Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

La reserpina aumenta la expresión de BDNF y PCNA, y disminuye la de caspasa-3, en células intersticiales (células de Leydig) de ratas / Reserpine increases BDNF and PCNA expression, but decreases caspase-3, in rat interstitial cells (Leydig cells)

La reserpina es un antipsicótico e hipotensor arterial que reduce significativamente los niveles de monoaminas centrales, y también es utilizada para modelar los cuadros depresivos humanos en animales de laboratorio. Este trabajo estudió, en ratas Wistar machos adolescentes, cómo la reserpina afecta indicadores moleculares de la función testicular, la cual se ha visto alterada en humanos deprimidos. Una semana luego de finalizado el tratamiento con reserpina (4 dosis de 0,0 o 1,0 mg/Kg, cada 2 días) la respuesta ansiosa y depresiva fue evaluada en un laberinto en cruz elevado. Posteriormente, se sacrificaron los animales y disecaron los testículos, los cuales fueron fijados e incluidos en bloques de parafina de donde se obtuvieron cortes histológicos de 6 µm de espesor. Estos se utilizaron para medir el diámetro de los túbulos seminíferos y para medir por inmunohistoquímica el porcentaje de células intersticiales (células de Leydig) positivas a (1) Factor neurotrófico derivado del cerebro, (2) antígeno nuclear de células en proliferación (BDNF y PCNA, respectivamente, por sus siglas en inglés), y a (3) caspasa-3. Se obtuvo también un índice de positividad al receptor de andrógenos en las células intersticiales. La expresión del receptor de andrógeno fue evaluada utilizando una escala semicuantitativa de escores (0, 1, 2 y 3) y el resto de las moléculas por presencia o ausencia de expresión de cada antígeno investigado en 300 células por preparado. Los resultados comportamentales indicaron alteraciones en la respuesta de ansiedad y una significativa depresión motora (e.g., mayor latencia en conductas de escape del sector blanco) en los animales tratados con reserpina. No se observaron diferencias en los diámetros de los túbulos seminíferos ni en la expresión del receptor de andrógeno, mientras que sí se encontró mayor proporción de células intersticiales positivas a BDNF y PCNA, y menor proporción de células positivas a caspasa-3, en los animales tratados. Los resultados corroboran la capacidad de la reserpina para reproducir rasgos comportamentales de la depresión. La administración de la droga, sin embargo, no parece reproducir a nivel testicular los efectos deletéreos encontrados en humanos deprimidos, e incluso los resultados sugieren que la reserpina puede mejorar algunos aspectos de la funcionalidad testicular relacionadas con la actividad de las células intersticiales en ratas.

Reserpine, a drug that depletes central monoamines, has been used as an antipsychotic and arterial hypotensive, and to model depression in animals. The present study analyzed, in adolescent male rats, the effects of chronic reserpine treatment on molecular indexes of testicular function. A week after termination of the treatment (4 doses of 0,0 or 1,0 mg/Kg/every 48 h) the animals were tested for anxiety response and depression patterns in an elevated plus maze. They were then euthanized, their testes dissected, fixed and embedded in paraffin to obtain blocks. Histological sections (6 µm) were obtained and used to measure the diameter of seminiferous tubules and the expression in Leydig cells of Brain-derived neurotrophic factor (BDNF), Proliferating cell nuclear antigen (PCNA), Caspase-3 and androgen receptors, by immunohistochemistry. Behavioral results indicated significant alterations in anxiety responses and a significant motor depression (e.g., greater latency to escape from the white sector). There were no differences between groups in the diameter of seminiferous tubules nor in the androgen receptors positivity. Reserpine-treated animals, however, exhibited more BDNF and PCNA positive cells, and less positive Caspase-3 cells in Leydig cells, than control animals. The results corroborate the efficacy of reserpine to reproduce some of the behavioral components of depression. The drug, however, does not seem to exert in rats the same effects on testicular function that have been found in humans diagnosed with depression. Furthermore the drug seems to enhance some aspects of testicular function related to Leydig cells function in rats.

