Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 133
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
J Pharm Pharmacol ; 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429940

RESUMO

BACKGROUND: We administered Bushen Huoxue Huazhuo Formula (BSHXHZF) and transplanted bone marrow mesenchymal stem cells (BMSCs) into mice with Wilson's disease (WD)-related liver fibrosis to evaluate the liver-protecting mechanism of this prescription. METHODS: Mice, randomly divided into different treatment groups, showed histopathological changes and degree of hepatocyte apoptosis. For hepatic hydroxyproline (Hyp) determination, transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-7 (BMP-7) mRNA and protein were measured. Chemical profiling of the extract of BSHXHZF using The liquid chromatography-mass spectrometry (LC-MS/MS) and revealing its antifibrosis mechanism using metabolomics. RESULTS: TCM+BMSC group livers exhibited few inflammatory cells. TUNEL revealed abundant brown apoptotic cells in model control groups, while the TCM+BMSC groups showed a significant increase in blue negative expression of liver cells. Hyp in toxic milk (TX) mice groups was significantly lower than that in model control groups (MG). Compared with MG, TGF-ß1 expression was significantly lower than all other groups, while BMP-7 expression was significantly higher. Metabolic analysis identified 20 potential biomarkers and 10 key pathways, indicating that BSHXHZF+BMSC intervention has a significant regulatory effect on metabolic disorders of these small molecule substances. CONCLUSION: BSHXHZF combined with BMSCs can inhibit liver fibrosis and hepatocyte apoptosis by improving related metabolic disorders, and achieving therapeutic effects in WD-related liver fibrosis.

2.
Int Immunopharmacol ; 129: 111580, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38310763

RESUMO

BACKGROUND: LL-37 (also known as murine CRAMP) is a human antimicrobial peptide that plays a crucial role in innate immune defence against sepsis through various mechanisms. However, its involvement in sepsis-induced lung injury remains unclear. OBJECTIVES: This work investigates the impact of LL-37 on pyroptosis generated by LPS in alveolar epithelial cells. The research utilizes both in vivo and in vitro sepsis-associated acute lung injury (ALI) models to understand the underlying molecular pathways. METHODS: In vivo, an acute lung injury model induced by sepsis was established by intratracheal administration of LPS in C57BL/6J mice, which were subsequently treated with low-dose CRAMP (recombinant murine cathelicidin, 2.5 mg.kg-1) and high-dose CRAMP (5.0 mg.kg-1). In vitro, pyroptosis was induced in a human alveolar epithelial cell line (A549) by stimulation with LPS and ATP. Treatment was carried out with recombinant human LL-37, or LL-37 was knocked out in A549 cells using small interfering RNA (siRNA). Subsequently, haematoxylin and eosin staining was performed to observe the histopathological changes in lung tissues in the control group and sepsis-induced lung injury group. TUNEL and PI staining were used to observe DNA fragmentation and pyroptosis in mouse lung tissues and cells in the different groups. An lactate dehydrogenase (LDH) assay was performed to measure the cell death rate. The expression levels of NLRP3, caspase1, caspase 1 p20, GSDMD, NT-GSDMD, and CRAMP were detected in mice and cells using Western blotting, qPCR, and immunohistochemistry. ELISA was used to assess the levels of interleukin (IL)-1ß and IL-18 in mouse serum, bronchoalveolar lavage fluid (BALF) and lung tissue and cell culture supernatants. RESULTS: The expression of NLRP3, caspase1 p20, NT-GSDMD, IL 18 and IL1ß in the lung tissue of mice with septic lung injury was increased, which indicated activation of the canonical pyroptosis pathway and coincided with an increase in CRAMP expression. Treatment with recombinant CRAMP improved pyroptosis in mice with lung injury. In vitro, treatment with LPS and ATP upregulated these classic pyroptosis molecules, LL-37 knockdown exacerbated pyroptosis, and recombinant human LL-37 treatment alleviated pyroptosis in alveolar epithelial cells. CONCLUSION: These findings indicate that LL-37 protects against septic lung injury by modulating the expression of classic pyroptotic pathway components, including NLRP3, caspase1, and GSDMD and downstream inflammatory factors in alveolar epithelial cells.


