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1.
Biochem Soc Trans ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581755

RESUMO

Type 2 immune responses commonly emerge during allergic reactions or infections with helminth parasites. Most of the cytokines associated with type 2 immune responses are IL-4, IL-5, and IL13, which are mainly produced by T helper 2 cells (TH2), eosinophils, basophils, mast cells, and group 2 innate lymphoid cells (ILC2s). Over the course of evolution, humans have developed type 2 immune responses to fight infections and to protect tissues from the potential collateral damage caused by inflammation. For example, worm parasites induce potent type 2 immune responses, which are needed to simultaneously clear the pathogen and to promote tissue repair following injury. Due to the strong type 2 immune responses induced by helminths, which can promote tissue repair in the damaged epithelium, their use has been suggested as a possible treatment for inflammatory bowel disease (IBD); however, the role of type 2 immune responses in the initiation and progression of IBD is not fully understood. In this review, we discuss the molecular and cellular mechanisms that regulate type 2 immune responses during intestinal homeostasis, and we briefly discuss the scarce evidence linking type 2 immune responses with the aetiology of IBD.

2.
Nat Commun ; 12(1): 4876, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385436

RESUMO

While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI "nurse" for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.


Assuntos
Técnicas Biossensoriais/instrumentação , Medicina de Precisão/instrumentação , Têxteis , Dispositivos Eletrônicos Vestíveis , Tecnologia sem Fio/instrumentação , Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , COVID-19/prevenção & controle , COVID-19/virologia , Desenho de Equipamento , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Medicina de Precisão/métodos , SARS-CoV-2/fisiologia , Suor/fisiologia
3.
Anal Chem ; 93(21): 7665-7672, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34004111

RESUMO

In solid-phase extraction (SPE), the extraction materials depend on the physicochemical interactions to obtain the target analytes from complex systems. However, many matrix interferences existing in real samples influence the extraction efficiency through these common interactions. Therefore, extraction materials based on more special interactions for biological systems need to be developed. In this work, live microorganisms including Escherichia coli and Staphylococcus aureus were considered as the potential biological SPE (bio-SPE) materials with their biological functions in the live state. To study the enrichment and selectivity of the bio-SPE, four antibacterial drugs and two non-antibacterial drugs were employed as the target analytes. The enrichment factor (EF) was used as the evaluation index. The results showed that when using chlorpheniramine (CPM) and ofloxacin (OFLO), the enrichment capacity of E. coli was better than that of S. aureus. When extracting a single analyte, the enrichment ability of E. coli for CPM was significantly higher than other analytes, and the EF was 8.5. In a mixture solution of antibacterial analytes, OFLO could be enriched mostly by E. coli. However, in the mixture solution of antibacterial and non-antibacterial analytes, CPM was enriched more than that of antibacterial analytes. In real rat plasma, bio-SPE using live E. coli could obviously extract CPM, while traditional liquid-liquid extraction could not. The confocal microscopy results showed that the extraction mechanism may not only depend on the surface adsorption of bacteria with analytes but also on the uptake into bacteria. This provides a valuable basis for the development of more biological separation materials based on biological interactions.


Assuntos
Escherichia coli , Preparações Farmacêuticas , Adsorção , Animais , Ratos , Extração em Fase Sólida , Staphylococcus aureus
4.
Nanomedicine (Lond) ; 16(9): 721-739, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33860675

RESUMO

Aim: The aim of this study was to develop a formulation that combines a phospholipid complex (PC) and self-microemulsifying drug delivery system (SMEDDS) to improve the bioavailability of poorly water-soluble resveratrol (RES), called RPC-SMEDDS. Methods: RES-PC (RPC) and RPC-SMEDDS were optimized by orthogonal experiment and central composite design, respectively. The characteristics and mechanism of intestinal absorption were studied by Ussing chamber model. The pharmacokinetics was evaluated in rats. Results: RES was the substrate of MRP2 and breast cancer resistance protein (BCRP) rather than P-gp. The prepared RPC-SMEDDS prevented the efflux mediated by MRP2 and BCRP and improved the bioavailability of RES. Conclusion: These results suggested that the combination system of PC and SMEDDS was a promising method to improve the oral bioavailability of RES.


