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1.
Phytomedicine ; 128: 155492, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479258

RESUMO

BACKGROUND: The damage of chemotherapy drugs to immune function and intestinal mucosa is a common side effect during chemotherapy. Astragalus polysaccharides (APS) exhibit immunomodulatory properties and are recognized for preserving the integrity of the human intestinal barrier. Nevertheless, their application and mechanisms of action in chemotherapy-induced immune damage and intestinal barrier disruption remain insufficiently explored. PURPOSE: This study delved into investigating how APS mitigates chemotherapy-induced immune dysfunction and intestinal mucosal injury, while also providing deeper insights into the underlying mechanisms. METHODS: In a chemotherapy mice model induced by 5-fluorouracil (5-Fu), the assessment of APS's efficacy encompassed evaluations of immune organ weight, body weight, colon length, and histopathology. The regulation of different immune cells in spleen was detected by flow cytometry. 16S rRNA gene sequencings, ex vivo microbiome assay, fecal microbiota transplantation (FMT), and targeted metabolomics analysis were applied to explore the mechanisms of APS effected on chemotherapy-induced mice. RESULTS: APS ameliorated chemotherapy-induced damage to immune organs and regulated immune cell differentiation disorders, including CD4+T, CD8+T, CD19+B, F4/80+CD11B+ macrophages. APS also alleviated colon shortening and upregulated the expression of intestinal barrier proteins. Furthermore, APS significantly restored structure of gut microbiota following chemotherapy intervention. Ex vivo microbiome assays further demonstrated the capacity of APS to improve 5-Fu-induced microbiota growth inhibition and compositional change. FMT demonstrated that the regulation of gut microbiota by APS could promote the recovery of immune functions and alleviate shortening of the colon length. Remarkably, APS significantly ameliorated the imbalance of linoleic acid (LA) and α-linolenic acid in polyunsaturated fatty acid (PUFA) metabolism. Further in vitro experiments showed that LA could promote splenic lymphocyte proliferation. In addition, both LA and DGLA down-regulated the secretion of NO and partially up-regulated the percentage of F4/80+CD11B+CD206+ cells. CONCLUSION: APS can effectively ameliorate chemotherapy-induced immune damage and intestinal mucosal disruption by regulating the composition of the gut microbiota and further restoring PUFA metabolism. These findings indicate that APS can serve as an adjuvant to improve the side effects such as intestinal and immune damage caused by chemotherapy.


Assuntos
Astrágalo , Ácidos Graxos Insaturados , Fluoruracila , Microbioma Gastrointestinal , Polissacarídeos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Camundongos , Astrágalo/química , Ácidos Graxos Insaturados/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Baço/efeitos dos fármacos , Transplante de Microbiota Fecal , Colo/efeitos dos fármacos
2.
Nat Commun ; 14(1): 5451, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37673856

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Pparα knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPARα by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPARα nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Masculino , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , PPAR alfa/genética , Ácidos e Sais Biliares , Citoplasma , Camundongos Knockout , Ácidos Graxos
3.
J Hazard Mater ; 448: 130929, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36860035

RESUMO

Soil petroleum pollution is an urgent problem in modern society, which seriously threatens the ecological balance and environmental safety. Aerobic composting technology is considered economically acceptable and technologically feasible for the soil remediation. In this study, the combined experiment of aerobic composting with the addition of biochar materials was conducted for the remediation of heavy oil-contaminated soil, and treatments with 0, 5, 10 and 15 wt% biochar dosages were labeled as CK, C5, C10 and C15, respectively. Conventional parameters (temperature, pH, NH4+-N and NO3--N) and enzyme activities (urease, cellulase, dehydrogenase and polyphenol oxidase) during the composting process were systematically investigated. Remediation performance and functional microbial community abundance were also characterized. According to experimental consequences, removal efficiencies of CK, C5, C10 and C15 were 48.0%, 68.1%, 72.0% and 73.9%, respectively. The comparison with abiotic treatments corroborated that biostimulation rather than adsorption effect was the main removal mechanism during the biochar-assisted composting process. Noteworthy, the biochar addition regulated the succession process of microbial community and increased the abundance of microorganisms related to petroleum degradation at the genus level. This work demonstrated that aerobic composting with biochar amendment would be a fascinating technology for petroleum-contaminated soil remediation.