Reserpine treatment activates AMP activated protein kinase (AMPK)

Reserpine is a well-known medicine for the treatment of hypertension, however the role of reserpine in cell signaling is not fully understood. Here, we report that reserpine treatment induces the phosphorylation of AMP activated protein kinase (AMPK) at threonine 172 (T172) in PC12 cells. Phosphorylation of AMPK T172 is regulated by upstream signaling molecules, and the increase of phospho-T172 indicates that AMPK is activated. When we examined the FOXO3a dependent transcription by using the FHRE-Luc reporter assay, reserpine treatment repressed the FHRE-Luc reporter activity in a dose dependent manner. Finally, we showed that reserpine treatment induced the phosphorylation of AMPK as well as cell death in MCF-7 cells. These results suggest that AMPK is a potential cellular target of reserpine.

Efflux Pump Inhibitor Carbonyl Cyanide-m-chlorophenylhydrazone (CCCP) Enhances Bacteriostatic Activity of Trimethoprim-sulfamethoxazole Against Clinical Stenotrophomonas maltophilia Isolates from Korea

Although trimethoprim-sulfamethoxazole (TMP-SXT) is considered the first-line therapy for Stenotrophomonas maltophilia infections, there is debate on the use of the bacteriostatic drug in serious infections, and recently, there has been an increasing occurrence of acquired resistance to TMP-SXT. In the present study, the effect of efflux pump inhibitors on the susceptibility of TMP-SXT and other antibiotics were investigated in S. maltophilia complex. The sul and/or dfrA genes were identified in only up to 27.8% of all 36 TMP-SXT-resistant S. maltophilia complex isolates. Thus, TMP-SXT resistance in S. maltophilia was not explained completely by the presence of sul and dfrA genes. Carbonyl cyanide-m-chlorophenylhydrazone (CCCP) decreased the minimum inhibitory concentration (MIC) of TMP-SXT by eight to 128 folds in all 14 isolates. In contrast, 2,4-dinitrophenol (DNP), phenyl-arginine-β-naphthylamide (PAβN), and reserpine did not reduce the MIC of TMP-SXT. In addition to TMP-SXT, slight decrease in MICs was observed for tigecycline and piperacillin/tazobactam by CCCP (by two folds) in one isolate. Although efflux pump may play a role in TMP-SXT resistance in S. maltophilia, inhibition of the efflux pump could be done by active proton pore.

Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are well known for contributing in AD disease, was also performed to predict anti-AD potential.

A doença de Alzheimer (DA) é uma doença neurodegenerativado sistema nervoso central, em rápido crescimento, e antioxidantes ajudam a suprimir o estresse oxidativo causado por radicais livres, responsávies pela DA. Avaliou-se, biologicamente, série de derivados sintéticos de indol selecionados para identificar novos antioxidantes. A maioria dos compostos avaliados apresentou de significativa a boa propriedade antioxidante (valor de IC50 399,07140.0 ± 50 µM). Eftuaram-se estudos de Teoria do Funcional de Densidade (DFT) com os compostos e os seus correspondentes radicais livres. As diferenças de energia entre os compostos protótipos e os radicais livres correspondentes proporcionaram boa justificativa para a tendência encontrada nos seus valores de IC50. O ancoramento in silico dos compostos com a acetilcolinesterase (AChE) e com a butirilcolinesterase (BChE), que contribuem para a DA, foi, também, realizado para prever o seu potencial anti-DA.

Efflux-mediated resistance identified among norfloxacin resistant clinical strains of group B Streptococcus from South Korea / 한국역학회지