Assuntos
Sistemas de Liberação de Medicamentos , Proteínas de Neoplasias , Fosfolipídeos , Resveratrol/farmacocinética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP , Administração Oral , Animais , Disponibilidade Biológica , Emulsões , Ratos , Solubilidade
5.
Artigo em Inglês | MEDLINE | ID: mdl-32835909

RESUMO

Molecularly imprinted polymers (MIPs) based on polydatin were prepared by precipitation polymerization method. Synthesis process of MIPs was optimized by discussion of functional monomers, porogens and the molar ratio of template- functional monomer-cross linker. Then, MIPs were prepared with polydatin as the template, 4-vinyl pyridine as the functional monomer, ethylene glycol dimethyl acrylate as the cross linker, acetonitrile as the porogen and the molar ratio of template-monomer-cross linker at 1:10:20. Scanning electron microscopy and Fourier transform infrared spectrometer were used to inspect macroscale and chemical bond of MIPs. Adsorption capability and selectivity of MIPs to polydatin were investigated by carrying out the static, dynamic and selective experiments. The results showed MIPs performed high adsorption ability and selectivity to polydatin, indicating MIPs could be used to separate and enrich polydatin from the complex systems. Finally, MIPs were applied as the adsorbent for isolation and purification of polydatin from the extract of Polygoni Cuspidati Rhizoma et Radix, rats' plasma and urine samples. MIPs were successfully used to separate polydatin from the Polygoni Cuspidati Rhizoma et Radix and recovery ranged from 89.2% to 91.6%. The maximum concentration of polydatin in rats' plasma and urine samples was 2.84 ± 0.0748 µg mL-1 and 2.64 ± 0.485 µg mL-1, respectively. Moreover, to compare with the MIPs method, organic solvent methods were used to analyze the polydatin in rats' plasma and urine samples. The results illustrated MIPs method was effective and selective for enrichment of polydatin from the medicinal plants and biological samples.


Assuntos
Medicamentos de Ervas Chinesas/química , Glucosídeos , Impressão Molecular/métodos , Estilbenos , Animais , Cromatografia Líquida de Alta Pressão , Fallopia japonica/química , Glucosídeos/sangue , Glucosídeos/isolamento & purificação , Glucosídeos/urina , Limite de Detecção , Modelos Lineares , Masculino , Polímeros Molecularmente Impressos , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Extração em Fase Sólida , Estilbenos/sangue , Estilbenos/isolamento & purificação , Estilbenos/urina
6.
Front Pharmacol ; 11: 811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32595495

RESUMO

Gegen Qinlian Decoction (GQD), a well-documented traditional Chinese Medicine (TCM) formula, was reported with convincing anti-diabetic effects in clinical practice. However, the precise antidiabetic mechanism of GQD remains unknown. In this study, the anti-hyperglycemic and/or lipid lowering effects of GQD were demonstrated in high-fat diet with a low dose of streptozotocin induced diabetic Sprague-Dawley rats and insulin resistance (IR)-3T3-L1 adipocytes. GQD treatment increased expression and activity levels of both PPARγ and PPARα in adipocytes, which transcriptionally affected an ensemble of glucose and lipid metabolic genes in vivo and in vitro. The results clearly indicated that GQD treatment intervened with multiple pathways controlled by concomitantly downstream effects of adipocytic PPARγ and PPARα, to influence two opposite lipid pathways: fatty acid oxidation and lipid synthesis. Antagonist GW9662 decreased the mRNA expression of Pparγ and target genes Adpn and Glut4 whereas GW6471 decreased the mRNA expression of Pparα and target genes Cpt-1α, Lpl, Mcad, Lcad, Acox1, etc. Nuclear location and activity experiments showed that more PPARγ and PPARα shuttled into nuclear to increase its binding activities with target genes. GQD decreased the phosphorylation level of ERK1/2 and/or CDK5 to elevate PPARγ and PPARα activities in IR-3T3-L1 adipocytes through post-translational modification. The increase in p-p38MAPK and SIRT1 under GQD treatment may be attributed to partially reduce PPARγ adipogenesis activity and/or activate PPARα activity. Compared with the rosiglitazone-treated group, GQD elevated Cpt-1α expression, decreased diabetic biomarker Fabp4 expression, which produced an encouraging lipid profile with triglyceride decrease partially from combined effects on upregulated adipocytic PPARγ and PPARα activities. These results suggested that GQD improved diabetes by intervening a diverse array of PPARγ and PPARα upstream and downstream signaling transduction cascades, which jointly optimized the expression of target gene profiles to promote fatty acid oxidation and accelerate glucose uptake and utilization than PPARγ full agonist rosiglitazone without stimulating PPARα activity. Thus, GQD showed anti-diabetic/or antihyperglycemic effects, partially through regulating adipocytic PPARα and PPARγ signaling systems to maintaining balanced glucose and lipid metabolisms. This study provides a new insight into the anti-diabetic effect of GQD as a PPARα/γ dual agonist to accelerate the clinical use.