Assuntos
Compostagem , Microbiota , Oryza , Petróleo , Solo
4.
Res Vet Sci ; 154: 59-65, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36463586

RESUMO

Ketosis is a metabolic disease of dairy cows in the perinatal period, ß-hydroxybutyrate (ß-HB) is the main component of ketosis. High levels of ß-HB can trigger oxidative stress and inflammatory response in dairy cows, leading to decreased milk yield and multiple postpartum diseases. Forsythin (FOR), the major constituent of the herbal medicine Forsythia, has anti-inflammatory, anti-oxidant, and antiviral effects. FOR was demonstrated to have an antioxidant effect on PC12 cells. However, the effects of FOR on ß-HB-stimulated bovine macrophages (BMs) has not been reported. Thus, the aim of the present study was to investigate the effects of FOR on ß-HB-stimulated BMs. Firstly, the CCK8 test confirmed that FOR (50, 100, 200 µg/mL) has no effect on BMs activity, and we selected these concentrations for subsequent experiments. Secondly, through detecting the oxidation indexes ROS, MDA and antioxidant indexes CAT and SOD, we confirmed the antioxidant effect of FOR on BMs. Next, qRT-PCR confirmed that FOR dramatically reduced the mRNA levels of IL-1ß and IL-6. Furthermore, the western blotting confirmed that FOR observably down-regulated ß-HB-stimulated phosphorylation of p38, ERK and Akt and up-regulated expression of Nrf2, and HO-1. Above results suggested that FOR plays antioxidant effects on ß-HB-induced BMs through p38, ERK and PI3K/Akt, Nrf2 and HO-1 signaling pathways. Therefore, we speculated that FOR may be a potential medicine to alleviate ß-HB-induced inflammatory response and provide a preliminary reference for the research and development of FOR.


Assuntos
Doenças dos Bovinos , Cetose , Ratos , Feminino , Bovinos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ácido 3-Hidroxibutírico/farmacologia , Estresse Oxidativo , Transdução de Sinais , Macrófagos/metabolismo , Cetose/metabolismo , Cetose/veterinária , Doenças dos Bovinos/induzido quimicamente , Doenças dos Bovinos/metabolismo
5.
J Inorg Biochem ; 229: 111725, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35063926

RESUMO

Widely used alumina nanoparticles (Al2O3 NPs) exposed to the environment pose a serious threat to human and animal health. The formation of heterophil extracellular traps (HETs) is a mechanism of innate immune defense against infection, but excessive HETs cause pathological damage. Here, we aim to explore the influence and mechanism of Al2O3 NPs on the formation of HETs in vitro, and further investigate the role of HETs release in histopathological damage after Al2O3 NPs treatment. Immunofluorescence analysis showed that Al2O3 NPs induced the formation of HETs, which was characterized by modified histones and elastase in the DNA backbone. Fluorescence microplate analysis showed that HETs formation was dependent on NADPH oxidase, P38, extracellular regulated protein kinases (ERK1/2) pathways and glycolysis. In vivo investigation showed that Al2O3 NPs significantly caused HETs release and liver damage. Biochemical analysis showed that Al2O3 NPs inhibited the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). Real-time fluorescence quantification results showed that Al2O3 NPs caused the overexpression of inflammation-related molecules interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), caspase-1 and caspase-11. All these changes were significantly changed by DNase I (Degradation reagent for HETs). Together, these suggest that Al2O3 NPs-induced HETs exacerbate liver injury by regulating oxidative stress and inflammatory responses, which provide a new perspective and potential prophylaxis and treatment targets for Al2O3 NPs toxicological research.


