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AIM: The aim of this study was to evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic-associated weight gain and metabolic syndrome. METHODS: One hundred thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome were recruited. They were randomly assigned to berberine (600 mg/d, n = 58) or placebo (n = 55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight. Secondary outcomes included body mass index, waist circumference, serum glucose and lipid profiles, and the severity of psychotic symptoms. RESULTS: Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD], -0.75; 95% CI, -1.42 to -0.07 [P = 0.031, d = 0.41]) and 12 weeks (MD, -1.08; 95% CI, -1.76 to -0.40 [P = 0.002, d = 0.59]). Patients who received berberine also showed statistically significant improvements in end point in body mass index (MD, -0.41; 95% CI, -0.65 to -0.17 [P = 0.001, d = 0.64]), total cholesterol (MD, -0.58; 95% CI, -0.74 to -0.41 [P < 0.001, d = 1.31]), low-density lipoprotein (MD, -0.52; 95% CI, -0.68 to -0.35 [P < 0.001, d = 1.19]), and glycated hemoglobin (MD, -0.09; 95% CI, -0.18 to 0 [P = 0.05, d = 0.37]). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo. CONCLUSION: The findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and metabolic syndrome.
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Antipsicóticos , Berberina , Síndrome Metabólico , Esquizofrenia , Antipsicóticos/efectos adversos , Berberina/efectos adversos , Método Doble Ciego , Humanos , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Aumento de PesoRESUMEN
OBJECTIVES: An herbal preparation called peony-glycyrrhiza decoction (PGD) may have the potential in reducing antipsychotic-related hyperprolactinemia (hyperPRL). This double-blind, randomized placebo-controlled study aimed to reevaluate the efficacy of PGD against antipsychotic-related hyperPRL. METHODS: Ninety-nine schizophrenic women who were under antipsychotic therapy and had symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/d) for 16 weeks. The severity of hyperPRL, psychosis, and abnormal involuntary movements was assessed at baseline and weeks 8 and 16 using standard instruments including the Prolactin Related Adverse Event Questionnaire. Blood levels of prolactin (PRL) and related pituitary and sex hormones were measured at the same time points. RESULTS: Peony-glycyrrhiza decoction treatment produced a significantly greater reduction of the Prolactin Related Adverse Event Questionnaire score at weeks 8 and 16 and a greater improvement on abnormal involuntary movements at end point compared with placebo, without altering the severity of psychosis. The group treated with PGD showed significantly higher proportion of having overall improvement on hyperPRL symptoms (χ = 4.010, P = 0.045) and menstrual resumption (χ = 4.549, P = 0.033) at week 8 than placebo. Serum PRL levels were similar in the 2 groups. CONCLUSIONS: Peony-glycyrrhiza decoction is effective in reducing antipsychotic-related hyperPRL and abnormal involuntary movement symptoms, but no reduction in blood PRL concentrations was observed. The underlying mechanisms of PGD's effects need further investigation (trial registration of NCT01852331 at www.clinicaltrials.gov).
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Antipsicóticos/efectos adversos , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Glycyrrhiza , Hiperprolactinemia/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , Paeonia , Extractos Vegetales/farmacología , Esquizofrenia/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Humanos , Hiperprolactinemia/sangre , Hiperprolactinemia/inducido químicamente , Extractos Vegetales/administración & dosificación , Esquizofrenia/sangre , Resultado del TratamientoRESUMEN
The purpose of the present study was to evaluate the anti-tumor effects of 18beta-glycyrrhetinic acid (GA), a natural compound extracted from liquorice, against pituitary adenoma and its underlying mechanisms in cultured cells and mouse model of xenografted tumor. GA induced cellular damage in rat pituitary adenoma-derived MMQ and GH3 cells, manifested as reduced cell viability, increased lactate dehydrogenase release, elevated intracellular reactive oxygen species (ROS) and Ca(2+) concentration. GA also caused G0/G1 phase arrest, increased apoptosis rate and increased mitochondrial membrane permeabilization by suppressing the mitochondrial membrane potential and down-regulating a ratio of B cell lymphoma 2 (Bcl-2) and Bax. GA activated calcium/calmodulin-dependent protein kinase II (CaMKII), c-Jun N-terminal kinase (JNK) and P38; but these activating effects were attenuated by pretreatment with N-acetyl-L-cysteine, a ROS inhibitor. Pretreatment with KN93, a CaMKII inhibitor, also abolished the GA activation of JNK and P38. GA remarkably inhibited growth of pituitary adenoma grafted on nude mice. These results suggest that the anti-pituitary adenoma effect of GA is associated with its apoptotic actions by activating mitochondria-mediated ROS/mitogen-activated protein kinase pathways in particular CaMKII that may serve a linkage between ROS accumulation and the activation of JNK and P38. This study provides experimental evidence in the support of further developing GA as a chemotherapeutic agent for pituitary adenoma.
