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1.
CNS Neurosci Ther ; 29(12): 4070-4081, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37392024

RESUMO

AIMS: This study systematically investigated structural and functional alterations in the thalamus and its subregions using multimodal magnetic resonance imaging (MRI) and examined its clinical relevance in tinnitus patients with different outcomes after sound therapy (narrowband noise). METHODS: In total, 60 patients with persistent tinnitus and 57 healthy controls (HCs) were recruited. Based on treatment efficacy, 28 patients were categorized into the effective group and 32 into the ineffective group. Five MRI measurements of the thalamus and its seven subregions, including gray matter volume, fractional anisotropy, fractional amplitude of low-frequency fluctuation, and functional connectivity (FC), were obtained for each participant and compared between the groups. RESULTS: Patients in both the groups exhibited widespread functional and diffusion abnormalities in the whole thalamus and several subregions, with more obvious changes observed in the effective group. All tinnitus patients had abnormal FC compared with the HCs; FC differences between the two patient groups were only observed in the striatal network, auditory-related cortex, and the core area of the limbic system. We combined the multimodal quantitative thalamic alterations and used it as an imaging indicator to evaluate prognosis before sound therapy and achieved a sensitivity of 71.9% and a specificity of 85.7%. CONCLUSION: Similar patterns of thalamic alterations were identified in tinnitus patients with different outcomes, with more obvious changes observed in the effective group. Our findings support the tinnitus generation hypothesis of frontostriatal gating system dysfunction. A combination of multimodal quantitative thalamic properties may be used as indicators to predict tinnitus prognosis before sound therapy.


Assuntos
Zumbido , Humanos , Zumbido/diagnóstico por imagem , Zumbido/terapia , Zumbido/patologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Sistema Límbico/patologia , Tálamo/diagnóstico por imagem
2.
Oxid Med Cell Longev ; 2021: 4706410, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745416

RESUMO

Loquat (Eriobotrya japonica Lindl.), a subtropical fruit tree native to Asia, is not only known to be nutritive but also beneficial for the treatment of diabetes in the south of China. To expand its development, this study was undertaken concerning the potential therapeutic role of total sesquiterpene glycosides (TSGs) from loquat leaves in insulin resistance (IR), the major causative factor of type 2 diabetes mellitus (T2DM). Male C57BL/6 mice were fed on high-fat diet (HFD) to induce IR and then were given TSG by oral administration at 25 and 100 mg/kg/day, respectively. TSG notably improved metabolic parameters including body weight, serum glucose, and insulin levels and prevented hepatic injury. Moreover, inflammatory response and oxidative stress were found to be remarkably alleviated in IR mice with TSG supplement. Further research in liver of IR mice demonstrated that TSG repaired the signalings of insulin receptor substrate-1 (IRS-1)/glucose transporter member 4 (GLUT4) and AMP-activated protein kinase (AMPK), which improved glucose and lipid metabolism and prevented lipid accumulation in liver. It was also observed that TSG suppressed the expression of transient receptor potential vanilloid 1 (TRPV1), whereas the signaling pathway of sirtuin-6 (SIRT6)/nuclear factor erythroid 2-related factor 2 (Nrf2) was significantly promoted. Based on the results, the current study demonstrated that TSG from loquat leaves potentially ameliorated IR in vivo by enhancing IRS-1/GLUT4 signaling and AMPK activation and modulating TRPV1 and SIRT6/Nrf2 signaling pathways.


Assuntos
Dieta Hiperlipídica , Eriobotrya/química , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosídeos/farmacocinética , Hiperglicemia/prevenção & controle , Hiperlipidemias/prevenção & controle , Resistência à Insulina , Animais , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Folhas de Planta , Sesquiterpenos/farmacologia , Sirtuínas/genética , Sirtuínas/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo
3.
Hum Brain Mapp ; 42(14): 4762-4776, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34231944