Assuntos
Óxido de Alumínio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Armadilhas Extracelulares/metabolismo , Inflamação/metabolismo , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Galinhas , Relação Dose-Resposta a Droga , Glicólise/fisiologia , Inflamação/induzido quimicamente , Inflamação/etiologia , Leucócitos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Transdução de Sinais/fisiologia
6.
J Agric Food Chem ; 70(1): 184-195, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35016506

RESUMO

The mechanisms of coffee against Parkinson disease (PD) remained incompletely elucidated. Numerous studies suggested that gut microbiota played a crucial role in the pathogenesis of PD. Here, we explored the further mechanisms of coffee against PD via regulating gut microbiota. C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce a PD mouse model, then treated with coffee for 4 consecutive weeks. Behavioral tests consisting of the pole test and beam-walking test were conducted to evaluate the motor function of mice. The levels of tyrosine hydroxylase (TH) and α-synuclein (α-syn) were assessed for dopaminergic neuronal loss. The levels of occludin, glial fibrillary acidic protein (GFAP), Bcl-2, Bax, cleaved caspase-3, and cytochrome c (Cyt c) were detected. Moreover, microbial components were measured by 16s rRNA sequencing. Our results showed that coffee significantly improved the motor deficits and TH neuron loss, and reduced the level of α-syn in the MPTP-induced mice. Moreover, coffee increased the level of BBB tight junction protein occludin and reduced the level of astrocyte activation marker GFAP in the MPTP-induced mice. Furthermore, coffee significantly decreased the levels of proapoptotic proteins, including Bax, cleaved caspase-3, and cytochrome c, while it increased the level of antiapoptotic protein Bcl-2, consequently preventing MPTP-induced apoptotic cascade. Moreover, coffee improved MPTP-induced gut microbiota dysbiosis. These findings suggested that the neuroprotective effects of coffee on PD were involved in the regulation of gut microbiota, which might provide a novel option to elucidate the effects of coffee on PD.


Assuntos
Microbioma Gastrointestinal , Fármacos Neuroprotetores , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Café , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S
7.
Bioengineered ; 12(1): 8043-8056, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34595989

RESUMO

The present study was focused on comparison of four typical fungicides in ginseng field to evaluate the impact of the different fungicides on the soil bacterial and fungal communities' composition and diversity by using high-throughput sequencing. Five treatments were designed comprising carbendazim (D), dimethyl disulfide (E), dazomet (M), calcium cyanamide (S), and control (C). The application of fungicide obviously altered the distribution of dominant fungal and bacterial communities and remarkably decreased the diversity (1099-763 and 6457-2245). The most abundant Proteobacteria obviously degenerate in fungicide-treated soil and minimum in E (0.09%) compared to control (25.72%). The relative abundance of Acidobacteria was reduced from 27.76 (C) to 7.14% after applying fungicide and minimum in E. The phylum Actinobacteria are both decomposers of organic matter and enemies of soil-borne pathogens, elevated from 11.62 to 51.54% and are high in E. The fungi community mainly distributed into Ascomycota that enriched from 66.09 to 88.21% and highin M and E (88.21 and 85.10%), and Basidiomycota reduced from 21.13 to 3.23% and low in M and E (5.27 and 3.23%). Overall, environmentally related fungicides decreased the diversity and altered the composition of bacterial and fungal communities, highest sensitivity present in dimethyl disulfide-treated soil.


Assuntos
Bactérias/classificação , Produtos Agrícolas/crescimento & desenvolvimento , Fungos/classificação , Fungicidas Industriais/efeitos adversos , Panax/crescimento & desenvolvimento , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Benzimidazóis/efeitos adversos , Carbamatos/efeitos adversos , Produtos Agrícolas/microbiologia , Cianamida/farmacologia , Dissulfetos/efeitos adversos , Fungos/efeitos dos fármacos , Fungos/genética , Fungos/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Panax/microbiologia , Filogenia , Microbiologia do Solo , Tiadiazinas/efeitos adversos
8.
Gene ; 763: 145061, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-32818595

RESUMO

Chinese cordyceps, the fruiting body of the Chinese caterpillar fungus (Ophiocordyceps sinensis, syn. Cordyceps sinensis), is among the most valuable traditional Chinese medicine fungi. Transcriptomic analysis of O. sinensis has revealed several aspects of its life cycle and ecological importance. However, the molecular mechanisms involved in fruiting body initiation remain unclear. The developmental transcriptomes were analyzed from three tissues at the fruiting body initiation stage, namely, the mycelium, sclerotium and primordium. Principal component analysis showed that in the three tissues, the gene expression patterns differed from each other. The functional analysis of differentially expressed genes showed that DNA synthesis and cell division were active in the primordium. In addition, the function of the mycelium was to absorb certain substances from the environment and the sclerotium was the metabolism center of O. sinensis. Genes participating in the mitogen-activated protein kinase (MAPK) signal pathway were involved in fruiting body initiation. Two environmental sensing genes, including a pheromone receptor gene (OSIN6252) and an amino acid sensing gene (OSIN6398), were highly expressed in the primordium, suggesting their important roles in initiation. These results provided insights into the orchestrated functions and gene profiles of different O. sinensis tissues at the key stage. These findings will aid in revealing the underlying mechanisms of fruiting body initiation, which will further benefit artificial cultivation.