OBJECTIVES: Group B Streptococcus (GBS), a common bowel commensal, is a major cause of neonatal sepsis and an emerging cause of infection in immune-compromised adult populations. Fluoroquinolones are used to treat GBS infections in those allergic to beta-lactams, but GBS are increasingly resistant to fluoroquinolones. Fluoroquinolone resistance has been previously attributed to quinolone resistance determining regions (QRDRs) mutations. We demonstrate that some of fluoroquinolone resistance is due to efflux-mediated resistance. METHODS: We tested 20 GBS strains resistant only to norfloxacin with no mutations in the QRDRs, for the efflux phenotype using norfloxacin and ethidium bromide as substrates in the presence of the efflux inhibitor reserpine. Also tested were 68 GBS strains resistant only to norfloxacin not screened for QRDRs, and 58 GBS strains resistant to ciprofloxacin, levofloxacin or moxifloxacin. Isolates were randomly selected from 221 pregnant women (35-37 weeks of gestation) asymptomatically carrying GBS, and 838 patients with GBS infection identified in South Korea between 2006 and 2008. The VITEK II automatic system (Biomerieux, Durham, NC, USA) was used to determine fluoroquinolone resistance. RESULTS: The reserpine associated efflux phenotype was found in more than half of GBS strains resistant only to norfloxacin with no QRDR mutations, and half where QRDR mutations were unknown. No evidence of the efflux phenotype was detected in GBS strains that were resistant to moxifloxacin or levofloxacin or both. The reserpine sensitive efflux phenotype resulted in moderate increases in norfloxacin minimum inhibitory concentration (average=3.6 fold, range=>1-16 fold). CONCLUSIONS: A substantial portion of GBS strains resistant to norfloxacin have an efflux phenotype.

Preventive Effect of Polysaccharide of Larimichthys crocea Swim Bladder on Reserpine Induced Gastric Ulcer in ICR Mice

This project's aim was to determine the reserpine-induced gastric ulcer preventive effect of polysaccharide of Larimichthys crocea swim bladder (PLCSB) in ICR mice. The anti-gastric ulcer effects of polysaccharide of Larimichthys crocea swim bladder was evaluated in mice model using morphological test, serum levels assay, cytokine levels assay, tissue contents analysis, reverse transcription-polymerase chain reaction (RT-PCR) analysis and western bolt assay. High concentration (50 mg/kg dose) of PLCSB reduced IFN-gamma as compared to low concentration (25 mg/kg dose) and control mice. SS and VIP serum levels of PLCSB treated mice were higher than those of control mice, and MOT and SP serum levels were lower than control mice. Gastric ulcer inhibitory index of PLCSB treatment groups mice were much lower than control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The SOD and GSH-Px activities of PLCSB treated mice were higher than control mice, close to normal mice and ranitidine treated mice. PLCSB treated mice also showed the similar contents of NO and MDA to normal group. By RT-PCR and western blot assay, PLCSB significantly induced inflammation in tissues of mice by downregulating NF-kappaB, iNOS, and COX-2, and upregulating IkappaB-alpha . These results suggest that PLCSB showed a good gastric ulcer preventive effect as the gastric ulcer drug of ranitidine. Polysaccharide of Larimichthys crocea swim bladder may be used as a drug material from marine products.

Effect of drugs; baehavior of mice measured by modified hole board head-dipping exploratory test parameter

The aim of this study was to determine head-dipping exploratory test parameter as a measure of strong modulating effect on brain and behavior. It was an observational animal study. University of Karachi. Period: Jan 2004 to July 2006. In this present study, drugs used reserpine, nux- vomica; anacardium and chlorpromazine were wide range of pharmacological actions. We evaluate the effectiveness of these drugs as agents with modulating effect on brain and behavior accessed by head dipping parameter. In this study, 25 mice were included belonging to both sexes. The study animals were divided into five groups of five animals each. Four groups were given drugs and one group was kept as control. Mice [20-35g] of either sex were used in this study. One group was kept as control for drugs. Mice were kept under room temperature. Tap-water was allowed ad-Lihitum.30 minutes after giving drugs, animals were observed for 10 minutes with two minutes of interval. Tablet crushed in 10ml of water, 1 cc was given. Screening method used was head dipping. Strychnos Nux-Vomica when used in a dose of 0.07mg has strong action on cholinergic system, CNS activity and frequent head dipping [39.8 +/- 28.8] was observed. Rauwolfia serpentine is an active alkaloid particularly present in reserpine [62.2 +/- 43.4] no significant head dipping effect was observed. Anacardium [37.2 +/- 28.6] and Chlorpromazine [39.4 +/- 32.4], show decrease effects. Keeping in view, the medicinal importance of these herbs, our present study was designed to screen these drugs for CNS activity on albino mice

Effect of sijunzi decoction on the intestinal glucose absorption in model rats of Pi-qi deficiency syndrome: an experimental research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Sijunzi Decoction (SD) on the intestinal absorption of glucose in model rats of Pi-qi deficiency syndrome (PQDS).</p><p><b>METHODS</b>PQDS rat model was established by subcutaneous injection of reserpine from the neck. The body weight and urine D-xylose excretion rates were measured. The glucose uptake rate was measured by jejunum perfusion. The intestinal mucosa was collected. The glucose transporter-2 (GLUT2) protein and mRNA expression levels were detected.</p><p><b>RESULTS</b>Compared with the normal control group, the body weight and D-xylose excretion rates decreased in the model group. Meanwhile, the glucose uptake and GLUT2 protein and mRNA expression levels decreased in the model group. The aforesaid indices were improved in the SD group.</p><p><b>CONCLUSION</b>SD could promote the recovery of glucose uptake in the small intestine of reserpine induced PQDS rats.</p>

Effect of euodiae fructus on hepatic energy metabolism-related mechanisms of reserpine-induced asthenia cold syndrome rats / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the effect of Euodiae Fructus on hepatic energy metabolism-related mechanisms of mitochondria of hepatic tissues of asthenia cold syndrome rats.</p><p><b>METHOD</b>Rats were subcutaneously injected with Reserpine to establish the model. After the oral administration with Euodiae Fructus for 12 d, the oxygen electrode method was adopted to determine the respiration efficiency. The expressions of Cox4, Atp5b, Ucp2,Pgc-1alpha, Nrf1, Tfam mRNA were assayed by using RT-PCR method.</p><p><b>RESULT</b>Euodiae Fructus 4.2 g x kg(-1) could obviously increase ST3 and RCR of asthenia cold syndrome rats, and expressions of Cox4, Ucp2 Nrf1 mRNA. It could also increase expressions of Atp5b and Pgc-1alpha mRNA, but with no statistical significance. No obvious change was observed in Tfam mRNA expression. Euodiae Fructus 4.2 g x kg(-1) could significantly increase ST3 and RCR of asthenia cold syndrome rats and Pgc-1alpha mRNA and Nrf1 mRNA expressions, and significantly decrease P/O, with no obvious impact on Cox4, AtpSb, Ucp2, Tfam mRNA expressions.</p><p><b>CONCLUSION</b>Euodiae Fructus can promote mitochondrial respiratory function and oxidative phosphorylation efficiency by improving Pgc-1alpha mRNA and Nrf1 mRNA expressions and regulating Cox4 and Atp5b mRNA in mitochondrial respiratory chain. It can also strengthen mitochondrial uncoupling respiration and add heat production by activating Ucp2 mRNA expression in liver.</p>

Influence of ferulic acid on the pain-depression dyad induced by reserpine / 药学学报

This study is to offer a clinical pain-depression dyad therapy of ferulic acid, the pain-depression dyad induced by reserpine was established and the dose-effect relationship of ferulic acid on ameliorating pain-depression dyad was explored. Mice were randomly divided into control group, reserpine + vechile and reserpine + ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)) groups. The reserpine treated mice were tested with thermal hyperalgesia, mechanicial allodynia and forced swimming tests, and the SOD and NO levels of hippocampus and frontal cortex were measured. Moreover, the HPLC-ECD was used to detect the changes of central monoamines concentrations. Compared with control group, reserpine can induce a significant decrease in the nociceptive threshold and increase in the immobility time of the forced swimming test. The results suggested that reserpine significantly increased the level of nitrite in hippocampus and frontal cortex and reduced the levels of SOD, 5-HT and NE in these two brain regions. However, these indexes can be a dose-dependently reversed by ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)). Ferulic acid can reverse pain-depression dyad, especially at the dose of 80 mg x kg(-1). In addition, it can influence oxidative stress and monoamine level.

Ação da fluoxetina sobre a dor aguda em ratos submetidos à constrição do nervo ciático / Fluoxetine action on acute pain in rats submitted to sciatic nerve constriction

JUSTIFICATIVA E OBJETIVOS: Os inibidores seletivos da recaptação de serotonina como a fluoxetina, têm sido apontados como alternativa ao uso dos antidepressivos tricíclicos para o tratamento da dor crônica, pela menor incidência de efeitos colaterais. O objetivo deste estudo foi estudar o efeito da serotonina na modulação da dor aguda, pela administração de fluoxetina, por meio do teste da formalina, em ratos, anteriormente submetidos à constrição do nervo ciático. MÉTODO: Foram estudados 24 ratos Wistar, machos, com peso médio de 300 g, distribuídos em 5 grupos: 1. Controle sem tratamento; 2. Constrição do nervo ciático; 3. Constrição do nervo ciático tratados com 5 mg.kg-1.dia de fluoxetina, por via oral durante 15 dias; 4. Constrição do nervo ciático tratados com 5 mg.kg-1 de reserpina, por via oral a cada 72h e com 5 mg.kg-1.dia de fluoxetina por via oral, durante 15 dias; 5. Constrição do nervo ciático tratados com 5 mg.kg-1 de reserpina por via oral em intervalos de 72h, durante 15 dias. Todos os animais foram submetidos ao teste da formalina modificado após os tratamentos especificados. RESULTADOS: A resposta na fase I, na fase intermediária e na fase II do teste da formalina não foi alterada pela constrição do ciático. O tratamento com reserpina ou fluoxetina não interferiu com as fases I e intermediária do teste da formalina nos grupos submetidos à constrição do ciático. O número de elevações da pata na fase II do teste da formalina aumentou nos animais tratados com fluoxetina e diminuiu nos animais tratados com reserpina. Nos animais tratados com a associação reserpina e fluoxetina houve redução do número de elevações da pata em comparação com os animais tratados apenas com a fluoxetina. CONCLUSÃO: O tratamento com fluoxetina aumentou a sensação dolorosa após estímulo agudo em ratos submetidos à constrição do ciático, evidenciando ação algogênica do fármaco neste modelo experimental.

BACKGROUND AND OBJECTIVES: Selective serotonin reuptake inhibitors, such as fluoxetine, have been suggested as alternative to tricyclic antidepressants to treat chronic pain, due to the lower incidence of side effects. This study aimed at observing the effects of serotonin on acute pain modulation, by the administration of fluoxetine through the formalin test in rats previously submitted to sciatic nerve constriction. METHOD: We used 24 male Wistar rats, with mean weight of 300 g and distributed in 5 groups: 1. Control untreated; 2. Sciatic nerve constriction; 3. Sciatic nerve constriction and treated with 5 mg.kg-1.day oral fluoxetine for 15 days; 4. Sciatic nerve constriction treated with 5 mg.kg-1 oral reserpine every 72 hours and with 5 mg.kg-1.day oral fluoxetine for 15 days; 5. Sciatic nerve constriction treated with 5 mg.kg-1 oral reserpine every 72 hours for 15 days. All animals were submitted to modified formalin test after treatment. RESULTS: Response in the phase I, intermediate and phase II formalin test was not changed by sciatic nerve constriction. Treatment with reserpine or fluoxetine has not interfered with first and intermediate formalin test phases in the groups submitted to sciatic nerve constriction. The number of flinches in the second formalin test phase has increased in animals treated with fluoxetine and has decreased in animals treated with reserpine. There has been decrease in the number of flinches in animals treated with the association reserpina and fluoxetine as compared to animals treated with fluoxetine alone. CONCLUSION: Fluoxetine has increased painful sensation after acute stimulation in rats submitted to sciatic nerve constriction, showing the algogenic action of the drug in this experimental model.

Altered expression of gamma-secretase components in animal model of major depressive disorder induced by reserpine administration / 한국실험동물학회지

Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of gamma-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (P<0.05). Expression and phosphorylation of MKP-1, which is a key factor in MDD pathology, were both higher in the RSP2-treated group than the vehicle- and 1 mg/kg reserpine (RSP1)-treated groups (P<0.02). Furthermore, full-length expression of amyloid precursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of gamma-secretase components decreased (P<0.03). Among the three components of the gamma-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.

Characterization of the interaction between reserpine and bovine serum albumin: Spectroscopic approaches.

The characteristics of the interaction between reserpine and bovine serum albumin (BSA) were studied by fluorescence, UV-vis absorption and Fourier transform infrared (FT-IR) spectroscopy. Spectroscopic analysis revealed that fluorescence quenching of BSA by reserpine was through a static quenching procedure. The binding constant KA of reserpine with BSA at 293, 301 and 309 K was 1.63, 1.78 and 2.35 × 105 moL-1 L respectively, which indicated degree of binding force between reserpine and BSA. There was one binding site between reserpine and BSA. The entropy and enthalpy changes were positive, indicating that interaction of reserpine and BSA was driven mainly by hydrophobic forces. The average binding distance between the donor (BSA) and the acceptor (reserpine) was about 3.84 nm based on the Förster non-radiation energy transfer theory. Results of synchronous fluorescence and FT-IR spectra indicated that the conformation and microenvironment of BSA were changed by the binding of reserpine. The results may provide important insights into the physiological activity of reserpine.

Efeitos da Marapuama (Ptychopeatalum Olacoides Benthan) nas alterações motoras induzidas por reserpina em camundongos / Motor fitness and work ability of the police officers of the Special Operations Group

Introdução e Objetivo: O motivo deste estudo foi avaliar a ação da Marapuama (Ptychopetatalum olacoides Benthan) nas alterações motoras induzidas pela droga reserpina em camundongos BalbC. Método: Foram utilizados doze camundongos Balb C, fêmeas, divididas em 2 grupos: controle (GC, n = 6 / 0,1 ml de solução oral,) e Marapuama (GM, n = 6 / 500mg/kg concentrada em 0,1 ml de solução oral por dia). A administração das soluções foi feita por gavagem durante 7 dias. Para a indução das alterações motoras semelhantes à Doença de Parkinson, os camundongos receberam por via intraperitoneal 1mg/Kg de resperpina (Sigma). A atividade motora foi avaliada pelo teste do Campo Aberto (BROADHURST,1960), 24 horas, 48 horas e 7 dias após a administração da reserpina. Para a análise estatística foi realizado o teste T-Student p ≤ 0,05. Resultados e discussão: os resultados obtidos mostraram que os camundongos tratados com Marapuama (Ptychopetatalum olacoides Benthan) apresentaram maior freqüência de locomoção do que os integrantes do grupo controle (GC). Quanto ao tempo de imobilidade, o grupo controle (GC) permaneceu mais tempo imóvel do que o grupo Marapuama (GM). A análise estatística mostrou-se significativa entrea comparação dos grupos nas primeiras 24 após a administração da reserpina. Conclusão: Concluiu-se que a fitoterápico Marapuma (Ptychopetatalum olacoides Benthan) apresentou a capacidade de aumentar a atividade motora dos animais sob ação da reserpina o que sugere uma possível capacidade de reduzir a bradicinesia que é um dos sintomas da doença de Parkinson.

Introduction and Objective: the aim of this study was to evaluate the action of Marapuama ( Ptychopetatalum olacoides Bentham ) in motor changes induced by reserpine in mice BalbC. Method: we used twelve Balb C female, divided into two groups: control group ( n = 6 / 0.1 ml of oral solution ) and Marapuama (GM, n = 6 / 500 mg / kg in 0.1 ml of concentrated oral solution per day). The drug administration was by gavage for 7 days. For the induction of motor disorders similar to Parkinson' s disease, the mice received intraperitoneal 1mg/kg resperpina (Sigma). The motor activity was evaluated by open test (BROADHURST, 1960), 24 hours, 48 hours and 7 days after administration of reserpine. For the statistical analysis was performed to test T-Student, p ≤ 0.05. Results and discussion: the results showed that mice treated with Marapuama ( Ptychopetatalum olacoides Bentham ) had higherfrequency of locomotion than members of the control group (CG). As for the immobility time, the control group ( CG ) remained immobile more time than the group Marapuama ( GM ). Statistical analysis was significant between the comparison groups in the first 24 after administration of reserpine. Conclusion: It was concluded that the phytotherapic Marapuma ( Ptychopetatalum olacoides Bentham ) had the ability to increase motor activity under the action of reserpine suggesting a possible ability to reduce bradykinesia, which is one of the symptoms of Parkinson' s disease.

[Study of buspirone effect on motor behavior in rats with parkinson disease caused by reserpine]

Death of dopaminergic neurons, in substantia nigra pars compacta, results in exsanguinations of neurotransmitter dopamine in corpus striatum and motor symptoms of Parkinson disease. However, deterioration of non-dopaminergic neurons, such as serotonergic and noradrenergic neurons, became one of fixed truths of Parkinson disease. It was suggested that these neurons deterioration has a role in motor symptoms, in addition to non-motor symptoms, such as depression, imperceptions and sleep disorders. So, the aim of research was testing Buspirone effect, a partial agonist of 5-HT[1A] auto serotonergic receptors, for improvement of Parkinsons' symptoms in Wister adult albino male rats with Parkinson disease caused by Reserpine [3 mg/kg]. And study of Buspirone effect on L-DOPA therapeutic activity and its important for dyskinesia treatment resulted from long term therapy with L-DOPA. The current study illustrated that low dosages of Buspirone [0.25, 1, 3 and 6 mg/Kg] improved the affected rats' movement, whereas high dosage [10 mg/kg] didn't improve the movement, by comparing these groups with control group which has injected with injected water. Also, this study revealed that Buspirone lows the therapeutic activity of L-DOPA, by comparing the motor behavior of affected groups, which treated with Buspirone [3, 6 and 10 mg/kg]+L-DOPA [100 mg/kg], with that treated only with 100 mg/kg of L-DOPA. As conclusion, our study appears Buspirone efficiency to improve the symptoms of Parkinson disease in animal samples, as it gives an area for clinical experiments for testing the effect of Buspirone [currently used for anxiety treatment] on Parkinson disease's symptoms, in patients suffering from side effects of L-DOPA

Evaluation of the role of striatal cannabinoid CB[1] receptors on movement activity of parkinsonian rats induced by reserpine

It has been observed cannabinoid CB[1] receptor signaling and the levels of endocannabinoid ligands significantly increased in the basal ganglia and cerebrospinal fluids of Parkinson's disease [PD] patients. These evidences suggest that the blocking of cannabinoid CB[1] receptors might be beneficial to improve movement disorders as a sign of PD. In this study, a dose-response study of the effects of intrastriatal injection of a cannabinoid CB[1] receptor antagonist, AM251 and agonist, ACPA, on movement activity was performed by measuring the catalepsy of reserpinized and non-PD [normal] rats with bar test. Also the effect of co-administration the most effective dose of AM251 and several doses of ACPA were assessed. AM251 decreases the reserpine induced catalepsy in dose dependent manner and ACPA causes catalepsy in normal rats in dose dependant manner as well. AM251 significantly reverse the cataleptic effect in all three groups [1, 10, 100ng/rat] that received ACPA. These results support this theory that cannabinoid CB[1] receptor antagonists might be useful to alleviate movement disorder in PD. Also continuance of ACPA induced catalepsy in induced catalepsy. Based on the present finding there is an incomplete overlapping between cannabinoid CB[1] receptor agonist and antagonist effects

[Effects of the activation of histamine H3 receptors on the locomotor activity induced by dopaminergic treatment in the reserpine-treated rat model of Parkinson's disease]

The present study was designed to investigate the effects of the activation of histamine H3 receptors, by selective agonist, on dopaminergic treatment-induced locomotor behavior in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia. Imetit, histamine H3 receptor agonist reduced the enhanced locomotor activity induced by L-DOPA 100 and 200 mg/kg, in a dose-dependent manner. The number of horizontal counts, following the injection of Imetit 7 mg/kg in combination with L-DOPA 200 mg/kg in reserpinised rats, was 1040 +/- 274 count/2h, which was significantly reduced compared to the horizontal activity following the injection of L-DOPA 200 mg/kg alone in reserpinised rats. The vertical count was significantly reduced by injection of imetit 7 mg/kg in combination with L-DOPA 200 mg/kg [560 +/- 110 count/2h]. The highest dose of Imetit 7 mg/kg that extensively reduced all locomotor parameters tested, did not significantly modify the increase in horizontal or vertical activity produced by quinpirole dopamine D2 agonist. The data suggest that histamine H3 receptor agonists can modulate the behavioural effects of L-DOPA, and may be useful for the treatment of the dyskinesia associated with long-term L-DOPA treatment of Parkinson's disease

Effect and mechanism of reserpine for changing salivary protein secretion in Pi-deficient rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of reserpine (RSP) for changing salivary protein secretion in Pi-deficient rats and to explore its possible mechanism.</p><p><b>METHODS</b>Twenty rats allocated in the RSP group were given subcutaneous injection of RSP [0.4 mg/(kg x d)] for 9 successive days, while the other 20 rats in the control group were injected with same volume of saline instead. On the 10th day, ten rats randomly selected from each group were subjected for extracting saliva to detect salivary amylase activity (sAA) before and after an acid stimulation; and drawing blood from the orbital vein to measure the contents of vasoactive intestinal peptide (VIP) and cyclic adenosine monophosphate (cAMP). Then they were sacrificed and their parotids were taken out for pathological examination with HE staining, as well as for VIP and cAMP measuring, and zymogen granules counting under a transmission electron microscope. The remainder animals were stopped injecting and normally fed to 40 days, then subjected to be detected as above-mentioned.</p><p><b>RESULTS</b>Food intake and body weight reduction were more significantly in the RSP group than in the control group. On the 10th day, the ratio of sAA before/after stimulation in the RSP group was 0.39 +/- 0.18, significantly lower than that in the control group (0.80 +/- 0.21, P < 0.01), but it was restored rapidly, reaching the normal range on the 25th day, on the 40th day, it became significantly different to the level on the 10th day (P < 0.05) and approached the level in the control group (P > 0.05). No significant pathological change of parotid was found in both groups; but the number of zymogen granules in the RSP group was remarkably more than that in the control group (41.4 +/- 4.9 vs 34.6 +/- 5.2, P < 0.01). Serum level of VIP in the RSP group was significantly less while that of cAMP was higher than that in the control group (22.5 +/- 13.1 mg/L vs 38.5 +/- 14.1 mg/L, and 125.8 +/- 15.5 micromol/L vs 105.3 +/- 16.7 micromol/L, both P < 0.05), but no inter-group difference was found in parotid tissue contents of both VIP and cAMP. All the indices detected became equivalent in the two groups on the 40th day.</p><p><b>CONCLUSION</b>The reduction of salivary protein in Pi-deficient rats induced by RSP may be related to the regulatory pathway of VIP and cAMP.</p>

Antiulcer and anticonvulsant activity of Croton zambesicus

The ethanolic root extract of Croton zambesicus was investigated for its potential to protect gastric mucosa against ulcers induced by indomethacin, ethanol and reserpine. The anticonvulsant activity of the root extract against pentylene tetrazol[PTZ]- and picrotoxin-induced convulsion in mice was also studied. The extract [27-81mg/kg] produced a significant [P<0.005-0.001] dose-dependent effects against the ulcerogenic effect of differents agents used; indomethacin, ethanol and reserpine. The effect of the extract was lower than that of the standard drug, cimetidine [100mg/kg] in the indomethacin and reserpine-induced ulcer models and higher than that of propranolol [40mg/kg] in ethanol- induced ulcer model. The extract [27-81mg/kg] could not protect mice from convulsion in both PTZ - and picrotoxin- induced convulsion. The root extract significantly [P<0.01-0.001] delayed the onset and latency of convulsion caused by PTZ and picrotoxin. The root extract possesses antiulcer and anticonvulsant properties