Assuntos
Lesão Pulmonar Aguda , Sepse , Animais , Humanos , Camundongos , Lesão Pulmonar Aguda/tratamento farmacológico , Trifosfato de Adenosina , Células Epiteliais Alveolares , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Sepse/complicações , Sepse/tratamento farmacológico
3.
Sci Total Environ ; 919: 170694, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325477

RESUMO

The uranium (U) containing leachate from uranium tailings dam into the natural settings, may greatly affect the downstream environment. To reveal such relationship between uranium contamination and microbial communities in the most affected downstream environment under drought stress, a 180 cm downstream artificial reservoir depth sediment profile was collected, and the microbial communities and related genes were analyzed by 16S rDNA and metagenomics. Besides, the sequential extraction scheme was employed to shed light on the distinct role of U geochemical speciations in shaping microbial community structures. The results showed that U content ranged from 28.1 to 70.1 mg/kg, with an average content of 44.9 mg/kg, significantly exceeding the value of background sediments. Further, U in all the studied sediments was related to remarkably high portions of mobile fractions, and U was likely deposited layer by layer depending on the discharge/leachate inputs from uranium-involving anthoropogenic facilities/activities upstream. The nexus between U speciation, physico-chemical indicators and microbial composition showed that Fe, S, and N metabolism played a vital role in microbial adaptation to U-enriched environment; meanwhile, the fraction of Ureducible and the Fe and S contents had the most significant effects on microbial community composition in the sediments under drought stress.


Assuntos
Urânio , Urânio/análise , Secas , Poluição Ambiental , Sedimentos Geológicos/química
4.
Environ Res ; 249: 118360, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38325779

RESUMO

For human health and environment safety, it is of great significance to develop novel materials with high effectiveness for removal of lead from not only aqueous solutions but also human body and traditional Chinese medicines. Here, functional kiwi peel composite, manganese dioxide decorated kiwi peel powder (MKPP), is proposed for the removal of Pb2+ effectively. The adsorption of Pb2+ in aqueous solution is a highly selective and endothermic process and kinetically follows a pseudo-second-order model, which can reach equilibrium with the capacity of 192.7 mg/g within 10 min. Comprehensive factors of hydration energy, charge-to-radius ratio and softness of Pb2+ make a stronger affinity between MKPP and Pb2+. The possible adsorption mechanism involves covalent bond, electrostatic force and chelation, etc. MKPP can be efficiently regenerated and reused with high adsorption efficiency after five cycles. Besides, MKPP can remove over 97% of Pb2+ from real water samples. MKPP can also alleviate lead poisoning to a certain extent and make the Pb level of TCM extract meet the safety standard. This work highlights that MKPP is a promising adsorbent for the removal of Pb2+ and provides an efficient strategy for reusing kiwi peel as well as dealing with the problem of Pb pollution.


Assuntos
Medicamentos de Ervas Chinesas , Chumbo , Compostos de Manganês , Óxidos , Poluentes Químicos da Água , Chumbo/isolamento & purificação , Chumbo/química , Compostos de Manganês/química , Adsorção , Óxidos/química , Medicamentos de Ervas Chinesas/química , Humanos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Medicina Tradicional Chinesa , Purificação da Água/métodos
5.
Cancer Res ; 84(6): 827-840, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38241695