RESUMO

Previous studies demonstrated that brain morphological differences and distinct patterns of neural activation exist in tinnitus patients with different prognoses after sound therapy. This study aimed to explore possible differences in intrinsic network-level functional connectivity (FC) in patients with different outcomes after sound therapy (narrow band noise). We examined intrinsic FC using resting-state functional magnetic resonance imaging in 78 idiopathic tinnitus patients (including 35 effectively treated and 43 ineffectively treated) and 52 healthy controls (HCs) via independent component analysis. We also investigated the associations between the differences in FC and clinical variables. Analyses revealed significantly altered intranetwork connectivity in the auditory network (AUN) and some nonauditory-related networks in the EG/IG patients compared to HCs; compared with EG patients, IG patients showed decreased intranetwork connectivity in the anterior default mode network (aDMN) and AUN. Meanwhile, robust differences were also evident in internetwork connectivity between some nonauditory-related networks (salience network and executive control network; posterior default mode network and dorsal attention network) in the EG relative to IG patients. We combined intranetwork connectivity in the aDMN and AUN as an imaging indicator to evaluate patient outcomes and screen patients before treatment; this approach reached a sensitivity of 94.3% and a specificity of 76.7%. Our study suggests that tinnitus patients with different outcomes show distinct network-level functional reorganization patterns. Intranetwork connectivity in the aDMN and AUN may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and screen patients before sound therapy.


Assuntos
Estimulação Acústica , Percepção Auditiva/fisiologia , Córtex Cerebral/fisiopatologia , Conectoma , Rede de Modo Padrão/fisiopatologia , Rede Nervosa/fisiopatologia , Reabilitação Neurológica , Zumbido/fisiopatologia , Zumbido/terapia , Estimulação Acústica/métodos , Adulto , Córtex Cerebral/diagnóstico por imagem , Rede de Modo Padrão/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Reabilitação Neurológica/métodos , Zumbido/diagnóstico por imagem
4.
Artigo em Inglês | MEDLINE | ID: mdl-33838149

RESUMO

The functional connectivity of the auditory network is considered to be important in the development of tinnitus. We hypothesized that sound therapy, as a commonly used effective treatment for tinnitus, can modulate the functional connectivity of the auditory network. In this prospective observational study, we recruited 27 tinnitus patients who had undergone 12 weeks of sound therapy and 27 matched healthy controls. For the two groups of subjects, resting-state functional magnetic resonance imaging was acquired both at baseline and at the 12th week. We utilized independent component analysis and seed-based functional connectivity analysis to characterize the connectivity features of the auditory network. Interaction effects between the two groups and the two scans within the auditory network were observed, which were driven by increased functional connectivity in the left primary auditory cortex (PAC) and decreased values in the secondary auditory cortex (SAC) in tinnitus patients after treatment. Increased connections between the auditory network and limbic network, as well as decreased values with the bilateral thalami, were identified. The effects were mainly driven by the functional connectivity alterations of the SAC rather than that of the PAC. Significant positive correlations between the percent improvement in the Tinnitus Handicap Inventory (THI) score and the percentage change rates of functional connectivity between the SAC and bilateral thalami were observed. Our study contributes to the understanding of the mechanism of tinnitus and effective sound therapy, providing evidence to support the theory of a gain adaptation mechanism that quantifies the recovered gating function of the thalamus in tinnitus patients.


Assuntos
Estimulação Acústica/métodos , Córtex Auditivo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Zumbido/diagnóstico por imagem , Zumbido/terapia , Adulto , Córtex Auditivo/fisiologia , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiologia , Estudos Prospectivos , Adulto Jovem
5.
Hum Brain Mapp ; 42(3): 753-765, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33098363

RESUMO

This study aimed to explore brain structural and white matter microstructural reorganization in the early stage of tinnitus and identify brain alterations that contribute to its relief after 6 months of sound therapy. We studied 64 patients with idiopathic tinnitus, including 29 patients who were categorized into an effective group (EG) and 35 who were categorized into an ineffective group (IG) according to the 6-month follow-up improvement of the Tinnitus Handicap Inventory score, along with 63 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging scanning on a 3-T magnetic resonance system. Differences in brain gray/white matter volume and white matter microstructure were evaluated using voxel-based morphometry analysis and tract-based spatial statistics among the three groups. Associations between brain reorganization and the improvement of tinnitus symptoms were also investigated. Compared with EG patients, IG patients experienced a significant gray matter volume decrease in the right middle frontal gyrus (MFG)/right precentral gyrus (PreCG). Meanwhile, both EG and IG patients showed significant changes (decrease or increase) in brain white matter integrity in the auditory-related or nonauditory-related white matter fiber tracts compared with HCs, while EG patients showed decreased axial diffusivity in the bilateral middle cerebellar peduncle (MCP) compared with IG patients. We combined the gray matter change of the MFG/PreCG and the white matter integrity of the bilateral MCP as an imaging indicator to evaluate the patient's prognosis and screen patients before treatment; this approach reached a sensitivity of 77.1% and a specificity of 82.8%. Our study suggests that there was a close relationship between brain reorganization and tinnitus improvement. The right MFG/PreCG and bilateral MCP may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and may be used to screen patients before sound therapy. These findings may provide new useful information that can lead to a better understanding of the tinnitus mechanism.


Assuntos
Córtex Cerebral/patologia , Substância Cinzenta/patologia , Pedúnculo Cerebelar Médio/patologia , Neuroimagem/normas , Avaliação de Resultados em Cuidados de Saúde , Zumbido/patologia , Zumbido/terapia , Substância Branca/patologia , Estimulação Acústica , Adulto , Córtex Cerebral/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Seguimentos , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pedúnculo Cerebelar Médio/diagnóstico por imagem , Sensibilidade e Especificidade , Zumbido/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
6.
Food Funct ; 11(4): 3516-3526, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32253400

RESUMO

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease with few successful treatments, and is strongly associated with cigarette smoking (CS). Since the novel coronavirus has spread worldwide seriously, there is growing concern that patients who have chronic respiratory conditions like COPD can easily be infected and are more prone to having severe illness and even mortality because of lung dysfunction. Loquat leaves have long been used as an important material for both pharmaceutical and functional applications in the treatment of lung disease in Asia, especially in China and Japan. Total flavonoids (TF), the main active components derived from loquat leaves, showed remarkable anti-inflammatory and antioxidant activities. However, their protective activity against CS-induced COPD airway inflammation and oxidative stress and its underlying mechanism still remain not well-understood. The present study uses a CS-induced mouse model to estimate the morphological changes in lung tissue. The results demonstrated that TF suppressed the histological changes in the lungs of CS-challenged mice, as evidenced by reduced generation of pro-inflammatory cytokines including interleukin 6 (IL-6), IL-1ß, tumor necrosis factor α (TNF-α), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) and diminished the protein expression of transient receptor potential vanilloid 1 (TRPV1). Moreover, TF also inhibited phosphorylation of IKK, IκB and NFκB and increased p-Akt. Interestingly, TF could inhibit CS-induced oxidative stress in the lungs of COPD mice. TF treatment significantly inhibited the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). In addition, TF markedly downregulated TRPV1 and cytochrome P450 2E1 (CYP2E1) and upregulated the expression of SOD-2, while the p-JNK level was observed to be inhibited in COPD mice. Taken together, our findings showed that the protective effect and putative mechanism of the action of TF resulted in the inhibition of inflammation and oxidative stress through the regulation of TRPV1 and the related signal pathway in lung tissues. It suggested that TF derived from loquat leaves could be considered to be an alternative or a new functional material and used for the treatment of CS-induced COPD.


Assuntos
Fumar Cigarros/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Eriobotrya/química , Flavonoides/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Canais de Cátion TRPV/imunologia , Animais , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/imunologia , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/química , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Transdução de Sinais/efeitos dos fármacos , Fumaça/efeitos adversos , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Canais de Cátion TRPV/genética
7.
Brain Imaging Behav ; 14(6): 2668-2678, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31900891

RESUMO

Altered functional connectivity (FC) of the thalamus has been proven to be an important finding in tinnitus patients. Tinnitus can be effectively desensitized by sound therapy. However, it is still unclear whether and how sound therapy affects the FC of the thalamus. Resting-state functional magnetic resonance imaging data and anatomical data were longitudinally collected from 25 idiopathic tinnitus patients before and after 12 weeks of sound therapy by using adjusted narrow band noise and from 25 matched healthy controls at the same time interval without any intervention. The FC of bilateral thalami were analyzed by setting the left and right thalamus as the regions of interest. Significant main effect of group on the FC of the thalamus were found mainly in the key components of the default mode network, limbic network, salience network, cognitive control network, auditory network and occipital region. FC values between the thalamus, inferior frontal gyrus (IFG), and anterior cingulate cortex (ACC) featured higher values in the tinnitus group at baseline compared to the healthy controls and restoration in tinnitus patients after treatment. Decreased Tinnitus Handicap Inventory (THI) scores and decreased FC values between the right thalamus and right IFG were positively correlated (r = 0.476, P = 0.016). Abnormal FC of the thalamus is associated with multiple brain networks. Sound therapy has a normalizing effect on the enhanced FC of the thalamus-IFG and thalamus-ACC, representing decreased tinnitus attention control and less involvement of the noise-canceling system.


Assuntos
Zumbido , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Tálamo/diagnóstico por imagem , Zumbido/diagnóstico por imagem , Zumbido/terapia
8.
J Oleo Sci ; 68(6): 581-589, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31092797

RESUMO

Non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease characterized by hepatic steatosis, affects 30-40% of the population in the world. The seed of Euryale ferox salisb. possesses several pharmacological actions, including metabolic syndrome. However, the seed coat of E. ferox was usually discarded as waste, which contains comparatively abundant polyphenols, and its biological activity has been rarely investigated. In this work, we evaluate the hepatoprotective effect of E. ferox seed coat extract (EFSCE), in NAFLD mice induced by high-fat diet (HFD). The HPLC-MS analysis indicated that the main components of EFSCE were polyphenols. And then, mice were treated with HFD for 4 weeks to induce NAFLD. The result showed that the body weight, weight of adipose tissue, the ratio of liver to body weight in NAFLD mice increased compared with control group. In addition, blood lipids parameters including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) also increased in NAFLD mouse model. It was showed that, after treated with EFSCE (15 and 30 mg/kg/day) for 4 weeks, the body weight, lipids deposition in the liver and blood lipids in HFD-induced NAFLD mice markedly reduced. Compared with NAFLD mice, EFSCE administration could also prevent malondialdehyde (MDA) overproduction and strengthen Superoxide Dismutase (SOD) activity to counteract oxidative stress. Moreover, EFSCE was also found effective in reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in HFD-induced NAFLD model, which indicated liver injury in NAFLD. Therefore, EFSCE (rich in polyphenols) is indicated as bioactive nature product for HFD-induced NAFLD treatment, by eliminating lipid accumulation and oxidative stress via regulation of IRs-1 and CYP2E1.


Assuntos
Citocromo P-450 CYP2E1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Proteínas Substratos do Receptor de Insulina/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Nymphaeaceae/química , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sementes/química , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Polifenóis/análise , Estimulação Química , Superóxido Dismutase/metabolismo
9.
Am J Otolaryngol ; 39(4): 401-409, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29655489

RESUMO

PURPOSE: We intend to assess the effectiveness of a novel tinnitus treatment therapy, the Cochleural Alternating Acoustic Beam Therapy (CAABT) using the psychoacoustic measures, the questionnaires and rs-fMRI. MATERIALS AND METHODS: In this study, we enrolled 11 older than 18 years old Chinese patients with normal hearing who had unilateral, chronic (longer than 6 months), sensorineural tinnitus, of frequencies between 125-8000 Hz, and an average loudness of 31 dB. The patients underwent the treatment with the CAABT method for 12 weeks and the outcomes were evaluated with tinnitus questionnaire scores, a set of psychoacoustic measures, and rs-fMRI testing before treatment and at 3 months. This was an earlier study of the controlled randomized clinical trial which was registered with ClinicalTrials.gov, number NCT02774122. RESULTS: Almost all the patients reported reduced tinnitus annoyance after the three-month treatment. The THI and VAS scores showed decreased tinnitus severity. The rs-fMRI results indicated that the right middle frontal gyrus and the right superior temporal gyrus displayed noticeable decreases of the ReHo values for the subjects between the before and after treatment, supporting the clinical evidence of significant tinnitus reduction. CONCLUSION: The therapy seemed effective in patients of varying severities, and no side effects were observed in this trial. The CAABT can be an alternative for those who are suitable for sound therapy once a large scale of and better controlled clinical studies have validated the findings of this experiment.


Assuntos
Estimulação Acústica/métodos , Zumbido/terapia , Adulto , Idoso , Audiometria de Tons Puros , Limiar Auditivo , Doença Crônica , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Zumbido/diagnóstico por imagem , Zumbido/fisiopatologia , Resultado do Tratamento
10.
Rev. bras. farmacogn ; 28(2): 239-242, Mar.-Apr. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1042262

RESUMO

ABSTRACT Folium Eriobotryae, the dried leaves of loquat (Eriobotrya japonica, (Thunb.) Lindl., Rosaceae), is a traditional Chinese medicine used to treat cough with phlegm in China. Fallen and growing loquat leaves were tested for their effect on coughing and expectoration in mice. HPLC-ELSD and HPLC-MS analyses of aqueous and ethanol extracts of fallen or growing leaves were used to identify the chemical components responsible for this effect. Both the aqueous and ethanol extracts of growing and fallen leaves of loquat contained antitussive and expectorant activities. Moreover, an aqueous extract of growing loquat leaves with a higher flavonoid content displayed a stronger expectorant activity while the ethanol extract of fallen loquat leaves that contained a higher content of triterpenoid acids induced a stronger antitussive activity.

11.
Biomed Pharmacother ; 97: 1125-1130, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29136950

RESUMO

Loquat (Eriobotrya japonica) leaf has displayed beneficial effect on metabolic syndrome. In our previously study, total sesquiterpene glycosides (TSG) isolated from Loquat leaf exhibited therapeutic effect on Non-alcoholic fatty liver disease (NAFLD) in vivo, but the accurate active compound remains unknown. Sesquiterpene glycoside 1 (SG1) is a novel compound, which is exclusively isolated from Loquat leaf, but its biological activity has been rarely reported. The present study was designed to evaluate the pharmacological effect of SG1, the main component of TSG, in oleic acid (OA)-induced HepG2 cell model of NAFLD with its related mechanisms of action. In this study, both SG1 and TSG were found to significantly reduce the lipid deposition in the cell model. They could also decrease total cholesterol (TC), triglyceride (TG) and intracellular free fatty acid (FFA) contents. Compared with OA-treated cells, the superoxide dismutase (SOD) level increased, and the malondialdehyde (MDA) and 4-hydroxynonenal levels respectively decreased after the administration of SG1 or TSG. The high dose of SG1 (140 µg/mL) displayed a similar therapeutic effect as TSG at 200 µg/mL. Both SG1 and TSG were found to suppress the expression of cytochrome P450 2E1 (CYP2E1) and the phosphorylation of c-jun terminal kinase (JNK) and its downstream target c-Jun in OA-treated cell. These results demonstrate again that TSG are probably the main responsible chemical profiles of Loquat leaf for the treatment of NAFLD, for which it can effectively improve OA-induced steatosis and reduce oxidative stress, probably by downregulating of CYP2E1 expression and JNK/c-Jun phosphorylation, while SG1 may be the principle compound.


Assuntos
Eriobotrya/química , Glicosídeos/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Colesterol/metabolismo , Citocromo P-450 CYP2E1/genética , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Ácidos Graxos não Esterificados/metabolismo , Glicosídeos/administração & dosagem , Glicosídeos/isolamento & purificação , Células Hep G2 , Humanos , Malondialdeído/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Ácido Oleico/toxicidade , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Sesquiterpenos/administração & dosagem , Sesquiterpenos/isolamento & purificação , Superóxido Dismutase/metabolismo , Triglicerídeos/metabolismo
12.
Biomed Pharmacother ; 91: 229-237, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28458161

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, which affects 20-40% of the population in the world. Loquat (Eriobotrya japonica) Leaf possesses several pharmacological actions. Many sesquiterpene glycosides were reported to be isolated exclusively from the Loquat Leaf, however, their biological activity has been rarely investigated. The present study was designed to evaluate the pharmacological effect of total sesquiterpene glycosides (TSG) in high-fat diet (HFD) induced NAFLD mice with its related mechanisms of action. Mice were fed with a normal diet or HFD for 8 weeks. TSG (25 and 100mg/kg/day), simvastatin (10mg/kg/day) or vehicle were orally administered for last 4 weeks of the 8-week HFD feeding period. From the result, it was showed that TSG significantly reduced the body weight and fat deposition in the liver of NAFLD mice. It also decreased total cholesterol (TC) and triglyceride (TG) contents in the serum. Compared with NAFLD mice, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased and decreased after the administration of TSG in a dose of 100mg/kg, respectively. TSG reduced alanine aminotransferase (ALT) activity as well. Finally, TSG was found to suppress the expression of cytochrome P450 2E1 (CYP2E1) and the phosphorylation of c-jun terminal kinase (JNK) in NAFLD mice. In summary, this study demonstrates that TSG reduces oxidative stress by downregulating of CYP2E1 expression and JNK phosphorylation in NAFLD, and alleviates NAFLD ultimately. TSG potentially serves as bioactive compounds for the treatment of NAFLD.


Assuntos
Inibidores do Citocromo P-450 CYP2E1/uso terapêutico , Citocromo P-450 CYP2E1/metabolismo , Eriobotrya/química , Glicosídeos/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Folhas de Planta/química , Sesquiterpenos/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Inibidores do Citocromo P-450 CYP2E1/farmacologia , Dieta Hiperlipídica , Glicosídeos/química , Glicosídeos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos ICR , Hepatopatia Gordurosa não Alcoólica/patologia , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos
13.
Acta Radiol ; 57(12): 1490-1496, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27012277

RESUMO

Background There are no established biomarkers predictive of the efficacy of treatment for ocular adnexal lymphoma (OAL). Purpose To evaluate the effectiveness of pretreatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) in predicting the response of OAL to chemotherapy. Material and Methods Twenty-one patients, who were pathologically diagnosed with OAL, were retrospectively analyzed. According to the National Comprehensive Cancer Network (NCCN) response evaluation criteria for non-Hodgkin's lymphoma, patients were divided into responders (n = 14) and non-responders (n = 7). The volume transfer constant (Ktrans), rate constant (Kep), extracellular extravascular volume fraction (Ve), and apparent diffusion coefficient (ADC) were computed. Two independent-sample tests were applied for statistical analysis. For significantly different parameters, receiver-operator characteristics curve analysis was performed. Results The Ktrans value (min-1), Kep value (min-1), and ADC value (10-3 mm2/s) were 0.76 ± 0.36 vs. 0.47 ± 0.18 (mean ± SD), 4.43 ± 1.29 vs. 3.14 ± 1.37, and 0.51 ± 0.12 vs. 0.66 ± 0.15, respectively, in the responders and non-responders groups. Significant differences were found between the two groups regarding these parameters ( P < 0.05). However, no significant difference was observed in Ve (min-1) between the groups ( P > 0.05). Ktrans, Kep, and ADC had a moderately predictive sensitivity or specificity. When Ktrans and ADC or the three parameters were combined, a considerably higher sensitivity (85.7%) and specificity (85.7%) with a significant discriminative accuracy (area under the curve = 0.929; P = 0.002) was found. Conclusion Ktrans, Kep, and ADC could potentially predict OAL response to chemotherapy. A combination of these DWI and DCE-MRI quantitative parameters might increase sensitivity and specificity.


Assuntos
Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Aumento da Imagem/métodos , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/tratamento farmacológico , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
14.
Biomed Chromatogr ; 29(12): 1791-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26033261

RESUMO

Folium Eriobotryae effective fraction (FEA), the extract of Folium Eriobotryae, had been used as anti-hyperglycemia and anti-hyperlipemia medicine in China. A previous study indicated that euscaphic acid, maslinic acid, corosolic acid, oleanolic acid and ursolic acid, the five structurally similar triterpene acids (containing two groups of structural isomers), are the major components of FEA. In the present study, we developed a specific and reliable LC-MS method for simultaneous determination of the five triterpene acids in rat plasma, and further investigated their pharmacokinetic properties after oral administration of FEA. Following a simple sample preparation, chromatographic separation was achieved on a C18 column with a mobile phase composed of methanol-0.1% ammonium acetate (80:20, v/v). Quantification was achieved by monitoring the selected ions at m/z 487.6 for euscaphic acid, m/z 471.5 for maslinic acid and corosolic acid, m/z 455.5 for oleanolic acid and ursolic acid and m/z 469.5 for internal standard. The method was validated to be specific, accurate and precise over the concentration ranges of 10-3000 ng/mL with limits of detections of 5 ng/mL for the five triterpene acids. Finally, the method was successfully applied to the pharmacokinetic study of the five structurally similar triterpene acids in rats after oral administration of FEA.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Triterpenos/sangue , Triterpenos/farmacocinética , Administração Oral , Animais , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Triterpenos/química , Triterpenos/isolamento & purificação
15.
World J Gastroenterol ; 19(27): 4386-92, 2013 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-23885151

RESUMO

AIM: To evaluate the efficacy and safety of baclofen for treatment of refractory gastroesophageal reflux-induced chronic cough (GERC) unresponsive to standard anti-reflux therapy. METHODS: Sixteen patients with refractory GERC were given an 8-wk course of baclofen 20 mg three times a day as an add-on therapy to omeprazole. Changes in the cough symptom score, cough threshold to capsaicin, reflux symptom score and possible adverse effects were determined after treatment. The variables of multi-channel intraluminal impedance combined with pH monitoring were compared between responders and non-responders to baclofen. RESULTS: Twelve of 16 patients completed treatment. Cough disappeared or improved in 56.3% (9/16) of patients, including 6 patients with acid reflux-induced cough (66.7%) and 3 patients with non-acid reflux-induced cough (33.3%). With baclofen treatment, the cough symptom score began to decrease at week 2, was clearly decreased at week 6 and reached a minimum at week 8. At the end of therapy, the lowest concentration of capsaicin required for induction of ≥ 2 and ≥ 5 coughs increased from 0.98 (1.46) to 1.95 (6.82) µmol/L (Z = -2.281, P = 0.024) and from 1.95 (7.31) to 7.8 (13.65) µmol/L (Z = -2.433, P = 0.014), respectively, and the reflux symptom score decreased from 8.0 ± 1.6 to 6.8 ± 0.8 (t = 2.454, P = 0.023). The number of acid reflux episodes was significantly lower in responders than in non-responders. The main adverse effects were somnolence, dizziness and fatigue. CONCLUSION: Baclofen is a useful, but suboptimal treatment option for refractory GERC.


Assuntos
Baclofeno/uso terapêutico , Tosse/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Relaxantes Musculares Centrais/uso terapêutico , Adulto , Capsaicina/uso terapêutico , Estudos de Coortes , Domperidona/uso terapêutico , Monitoramento do pH Esofágico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento
16.
Zhong Yao Cai ; 31(9): 1351-4, 2008 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19180956

RESUMO

OBJECTIVE: To investigate the chemical constituents from Loquat leaf (Eriobotrya japonica). METHODS: Compounds were isolated by a combination of silica gel and ODS column chromatographies and preparative TLC and HPLC, their structures were identified by chemical and spectral methods. RESULTS: Nine triterpenes were isolated and identified as methyl betuliate (I), oleanolic acid (II), ursolic acid (III), methyl maslinate (IV), methyl corosolate, (methyl 2alpha-3alpha-dihydroxyurs-12-en-28-oate, V), maslinic acid (VI), corosolic acid (VII), tormentic acid (VIII), euscaphic acid (IX) from loquat leaf. CONCLUSION: Compounds I and V are obtained from this plant and Eriobotrya genus for the first time.


Assuntos
Plantas Medicinais/química , Rosaceae/química , Triterpenos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Folhas de Planta/química , Triterpenos/química , Ácido Ursólico
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