Assuntos
Cordyceps/genética , Carpóforos/genética , Transcriptoma , Cordyceps/crescimento & desenvolvimento , Cordyceps/metabolismo , Carpóforos/crescimento & desenvolvimento , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Micélio/genética , Micélio/crescimento & desenvolvimento , Feromônios/metabolismo
9.
Burns ; 46(4): 850-859, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31672469

RESUMO

OBJECTIVE: To investigate the effects of music and/or tramadol on pain and anxiety in burn outpatients undergoing dressing changes. DESIGN: Randomized controlled trial. SETTING: Burns and Plastic Reconstruction Unit. PARTICIPANTS: Patients (N=180) with burns on up to 10%-30% of the total body surface area (TBSA). INTERVENTIONS: The patients were randomly allocated to 4 equal-sized groups as follows: (1) tramadol group (TG), patients received 100mg of tramadol orally 20min before the dressing change; (2) music group (MG), patients listened to self-selected music during the dressing change; (3) music-plus-tramadol group (MTG), patients received tramadol and listened to self-selected music; and (4) control group (CG), patients received a routine dressing change only. All patients underwent the interventions once per day for 2days. MAIN OUTCOME MEASURES: McGill Pain Questionnaire Short Form (MPQ-SF) (primary outcome), McGill Pain Persian version of Burn Specific Pain Anxiety Scale (BSPAS) (primary outcome), and heart rate (HR) and overall patient satisfaction (secondary outcomes). RESULTS: The results showed that music-plus-tramadol group (MTG) had better outcomes with respect to pain and anxiety management during dressing changes. CONCLUSIONS: In comparison with music or tramadol alone, the integration of music and tramadol offers a secure and favorable treatment choice to relieve pain and anxiety, ultimately improving the satisfaction levels of burn outpatients during dressing changes.


Assuntos
Analgésicos Opioides/uso terapêutico , Ansiedade/terapia , Bandagens , Queimaduras/terapia , Musicoterapia , Dor Processual/terapia , Tramadol/uso terapêutico , Administração Oral , Adulto , Ansiedade/psicologia , Superfície Corporal , Queimaduras/patologia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Música , Manejo da Dor/métodos , Medição da Dor , Dor Processual/psicologia , Satisfação do Paciente , Adulto Jovem
10.
Mitochondrial DNA B Resour ; 4(2): 3725-3726, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33366161

RESUMO

Rheum palmatum has a long history in medicine, which is one of the main export medicinal herb in China. The complete chloroplast genome of R. palmatum was assembled and reported in this study. The R. palmatum chloroplast genome was 161,541 bp in length as the circular and consisted a large single-copy (LSC) region of 86,519 bp, a small single-copy (SSC) region of 13,112 bp and a pair of inverted-repeat (IR) regions of 30,955 bp. The nucleotide composition was asymmetric 31.2% A (Adenine), 31.5% T (Thymine), 19.0% C (Cytosine), and 18.3% G (Guanine) with an overall G + C content of 37.3%. It encoded 131 genes, including 86 protein-coding genes (76 PCG species), 37 transfer RNA genes (26 tRNAs species), and eight ribosomal RNA genes (four rRNAs species). The Phylogenetic relationships used neighbour-joining (NJ) method and the result showed that R. palmatum and Rheum officinale are phylogenetically related to each other in the family Polygonaceae. This study will be very important for Chinese medicinal herb research value and clinical drug development for future in China.