RESUMO

N6-methyladenosine (m6A) RNA modification is the most common and conserved epigenetic modification in mRNA and has been shown to play important roles in cancer biology. As the m6A reader YTHDF1 has been reported to promote progression of hepatocellular carcinoma (HCC), it represents a potential therapeutic target. In this study, we evaluated the clinical significance of YTHDF1 using human HCC samples and found that YTHDF1 was significantly upregulated in HCCs with high stemness scores and was positively associated with recurrence and poor prognosis. Analysis of HCC spheroids revealed that YTHDF1 was highly expressed in liver cancer stem cells (CSC). Stem cell-specific conditional Ythdf1 knockin (CKI) mice treated with diethylnitrosamine showed elevated tumor burden as compared with wild-type mice. YTHDF1 promoted CSCs renewal and resistance to the multiple tyrosine kinase inhibitors lenvatinib and sorafenib in patient-derived organoids and HCC cell lines, which could be abolished by catalytically inactive mutant YTHDF1. Multiomic analysis, including RNA immunoprecipitation sequencing, m6A methylated RNA immunoprecipitation sequencing, ribosome profiling, and RNA sequencing identified NOTCH1 as a direct downstream of YTHDF1. YTHDF1 bound to m6A modified NOTCH1 mRNA to enhance its stability and translation, which led to increased NOTCH1 target genes expression. NOTCH1 overexpression rescued HCC stemness in YTHDF1-deficient cells in vitro and in vivo. Lipid nanoparticles targeting YTHDF1 significantly enhanced the efficacy of lenvatinib and sorafenib in HCC in vivo. Taken together, YTHDF1 drives HCC stemness and drug resistance through an YTHDF1-m6A-NOTCH1 epitranscriptomic axis, and YTHDF1 is a potential therapeutic target for treating HCC. SIGNIFICANCE: Inhibition of YTHDF1 expression suppresses stemness of hepatocellular carcinoma cells and enhances sensitivity to targeted therapies, indicating that targeting YTHDF1 may be a promising therapeutic strategy for liver cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Sorafenibe , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Adenosina/farmacologia , RNA Mensageiro , RNA , Receptor Notch1/genética , Proteínas de Ligação a RNA/genética
6.
Chem Commun (Camb) ; 60(9): 1160-1163, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38192227

RESUMO

A pillar[5]arene-modified polydopamine (PDA-P[5]OH) displaying pH/NIR dual-responsive properties was constructed successfully in situ for targeted chemo-photothermal cancer therapy.


Assuntos
Hipertermia Induzida , Indóis , Nanopartículas , Neoplasias , Polímeros , Humanos , Fototerapia , Doxorrubicina , Neoplasias/tratamento farmacológico
7.
Environ Pollut ; 344: 123235, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38159635

RESUMO

The extraction and utilization of uranium (U) ores have led to the release of significant amounts of potentially toxic metal(loid)s (PTMs) into the environment, constituting a grave threat to the ecosystem. However, research on the distribution and migration mechanism of U, chromium (Cr), and their accompanying PTMs in soil-plant system around U hydrometallurgical area remains insufficient and poorly understood. Herein, the distribution, migration, and risk level of PTMs were evaluated in soil and plant samples around U hydrometallurgical area, Northern Guangdong, China. The results demonstrated that the maximum content of U and Cr found in the analyzed soils were up to 84.2 and 238.9 mg/kg, respectively. These values far exceed the soil background values in China and other countries. The highest content of U (53.6 mg/kg) was detected in Colocasia antiquorum Schott, and the highest content of Cr (349.5 mg/kg) was observed in Pteridium aquilinum, both of which were enriched in their roots. The risk assessment of PTMs demonstrated that the study area suffered from severe pollution (PN > 3), especially from U, Cr, Th, and As, suggesting the non-negligible anthropogenic impacts. Hence, in light of the significant ecological hazard posed by the U hydrometallurgical area, it is imperative to implement appropriate restoration measures to ensure the human health and maintain the stability of the ecosystem.


Assuntos
Metais Pesados , Poluentes do Solo , Urânio , Humanos , Urânio/análise , Metais Pesados/análise , Cromo , Solo , Ecossistema , Monitoramento Ambiental/métodos , Poluentes do Solo/análise , China , Medição de Risco
8.
Phytochemistry ; 217: 113923, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37963510

RESUMO

Terpenoids are the largest class of all known natural products, possessing structural diversity and numerous biological activities. Ten previously undescribed terpenoid glycosides, glechlongsides A-J (1-10), were isolated from the ethanol extract of the whole plant of Glechoma longituba, including diterpenoid glycoside and pentacyclic triterpenoid saponin. The structures of these compounds were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra. In addition, glechlongsides F-I (6-9) exhibited weak cytotoxicity against human cancer cell lines BGC-823, Be1, HCT-8, A2780, and A549 with IC50 values ranging from 3.77 to 30.95 µM, respectively.