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Adenoma/patología , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Ácido Glicirretínico/análogos & derivados , Neoplasias Hipofisarias/patología , Transducción de Señal/efectos de los fármacos , Adenoma/tratamiento farmacológico , Animales , Antiinflamatorios/uso terapéutico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Ácido Glicirretínico/farmacología , Ácido Glicirretínico/uso terapéutico , Humanos , L-Lactato Deshidrogenasa/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Desnudos , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Neoplasias Hipofisarias/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Factores de Tiempo , Trasplante Heterólogo/métodosRESUMEN
Numerous studies have shown robust neuroprotective effects of paeoniflorin (PF), a natural compound derived from the herbal medicine Paeony radix. In the present study, we determined associations of PF neuroprotection with its modulation of various apoptotic and anti-apoptotic pathways. PF (50-400 µM) pretreatment significantly improved viability of differentiated PC12 cells exposed to methyl-4-phenylpyridine ion (MPP(+)), a neurotoxin, and inhibited over-release of lactate dehydrogenase, a biomarker of neuronal cell death. PF also ameliorated MPP(+)-induced nuclear and mitochondrial apoptotic alteration and intracellular calcium overload. PF treatment reversed MPP(+) suppression of activity of B cell lymphoma-extra large, which is a mitochondrial membrane molecule that protects cells from DNA damage-induced apoptosis, and strikingly inhibited the enhanced level of cleaved poly(ADP-ribose)polymerase, which is involved in the process of apoptosis. PF alone and coadministration with MPP(+) enhanced phospho activation of extracellular signal-regulated kinases, Akt, and its downstream element glycogen synthase kinase-3, but the effects were completely abolished in the presence of their blockers PD98059 and LY294002. The presence of the blockers also diminished the potency of PF in improving viability of MPP(+)-exposed cells. These results indicate that neuroprotective effects of PF are related to its modulation of multiple anti-apoptotic and pro-apoptotic pathways, including blockade of intracellular calcium overload, prevention of mitochondrial membrane integrity, inhibition of pro-apoptotic molecules, and up-regulation of anti-apoptotic proteins associated with cell survival and proliferation. The study provides evidence supporting PF as a potential therapeutic agent used for the treatment of neurodegenerative diseases and neural injury.
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Apoptosis/efectos de los fármacos , Benzoatos/farmacología , Hidrocarburos Aromáticos con Puentes/farmacología , Diferenciación Celular/efectos de los fármacos , Glucósidos/farmacología , Fármacos Neuroprotectores/farmacología , Transducción de Señal/efectos de los fármacos , 1-Metil-4-fenilpiridinio , Animales , Calcio/metabolismo , Supervivencia Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Monoterpenos , Células PC12 , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Proteína bcl-X/metabolismoRESUMEN
Electroacupuncture (EA) and electroconvulsive therapy (ECT) are often used in the management of schizophrenia. This study sought to determine whether additional EA and ECT could augment antipsychotic response and reduce related side effects. In this retrospective controlled study, 287 hospitalized schizophrenic patients who received antipsychotics (controls, n = 50) alone or combined with EA (n = 101), ECT (n = 55) or both (EA + ECT, n = 81) were identified. EA and ECT were conducted for 5 and 3 sessions per week, respectively, with a maximum of 12 sessions for ECT during hospitalization. The Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were used to assess the severity of psychotic symptoms. Clinical response on SAPS and SANS, weight gain, and adverse events were compared. Survival analysis revealed that the ECT and EA + ECT groups had markedly greater clinical response rate than controls on SAPS [72.7 and 90.1% vs. 64.0%; relative risk (RR), 1.974 and 2.628, respectively, P ≤ 0.004] and on SANS (67.3 and 70.4% vs. 42.0%; RR, 1.951 and 2.009, respectively, P ≤ 0.015). A significantly greater response rate on SANS than controls was also observed in the EA group (64.4% vs. 42.0%; RR = 1.938, P = 0.008). EA-containing regimens remarkably reduced weight gain and incidences of headache, insomnia, dry mouth, and electrocardiographic abnormalities. These results suggest that EA and ECT can serve as additional treatment for enhancing antipsychotic response and reduce the side effects in hospitalized patients with schizophrenia. Clinical Trial Registration: http://www.chictr.org.cn/showprojen.aspx?proj=38901, identifier ChiCTR1900023563.