7.
Reprod Toxicol ; 93: 163-168, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32109521

RESUMO

Nuclear receptors (NRs) rapidly activate/repress gene expression to detour immune responses and allow tissue adaptation to constant environmental changes. However, the effect of combined NRs in the immune system is often unclear due to the lack of reliable experimental models that recapitulate the complex interaction between NRs in vivo. Here, we used the zebrafish to investigate the immunological outcome of combining the activation of retinoic acid receptor (RAR), liver X receptor (LXR) and the cytoplasmic sensor aryl hydrocarbon receptor (AHR). Although simultaneous activation did not affect the expression of respective bona-fide target genes, RAR-induced il17a/f3 was antagonized by LXR and AHR, whereas il22 was antagonized by AHR but not LXR. In addition, RA decreased il10 expression, which was further decreased by LXR activation. Thus, using combinatorial NR activation in zebrafish larvae, we show that LXR antagonizes the expression of selected RA-induced cytokines and provide a strategy to tailor the cytokine milieu.


Assuntos
Citocinas/genética , Receptores X do Fígado/metabolismo , Tretinoína/farmacologia , Proteínas de Peixe-Zebra/metabolismo , Animais , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores do Ácido Retinoico/metabolismo , Peixe-Zebra
8.
Se Pu ; 38(10): 1170-1178, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34213113

RESUMO

Capillary electrophoresis (CE) shows enormous potential for application in new drug research and development. Because of the aqueous medium employed as the running buffer in CE, drug screening can be carried out in an environment similar to that in physiological testing media. Drug screening methods based on CE are different from other instrumental measurements in vitro. CE can not only sustain the biological activity of the screened molecules and ligands, but also help evaluate the interactions between the receptors and the ligands. Based on these interactions, some important pharmacological parameters related to drug screening, such as the association constant Kb, bonding rate constant Kon, and dissociation rate constant Koff, can be determined by CE. Thus, CE is an effective tool for simulating and predicting the entire interaction process between receptors and drugs in vivo. In this review, the history of CE for drug screening is revisited. The theories, common methods for drug screening by CE, and some application examples and related technologies are reviewed. The methods of drug screening by means of affinity CE and kinetic CE are introduced. Some selected studies on different ligands at the molecular and cellular level are reported, along with examples several types of drugs. Techniques based on a combination of CE with mass spectrometry and chemiluminescence are reviewed, with focus on the screening of candidate drugs and active compounds from traditional Chinese medicine. The application prospect of drug screening by CE combined with a DNA-encoded compound library is introduced. This paper discusses the core of the fraction collection step in CE and emphasizes the significance of combining CE with systematic evolution of ligands by exponential enrichment. In conclusion, various optional methods for CE drug screening would pave the way for new concepts related to drug screening and evaluation in the future.