Assuntos
Lamiaceae , Neoplasias Ovarianas , Humanos , Feminino , Terpenos/farmacologia , Glicosídeos/farmacologia , Glicosídeos/química , Linhagem Celular Tumoral , Extratos Vegetais , Lamiaceae/química , Estrutura Molecular
9.
Environ Sci Technol ; 57(41): 15422-15431, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37797956

RESUMO

Arsenic (As) exposure has been related to many diseases, including cancers. Given the antioxidant and anti-inflammatory properties, the dietary supplementation of polyphenols may alleviate As toxicity. Based on a mouse bioassay, this study investigated the effects of chlorogenic acid (CA), quercetin (QC), tannic acid (TA), resveratrol (Res), and epigallocatechin gallate (EGCG) on As bioavailability, biotransformation, and toxicity. Intake of CA, QC, and EGCG significantly (p < 0.05) increased total As concentrations in liver (0.48-0.58 vs 0.27 mg kg-1) and kidneys (0.72-0.93 vs 0.59 mg kg-1) compared to control mice. Upregulated intestinal expression of phosphate transporters with QC and EGCG and proliferation of Lactobacillus in the gut of mice treated with CA and QC were observed, facilitating iAsV absorption via phosphate transporters and intestinal As solubility via organic acid metabolites. Although As bioavailability was elevated, serum levels of alpha fetoprotein and carcinoembryonic antigen of mice treated with all five polyphenols were reduced by 13.1-16.1% and 9.83-17.5%, suggesting reduced cancer risk. This was mainly due to higher DMAV (52.1-67.6% vs 31.4%) and lower iAsV contribution (4.95-10.7% vs 27.9%) in liver of mice treated with polyphenols. This study helps us develop dietary strategies to lower As toxicity.


Assuntos
Arsênio , Polifenóis , Camundongos , Animais , Polifenóis/farmacologia , Arsênio/toxicidade , Disponibilidade Biológica , Suplementos Nutricionais , Biotransformação , Proteínas de Transporte de Fosfato
10.
Nat Commun ; 14(1): 4628, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37532754

RESUMO

Chemotherapy remains as the first-choice treatment option for triple-negative breast cancer (TNBC). However, the limited tumor penetration and low cellular internalization efficiency of current nanocarrier-based systems impede the access of anticancer drugs to TNBC with dense stroma and thereby greatly restricts clinical therapeutic efficacy, especially for TNBC bone metastasis. In this work, biomimetic head/hollow tail nanorobots were designed through a site-selective superassembly strategy. We show that nanorobots enable efficient remodeling of the dense tumor stromal microenvironments (TSM) for deep tumor penetration. Furthermore, the self-movement ability and spiky head markedly promote interfacial cellular uptake efficacy, transvascular extravasation, and intratumoral penetration. These nanorobots, which integrate deep tumor penetration, active cellular internalization, near-infrared (NIR) light-responsive release, and photothermal therapy capacities into a single nanodevice efficiently suppress tumor growth in a bone metastasis female mouse model of TNBC and also demonstrate potent antitumor efficacy in three different subcutaneous tumor models.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias de Mama Triplo Negativas , Animais , Humanos , Camundongos , Feminino , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/patologia , Biomimética , Linhagem Celular Tumoral , Fototerapia , Microambiente Tumoral
11.
Environ Pollut ; 335: 122262, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37506804

RESUMO

Even though uranium (U) is considered to be an essential strategic resource with vital significance to nuclear power development and climate change mitigation, U exposure to human and ecological environment has received growing concerns due to its both highly chemically toxic and radioactively hazardous property. In this study, a composite (M-BC) based on Ficus macrocarpa (banyan tree) aerial roots biochar (BC) modified by δ-MnO2 was designed to separate U(VI) from synthetic wastewater. The results showed that the separation capacity of M-BC was 61.53 mg/g under the solid - liquid ratio of 1 g/L, which was significantly higher than that of BC (12.39 mg/g). The separation behavior of U(VI) both by BC and M-BC fitted well with Freundlich isothermal models, indicating multilayer adsorption occurring on heterogeneous surfaces. The reaction process was consistent with the pseudo-second-order kinetic model and the main rate-limiting step was particle diffusion process. It is worthy to note that the removal of U(VI) by M-BC was maintained at 94.56% even after five cycles, indicating excellent reusability and promising application potential. Multiple characterization techniques (e.g. Scanning Electron Microscope-Energy Dispersive Spectrometer (SEM-EDS), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Brunauer-Emmett-Teller (BET) and X-ray Photoelectron Spectroscopy (XPS)) uncovered that U(VI) complexation with oxygen-containing functional groups (e.g. O-CO and Mn-O) and cation exchange with protonated ≡MnOH were the dominant mechanisms for U(VI) removal. Application in real uranium wastewater treatment showed that 96% removal of U was achieved by M-BC and more than 92% of co-existing (potentially) toxic metals such as Tl, Co, Pb, Cu and Zn were simultaneously removed. The work verified a feasible candidate of banyan tree aerial roots biowaste based δ-MnO2-modified porous BC composites for efficient separation of U(VI) from uranium wastewater, which are beneficial to help address the dilemma between sustainability of nuclear power and subsequent hazard elimination.