11.
Trials ; 18(1): 428, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28915826

RESUMO

BACKGROUND: Stroke is the prime cause of morbidity and mortality in the general population, and hypertension will increase the recurrence and mortality of stroke. We report a protocol of a pragmatic randomized controlled trial (RCT) using blood pressure (BP)-lowering acupuncture add-on treatment to treat patients with hypertension and stroke. METHODS: This is a large-scale, multicenter, subject-, assessor- and analyst-blinded, pragmatic RCT. A total of 480 patients with hypertension and ischemic stroke will be randomly assigned to two groups: an experimental group and a control group. The experimental group will receive "HuoXueSanFeng" acupuncture combined with one antihypertensive medication in addition to routine ischemic stroke treatment. The control group will only receive one antihypertensive medication and basic treatments for ischemic stroke. HuoXueSanFeng acupuncture will be given for six sessions weekly for the first 6 weeks and three times weekly for the next 6 weeks. A 9-month follow-up will, thereafter, be conducted. Antihypertensive medication will be adjusted based on BP levels. The primary outcome will be the recurrence of stroke. The secondary outcomes including 24-h ambulatory BP, the TCM syndrome score, the Short Form 36-item Health Survey (SF-36), the National Institute of Health Stroke Scale (NIHSS), as well as the Barthel Index (BI) scale will be assessed at baseline, 6 weeks and 12 weeks post initiating treatments; cardiac ultrasound, carotid artery ultrasound, transcranial Doppler, and lower extremity ultrasound will be evaluated at baseline and 12 weeks after treatment. The safety of acupuncture will also be assessed. DISCUSSION: We aim to determine the clinical effects of controlling BP for secondary prevention of stroke with acupuncture add-on treatment. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02967484 . Registered on 13 February 2017; last updated on 27 June 2017.


Assuntos
Pressão Sanguínea , Hipertensão/terapia , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle , Terapia por Acupuntura/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , China , Protocolos Clínicos , Terapia Combinada , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Estudos Prospectivos , Recidiva , Projetos de Pesquisa , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
12.
Zhongguo Zhen Jiu ; 36(5): 459-62, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-27509600

RESUMO

OBJECTIVE: To observe the clinical effects of acupuncture method of "Huoxue Sanfeng, Shugan Jianpi" (activating blood and eliminating wind, soothing liver and strengthening spleen) on morning blood pressure in patients with cerebral infraction combined with essential hypertension. METHODS: Sixty-eight patients were randomly divided into an observation group and a control group, 34 cases in each one. The patients in the two groups were treated with acupuncture method of "Xingnao Kaiqiao" (consciousness-restoring resuscitation) and oral administration of nifedipine. In addition, patients in the observation group were treated with acupuncture method of "Huoxue Sanfeng, Shugan Jianpi" that met the criteria of standard manipulation, in which bilateral Renying (ST 9), Quchi (LI 11), Hegu (LI 4), Zusanli (ST 36) and Taichong (LR 3) were selected. The treatment was given once a day, five times a week, for totally six weeks. The improvement and control rate of morning blood pressure in the two groups were observed. RESULTS: (1) After treatment, the morning blood pressures were decreased significantly in the two groups (all P < 0.05); after 15 treatments, the reduction of systolic pressure and diastolic pressure in the observation group was superior to that in the control group, but the difference was not significant (both P > 0.05); after 30 treatments, the reduction of systolic pressure and diastolic pressure in the observation group was significantly superior to that in the control group (both P < 0.05). (2) After 30 treatments, the control rate of morning blood pressure in the observation group was significantly higher than that in the control group [82.4% (28/34) vs 58.8% (20/34), P < 0.05]. CONCLUSION: Acupuncture method of "Huoxue Sanfeng, Shugan Jianpi", characterized with standard manipulation criteria, can effectively control morning blood pressure in patients with cerebral infraction combined with essential hypertension.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Pressão Sanguínea , Infarto Cerebral/terapia , Hipertensão/terapia , Adulto , Idoso , Infarto Cerebral/fisiopatologia , Hipertensão Essencial , Feminino , Humanos , Hipertensão/fisiopatologia , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Baço/fisiopatologia , Resultado do Tratamento
13.
BMC Complement Altern Med ; 16(1): 286, 2016 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-27520089