Assuntos
Avaliação Pré-Clínica de Medicamentos , Eletroforese Capilar , Cinética , Ligantes , Espectrometria de Massas
9.
Int J Nanomedicine ; 14: 9721-9730, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849464

RESUMO

Background: Most of the oral drugs have the properties of weak intestinal absorption and low bioavailability, which leads to little treatment to diseases. By nanotechnology, these drugs can be efficiently delivered to pass biological barriers and promote the cell uptake ability for the enhancement of the oral bioavailability. Methods: The present work chose the prepared curcumin-loaded galactosylated albumin nanoparticles (Gal-BSA NPs) as the nano-drug samples to study the intestinal capacity and the oral bioavailability. Results: The cell uptake assay showed that the Gal-BSA NPs could promote the internalization of more curcumin into the Caco-2 cells. Moreover, the cell uptake mechanism of Gal-BSA-Cur NPs depended on the clathrin-mediated endocytosis transport. The intestinal permeation assay using one Ussing chamber exhibited that the absorptive amounts of curcumin in Gal-BSA-Cur NPs group were 1.5-fold of pure curcumin group. Meanwhile, the permeation mechanism of Gal-BSA-Cur NPs across the intestine mainly depended on the passive transport. The pharmacokinetics study in vivo suggested that the oral bioavailability of Gal-BSA-Cur NPs was improved by 1.4-fold compared with pure curcumin. Conclusion: All results demonstrated that Gal-BSA NPs could improve the intestinal absorption capacity and oral bioavailability of curcumin through the double absorption mechanisms of the clathrin-mediated endocytosis and the passive transport.


Assuntos
Curcumina/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Nanopartículas/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Curcumina/administração & dosagem , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Endocitose/efeitos dos fármacos , Galactose/química , Humanos , Masculino , Nanopartículas/química , Ratos Sprague-Dawley , Soroalbumina Bovina/química
10.
Medicine (Baltimore) ; 98(19): e15561, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083221

RESUMO

Insulin-like growth factor binding proteins (IGFBPs) are a family of proteins binding to insulin-like growth factors, generally consisting 6 high-affinity IGFBPs, namely IGFBP1 through IGFBP6. IGFBP family members have been indicated to be involved in the development and progression of tumors and may be useful prognostic biomarkers in various malignancies. However, the prognostic role of individual IGFBPs, especially at the mRNA level in breast cancer patients remains elusive.We accessed the prognostic roles of IGFBPs family (IGFBP1-6) in breast cancer through the "Kaplan-Meier plotter" online database and OncoLnc database.Our results showed that the high expression of IGFBP1 mRNA was associated with favorable relapsed free survival (RFS) in all breast cancer patients. The high expression of IGFBP2 mRNA was associated with favorable overall survival (OS) and RFS in all breast cancer patients. The high expression of IGFBP3 mRNA was significantly correlated to worsen RFS in all breast cancer patients. The high expression of IGFBP4 mRNA was associated with favorable OS, RFS, distant metastasis-free survival, and post-progression survival in all breast cancer patients.Our results indicated that expression of IGFBPs mRNA may have prognostic values in breast cancer patients, and have a benefit for developing tools to predict the prognosis more accurately.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/diagnóstico , Gradação de Tumores , Prognóstico , RNA Mensageiro/metabolismo
11.
Gene ; 680: 43-50, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30244138

RESUMO

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a major dose- and therapy-limiting side effect that is particularly difficult to treat. Huachansu, an aqueous extract from toad skin, is a widely used anti-cancer natural product in China. Clinical findings have established the safety and effectiveness of Huachansu in combination with chemotherapy to promote the therapeutic efficacy while alleviate the side effects, especially cancer-related pain symptoms. Unfortunately, experimental data on the effects and mechanisms of Huachansu in combination with chemotherapy is not available. In this study, the effects of Huachansu were tested in vivo on a rat model of oxaliplatin-induced CIPNP. The results show, a single injection of Huachansu 2.5 g/kg produced a short-term analgesic effect on pre-established oxaliplatin-induced CIPNP after 60 min, as indicated by decreased mechanical and thermal hypersensitivity in comparison to oxaliplatin-treated rats. Repeated doses of Huachansu, given during CIPNP induction, prevented the development of oxaliplatin-induced CIPNP. This prophylactic effect of Huachansu was associated with suppressed oxaliplatin-induced TRPV1 up-regulation in the dorsal root ganglia and spinal astrocyte activation. These findings reveal Huachansu therapeutic potential in treating and preventing CIPNP.


Assuntos
Venenos de Anfíbios/administração & dosagem , Analgésicos/administração & dosagem , Neuralgia/prevenção & controle , Compostos Organoplatínicos/efeitos adversos , Canais de Cátion TRPV/metabolismo , Venenos de Anfíbios/farmacologia , Analgésicos/farmacologia , Animais , Astrócitos/metabolismo , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Masculino , Neuralgia/induzido quimicamente , Neuralgia/metabolismo , Oxaliplatina , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
12.
Biomed Pharmacother ; 108: 76-84, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30218861

RESUMO

Chemotherapy-induced peripheral neuropathic pain is a major limiting factor affecting cancer patients. No effective treatment is currently available. Cinobufacini, an aqueous extract from toad skin, is a widely used anti-cancer drug in China. Clinical evidence has demonstrated the safety and effectiveness of cinobufacini in combination with chemotherapy to promote the therapeutic efficacy while alleviating side effects, especially cancer-related pain symptoms. In this study, the effects of cinobufacini were investigated in a rat model of paclitaxel-induced peripheral neuropathic pain (PIPNP) to better understand and expand its clinical application. A single injection of cinobufacini (2.5 g/kg, i.p.) alleviated pre-established PIPNP, as indicated by decreased mechanical and thermal hypersensitivity compared with paclitaxel-treated rats. Repeated cinobufacini (1.25 and 2.5 g/kg, i.p.), given during the induction of PIPNP, prevented the establishment of paclitaxel-induced mechanical and thermal hypersensitivity. This preventative effect was associated with suppressed paclitaxel-induced TRPV1 up-regulation and spinal astrocyte activation, as well as decreased production of spinal TNF-α and IL-1ß. These findings reveal cinobufacini as a therapeutic potential to treat and prevent paclitaxel-induced peripheral neuropathic pain.


Assuntos
Venenos de Anfíbios/uso terapêutico , Astrócitos/patologia , Neuralgia/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Paclitaxel/efeitos adversos , Medula Espinal/patologia , Canais de Cátion TRPV/metabolismo , Regulação para Cima , Venenos de Anfíbios/química , Venenos de Anfíbios/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Citocinas/metabolismo , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Hiperalgesia/patologia , Inflamação/patologia , Masculino , Neuralgia/induzido quimicamente , Neuralgia/complicações , Neuralgia/patologia , Fármacos Neuroprotetores/farmacologia , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
13.
Zhongguo Zhong Yao Za Zhi ; 42(10): 1939-1944, 2017 May.
Artigo em Chinês | MEDLINE | ID: mdl-29090554

RESUMO

To observe the anti-hyperglycemic effect of Puerariae Lobatae Radix in hepatocyte insulin resistance(IR) models, and investigate its preliminary molecular mechanism. IR-HepG2 cell model was stably established with 1×10-9 mol•L⁻¹ insulin plus 3.75×10-6 mol•L-1 dexamethasone treatment for 48 h according to optimized protocol in our research group. After IR-HepG2 cells were treated with different concentrations(5%,10% and 15%) of Puerariae Lobatae Radix-containing serum, cell viability was detected by CCK-8 assay; the glucose consumptions in IR-HepG2 cells were separately detected at different time points (12, 15, 18, 21, 24, 30, 36 h) by using glucose oxidase method; intracellular glycogen content was detected by anthrone method; and the protein expression levels of leptin receptor (Ob-R), insulin receptor substrate-2 (IRS2), glucose transporter 1(GLUT1) and GLUT2 were detected by Western blot assay. The results showed that Puerariae Lobatae Radix-containing serum (5%, 10% and 15%) had no significant effect on IR-HepG2 cell viability; 5% and 10% Puerariae Lobatae Radix-containing serum significantly increased glucose consumption of IR-HepG2 cells (P<0.01) at 18, 21 and 24 h; 15% Puerariae Lobatae Radix-containing serum elevated the glucose consumption of IR-HepG2 cells at 15 h (P<0.05), and significantly elevated the glucose consumption at 18, 21, 24 and 30 h (P<0.01) in a dose-dependent manner. The optimized time of anti-hyperglycemic effect was defined as 24 h, and further study showed that Puerariae Lobatae Radix-containing serum could increase intracellular glycogen content after 24 h treatment (P<0.01), and up-regulate IRS2, Ob-R, GLUT1 and GLUT2 protein expression levels. Our results indicated that Puerariae Lobatae Radix-containing serum could achieve the anti-hyperglycemic effect through important PI3K/PDK signaling pathway partially by up-regulating the expression levels of Ob-R and IRS2, GLUT1 and GLUT2 in IR-HepG2 cells, accelerating the glucose transport into hepatocytes and increasing hepatic glycogen synthesis to enhance the anti-hyperglycemic effect of IR-HepG2 cells.