Assuntos
Urânio , Poluentes Químicos da Água , Humanos , Águas Residuárias , Urânio/análise , Óxidos , Porosidade , Compostos de Manganês , Carvão Vegetal/química , Adsorção , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análise
12.
J Sci Food Agric ; 103(12): 5938-5948, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37186089

RESUMO

BACKGROUND: Ultrasound is widely used as a novel non-thermal processing technique to improve protein properties. In recent decades, applying ultrasound-assisted emulsification (UAE) to produce protein-stabilized emulsion has attracted people's attention. Instead of applying ultrasound to treat a single protein solution, UAE treatment refers to the use of sonication to a mixture of protein and oil. The purpose of this study was to compare the different effects of ultrasound treatment on the properties of myofibrillar protein (MP) in the presence or absence of soybean oil. A suitable sonication power was selected based on the change in emulsion properties. RESULTS: 300 W sonication power was selected because of its most effectively decreased emulsion droplet size and increased absolute zeta potential. Sonication more significantly increased the protein carbonyl content and disulfide bonds of the MP-soybean oil sample compared with the MP sample. Due to the presence of oil, ultrasound could unfold more protein molecules, illustrated by a lower α-helix content and intrinsic fluorescence intensity, and a higher surface hydrophobicity. Results of liquid chromatography-tandem mass spectrometry illustrated that sonication enhanced the myosin heavy chain and actin content at the soybean oil interface as well as accelerated the myosin light chain to separate from myosin in the MP-soybean oil system. CONCLUSION: Ultrasound treatment could lead to a higher level of protein oxidation and greater protein molecule exposure in the MP in the presence of oil system than in the oil-free MP system. © 2023 Society of Chemical Industry.


Assuntos
Óleo de Soja , Humanos , Óleo de Soja/química , Emulsões/química , Carbonilação Proteica , Oxirredução , Interações Hidrofóbicas e Hidrofílicas
13.
Chem Biol Interact ; 381: 110545, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37236577

RESUMO

Obesity is of public concern worldwide, and it increases the probability of developing a number of comorbid diseases, including NAFLD. Recent research on obesity drugs and health demands have shown the potential of natural plant extracts for preventing and treating obesity and their lack of toxicity and treatment-related side effects. We have demonstrated that tuberostemonine (TS), an alkaloid extracted from the traditional Chinese medicine Stemona tuberosa Lour can inhibit intracellular fat deposition, reduce oxidative stress, increase cellular adenosine triphosphate (ATP), and increase mitochondrial membrane potential. It effectively reduced weight gain and fat accumulation caused by a high-fat diet, and regulated liver function and blood lipid levels. Moreover, it regulate glucose metabolism and improved energy metabolism in mice. TS also decreased high-fat diet-induced obesity and improved lipid and glucose metabolism disorders in mice, with no significant side effects. In conclusion, TS was shown to be a safe alternative for obese patients and might be developed as an antiobesity and anti-nonalcoholic fatty liver drug.