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Estrogen-stimulating principles have been demonstrated to relieve postmenopausal syndrome effectively. Gardenia jasminoides Ellis (GJE) is an herbal medicine possessing multiple pharmacological effects on human health with low toxicity. However, the therapeutic effects of GJE on the management of postmenopausal syndrome and its mechanism of action have not been fully elucidated. In this study, network pharmacology-based approaches were employed to examine steroidogenesis under the influence of GJE. In addition, the possibility of toxicity of GJE was ruled out and four probable active compounds were predicted. In parallel, a chromatographic fraction of GJE with estrogen-stimulating effect was identified and nine major compounds were isolated from this active fraction. Among the nine compounds, four of them were identified by network pharmacology, validating the use of network pharmacology to predict active compounds. Then the phenotypic approaches were utilized to verify that rutin, chlorogenic acid (CGA) and geniposidic acid (GA) exerted an estrogen-stimulating effect on ovarian granulosa cells. Furthermore, the results of target-based approaches indicated that rutin, CGA, and GA could up-regulate the FSHR-aromatase pathway in ovarian granulosa cells. The stimulation of estrogen production by rat ovarian granulosa cells under the influence of the three compounds underwent a decline when the follicle-stimulating hormone receptor (FSHR) was blocked by antibodies against the receptor, indicating the involvement of FSHR in the estradiol-stimulating activity of the three compounds. The effects of the three compounds on estrogen biosynthesis- related gene expression level were further confirmed by Western blot assay. Importantly, the MTT results showed that exposure of breast cancer cells to the three compounds resulted in reduction of cell viability, demonstrating the cytotoxicity of the three compounds. Collectively, rutin, chlorogenic acid and geniposidic acid may contribute to the therapeutic potential of GJE for the treatment of postmenopausal syndrome.
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BACKGROUND: Transcutaneous electrical acupoint stimulation (TEAS) is thought to have potential to treat obsessive-compulsive disorder (OCD). OBJECTIVE: The purpose of this study was to determine whether adding TEAS to cognitive behavioral therapy (CBT) and clomipramine would improve the efficacy of these conventional treatments in OCD. METHODS: In this randomized controlled trial, 360 OCD patients were assigned to receive TEAS combined with CBT plus clomipramine (Group A, n = 120), TEAS combined with CBT plus placebo (Group B, n = 120), and simulated (placebo) TEAS combined with CBT plus clomipramine (Group C, n = 120) for 12 weeks. The primary outcome was measured using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). RESULTS: OCD symptoms in all patients reduced over time, however Groups A and B had a significantly greater reduction in Y-BOCS total score and the subscale for obsession and compulsion between week 2 and week 12 compared to Group C. Groups A and B had similar scores on these measures. Both groups had significantly higher rates of clinical response than Group C (88.3% and 81.7% vs. 67.5%, respectively, p < 0.001); and higher rates of remission (30.0% and 22.5% vs. 9.2%, respectively, p < 0.001). Group B experienced fewer adverse events than the other two groups. CONCLUSIONS: TEAS enhances the efficacy of conventional OCD interventions and avoids the adverse effects associated with conventional pharmacological treatment. It can be considered as an effective adjunct intervention for OCD.
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Puntos de Acupuntura , Trastorno Obsesivo Compulsivo/terapia , Estimulación Eléctrica Transcutánea del Nervio/métodos , Adolescente , Adulto , Anciano , Clomipramina/uso terapéutico , Terapia Cognitivo-Conductual , Terapia Combinada , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D2 receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL.