Assuntos
Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 2/metabolismo , Glucose/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Pueraria/química , Receptores para Leptina/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 2/genética , Células Hep G2 , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Raízes de Plantas/química , Receptores para Leptina/genética
14.
Zhongguo Zhong Yao Za Zhi ; 42(23): 4641-4648, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29376265

RESUMO

To investigate the effects of Gegen Qinlian decoction(GQD) in improving adipocytic insulin resistance(IR) and explore its related molecular mechanism. Diabetic rats models were induced by high glucose and high-fat diet with a small dose of streptozotocin, and after GQD treatment for 3 months, blood biochemical indexes such as fasting blood-glucose(FBG), insulin, glycosylated serum protein(GSP) and HOMA-IRI were detected and assessed. After the total RNA was extracted from the adipose tissue of diabetic SD rats, PPARγ, ADPN, GLUT4, GLUT2, ACACA and ACACB mRNA expression levels were separately detected by qPCR. Then, stable IR-3T3-L1 adipocyte model was built with 1 µmol•L⁻¹ dexamethasone. After the cell viability was detected by CCK-8 assay, 5%, 10% and 15% GQD-containing serum(GQD-CS) were respectively used to treat IR-3T-L1 adipocytes for 24 h. The contents of glucose, nonesterified fatty acid(NEFA) and adiponectin in cell culture supernatants were separately detected whereas the intracellular triglyceride(TG) contents of IR-3T3-L1 adipocytes were also measured. The ADPN, PPARγ and GLUT4 mRNA and protein expression levels were respectively detected by qPCR and Western blot in IR-3T3-L1 adipocytes. Results showed that GQD significantly decreased fasting blood glucose, insulin and GSP(P<0.01), and down-regulated HOMA-IRI(P<0.05) after the high-fat diet/streptozotocin-induced diabetic SD rats were treated for three months, with a good hypoglycemic effect. Moreover, PPARγ, ADPN, GLUT4, GLUT2, ACACA and ACACB mRNA expression levels were significantly elevated in the adipose tissue of GQD-treated diabetic SD rats. The 5%, 10% and 15% GQD-CS significantly increased glucose consumption of IR-3T3-L1 adipocytes at 24 h treatment(P<0.01), significantly decreased the intracellular TG content (P<0.01), and down-regulated NEFA to a certain extent but not significantly. Moreover, GQD-CS significantly up-regulated GLUT4 and ADPN expression. The results indicated that GQD could activate PPARγ to ameliorate adipocytic insulin resistance in the diabetic SD rats and IR-3T3-L1 adipocytes.


Assuntos
Adipócitos/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Resistência à Insulina , PPAR gama/agonistas , Células 3T3-L1 , Animais , Glucose , Insulina , Camundongos , Ratos , Ratos Sprague-Dawley
15.
Zhongguo Zhong Yao Za Zhi ; 41(11): 1983-1989, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28901090

RESUMO

Adipocytokines are closely associated with insulin resistance (IR) in adipose tissues, and they are more and more seriously taken in the study of the development of diabetes. This experiment was mainly to study the effect of berberine on mRNA expression levels of PPARγ and adipocytokines in insulin resistant adipocytes, and investigate the molecular mechanism of berberine in enhancing insulin sensitization and application advantages of droplet digital PCR (ddPCR). ddPCR absolute quantification analysis was taken in this experiment to simply and intuitively determine the appropriate reference genes. ddPCR and quantitative Real-time PCR (qPCR) were used to compare the effect of different doses of berberine (10, 20, 50, 100 µmol•L⁻¹) on mRNA expression levels of PPARγ, adiponectin, resistin and leptin in IR 3T3-L1adipocytes. Antagonist GW9662 was added to study the inherent correlation between PPARγ and adiponectin mRNA expression levels. ddPCR results showed that the expression level of ß-actin in adipocytes was stable, and suitable as reference gene for normalization of quantitative PCR data. Both of ddPCR and qPCR results showed that, as compared with IR models, the mRNA expression levels of adiponectin were decreased in the treatment with berberine (10, 20, 50, 100 µmol•L⁻¹) in a dose-dependent manner (P<0.01); the expression of PPARγ was decreased by 20, 50, 100 µmol•L⁻¹ berberine in a dose-dependent manner in qPCR assay (P<0.01) and decreased only by 50 and 100 µmol•L⁻¹ berberine in ddPCR assay (P<0.05). PPARγ specific antagonist GW9662 intervention experiment showed that adiponectin gene expression was directly relevant with PPARγ (P<0.05). ddPCR probe assay showed that various doses of berberine could significantly reduce mRNA expression levels of resistin and leptin (P<0.01) in a dose-dependent manner. In conclusion, berberine enhanced insulin sensitization effect not by up-regulating adiponect in expression of transcriptional level in PPARγ-dependent manner, but may by the elevated multimerization of adiponectin in the posttranslational regulation level. Berberine down-regulated the resistin and leptin expression levels, which could alleviate lipolysis and improve IR in adipocytes. ddPCR provided better sensitivity and linear range than qPCR, with obvious technical advantages for the detection of low abundance expression of target genes.


Assuntos
Adipócitos/efeitos dos fármacos , Adipocinas/metabolismo , Berberina/farmacologia , Resistência à Insulina , PPAR gama/metabolismo , Células 3T3-L1 , Animais , Camundongos , RNA Mensageiro/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 41(14): 2687-2694, 2016 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-28905607

RESUMO

This study aimed to explore the mechanism of Chinese traditional medicine, Kudzu root(Chinese name:Ge-Gen; Latin name: Puerariae Lobatae Radix) how to improving insulin resistance (IR) through the regulation of the glucose and lipid metabolism in the IR-3T3-L1 adipocytes. After the 3T3-L1 mouse preadipocytes were differentiated into mature adipocytes, IR model(IR-3T3-L1) was built with 1 µmol•L-1 dexamethasone treatment for 96 h. IR adipocytes were treated with different concentrations (5%,10% and 15%) of Ge-Gen containing serum (GG-CS)for 12 h or 24 h, whereas rosiglitazone group as positive control in this study. The glucose contents in cell culture supernatants were detected by glucose oxidase assay and the intracellular triglyceride (TG) contents were measured by glycerol phosphate oxidase assay respectively.The mRNA expression levels of PPARγ, ADPN, GLUT4, LPL, FABP4 and FASn gene were determined by real-time quantitative PCR(qPCR).Results showed that IR-3T3-L1 adipocytes significantly increased glucose consumption (P<0.01)and decreased TG contents (P<0.01) as compared with the normal control group, the glucose consumption significantly increased with the treatment of GG-CS (P<0.01) by dose-dependent and time-dependent manners,whereas the intracellular TG content was sigificantly decreased (P<0.01) by dose-dependent manner.qPCR analysis revealed that 10% and 15% GG-CS significantly up-regulated the mRNA expression level of PPARγ, ADPN and GLUT4 (P<0.01) with the same dose-dependent manner,whereas the GLUT4 mRNA expression was showed similar expression pattern with the treatment of 10% and 15% GG-CS (P<0.01).We also detected the mRNA expression levels of several important lipid-metabolizing enzymes such as LPL, FASn and FABP4 by PPARγ regulation. 15% GG-CS elevated LPL mRNA expression (P<0.05);10% and 15% GG-CS enhanced the FASn mRNA expression (P<0.01), whereas 5%,10% and 15% GG-CS down-regulated FABP4 mRNA expression (P<0.01). Together, our results indicated that GG could regulate the glucose and lipid metabolism to ameliorate IR with multi-target manners in 3T3-L1 adipocytes.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Glucose/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Pueraria/química , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Animais , Camundongos , Raízes de Plantas/química
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