Assuntos
Alcaloides , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Obesidade/etiologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Alcaloides/farmacologia , Lipídeos , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , Fígado/metabolismo
14.
J Environ Radioact ; 262: 107168, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37003252

RESUMO

Arsenic (As) and uranium (U) frequently occur together naturally and, in consequence, transform into cocontaminants at sites of uranium mining and processing, yet the simultaneous interaction process of arsenic and uranium has not been well documented. In the present contribution, the influence of arsenate on the removal and reduction of uranyl by the indigenous microorganism Kocuria rosea was characterized using batch experiments combined with species distribution calculation, SEM-EDS, FTIR, XRD and XPS. The results showed that the coexistence of arsenic plays an active role in Kocuria rosea growth and the removal of uranium under neutral and slightly acidic conditions. U-As complex species of UO2HAsO4 (aq) had a positive effect on uranium removal, while Kocuria rosea cells appeared to have a large specific surface area serving as attachment sites. Furthermore, a large number of nano-sized flaky precipitates, constituted by uranium and arsenic, attached to the surface of Kocuria rosea cells at pH 5 through P=O, COO-, and C=O groups in phospholipids, polysaccharides, and proteins. The biological reduction of U(VI) and As(V) took place in a successive way, and the formation of a chadwickite-like uranyl arsenate precipitate further inhibited U(VI) reduction. The results will help to design more effective bioremediation strategies for arsenic-uranium cocontamination.


Assuntos
Arsênio , Monitoramento de Radiação , Urânio , Arseniatos/química , Urânio/metabolismo
15.
Phytother Res ; 37(8): 3617-3630, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37092723

RESUMO

Long-term high-fat diet (HFD) will lead to obesity and their complications. Echinocystic acid (EA), a triterpene, shows anti-inflammatory and antioxidant effects. We predict that EA supplementation can prevent obesity, diabetes, and nonalcoholic steatohepatitis. To test our hypothesis, we investigated the effects of EA supplementation on mice with HFD-induced obesity in vivo and in vitro by adding EA to the diet of mice and the medium of HepG2 cells, the protein target of EA was analyzed by molecular docking. The results showed that EA ameliorated obesity and inhibited blood triglyceride and liver triglyceride concentrations than those in the HFD groups. The data on molecular docking indicated that FABP1 was a potential target of EA. Further experimental results confirmed that EA affected the triglyceride level by regulating the function of FABP1. This study may provide a new potential inhibitor for FABP1 and a new strategy for the treatment of obesity.


Assuntos
Fígado , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Simulação de Acoplamento Molecular , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/metabolismo , Triglicerídeos , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos
16.
Phytother Res ; 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37010930

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a major health problem. However, no effective treatments are currently available. Thus, there is a critical need to develop novel drugs that can prevent and treat NAFLD with few side effects. In this study, Tussilagone (TUS), a natural sesquiterpene isolated from Tussilago farfara L, was explored in vitro and in vivo for its potential to treat NAFLD. Our results showed that in vitro TUS reduced oleic acid palmitate acid-induced triglyceride and cholesterol synthesis in HepG2 cells, reduced intracellular lipid droplet accumulation, improved glucose metabolism disorders and increased energy metabolism and reduced oxidative stress levels. In vivo, TUS significantly reduced fat accumulation and improved liver injury in high-fat diet (HFD)-induced mice. TUS treatment significantly increased liver mitochondrial counts and antioxidant levels compared to the HFD group of mice. In addition, TUS was found to reduce the expression of genes involved in lipid synthesis sterol regulatory element binding protein-1 (SREBP1), fatty acid synthase (FASN), and stearoy-CoA desaturase 1 (SCD1) in vitro and in vivo. Our results suggest that TUS may be helpful in the treatment of NAFLD, suggesting that TUS is a promising compound for the treatment of NAFLD. Our findings provided novel insights into the application of TUS in regulating lipid metabolism.