RESUMO

BACKGROUND: Gigantol and syringic acid (SA) have been shown to synergistically prevent formation of diabetic cataract (DC). However, the exact mechanism of this effect is unknown. Here, we investigate the effect of these compounds on the activity of aldose reductase (AR) and cataract formation. METHODS: We examined the synergistic anti-cataract efficacy of gigantol and SA in the high glucose- and streptozotocin -induced DC rat model; synergism was evaluated using Jin's formula. We investigated possible mechanisms of action by measuring AR expression and activity and levels of sorbitol using enzyme kinetics, Western blot, and RT-PCR. Finally, we examined binding interaction between AR and both compounds using a combination of site-directed mutagenesis, recombinant expression of wild-type and mutant proteins, and enzyme kinetics. RESULTS: Combination treatment of gigantol and SA synergistically protected both HLECs(human lens epithelial cells) grown in vitro and DC formation in STZ-induced rats in vivo. Synergism was attributed to inhibition of AR activity, downregulation of AR expression via impaired transcription, and decreased sorbitol levels. Enzyme kinetics studies showed that the activity of an AR Asn160Ala mutant protein was significantly decreased compared to wild-type AR, confirming that Asn160 is a key residue for interaction between AR and both compounds. CONCLUSION: Combined administration of gigantol and SA synergize to enhance anti-cataract efficacy. The synergistic effect is mainly attributed to disruption of the polyol pathway and inhibition of AR activity.


Assuntos
Aldeído Redutase/efeitos dos fármacos , Bibenzilas/farmacologia , Catarata/prevenção & controle , Complicações do Diabetes/prevenção & controle , Ácido Gálico/análogos & derivados , Guaiacol/análogos & derivados , Aldeído Redutase/metabolismo , Animais , Bibenzilas/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Ácido Gálico/química , Ácido Gálico/farmacologia , Guaiacol/química , Guaiacol/farmacologia , Humanos , Masculino , Ratos , Ratos Wistar
14.
Zhongguo Zhen Jiu ; 36(2): 221-4, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-27348935

RESUMO

The low-risk mild hypertension constitutes a considerable proportion in hypertension. Through searching CNKI, Wanfang database, VIP database and PubMed database, literature during the last 10 years was collected and reviewed. It was indicated that excessive diagnosis, insufficient evidence of drug treatment, and poor drug adherence existed in low-risk mild hypertension, however, acupuncture at Renying (ST 9) and other therapies had remarkable effects. This paper mainly expounded the diagnosis and treatment status of low-risk mild hypertension as well as the research summary of acupuncture for low-risk mild hypertension.


Assuntos
Terapia por Acupuntura , Hipertensão/terapia , Pontos de Acupuntura , Terapia por Acupuntura/tendências , Humanos , PubMed/estatística & dados numéricos
15.
J Ethnopharmacol ; 172: 238-46, 2015 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-26119284

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium aurantiacum var. denneanumis widespread in southern China, locally known as "Shihu", "Huangcao" or "Fengdou", has long been used in traditional Chinese medicine for antipyretic, immunomodulatory, anti-aging effects and eye benefiting. AIM OF THIS STUDY: To investigate the effects of gigantol extracted from the stem of D. aurantiacum var. denneanum on the formation of galactose-induced cataractogenesis and the potential mechanisms underlying these effects. MATERIALS AND METHODS: Cataract lens models were induced by d-galactose both in vitro and in vivo. The transparency of the rat lenses in vitro and in vivo was observed with an anatomical microscope and a slit lamp microscope. The differential protein and action targets of gigantol were determined and compared among the control group, model group, and gigantol group using two-dimensional electrophoresis and mass spectrometry (MS). Enzyme kinetics was used to show the ability of gigantol to respress aldose reductase (AR) and inducible nitric oxide synthase (iNOS). Quantitative real-time PCR (RT-qPCR). was used to detect repression of the expression of AR and iNOS genes. Molecular docking and dynamic simulation were used to predict the interaction points and combination patterns between gigantol, AR, and iNOS. RESULTS: Gigantol was found to prevent galactose-induced damage to the rat lenses both in vitro and in vivo, to delay lens turbidity, and to keep the lenses transparent. Differential proteomes, MS, and RT-qPCR showed AR and iNOS to be the target proteins of gigantol. Gigantol reduced the galactose-induced AR and iNOS mRNA expression by 51.2% and 60.9%, respectively. The IC50 of gigantol for inhibition of AR and iNOS activities were 65.67 µg/mL and 8.768 µg/mL, respectively. Gigantol-AR binding sites were Trp111, His110, Tyr48, and Trp20, and gigantol-iNOS binding sites were Ile195 and Gln257. The main forms of interaction were hydrophobic forces, hydrogen bonds, and van der Waals forces. CONCLUSION: Gigantol extracted from D. aurantiacum var. denneanum was found to inhibit galactose-induced formation of cataracts through repression of the gene expression and activity of AR and iNOS.


Assuntos
Antioxidantes/farmacologia , Bibenzilas/farmacologia , Catarata/prevenção & controle , Dendrobium/química , Guaiacol/análogos & derivados , Animais , Antioxidantes/isolamento & purificação , Bibenzilas/isolamento & purificação , Catarata/etiologia , Medicamentos de Ervas Chinesas , Galactosemias/complicações , Guaiacol/isolamento & purificação , Guaiacol/farmacologia , Cristalino/efeitos dos fármacos , Cristalino/patologia , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Pressão Osmótica/efeitos dos fármacos , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real
16.
Zhongguo Zhong Yao Za Zhi ; 37(16): 2429-34, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23234143

RESUMO

OBJECTIVE: To study the anti-cataract effect of gigantol combined with syringic acid and their action mechanism. METHOD: H202-induced lens oxidative injury in vitro rat model was establish to observe the impact of gigantol combined with syringic acid on lens transparency under a dissecting microscope. D-galactose-induced cataract rat model was established to observe the impact of gigantol combined with syringic acid on lens transparency under a slit-lamp. UV spectrophotometry was adopted to detect the inhibitory activity of gigantol combined with syringic acid against AR. Molecular docking method was used to detect binding sites, binding types and pharmacophores of gigantol combined with syringic acid in prohibiting aldose reductase. RESULT: Both in vitro and in vivo experiments showed a good anti-sugar cataract activity in the combination of gigantol and syringic acid and a better collaborative effect than single component-gigantol and syringic acid and positive control drug Catalin. Molecular docking and dynamic simulation showed their collaborative AR-inhibiting amino acid residue was Asn160 and the major acting force was Van der Waals' force, which formed common pharmacophores. CONCLUSION: Gigantol combined with syringic acid shows good anti-cataract, their action mechanism is reflected in their good collaborative inhibitory effect on AR.


Assuntos
Catarata/tratamento farmacológico , Ácido Gálico/análogos & derivados , Guaiacol/análogos & derivados , Aldeído Redutase/antagonistas & inibidores , Animais , Bibenzilas , Catarata/enzimologia , Sinergismo Farmacológico , Feminino , Ácido Gálico/farmacologia , Guaiacol/farmacologia , Humanos , Técnicas In Vitro , Cristalino/efeitos dos fármacos , Cristalino/enzimologia , Masculino , Ratos , Ratos Wistar
17.
Artigo em Inglês | MEDLINE | ID: mdl-23365598

RESUMO

Objective. Effects of Syringic acid (SA) extracted from dendrobii on diabetic cataract (DC) pathogenesis were explored. Methods. Both in vitro and in vivo DC lens models were established using D-gal, and proliferation of HLEC exposed to SA was determined by MMT assay. After 60-day treatment with SA, rat lens transparency was observed by anatomical microscopy using a slit lamp. SA protein targets were extracted and isolated using 2-DE and MALDI TOF/TOF. AR gene expression was investigated using qRT-PCR. Interaction sites and binding characteristics were determined by molecule-docking techniques and dynamic models. Results. Targeting AR, SA provided protection from D-gal-induced damage by consistently maintaining lens transparency and delaying lens turbidity development. Inhibition of AR gene expression by SA was confirmed by qRT-PCR. IC(50) of SA for inhibition of AR activity was 213.17 µg/mL. AR-SA binding sites were Trp111, His110, Tyr48, Trp20, Trp79, Leu300, and Phe122. The main binding modes involved hydrophobic interactions and hydrogen bonding. The stoichiometric ratio of non-covalent bonding between SA and AR was 1.0 to 13.3. Conclusion. SA acts to prevent DC in rat lenses by inhibiting AR activity and gene expression, which has potential to be developed into a novel drug for therapeutic management of DC.

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