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Glycyrrhiza/química , Hiperprolactinemia/terapia , Paeonia/química , Extractos Vegetales/uso terapéutico , Prolactina/sangre , Animales , Antipsicóticos/efectos adversos , Antagonistas de los Receptores de Dopamina D2/efectos adversos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Femenino , Hiperprolactinemia/inducido químicamente , Hiperprolactinemia/metabolismo , Hipotálamo/metabolismo , Metoclopramida/efectos adversos , Hipófisis/metabolismo , Progesterona/sangre , Ratas Sprague-Dawley , Receptores de Dopamina D2/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
OBJECTIVES: To review and evaluate the efficacy and safety of tian jiu therapy on san fu tian for adults with asthma. METHODS: A literature search through August 31, 2013, was done to identify comparative studies evaluating effective rate, pulmonary function, immune response, recurrence rate, quality of life, and adverse events. The Cochrane Library, PubMed, EMBASE, and Chinese National Knowledge Infrastructure were searched; only randomized controlled trials with treatment groups using tian jiu therapy were included. Cochrane Collaboration's risk of bias tool and Review Manager software, version 5.2, were used for the data synthesis. RESULTS: Six studies involving 657 patients were identified. tian jiu therapy was more effective than the control intervention (odds ratio [OR], 3.51; 95% confidence interval [CI], 2.05-6.00; p<0.00001; I(2)=18%). The treatment group had a bigger decrease in IgE level (standard mean difference [SMD], -1.40; 95% CI, -2.18 to -0.63; p=0.0004; I(2)=85%) and Eosinophil (Eos) level (SMD, -4.26; 95% CI, -6.28 to -2.23; p<0.00001; I(2)=91%) compared with the control group. Included studies had a high risk of bias. Few adverse effects were reported in the included studies, and no serious adverse responses occurred. Adverse effects did not result in any dropouts. CONCLUSIONS: All studies indicated that tian jiu therapy has a positive effect on adults with asthma and that it is relatively safe because of its noninvasive nature. However, the limitations of the research design of the existing studies resulted in high risk of bias. More randomized controlled trials of better methodologic quality are needed to further confirm efficacy and safety of this therapy.
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Puntos de Acupuntura , Terapia por Acupuntura , Asma/terapia , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Adulto , Asma/sangre , Asma/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Eosinófilos/metabolismo , Humanos , Inmunoglobulina E/sangre , Oportunidad RelativaRESUMEN
OBJECTIVE: The purpose of this study was to investigate antitumour effects of liquiritigenin (LQ) on pituitary adenoma in in-vitro and in-vivo models. METHODS: The effects of LQ on cell viability, apoptosis rate, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) level and various apoptosis-related mediators were examined in MMQ and GH3 cells that are derived from rat pituitary adenoma. Antitumour effect of LQ was also examined in the mouse model of GH3-xenografted tumour. KEY FINDINGS: LQ inhibited cell viability, caused G1 phase arrest and initiated apoptosis in both MMQ and GH3 cells. LQ dissipated MMP, increased intracellular ROS level and cytosol cytochrome C, and reduced the expression of Ras, B-cell lymphoma 2 and B-cell lymphoma-extra large. LQ also inhibited the activation of extracellular signalling-regulated kinases (ERKs) and the translocation of from cytoplasm to nucleus. LQ markedly reduced tumour size without affecting bodyweight in mice with GH3 cells xenograft. CONCLUSIONS: LQ effectively inhibits pituitary adenoma tumour growth and induces cell apoptotic death mainly via Ras/ERKs and ROS-dependent mitochondrial pathways, suggesting that LQ is a potential suppressor of pituitary adenoma.
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Flavanonas/uso terapéutico , Mitocondrias/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fitoterapia , Neoplasias Hipofisarias/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Animales , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Transporte Biológico , Citocromos c/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Flavanonas/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias Hipofisarias/metabolismo , Extractos Vegetales/farmacología , Ratas , Transducción de Señal , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The platelet serotonergic system has potential biomarker utility for major depressive disorder (MDD). In the present study, platelet expression of 5-HT1A receptors and serotonin transporter (SERT) proteins, and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were quantified in 53 patients with MDD and 22 unaffected controls. All were drug-free, non-smokers and had no other psychiatric and cardiovascular comorbidity. The severity of depression symptoms was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Self-rating Depression Scale (SDS). Patients with MDD had significantly higher expression of platelet 5-HT1A receptors but significantly lower contents of platelet 5-HT, platelet-poor plasma (PPP) 5-HT and PPP 5-HIAA compared to healthy controls, and this was correlated with the severity of depression. SERT expression did not differ between the two groups. Correlation analysis confirmed a strong, inverse relationship between the 5-HT1A receptor expression and the 5-HT and 5-HIAA levels. Thus overexpression of platelet 5-HT1A receptors and reduced 5-HT tone may function as a peripheral marker of depression.
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Plaquetas/metabolismo , Trastorno Depresivo Mayor/sangre , Receptor de Serotonina 5-HT1A/sangre , Adulto , Análisis de Varianza , Femenino , Humanos , Ácido Hidroxiindolacético/sangre , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Serotonina/sangre , Estadística como Asunto , Adulto JovenRESUMEN
Acupuncture possesses the antidepressant potential. In this 6-week randomized controlled trial with 4-week follow-up, 160 patients with major depressive disorder (MDD) were randomly assigned to paroxetine (PRX) alone (n = 48) or combined with 18 sessions of manual acupuncture (MA, n = 54) or electrical acupuncture (EA, n = 58). Treatment outcomes were measured mainly using the 17-item Hamilton Depression Rating Scale (HAMD-17), Self-rating Depression Scale (SDS), clinical response and remission rates. Average PRX dose taken and proportion of patients who required an increased PRX dose due to symptom aggravation were also obtained. Both additional MA and EA produced a significantly greater reduction from baseline in score on HAMD-17 and SDS at most measure points from week 1 through week 6 compared to PRX alone. The clinical response was markedly greater in MA (69.8%) and EA (69.6%) groups than the group treated with PRX alone (41.7%, P = 0.004). The proportion of patients who required an increase dose of PRX due to symptom aggravation was significantly lower with MA (5.7%) and EA (8.9%) than PRX alone (22.9%, P = 0.019). At 4 weeks follow-up after completion of acupuncture treatment, patients with EA, but not MA, continued to show significantly greater clinical improvement. Incidence of adverse events was not different in the three groups. Our study indicates that acupuncture can accelerate the clinical response to selective serotonin reuptake inhibitors (SSRIs) and prevent the aggravation of depression. Electrical acupuncture may have a long-lasting enhancement of the antidepressant effects (Trial Registration: ChiCTR-TRC-08000278).
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Terapia por Acupuntura/métodos , Terapia Combinada/métodos , Trastorno Depresivo Mayor/terapia , Paroxetina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Terapia por Acupuntura/efectos adversos , Terapia por Acupuntura/instrumentación , Adulto , Trastorno Depresivo Mayor/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Paroxetina/administración & dosificación , Paroxetina/efectos adversos , Escalas de Valoración Psiquiátrica , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Clinical studies have demonstrated the effectiveness of an herbal preparation called Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL). In the present study, we further examined the pharmacological action of PGD on prolactin (PRL) secretion using in vitro and in vivo models, with specific attention to the role of dopaminergic mediators and other sex hormones. Treatment with PGD at 1-5mg/ml significantly suppressed PRL secretion and synthesis in MMQ cells, a model of hyperPRL derived from pituitary adenoma cells. The suppressive effects were completely abolished by pretreatment with 10µM haloperidol, a dopamine D(2) receptor antagonist. Consistent with a D(2)-action, PGD did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D(2) receptor expression but significantly increased the expression of D(2) receptors and dopamine transporters (DAT) in PC12 cells. In a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide (MCP), chronic PGD (2.5-10g/kg daily) significantly reduced elevated serum PRL. The reduction in magnitude was similar to that elicited by bromocriptine (BMT), a dopamine D(2) receptor agonist currently used for treatment of hyperPRL. Neither PGD nor BMT altered serum estradiol, but PGD reversed decreased serum progesterone to control level, whereas BMT did not. These results indicate that the anti-hyperPRL effects of PGD are associated not only with D(2) receptor and DAT modulation, but also with a normalization of other sex hormone dysfunction. This experimental evidence supports clinical use of PGD as an effective treatment of antipsychotic-induced hyperPRL.
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Glycyrrhiza/química , Hiperprolactinemia/tratamiento farmacológico , Paeonia/química , Fitoterapia/métodos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Receptores de Dopamina D2/metabolismo , Animales , Bromocriptina/farmacología , Línea Celular , Modelos Animales de Enfermedad , Dopamina/biosíntesis , Antagonistas de los Receptores de Dopamina D2 , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Relación Dosis-Respuesta a Droga , Estradiol/metabolismo , Femenino , Haloperidol/farmacología , Interacciones de Hierba-Droga , Hiperprolactinemia/sangre , Hiperprolactinemia/inducido químicamente , Metoclopramida/efectos adversos , Células PC12 , Extractos Vegetales/antagonistas & inhibidores , Progesterona/metabolismo , Prolactina/biosíntesis , Prolactina/metabolismo , Conejos , Ratas Sprague-Dawley , Receptores de Dopamina D2/agonistasRESUMEN
BACKGROUND: Previous studies suggest that electroacupuncture possesses therapeutic benefits for depressive disorders. The purpose of this study was to determine whether dense cranial electroacupuncture stimulation (DCEAS) could enhance the antidepressant efficacy in the early phase of selective serotonin reuptake inhibitor (SSRI) treatment of major depressive disorder (MDD). METHODS: In this single-blind, randomized, controlled study, patients with MDD were randomly assigned to 9-session DCEAS or noninvasive electroacupuncture (n-EA) control procedure in combination with fluoxetine (FLX) for 3 weeks. Clinical outcomes were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), Clinical Global Impression-severity (CGI-S), and Self-rating Depression Scale (SDS) as well as the response and remission rates. RESULTS: Seventy-three patients were randomly assigned to n-EA (nâ=â35) and DCEAS (nâ=â38), of whom 34 in n-EA and 36 in DCEAS group were analyzed. DCEAS-treated patients displayed a significantly greater reduction from baseline in HAMD-17 scores at Day 3 through Day 21 and in SDS scores at Day 3 and Day 21 compared to patients receiving n-EA. DCEAS intervention also produced a higher rate of clinically significant response compared to n-EA procedure (19.4% (7/36) vs. 8.8% (3/34)). The incidence of adverse events was similar in the two groups. CONCLUSIONS: DCEAS is a safe and effective intervention that augments the antidepressant efficacy. It can be considered as an additional therapy in the early phase of SSRI treatment of depressed patients. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN88008690.
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Trastorno Depresivo Mayor/terapia , Electroacupuntura/métodos , Adulto , Anciano , Antidepresivos de Segunda Generación/administración & dosificación , Terapia Combinada , Terapia Electroconvulsiva/métodos , Femenino , Fluoxetina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Método Simple Ciego , Cráneo/anatomía & histología , Cráneo/fisiología , Resultado del TratamientoRESUMEN
BACKGROUND: The prevalence and risk of cardiovascular disease increase after menopause in correlation with the progression of abnormality in the serum lipid profile and the deprivation of estrogen. Erxian decoction (EXD), a Chinese medicinal formulation for treating menopausal syndrome, stimulates ovarian estrogen biosynthesis. This study investigates whether EXD improves the serum lipid profile in a menopausal rat model. METHODS: Twenty-month-old female Sprague Dawley rats were treated with EXD and its constituent fractions. Premarin was administered for comparison. After eight weeks of treatment, rats were sacrificed and the serum levels of total cholesterol, triglyceride, high-density-lipoprotein cholesterol and low-density-lipoprotein cholesterol were determined. The hepatic protein levels of 3-hydroxy-3-methyl-glutaryl-CoA reductase and low-density-lipoprotein receptor were assessed with Western blot. RESULTS: The serum levels of total cholesterol and low-density-lipoprotein cholesterol were significantly lower in the EXD-treated group than in the constituent fractions of EXD or premarin groups. However, the serum levels of triglyceride and high-density-lipoprotein cholesterol were not significantly different from the control groups. Results from Western blot suggest that EXD significantly down-regulated the protein level of 3-hydroxy-3-methyl-glutaryl-CoA reductase and up-regulated low-density-lipoprotein receptor. Conclusion EXD improves serum lipid profile in a menopausal rat model through the suppression of the serum levels of total cholesterol and low-density-lipoprotein cholesterol, possibly through the down-regulation of the 3-hydroxy-3-methyl-glutaryl-CoA and up-regulation of the low-density-lipoprotein receptor.
RESUMEN
BACKGROUND: Herb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia. METHODS AND FINDINGS: In this retrospective, cross-sectional study, 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM) use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI) 34.2%-38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, ORâ=â3.44, 95% CI 2.80-4.24). However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, ORâ=â2.06, 95% CI 2.06-4.83). Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes. CONCLUSIONS: Concomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated.