5)-Araf-(1→, →3)-Rhap-(1→, GalpA-(1→, →3,4)-Galp-(1→, →4)-GalpA-(1→, →5)-Araf-(1→, →2,4)-Rhap-(1→, Rhap-(1→ and Araf-(1→ according to FT-IR, methylation and NMR analyses. In addition, GTPS3-1 inhibited the production of NO, TNF-α and IL-6 in a dose-dependent manner, which resulted in the amelioration of inflammatory injury in LPS-induced RAW 264.7 cells. These results would provide a theoretical basis for practical application of the novel polysaccharide as an anti-inflammatory adjuvant.


Asunto(s)
Pectinas , Factor de Necrosis Tumoral alfa , Pectinas/farmacología , Pectinas/química , Interleucina-6 , Espectroscopía Infrarroja por Transformada de Fourier , , Polisacáridos/química
6.
Metabolites ; 12(10)2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36295824

RESUMEN

Lappaconitine (LA) is a C-18 diterpene alkaloid isolated from Aconitum sinomontanum Nakai that has been shown to relieve mild to moderate discomfort. Various researchers have tried to explain the underlying mechanism of LA's effects on chronic pain. This article uses metabolomics technology to investigate the metabolite alterations in the dorsal root ganglion (DRG) when lappaconitine hydrobromide (LAH) was injected in an inflammatory pain model, to explain the molecular mechanism of its analgesia from a metabolomics perspective. The pain model used in this study was a complete Freund's adjuvant (CFA)-induced inflammatory pain model in rats. There were two treatment groups receiving different dosages of LAH (4 mg/kg LAH and 8 mg/kg LAH). The analgesic mechanism of LAH was investigated with an analgesic behavioral test, tissue sections, and metabolomics. The results of the analgesic behavioral experiment showed that both 4 mg/kg LAH and 8 mg/kg LAH could significantly improve the paw withdrawal latency (PWL) of rats. The tissue section results showed that LAH could reduce the inflammatory response and enlargement of the paw and ankle of rats and that there was no significant difference in the tissue sections of the DRG. The metabolomics results showed that retinol metabolism and glycerophospholipid metabolism in the CFA-induced inflammatory pain model were significantly affected and may exacerbate the inflammatory reactions and initiate persistent pain; in addition, the linoleic acid metabolism, arachidonic acid metabolism, and alanine, aspartate, and glutamate metabolism were also slightly affected. Among them, the alpha-linolenic acid metabolism was up-regulated after LAH treatment, while the retinol metabolism was down-regulated. These results suggest that LAH could effectively reduce inflammatory pain and might achieve this by regulating the lipid metabolism in the rat DRG.

7.
Molecules ; 27(18)2022 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-36144523

RESUMEN

Toona sinensis (A. Juss.) Roem is an edible medicinal plant that belongs to the genus Toona within the Meliaceae family. It has been confirmed to display a wide variety of biological activities. During our continuous search for active constituents from the seeds of T. sinensis, two new acyclic diterpenoids (1-2), together with five known limonoid-type triterpenoids (3-7), five known apotirucallane-type triterpenoids (8-12), and three known cycloartane-type triterpenoids (13-15), were isolated and characterized. Their structures were identified based on extensive spectroscopic experiments, including nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectra (HR-ESI-MS), and electronic circular dichroism (ECD), as well as the comparison with those reported in the literature. We compared these findings to those reported in the literature. Compounds 5, 8, and 13-14 were isolated from the genus Toona, and compounds 11 and 15 were obtained from T. sinensis for the first time. The antidiabetic nephropathy effects of isolated compounds against high glucose-induced oxidative stress and inflammation in rat glomerular mesangial cells (GMCs) were assessed in vitro. The results showed that new compounds 1 and 2 could significantly increase the levels of Nrf-2/HO-1 and reduce the levels of NF-κB, TNF-α, and IL-6 at concentrations of 30 µM. These results suggest that compounds 1 and 2 might prevent the occurrence and development of diabetic nephropathy (DN) and facilitate the research and development of new antioxidant and anti-inflammatory drugs suitable for the prevention and treatment of DN.


Asunto(s)
Nefropatías Diabéticas , Limoninas , Triterpenos , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Glucosa/farmacología , Hipoglucemiantes/farmacología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Interleucina-6/farmacología , Limoninas/farmacología , Limoninas/uso terapéutico , Células Mesangiales , FN-kappa B/farmacología , Estrés Oxidativo , Ratas , Semillas , Terpenos/farmacología , Terpenos/uso terapéutico , Toona , Triterpenos/química , Factor de Necrosis Tumoral alfa/farmacología
8.
Acupunct Med ; 40(4): 360-368, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35034504

RESUMEN

BACKGROUND AND AIM: Disordered hepatic energy metabolism is found in obese rats with insulin resistance (IR). There are insufficient experimental studies of electroacupuncture (EA) for IR and type 2 diabetes mellitus (T2DM). The aim of this study was to probe the effect of EA on disordered hepatic energy metabolism and the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/ribosomal protein S6 kinase, 70-kDa (p70S6K) signaling pathway. METHODS: Zucker Diabetic Fatty (ZDF) rats were randomly divided into three groups: EA group receiving EA treatment; Pi group receiving pioglitazone gavage; and ZF group remaining untreated (n = 8 per group). Inbred non-insulin-resistant Zucker lean rats formed an (untreated) healthy control group (ZL, n = 8). Fasting plasma glucose (FPG), fasting insulin (FINS), C-peptide, C-reactive protein (CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) indices were measured. Hematoxylin-eosin (H&E) staining was used to investigate the liver morphologically. The mitochondrial structure of hepatocytes was observed by transmission electron microscopy (TEM). Western blotting was adopted to determine protein expression of insulin receptor substrate 1 (IRS-1), mTOR, mTORC1, AMPK, tuberous sclerosis 2 (TSC2) and p70S6K, and their phosphorylation. RT-PCR was used to quantify IRS-1, mTOR, mTORC1, AMPK and p70S6K mRNA levels. RESULTS: Compared with the ZF group, FPG, FINS, C-peptide, CRP and HOMA-IR levels were significantly reduced in the EA group (p < 0.05, p < 0.01). Evaluation of histopathology showed improvement in liver appearances following EA. Phosphorylation levels of AMPK, mTOR and TSC2 decreased, and IRS-1 and p70S6K increased, in hepatocytes of the ZF group, while these negative effects appeared to be alleviated by EA. CONCLUSIONS: EA can effectively ameliorate IR and regulate energy metabolism in the ZDF rat model. AMPK/mTORC1/p70S6K and related molecules may represent a potential mechanism of action underlying these effects.


Asunto(s)
Diabetes Mellitus Tipo 2 , Electroacupuntura , Resistencia a la Insulina , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Péptido C/metabolismo , Péptido C/farmacología , Diabetes Mellitus Tipo 2/terapia , Metabolismo Energético , Insulina/metabolismo , Mamíferos/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratas , Ratas Zucker , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/farmacología , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/farmacología
9.
Nat Prod Res ; 36(6): 1593-1598, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33624565

RESUMEN

Toona sinensis is a medicinal and edible plant that belongs to the genus Toona of family Meliaceae. Phytochemical investigations carried out on this plant, seven apotirucallane-type triterpenoids (1-7), two cycloartane-type triterpenoids (8-9), four sterols (10-13), two sesquiterpenes (14-15), four phenols (16-19), and one lignin (20) were isolated from the pericarp of T. sinensis by silica gel column and preparative middle pressure liquid chromatography. Their structures were identified by interpretation of NMR and comparison with those reported in the literature. Compounds 11-12, 15-16, and 18 were isolated from the family Meliaceae, compounds 13-14 were obtained from the genus Toona, and compound 19 was obtained from T. sinensis for the first time. Additionally, the cytotoxicity and polyol pathway (PP) inhibitory activities of active constituents were evaluated in rat glomerular mesangial cells cultured under high glucose conditions, suggesting their potential application for a PP inhibitor.


Asunto(s)
Meliaceae , Toona , Animales , Meliaceae/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polímeros , Ratas
10.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6224-6230, 2021 Dec.
Artículo en Chino | MEDLINE | ID: mdl-34951249

RESUMEN

Alzheimer's disease(AD) patients in China have been surging, and the resultant medical burden and care demand have a huge impact on the development of individuals, families, and the society. The active component compound of Epimedii Folium, Astragali Radix, and Puerariae Lobatae Radix(YHG) can regulate the expression of iron metabolism-related proteins to inhibit brain iron overload and relieve hypofunction of central nervous system in AD patients. Hepcidin is an important target regulating iron metabolism. This study investigated the effect of YHG on the expression of a disintegrin and metalloprotease-17(ADAM17), a key enzyme in the hydrolysis of ß amyloid precursor protein(APP) in HT22 cells, by mediating hepcidin. To be specific, HT22 cells were cultured in vitro, followed by liposome-mediated siRNA transfection to silence the expression of hepcidin. Real-time PCR and Western blot were performed to examine the silencing result and the effect of YHG on hepcidin in AD cell model. HT22 cells were randomized into 7 groups: control group, Aß25-35 induction(Aß) group, hepcidin-siRNA(siRNA) group, Aß25-35 + hepcidin-siRNA(Aß + siRNA) group, Aß25-35+YHG(Aß+YHG) group, hepcidin-siRNA+YHG(siRNA+YHG) group, Aß25-35+hepcidin-siRNA+YHG(Aß+siRNA+YHG) group. The expression of ADAM17 mRNA in cells was detected by real-time PCR, and the expression of ADAM17 protein by immunofluorescence and Western blot. Immunofluorescence showed that the ADAM17 protein expression was lower in the Aß group, siRNA group, and Aß+siRNA group than in the control group(P<0.05) and the expression was lower in the Aß+siRNA group(P<0.05) and higher in the Aß+YHG group(P<0.05) than in the Aß group. Moreover, the ADAM17 protein expression was lower in the Aß+siRNA group(P<0.05) and higher in the siRNA+YHG group(P< 0.05) than in the siRNA group. The expression was higher in the Aß+siRNA+YHG group than in the Aß+siRNA group(P<0.05). The results of Western blot and real-time PCR were consistent with those of immunofluorescence. The experiment showed that YHG induced hepcidin to up-regulate the expression of ADAM17 in AD cell model and promote the activation of non-starch metabolic pathways, which might be the internal mechanism of YHG in preventing and treating AD.


Asunto(s)
Enfermedad de Alzheimer , Medicamentos Herbarios Chinos , Pueraria , Proteína ADAM17 , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides , Medicamentos Herbarios Chinos/farmacología , Hepcidinas/genética , Humanos
11.
Int Heart J ; 62(4): 900-909, 2021 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-34234076

RESUMEN

Virus myocarditis (VMC) is a common cardiovascular disease and a major cause of sudden death in young adults. However, there is still a lack of effective treatments. Our previous studies found that calpain activation was involved in VMC pathogenesis. This study aims to explore the underlying mechanisms further. Neonatal rat cardiomyocytes (NRCMs) and transgenic mice overexpressing calpastatin (Tg-CAST), the endogenous calpain inhibitor, were used to establish VMC model. Hematoxylin and eosin and Masson staining revealed inflammatory cell infiltration and fibrosis. An ELISA array detected myocardial injury. Cardiac function was measured using echocardiography. CVB3 replication was assessed by capsid protein VP1. Apoptosis was measured by TUNEL staining, flow cytometry, and western blot. The endoplasmic reticulum (ER) stress-related proteins were detected by western blot. Our data showed that CVB3 infection resulted in cardiac injury, as evidenced by increased inflammatory responses and fibrosis, which induced myocardial apoptosis. Inhibiting calpain, both by PD150606 and calpastatin overexpression, could attenuate these effects. Furthermore, ER stress was activated during CVB3 infection. However, calpain inhibition could downregulate some ER stress-associated protein levels such as GRP78, pancreatic ER kinase-like ER kinase (PERK), and inositol-requiring enzyme-1α (IRE-1α), and ER stress-related apoptotic factors, during CVB3 infection. In conclusion, calpain inhibition attenuated CVB3-induced myocarditis by suppressing ER stress, thereby inhibiting cardiomyocyte apoptosis.


Asunto(s)
Acrilatos/uso terapéutico , Calpaína/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Miocarditis/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Acrilatos/farmacología , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Calpaína/antagonistas & inhibidores , Infecciones por Coxsackievirus/tratamiento farmacológico , Infecciones por Coxsackievirus/metabolismo , Evaluación Preclínica de Medicamentos , Chaperón BiP del Retículo Endoplásmico , Enterovirus Humano B , Ratones Transgénicos , Miocarditis/tratamiento farmacológico , Miocarditis/virología , Ratas Sprague-Dawley
12.
Phytother Res ; 35(7): 3898-3915, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33860590

RESUMEN

Isoliquiritigenin (ISO) is a flavonoid extracted from the root of licorice, which serves various biological and pharmacological functions including antiinflammatory, antioxidation, liver protection, and heart protection. However, the mechanism of its action remains elusive and the direct target proteins of ISO have not been identified so far. Through cell-based screening, we identified ISO as a potent lipid-lowering compound. ISO treatment successfully ameliorated fatty acid-induced cellular lipid accumulation and improved nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) by increasing PPARα-dependent lipid oxidation and decreasing SREBPs-dependent lipid synthesis. Both these signaling required the activation of SIRT1. Knockdown of SIRT1 resulted in the reversal of ISO beneficiary effects suggesting that the lipid-lowering activity of ISO was regulated by SIRT1 expression. To identify the direct target of ISO, limited proteolysis combined with mass spectrometry (LiP-SMap) strategy was applied and IQGAP2 was identified as the direct target for ISO in regulating lipid homeostasis. In the presence of ISO, both mRNA and protein levels of SIRT1 were increased; however, this effect was abolished by blocking IQGAP2 expression using siRNA. To explore how IQGAP2 regulated the expression level of SIRT1, proteome profiler human phospho-kinase array kit was used to reveal possible phosphorylated kinases and signaling nodes that ISO affected. We found that through phosphorylation of CREB, ISO transduced signals from IQGAP2 to upregulate SIRT1 expression. Thus, we not only demonstrated the molecular basis of ISO in regulating lipid metabolism but also exhibited for the first time a novel IQGAP2-CREB-SIRT1 axis in treating NAFLD/NASH.


Asunto(s)
Chalconas , Enfermedad del Hígado Graso no Alcohólico , Animales , Chalconas/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Metabolismo de los Lípidos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Sirtuina 1/metabolismo , Proteínas Activadoras de ras GTPasa/metabolismo
13.
Cell Metab ; 33(3): 565-580.e7, 2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33657393

RESUMEN

Stimulation of adipose tissue thermogenesis is regarded as a promising avenue in the treatment of obesity. However, pharmacologic engagement of this process has proven difficult. Using the Connectivity Map (CMap) approach, we identified the phytochemical hyperforin (HPF) as an anti-obesity agent. We found that HPF efficiently promoted thermogenesis by stimulating AMPK and PGC-1α via a Ucp1-dependent pathway. Using LiP-SMap (limited proteolysis-mass spectrometry) combined with a microscale thermophoresis assay and molecular docking analysis, we confirmed dihydrolipoamide S-acetyltransferase (Dlat) as a direct molecular target of HPF. Ablation of Dlat significantly attenuated HPF-mediated adipose tissue browning both in vitro and in vivo. Furthermore, genome-wide association study analysis indicated that a variation in DLAT is significantly associated with obesity in humans. These findings suggest that HPF is a promising lead compound in the pursuit of a pharmacological approach to promote energy expenditure in the treatment of obesity.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Floroglucinol/análogos & derivados , Transducción de Señal/efectos de los fármacos , Terpenos/farmacología , Termogénesis/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Sitios de Unión , Frío , Acetiltransferasa de Residuos Dihidrolipoil-Lisina/química , Acetiltransferasa de Residuos Dihidrolipoil-Lisina/metabolismo , Humanos , Hypericum/química , Hypericum/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Proteínas Mitocondriales/química , Proteínas Mitocondriales/metabolismo , Simulación del Acoplamiento Molecular , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/patología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Floroglucinol/química , Floroglucinol/metabolismo , Floroglucinol/farmacología , Floroglucinol/uso terapéutico , Terpenos/química , Terpenos/metabolismo , Terpenos/uso terapéutico , Termogénesis/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Regulación hacia Arriba/efectos de los fármacos
14.
MedComm (2020) ; 2(4): 730-755, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34977874

RESUMEN

Necroptosis, a distinctive type of programmed cell death different from apoptosis or necrosis, triggered by a series of death receptors such as tumor necrosis factor receptor 1 (TNFR1), TNFR2, and Fas. In case that apoptosis process is blocked, necroptosis pathway is initiated with the activation of three key downstream mediators which are receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). The whole process eventually leads to destruction of the cell membrane integrity, swelling of organelles, and severe inflammation. Over the past decade, necroptosis has been found widely involved in life process of human beings and animals. In this review, we attempt to explore the therapeutic prospects of necroptosis regulators by describing its molecular mechanism and the role it played in pathological condition and tissue homeostasis, and to summarize the research and clinical applications of corresponding regulators including small molecule inhibitors, chemicals, Chinese herbal extracts, and biological agents in the treatment of various diseases.

15.
Food Chem ; 338: 127991, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-32950867

RESUMEN

Photoperiod and temperature are vital environmental factors that regulate plant developmental processes. However, the roles of these factors in garlic bulb enlargement are unclear. In this report, responses of garlic bulb morphology and physiology to combinations of photoperiod (light/dark: 10/14 h, 12/12 h, 14/10 h) and temperature (light/dark: 25/18 °C, 30/20 °C) were investigated. For garlic cultivar G103, bulb characteristics, phytohormones (IAA, ABA, ZT, tZR, JA), allicin and phenolic acids (p-coumaric and p-hydroxybenzoic) were highest under a photoperiod of 14 h at 30 °C. Maximum GA was observed under 14 h + 30 °C for cv. G2011-5. Maximum caffeic, ferulic and vanillic acids were detected for cv. G2011-5 at 14 h + 30 °C, 12 h + 25 °C and 14 h + 25 °C, respectively. Flavonoids (myricetin, quercetin, kaempferol and apigenin) were not detected in this trial. This is the first report describing the impact of long periods of light duration and higher temperatures on garlic morphology, phytohormones, phenolic acids and allicin content.


Asunto(s)
Ajo/crecimiento & desarrollo , Ajo/efectos de la radiación , Fotoperiodo , Tallos de la Planta/crecimiento & desarrollo , Tallos de la Planta/efectos de la radiación , Temperatura , Tallos de la Planta/química
16.
J Fish Biol ; 98(1): 208-218, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33000466

RESUMEN

Selenium, as an essential trace element, interferes through selenoproteins in many physiological processes of plants and mammals. Its antiviral activity has recently attracted much attention because selenium improves the antiviral capacity of animal cells against a few viruses relevant to human diseases. In this study, the red elemental selenium was purified from the fermentative culture of Herbaspirillum camelliae WT00C and then used to culture epithelioma papulosum cyprinid (EPC) cells or feed crucian carp and zebrafish. Finally, its antiviral effects were investigated at the cell level and living fishes after spring viraemia of carp virus infection. At the cell level, 5, 10 and 20 µg ml-1 red elemental selenium significantly induced the expression of interferon (IFN) and ISG15 genes in EPC cells. The viral TCID50 (50% tissue culture infective dose) values in the EPC cells incubated with 5, 10 and 20 µg ml-1 red elemental selenium were significantly less than those of the control. More expression of IFN and ISG15 genes and less TCID50 values indicate that red elemental selenium indeed improves the antiviral capability of EPC cells. In the crucian carp fed with the food containing 5 and 10 µg g-1 red elemental selenium, IFN expressions showed 13- and 39-fold increases at the 16th day of post-injection, and its expression was dependent on selenium concentrations. Meanwhile, no fish death occurred in all the experimental groups. In the zebrafish fed with the red worm containing 5 µg g-1 red elemental selenium, IFN and Mx expressions and survival rate were significantly higher than those of the control. The results of this study show that red elemental selenium indeed improves the antiviral activity of fish. The antiviral effects of selenium mainly come from its immune regulation through its incorporation into selenoproteins. The optimum level of selenium contributes to improving fish immunity, whereas excess selenium causes excessive immune and inflammatory responses.


Asunto(s)
Carpas/inmunología , Enfermedades de los Peces/tratamiento farmacológico , Enfermedades de los Peces/inmunología , Infecciones por Rhabdoviridae/veterinaria , Selenio/farmacología , Viremia/veterinaria , Pez Cebra/inmunología , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Animales , Antivirales/farmacología , Carcinoma , Carpas/virología , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , Interferones/genética , Rhabdoviridae , Infecciones por Rhabdoviridae/tratamiento farmacológico , Infecciones por Rhabdoviridae/inmunología , Selenio/uso terapéutico , Viremia/tratamiento farmacológico , Viremia/inmunología , Pez Cebra/virología
17.
Int J Biol Macromol ; 161: 1346-1357, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32784023

RESUMEN

In this study, two homogeneous polysaccharides (PFC-1 and PFC-2) having anti-atherosclerotic activity were isolated from Fructus Corni. PFC-1 and PFC-2 were 1,6-α-glucans with the molecular weight of 4.4 kDa and 82.0 kDa, respectively. In the in vitro experiments, PFC-1 and PFC-2 showed significant inhibitory effects on the cholesterol accumulation in RAW264.7 macrophages induced by oxidized low-density lipoproteins (ox-LDL), and the inhibitory rate of PFC-2 was 81.62%. Apolipoprotein E-deficient (ApoE-/-) mice fed high-fat diet (HFD) were used to evaluate the anti-atherosclerotic effects of PFC-2 in vivo. The aortic root lipid area decreased by 55.01% in the PFC-2-administered group as compared to the model group. PFC-2 decreased the levels of serum low-density lipoprotein cholesterol, total cholesterol, triglycerides, and malondialdehyde, increased the superoxide dismutase activity, and reduced the contents of lipid and macrophages in the aortic sinus plaque in ApoE-/- mice fed with HFD. Furthermore, PFC-2 markedly inhibited the expression of type A1 scavenger receptor (SR-A1) and cluster of differentiation 36 (CD36) in ox-LDL-treated macrophages. Taken together, 1,6-α-glucans from Fructus Corni showed significant anti-atherogenic effect, and the mechanism is related to enhanced antioxidant activity of the ApoE-/- mice and down-regulated the expression of SR-A1 and CD36 proteins in macrophages.


Asunto(s)
Cornus/química , Glucanos/química , Glucanos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Apolipoproteínas E/genética , Aterosclerosis/tratamiento farmacológico , Biomarcadores , Supervivencia Celular/efectos de los fármacos , Colesterol/sangre , Modelos Animales de Enfermedad , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Células Espumosas/patología , Glucanos/aislamiento & purificación , Inmunohistoquímica , Lipoproteínas LDL , Espectroscopía de Resonancia Magnética , Metilación , Ratones , Ratones Noqueados , Peso Molecular , Monosacáridos/química , Extractos Vegetales/aislamiento & purificación , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Células RAW 264.7 , Análisis Espectral , Relación Estructura-Actividad
18.
J Hazard Mater ; 395: 122679, 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32330780

RESUMEN

Cadmium (Cd) contamination is a serious threat to plants and humans. Application of silicon (Si) or nitric oxide (NO) could alleviate Cd accumulation and toxicity in plants, but whether they have joint effects on alleviating of Cd accumulation and toxicity are not known. Therefore, the combined effect of Si and NO application on maize growth, Cd uptake, Cd transports and Cd accumulation were investigated in a pot experiment. Here, we reported that Cd stress decreased growth, caused Cd accumulation in plants. The combined application of Si and NO triggered a significant response in maize, increasing plant growth and reducing Cd uptake, accumulation, translocation and bioaccumulation factors under Cd stress. The grain Cd concentration was decreased by 66 % in the Si and NO combined treatment than Cd treatment. Moreover, the combined application of Si and NO reduced Cd health risk index in maize more effectively than either treatment alone. This study provided new evidence that Si and NO have a strong joint effect on alleviating the adverse effects of Cd toxicity by decreasing Cd uptake and accumulation. We advocate for supplement of Cd-contaminated soil with Si fertilizers and treatment of crops with NO as a practical approach to alleviating Cd toxicity.


Asunto(s)
Cadmio , Contaminantes del Suelo , Cadmio/análisis , Cadmio/toxicidad , Humanos , Óxido Nítrico , Silicio , Contaminantes del Suelo/análisis , Contaminantes del Suelo/toxicidad , Zea mays
19.
Int J Biol Macromol ; 146: 756-762, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31712152

RESUMEN

In this study, purification of polysaccharide ulvan by anion exchange chromatography was prepared, and the major polysaccharide fraction (FU) was collected at 1.0 M NaCl elute by anion exchange chromatography, then high sulfate content purified ulvan (HFU) was prepared with sulfur trioxide/N,N-dimethylformamide (SO3-DMF) in formamide. The antioxidant activity and the antihyperlipidemic activity of HFU in mice were determined. The results showed that treatment with HFU could improve the antioxidant and antihyperlipidemic activity. Compared with the hyperlipidemic group, the antihyperlipidemic activity of HFU (125 mg/kg) was the strongest, TC concentrations were significantly decreased by 26.7% (P < .01), significantly reduced LDL-C (32.6%, P < .01), significantly increased HDL-C (19.6%, P < .01), and HFU-treated group (250 mg/kg) exhibited optimal effects on TG (29.0%, P < .01); the HFU groups at the doses of 125 mg/kg could significantly decrease the MDA (29.9%, P < .01); the HFU groups at the doses of 500 mg/kg could increase the activities of GSH-Px obviously (19.9%, P < .01).


Asunto(s)
Antioxidantes/farmacología , Hipolipemiantes/farmacología , Extractos Vegetales/farmacología , Polisacáridos/química , Sulfatos/química , Ulva/química , Animales , Antioxidantes/química , Peso Corporal/efectos de los fármacos , Modelos Animales de Enfermedad , Radical Hidroxilo/análisis , Hipolipemiantes/química , Masculino , Ratones , Peso Molecular , Monosacáridos/aislamiento & purificación , Extractos Vegetales/química , Superóxidos/análisis
20.
J Med Food ; 23(2): 153-160, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31747350

RESUMEN

Oxidative stress triggered by hyperglycemia is thought to be a major factor in the development of liver disease during diabetes mellitus (DM). The aim of this study was to determine the antioxidant capacity of aqueous extracts of selenium-enriched Auricularia auricular (AESA) and further investigate the hepatic protection and potential mechanism of AESA in a mouse model of diabetes. An in vitro antioxidant assay confirmed that AESA exhibited better antioxidant capacity characterized by increased reducing power and scavenging capacity of free radicals, such as diphenyl picrylhydrazyl radical, hydroxyl radical, and superoxide radical. The diabetic model was induced by high-fat diet combined with a single injection of streptozotocin in C57BL/6 mice. Our results showed that AESA treatment improved diabetes-induced disorders of lipid metabolisms and alleviated liver damage in diabetic mice. Furthermore, the antioxidant enzyme activities of glutathione peroxidase and catalase in liver were increased and malondialdehyde level was decreased with AESA treatment compared with those in the DM group. In parallel, AESA significantly reduced the contents of tumor necrosis factor-alpha and interleukin-1beta in liver in comparison with the DM group. In addition, western blot results showed that the expression of receptor for advanced glycation end products (RAGE), phospho-c-Jun NH2-terminal kinase, phospho-extracellular signal-regulated kinase, and phospho-p38 kinase were remarkably decreased in AESA treatment group compared with DM group. Taken together, supplementation of AESA may effectively attenuate diabetic hepatopathology by exerting antioxidant function through the RAGE/mitogen-activated protein kinase pathway.


Asunto(s)
Antioxidantes/farmacología , Basidiomycota/metabolismo , Dieta Alta en Grasa/efectos adversos , Hepatopatías/tratamiento farmacológico , Selenio/farmacología , Animales , Diabetes Mellitus Experimental , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Prueba de Tolerancia a la Glucosa , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hepatopatías/etiología , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Estreptozocina/efectos adversos , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
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