17.
J Ethnopharmacol ; 313: 116561, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37121453

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang (LWDH) is a classic prescription that has been used to the treatment of "Kidney-Yin" deficiency syndrome for more than 1000 years in China. Recent studies have confirmed that LWDH can prevent the progression of renal fibrosis. Numerous studies have demonstrated the critical role that TRPC6 plays in the development of renal fibrosis. Due to the complex composition of LWDH and its remarkable therapeutic effect on renal fibrosis, it is possible to discover new active ingredients targeting TRPC6 for the treatment of renal fibrosis. AIM OF STUDY: This study aimed to identify selective TRPC6 inhibitors from LWDH and evaluate their therapeutical effects on renal fibrosis. MATERIALS AND METHODS: Computer-aided drug design was used to screen the biologically active ingredients of LWDH, and their affinities to human TRPC6 protein were detected by microcalorimetry. TRPC6, TRPC3, and TRPC7 over-expressed HEK293 cells were constructed, and the selective activities of the compounds on TRPC6 were determined by measuring [Ca2+]i in these cells. To establish an in vitro model of renal fibrosis, human renal proximal tubular epithelial HK-2 cells were stimulated with TGF-ß1. The therapeutic effects of LWDH compounds on renal fibrosis were then tested by detecting the related proteins. TRPC6 was knocked-down in HK-2 cells to investigate the effects of LWDH active ingredients on TRPC6. Finally, a unilateral ureteral obstruction model of renal fibrosis was established to test the therapeutic effect. RESULTS: From hundreds of LWDH ingredients, 64 active components with oral bioavailability ≥30% and drug-likeness index ≥0.18 were acquired. A total of 10 active components were obtained by molecular docking with TRPC6 protein. Among them, 4 components had an affinity with TRPC6. Piperlonguminine (PLG) had the most potent affinity with TRPC6 and blocking effect on TRPC6-mediated Ca2+ entry. A 100 µM of PLG showed no detectable inhibition on TRPC1, TRPC3, TRPC4, TRPC5, or TRPC7-mediated Ca2+ influx into cells. In vitro results indicated that PLG concentration-dependently inhibited the abnormally high expression of α-smooth muscle actin (α-SMA), collagen I, vimentin, and TRPC6 in TGF-ß1-induced HK-2 cells. Consistently, PLG also could not further inhibit TGF-ß1-induced expressions of these protein biomarkers in TRPC6 knocked-down HK-2 cells. In vivo, PLG dose-dependently reduced urinary protein, serum creatinine, and blood urea nitrogen levels in renal fibrosis mice and markedly alleviated fibrosis and the expressions of α-SMA, collagen I, vimentin, and TRPC6 in kidney tissues. CONCLUSION: Our results showed that PLG had anti-renal fibrosis effects by selectively inhibiting TRPC6. PLG might be a promising therapeutic agent for the treatment of renal fibrosis.


Assuntos
Nefropatias , Obstrução Ureteral , Humanos , Camundongos , Animais , Canal de Cátion TRPC6/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Vimentina , Células HEK293 , Simulação de Acoplamento Molecular , Nefropatias/metabolismo , Obstrução Ureteral/metabolismo , Fibrose , Colágeno/metabolismo , Rim
18.
Food Chem ; 417: 135898, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36934707

RESUMO

The quality and safety of fresh-cut pineapple deteriorate during handling and storage due to physicochemical and microbial changes, so its preservation has attracted extensive attention. This study prepared sustained-release tea tree essential oil (TTO) solid preservative (SP) with an encapsulation efficiency of 71.45% and applied it on fresh-cut pineapple in modified atmospheres packaging (MAP). Results showed that TTO adsorbed on nano silicon dioxide (SiO2) was embedded in the starch-carboxymethyl cellulose network structure by extrusion. The hydrogen bond and hydrophobic interaction resulted in compact structure and good sustained-release performance of SP. The SP improved sensory quality and reduced nutrient loss and microbial spoilage of fresh-cut pineapple, which extended its shelf-life to four days. In addition, antioxidant capacity was enhanced with increasing antioxidant enzyme activity, antioxidant content, and 2,2-diphenyl-1-picrylhydrazine scavenging capacity and decreasing MDA accumulation. Therefore, sustained-release TTO solid preservative has potential for the preservation of fresh-cut pineapple.


Assuntos
Ananas , Óleo de Melaleuca , Antioxidantes , Atmosfera , Preparações de Ação Retardada , Embalagem de Alimentos/métodos , Dióxido de Silício/química
19.
Carbohydr Polym ; 309: 120679, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36906362

RESUMO

Improving the qualities of vegetable oil replaced animal fat meat products is particularly fascinating for the development of healthy meat products. This work was designed to investigate the effects of different carboxymethyl cellulose (CMC) concentrations (0.01 %, 0.05 %, 0.1 %, 0.2 %, and 0.5 %) on the emulsifying, gelation, and digestive properties of myofibrillar protein (MP)-soybean oil emulsions. The changes in MP emulsion characteristics, gelation properties, protein digestibility, and oil release rate were determined. Results demonstrated that CMC addition decreased the average droplet size and increased the apparent viscosity, storage modulus, and loss modulus of MP emulsions, and a 0.5 % CMC addition significantly increased the storage stability during 6 weeks. Lower CMC addition (0.01 % to 0.1 %) increased the hardness, chewiness, and gumminess of emulsion gel especially for the 0.1 % CMC addition, while higher CMC (0.5 %) content decreased the texture properties and water holding capacity of emulsion gels. The addition of CMC decreased protein digestibility during the gastric stage, and 0.01 % and 0.05 % CMC addition significantly decreased the free fatty acid release rate. In summary, the addition of CMC could improve the stability of MP emulsion and the texture properties of the emulsion gels, and decrease protein digestibility during the gastric stage.


Assuntos
Carboximetilcelulose Sódica , Óleo de Soja , Animais , Emulsões , Proteínas Musculares , Géis
20.
J Ethnopharmacol ; 307: 116249, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36775080

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Gynochthodes officinalis (F.C.How) Razafim. & B.Bremer (G. officinalis) has been historically as tonics to treat impotence. Fermentation is an ancient processing method for traditional Chinese medicine. Whether fermentation affects the therapeutic effects of G. officinalis on diabetic erectile dysfunction has so far remained unknown. AIMS OF THE STUDY: In this research, we aim to determine the effect of fermented or unfermented G. officinalis root extract on diabetes mellitus-induced erectile dysfunction (DMED) and the potential mechanisms. MATERIALS AND METHODS: Candida sp. B5, Lactobacillus sp. Y5 and Lactobacillus sp. R2 are applied for the fermentation of G. officinalis. The optimum fermentation conditions of G. officinalis are investigated. Sprague-Dawley rats were used to establish a diabetic erectile dysfunction model, treated with different concentrations of fermented or unfermented G. officinalis, to compare the effect of fermented or unfermented G. officinalis on DMED and explore underlying mechanisms by assessment of intracavernous pressure, ELISA, Western blot, Masson's trichrome staining, and immunofluorescence. The corpus cavernosum smooth muscle cells (CCSMCs) and Schwann cells were isolated and used to investigate the effect of fermented or unfermented G. officinalis on hydrogen peroxide (H2O2)-induced apoptosis. RESULTS: The results reveal the optimum fermentation conditions of G. officinalis using Lactobacillus sp. Y5 were determined to be 35 °C, the ratio of solid to liquid 1:10, and six days of fermentation. The fermentation increases the abundance of major active ingredients within G. officinalis. After fermented or unfermented G. officinalis treatment for eight weeks by oral gavage at a dose of 100 mg kg-1 or 300 mg kg-1, the results show that the fermentation enhances the effect of G. officinalis on diabetic erectile dysfunction detected by intracavernous pressure. The protein expressions of the PI3K/Akt/eNOS pathway were upregulated in diabetic rats after fermented or unfermented G. officinalis treatment, while the level of oxidative stress was significantly reduced. Meanwhile, Masson's trichrome staining also displayed an improvement in the ratio of smooth muscle to collagen. In vitro experiments confirmed that fermented or unfermented G. officinalis protected CCSMCs and Schwann cells from apoptosis. In contrast, fermented G. officinalis showed a fortified protective effect over unfermented G. officinalis. CONCLUSION: Our findings suggest that fermentation can increase the composition of main active ingredients in G. officinalis and enhance its role in diabetic erectile dysfunction. It augurs the potential therapeutic application of fermented G. officinalis well for treating diabetic erectile dysfunction.


Assuntos
Diabetes Mellitus Experimental , Disfunção Erétil , Animais , Humanos , Masculino , Ratos , Diabetes Mellitus Experimental/metabolismo , Disfunção Erétil/tratamento farmacológico , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Ereção Peniana , Pênis , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Medicina Tradicional Chinesa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA